Booil Jo

All Publications

• Teleyoga for Patients With Alzheimer's Disease and Chronic Musculoskeletal Pain and Their Caregivers: A Feasibility Study. Global advances in integrative medicine and health Allende, S., Mahoney, L., Francisco, J. M., Fitz, K., Keaney, A., Parker-Bridges, K., Mahoney, H., Jo, B., Greenberg, J., Bayley, P. J. 2024; 13: 27536130241240405

  Abstract

  Chronic musculoskeletal pain is common in patients with Alzheimer's disease (AD), and there is growing awareness that chronic pain has an impact on the progression of dementia. Yoga has shown promise in treating chronic pain. However, attending in-person yoga can be difficult for AD patients.To assess the feasibility, acceptability and preliminary efficacy of an online yoga (teleyoga) protocol suitable for AD patients with chronic pain, and their caregivers.Patients with comorbid mild AD and chronic musculoskeletal pain (n = 15, 57-95 y/o; 73% Female) and their caregivers (n = 15, 50-75 y/o; 67% Female) received 12-week of teleyoga individually (n = 5 dyads) or in groups (n = 10 dyads). Study measures included standard feasibility metrics, and secondary outcomes included the Brief Pain Inventory-Short Form (BPI-SF), Beck Depression Inventory-II (BDI-II), and cognitive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Caregivers also completed measures of caregiver burden, and quality of life (Short Form Health Survey-36, SF-36).Feasibility measures showed adequate treatment adherence (85.1% in patients and 86.3% in caregivers), acceptability (mean acceptability rating = 3.0 for patients and 3.3 for caregivers, indicating positive approval), recruitment rate (n = 16 dyads within 1-year), retention rate (87%), missing data rate (.03%), and fidelity of treatment delivery (87%). Preliminary efficacy findings in the AD group showed significant reductions in pain severity (BPI-SF mean Δ = -.93, P = .045) and depression (BDI-II; mean Δ = -9.85, P = .005). %). Preliminary efficacy findings in the caregiver group showed significant reductions in depression (BDI-II mean Δ = -6.88, P = .036) and fatigue (SF-36 mean Δ = 9.81, P = .021).Results show that teleyoga is a feasible treatment for patients with comorbid mild AD and chronic musculoskeletal pain. Results also provide preliminary evidence of health benefits of teleyoga for both AD patients and their caregivers.

  View details for DOI 10.1177/27536130241240405

  View details for PubMedID 38545336

  View details for PubMedCentralID PMC10966998

• Sex-Specific Vulnerability to Externalizing Problems: Sensitivity to Early Stress and Nucleus Accumbens Activation Over Adolescence. Biological psychiatry Borchers, L. R., Yuan, J. P., Leong, J. K., Jo, B., Chahal, R., Ryu, J., Nam, A., Coury, S. M., Gotlib, I. H. 2024

  Abstract

  Exposure and sensitivity to early life stress (ELS) are related to increased risk for psychopathology in adolescence. While cross-sectional studies have reported blunted nucleus accumbens (NAcc) activation in the context of these associations, researchers have not yet assessed the effects of ELS on developmental trajectories of activation. We examined whether trajectories are affected by stress and the moderating role of biological sex in predicting vulnerability to symptoms of psychopathology.Adolescents (n=173) completed three assessments at two-year intervals across puberty (ages 9-18 years). At baseline we assessed objective ELS and stress sensitivity using the Traumatic Events Screening Inventory for Children. At all timepoints we assessed NAcc activation using the Monetary Incentive Delay task and externalizing, internalizing, and total problems using the Youth Self-Report. We correlated NAcc trajectories (extracted using linear mixed effects models) with ELS and stress sensitivity, and conducted multivariate regression analysis to examine the interaction of NAcc trajectories and biological sex in predicting symptoms of psychopathology.Symptoms increased over adolescence. Stress sensitivity, but not objective ELS, was associated with decreasing trajectories of NAcc activation. Biological sex interacted with NAcc trajectories to predict psychopathology: boys, but not girls, with decreasing NAcc activation had more severe externalizing problems in adolescence. These findings were replicated in the putamen and caudate but not in the medial prefrontal cortex or control brain regions.NAcc activation may be a sex-specific marker of externalizing problems in adolescence. Efforts to reduce stress sensitivity may help to decrease symptoms of psychopathology in adolescent boys.

  View details for DOI 10.1016/j.biopsych.2024.01.011

  View details for PubMedID 38272286

• Early life stress predicts trajectories of emotional problems and hippocampal volume in adolescence. European child & adolescent psychiatry Buthmann, J. L., Miller, J. G., Uy, J. P., Coury, S. M., Jo, B., Gotlib, I. H. 2023

  Abstract

  Exposure to early life stress (ELS) has been consistently associated with adverse emotional and neural consequences in youth. The development of brain structures such as the hippocampus, which plays a significant role in stress and emotion regulation, may be particularly salient in the development of psychopathology. Prior work has documented smaller hippocampal volume (HCV) in relation to both ELS exposure and risk for psychopathology. We used longitudinal k-means clustering to identify simultaneous trajectories of HCV and emotional problems in 155 youth across three assessments conducted approximately two years apart (mean baseline age = 11.33 years, 57% female). We also examined depressive symptoms and resilience approximately two years after the third timepoint. We identified three clusters of participants: a cluster with high HCV and low emotional problems; a cluster with low HCV and high emotional problems; and a cluster with low HCV and low emotional problems. Importantly, severity of ELS was associated with greater likelihood of belonging to the low HCV/high symptom cluster than to the low HCV/low symptom cluster. Further, low HCV/high symptom participants had more depressive symptoms and lower resilience scores than did participants in the low HCV/low symptom, but not than in the high HCV/low symptom cluster. Our findings suggest that smaller HCV indexes biological sensitivity to stress. This adds to our understanding of the ways in which ELS can affect hippocampal and emotional development in young people and points to hippocampal volume as a marker of susceptibility to context.

  View details for DOI 10.1007/s00787-023-02331-4

  View details for PubMedID 38135803

  View details for PubMedCentralID 6179355

• Who Responds to an Adaptive Intervention for Adolescents With Anorexia Nervosa Being Treated With Family-Based Treatment? Outcomes From a Randomized Clinical Trial. Journal of the American Academy of Child and Adolescent Psychiatry Lock, J. D., Le Grange, D., Bohon, C., Matheson, B., Jo, B. 2023

  Abstract

  Anorexia Nervosa (AN) is a serious psychiatric disorder with high morbidity and mortality. The current evidence supports the use of Family-Based Treatment (FBT), but recovery rates are about 40%. Improving treatment outcomes among adolescents will save lives, improve health, and prevent chronicity. This study examined the relative efficacy of adding Intensive Parental Coaching (IPC) to standard FBT for those who do not respond by weight gain of 2.4 kg by session 4, a clinical predictor of outcome at the end of treatment (EOT), to improve remission rates (>94% of expected mean body mass index (mBMI)).107 adolescents and their families were recruited, of whom 69 failed to respond early and were randomized to continue with standard FBT or to receive 3 sessions of IPC. Participants were adolescents with DSM-5 AN between the ages of 12-18 years recruited from across the US; 6.5% were male participants and 11% were Hispanic.Main outcomes were mBMI >94% expected for age, height, and sex. Secondary outcomes include change in eating-related cognitions. Adding IPC to early non-responders did not improve outcomes except for those whose parents demonstrated low parental self-efficacy at baseline (moderator). Early weight gain of 2.4kg by session 4 was replicated as a predictor of end of treatment remission.Parental self-efficacy (PSE) moderates IPC as an adaptive treatment for adolescent AN. Baseline PSE assessment can be used to identify those families most likely to benefit from adding IPC to FBT. Future studies should consider earlier interventions to improve early response rates.

  View details for DOI 10.1016/j.jaac.2023.10.012

  View details for PubMedID 38142046

• Multimodal Exercise and Cognitive Training Program Improves Cognitive Function in Amnestic Mild Cognitive Impairment. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Fairchild, J. K., Myers, J., Louras, P., Jo, B., McNerney, M. W., Hallmayer, J., Yesavage, J. 2023

  Abstract

  To investigate the preliminary efficacy of a combined physical exercise + cognitive training intervention for older adults with amnestic mild cognitive impairment (aMCI).Randomized clinical trial.Veteran Affairs Hospital, Palo Alto, CA.Sample included 72 community-dwelling volunteers (mean age 72.4 ± 9.5) diagnosed with aMCI.Participants were randomized to either a combined aerobic and resistance exercise + cognitive training (CARE+CT) or stretching exercise + CT (SE+CT).Primary outcomes included intervention specific assessments of word list and name-face recall. Secondary cognitive outcomes included standardized composite scores that reflect cognitive domains (e.g., learning and memory, executive function, processing speed, visuospatial ability, language). Secondary physiological outcomes included VO2 max and functional capacity (e.g., distance walked 6-minute walk test). APOE and BDNF were determined from whole blood samples.Controlling for age and employment status, linear mixed effects models revealed that all participants experienced significant improvement in the delayed recall of word list, learning and memory and executive function. Only the CARE+CT condition had significant improvement in processing speed and functional capacity. APOE4 status impacted cognitive benefits of those in the SE+CT condition.Results provide preliminary support for combined exercise and cognitive training interventions for older adults with aMCI. Further research is needed to understand the mechanisms involved as well as the impact of these interventions in diverse samples.ClinicalTrials.gov Identifier: NCT01962038.

  View details for DOI 10.1016/j.jagp.2023.12.002

  View details for PubMedID 38220592

• Novel effects of Ras-MAPK pathogenic variants on the developing human brain and their link to gene expression and inhibition abilities. Translational psychiatry Rai, B., Naylor, P. E., Siqueiros-Sanchez, M., Wintermark, M., Raman, M. M., Jo, B., Reiss, A. L., Green, T. 2023; 13 (1): 245

  Abstract

  The RASopathies are genetic syndromes associated with pathogenic variants causing dysregulation of the Ras/mitogen-activated protein kinase (Ras-MAPK) pathway, essential for brain development, and increased risk for neurodevelopmental disorders. Yet, the effects of most pathogenic variants on the human brain are unknown. We examined: (1) How Ras-MAPK activating variants of PTPN11/SOS1 protein-coding genes affect brain anatomy. (2) The relationship between PTPN11 gene expression levels and brain anatomy, and (3) The relevance of subcortical anatomy to attention and memory skills affected in the RASopathies. We collected structural brain MRI and cognitive-behavioral data from 40 pre-pubertal children with Noonan syndrome (NS), caused by PTPN11 (n = 30) or SOS1 (n = 10) variants (age 8.53 ± 2.15, 25 females), and compared them to 40 age- and sex-matched typically developing controls (9.24 ± 1.62, 27 females). We identified widespread effects of NS on cortical and subcortical volumes and on determinants of cortical gray matter volume, surface area (SA), and cortical thickness (CT). In NS, we observed smaller volumes of bilateral striatum, precentral gyri, and primary visual area (d's < -0.8), and extensive effects on SA (d's > |0.8|) and CT (d's > |0.5|) relative to controls. Further, SA effects were associated with increasing PTPN11 gene expression, most prominently in the temporal lobe. Lastly, PTPN11 variants disrupted normative relationships between the striatum and inhibition functioning. We provide evidence for the effects of Ras-MAPK pathogenic variants on striatal and cortical anatomy as well as links between PTPN11 gene expression and cortical SA increases, and striatal volume and inhibition skills. These findings provide essential translational information on the Ras-MAPK pathway's effect on human brain development and function.

  View details for DOI 10.1038/s41398-023-02504-4

  View details for PubMedID 37407569

  View details for PubMedCentralID 4115674

• Reorienting Latent Variable Modeling for Supervised Learning. Multivariate behavioral research Jo, B., Hastie, T. J., Li, Z., Youngstrom, E. A., Findling, R. L., Horwitz, S. M. 2023: 1-15

  Abstract

  Despite its potentials benefits, using prediction targets generated based on latent variable (LV) modeling is not a common practice in supervised learning, a dominating framework for developing prediction models. In supervised learning, it is typically assumed that the outcome to be predicted is clear and readily available, and therefore validating outcomes before predicting them is a foreign concept and an unnecessary step. The usual goal of LV modeling is inference, and therefore using it in supervised learning and in the prediction context requires a major conceptual shift. This study lays out methodological adjustments and conceptual shifts necessary for integrating LV modeling into supervised learning. It is shown that such integration is possible by combining the traditions of LV modeling, psychometrics, and supervised learning. In this interdisciplinary learning framework, generating practical outcomes using LV modeling and systematically validating them based on clinical validators are the two main strategies. In the example using the data from the Longitudinal Assessment of Manic Symptoms (LAMS) Study, a large pool of candidate outcomes is generated by flexible LV modeling. It is demonstrated that this exploratory situation can be used as an opportunity to tailor desirable prediction targets taking advantage of contemporary science and clinical insights.

  View details for DOI 10.1080/00273171.2023.2182753

  View details for PubMedID 37229653

• Neuropsychiatric phenotypes in children with Noonan syndrome. Developmental medicine and child neurology Naylor, P. E., Bruno, J. L., Shrestha, S. B., Friedman, M., Jo, B., Reiss, A. L., Green, T. 2023

  Abstract

  AIM: We investigated neuropsychiatric outcomes in children with Noonan syndrome and addressed limitations in previous research with a focus on prepubertal children, comparison to typically developing children, comprehensive neuropsychiatric evaluation, and controlling for overall cognitive abilities.METHOD: Forty-five children with Noonan syndrome (mean=8years 6months, SD=2years 2months; 29 females) and 40 typically developing children (mean=8years 9months, SD=2years; 22 females) were evaluated with objective, parent-report, and psychiatric interview measures.RESULTS: Children with Noonan syndrome demonstrated elevated symptoms across attention-deficit/hyperactivity disorder (ADHD) (attention, hyperactivity, and inhibition), autism spectrum disorder (ASD) (maintaining social relationships, behavioral rigidity, and sensory sensitivity), and oppositional defiant disorder (ODD) (aggression) symptom clusters relative to typically developing children (all p<0.05). Group differences in nearly all parent-report measures were significant after accounting for variations in intellectual functioning, suggesting that increased neurodevelopmental symptoms are not simply driven by overall intelligence. Twenty out of 42 children with Noonan syndrome met criteria for ADHD, eight out of 42 for ODD, and 11 out of 43 demonstrated clinically significant symptoms seen in children with ASD.INTERPRETATION: Children with Noonan syndrome are at increased risk for a range of ADHD, ASD, and ODD associated symptoms. A dimensional approach reveals significant ASD symptoms in Noonan syndrome that do not emerge when using the currently accepted categorical diagnostic approach.

  View details for DOI 10.1111/dmcn.15627

  View details for PubMedID 37130201

• Cognitive Control Predicts Alleviation of OCD Symptoms by Ketamine Van Roessel, P., Asgari, S., Jo, B., Williams, L., Rodriguez, C. ELSEVIER SCIENCE INC. 2023: S311-S312

  View details for Web of Science ID 000993018500756

• Adolescent brain development in girls with Turner syndrome. Human brain mapping Lozano Wun, V., Foland-Ross, L. C., Jo, B., Green, T., Hong, D., Ross, J. L., Reiss, A. L. 2023

  Abstract

  Turner syndrome (TS) is a common sex chromosome aneuploidy in females associated with various physical, cognitive, and socio-emotional phenotypes. However, few studies have examined TS-associated alterations in the development of cortical gray matter volume and the two components that comprise this measure-surface area and thickness. Moreover, the longitudinal direct (i.e., genetic) and indirect (i.e., hormonal) effects of X-monosomy on the brain are unclear. Brain structure was assessed in 61 girls with TS (11.3 ± 2.8 years) and 55 typically developing girls (10.8 ± 2.3 years) for up to 4 timepoints. Surface-based analyses of cortical gray matter volume, thickness, and surface area were conducted to examine the direct effects of X-monosomy present before pubertal onset and indirect hormonal effects of estrogen deficiency/X-monosomy emerging after pubertal onset. Longitudinal analyses revealed that, whereas typically developing girls exhibited normative declines in gray matter structure during adolescence, this pattern was reduced or inverted in TS. Further, girls with TS demonstrated smaller total surface area and larger average cortical thickness overall. Regionally, the TS group exhibited decreased volume and surface area in the pericalcarine, postcentral, and parietal regions relative to typically developing girls, as well as larger volume in the caudate, amygdala, and temporal lobe regions and increased thickness in parietal and temporal regions. Surface area alterations were predominant by age 8, while maturational differences in thickness emerged by age 10 or later. Taken together, these results suggest the involvement of both direct and indirect effects of X-chromosome haploinsufficiency on brain development in TS.

  View details for DOI 10.1002/hbm.26327

  View details for PubMedID 37126641

• Efficacy of Ketamine in Unmedicated Adults With OCD: A Randomized Controlled Trial Rodriguez, C., Chen, C., Glover, G., Jo, B., Spielman, D., Williams, L., van Roessel, P., DeBattista, C., Wintermark, M., Lombardi, A., Pinto, A., Valentine, K., Filippou-Frye, M., Hawkins, J., McCarthy, E., Mukunda, P., Varias, A., Wilson, J., Wright, B. ELSEVIER SCIENCE INC. 2023: S83

  View details for Web of Science ID 000993018500200

• Emotion regulation and choice of bilateral mastectomy for the treatment of unilateral breast cancer. Cancer medicine Zhang, J. X., Kurian, A. W., Jo, B., Nouriani, B., Neri, E., Gross, J. J., Spiegel, D. 2023

  Abstract

  There has been steadily increasing use of bilateral mastectomy (BMX) in the treatment of primary breast cancer (BC). In this study, we utilized functional magnetic resonance imaging (fMRI) to examine the influence of emotion regulation on the decision of newly diagnosed BC patients to choose BMX rather than non-BMX treatments.We recruited 123 women with unilateral BC, 61 of whom received BMX and 62 of whom received non-BMX treatments, and 39 healthy controls. While participants were in the fMRI scanner, we showed them BC-related and non-BC-negative images. In one condition, they were instructed to watch the images naturally. In another, they were instructed to regulate their negative emotion. We compared the fMRI signal during these conditions throughout the brain.With non-BC-negative images as the baseline, BC patients showed greater self-reported reactivity and neural reactivity to BC-related images in brain regions associated with self-reflection than did controls. Among the BC patients, the BMX group showed weaker activation in prefrontal emotion regulation brain regions during emotion regulation than did the non-BMX group.BC patients are understandably emotionally hyper-reactive to BC-related stimuli and those who ultimately received BMX experience more difficulty in regulating BC-related negative emotion than non-BMX BC patients. These findings offer neuropsychological evidence that difficulty in managing anxiety related to the possibility of cancer recurrence is a factor in surgical treatment decision-making and may be an intervention target with the goal of strengthening the management of cancer-related anxiety by nonsurgical means.NCT03050463.

  View details for DOI 10.1002/cam4.5963

  View details for PubMedID 37083300

• Group trauma focused cognitive behavior therapy for parents of premature infants compared to individual therapy intervention. Early human development Shaw, R. J., Moreyra, A., Simon, S., Wharton, E., Dowtin, L. L., Armer, E., Goldman, L. W., Borkovi, T., Neri, E., Jo, B., Hintz, S., Van Meurs, K., Horwitz, S. M. 2023; 181: 105773

  Abstract

  The current study compares results of a group-based intervention developed to reduce symptoms of posttraumatic stress, depression, and anxiety in parents of premature infants with a prior study using an individual version of the treatment manual.26 mothers of preterm infants (25-34 weeks' gestational age; >600 g) received 6 sessions of trauma-focused cognitive behavior therapy (CBT). Outcomes were compared with those of a previously published RCT, which tested an individual therapy based on the same model in a group of 62 mothers. Results were also compared across in-person and telehealth treatment.From baseline to follow up, the individual intervention showed greater improvement in trauma symptoms assessed with the Davidson Trauma Scale (d = 0.48, p = 0.016), although both conditions showed clinically significant improvement. Similar patterns were found for maternal depression and anxiety. In-person treatment was found to be superior to telehealth treatment administered during the COVID-19 pandemic, although the difference was not significant.Group-based trauma focused CBT is an effective treatment modality for parents of premature infants with symptoms of psychological distress but not as effective as individual therapy using the same treatment model.

  View details for DOI 10.1016/j.earlhumdev.2023.105773

  View details for PubMedID 37119727

• Beyond maintaining safety: Examining the benefit of emotion-centered problem solving therapy added to safety planning for reducing late life suicide risk. Contemporary clinical trials Beaudreau, S. A., Lutz, J., Wetherell, J. L., Nezu, A. M., Nezu, C. M., O'Hara, R., Gould, C. E., Roelk, B., Jo, B., Hernandez, B., Samarina, V., Otero, M. C., Gallagher, A., Hirsch, J., Funderburk, J., Pigeon, W. R. 2023: 107147

  Abstract

  Few clinical trials have examined brief non-pharmacological treatments for reducing suicide risk in older Veterans, a high-risk group. Problem Solving Therapy (PST) is a promising psychosocial intervention for reducing late life suicide risk by increasing adaptive coping to problems through effective problem solving and related coping skills. The current randomized clinical trial will compare the efficacy of six telephone-delivered sessions of Safety Planning (enhanced usual care; EUC) only or an updated version of PST (emotion-centered PST [EC-PST]) + EUC to determine the added clinical benefit of EC-PST for reducing severity of suicidal ideation and for increasing reasons for living, a critical protective factor. Participants randomized to EC-PST + EUC or EUC only will be 150 Veterans (75 each) with active suicidal ideation who are aged 60 or older; have a current DSM-5 anxiety, depressive, and/or trauma-related disorder; and without significant cognitive impairment. Primary outcomes (Geriatric Suicide Ideation Scale and Reasons for Living-Older Adults scale) will be assessed at 11 timepoints: baseline, after each of 6 treatment sessions, posttreatment, and at follow-up at 1, 3, and 6 months posttreatment, and analyzed using mixed effects modeling. Additionally, moderators and mediators of primary outcomes will be examined-functional disability, executive dysfunction, and problem-solving ability. Qualitative feedback from participants will identify potential Veteran-centric changes to the EC-PST protocol and to EUC. Ultimately, the goal of this study is to inform the evidence-based clinical practice guidelines for treatments to reduce suicide risk in older Veterans and specifically to inform clinical decision-making regarding the merit of adding EC-PST to EUC.

  View details for DOI 10.1016/j.cct.2023.107147

  View details for PubMedID 36921689

• Novel effects of Ras-MAPK pathogenic variants on the developing human brain and their link to gene expression and inhibition abilities. Research square Rai, B., Naylor, P., Sanchez, M. S., Wintermark, M., Raman, M., Jo, B., Reiss, A., Green, T. 2023

  Abstract

  The RASopathies are genetic syndromes associated with pathogenic variants causing dysregulation of the Ras/mitogen-activated protein kinase (Ras-MAPK) pathway, essential for brain development, and increased risk for neurodevelopmental disorders. Yet, the effects of most pathogenic variants on the human brain are unknown. We examined: 1. How Ras-MAPK activating variants of PTPN11 / SOS1 protein-coding genes affect brain anatomy. 2. The relationship between PTPN11 gene expression levels and brain anatomy, and 3. The relevance of subcortical anatomy to attention and memory skills affected in the RASopathies. We collected structural brain MRI and cognitive-behavioral data from 40 pre-pubertal children with Noonan syndrome (NS), caused by PTPN11 ( n  = 30) or SOS1 ( n  = 10) variants (age 8.53 ± 2.15, 25 females), and compared them to 40 age- and sex-matched typically developing controls (9.24 ± 1.62, 27 females). We identified widespread effects of NS on cortical and subcortical volumes and on determinants of cortical gray matter volume, surface area (SA) and cortical thickness (CT). In NS, we observed smaller volumes of bilateral striatum, precentral gyri, and primary visual area ( d 's<-0.8), and extensive effects on SA ( d 's>|0.8|) and CT ( d 's>|0.5|) relative to controls. Further, SA effects were associated with increasing PTPN11 gene expression, most prominently in the temporal lobe. Lastly, PTPN11 variants disrupted normative relationships between the striatum and inhibition functioning. We provide evidence for effects of Ras-MAPK pathogenic variants on striatal and cortical anatomy as well as links between PTPN11 gene expression and cortical SA increases, and striatal volume and inhibition skills. These findings provide essential translational information on the Ras-MAPK pathway's effect on human brain development and function.

  View details for DOI 10.21203/rs.3.rs-2580911/v1

  View details for PubMedID 36865206

  View details for PubMedCentralID PMC9980214

• Longitudinal investigation of cognition, social competence, and anxiety in children and adolescents with Turner syndrome. Hormones and behavior Jordan, T. L., Klabunde, M., Green, T., Hong, D. S., Ross, J. L., Jo, B., Reiss, A. L. 2023; 149: 105300

  Abstract

  Turner syndrome (TS), a common neurogenetic disorder caused by complete or partial absence of an X chromosome in females, is characterized by distinct physical, cognitive, and social-emotional features. Girls with TS typically display average overall intellectual functioning with relative strength in verbal abilities and weaknesses in visuospatial processing, executive function (EF), and social cognition. This study was designed to better understand longitudinal trajectories of cognitive and social-emotional domains commonly affected in TS. Participants included 57 girls with monosomic 45,X TS and 55 age- and verbal-IQ matched girls who completed behavioral, child-report, and parent-report measures across four timepoints. Group differences in visuospatial processing, EF, social cognition, and anxiety were assessed longitudinally. Potential effects of estrogen replacement therapy (ERT) were assessed cross-sectionally on an exploratory basis. The TS group showed poorer performance on measures of visuospatial processing, EF, and social cognition, but not anxiety, compared to controls throughout childhood and adolescence. There were no significant group differences in the trajectory of skill development over time. Exploratory analyses within the TS group revealed that girls who were receiving ERT showed better performance on measures of overall IQ, expressive vocabulary, and visuospatial processing compared to those not receiving ERT. Consistent with existing literature, weaknesses in visuospatial processing, EF, and social competence among girls with TS persisted throughout childhood and adolescence. Exploratory analyses suggest that ERT may help improve some aspects of cognitive function in TS, although other pre-existing, nonhormonal differences between the two TS subgroups may alternatively explain these findings, given our study design. Future studies are needed to examine potential impacts of ERT on cognitive and social-emotional development in TS.

  View details for DOI 10.1016/j.yhbeh.2022.105300

  View details for PubMedID 36640638

• Moderators and Mediators of a Digital Cognitive Behavior Therapy-Guided Self-Help Intervention for Eating Disorders: Informing Future Design Efforts JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY Graham, A. K., Fitzsimmons-Craft, E. E., Sadeh-Sharvit, S., Balantekin, K. N., Eichen, D. M., Firebaugh, M., Goel, N. J., Monterubio, G. E., Karam, A. M., Flatt, R. E., Jo, B., Jacobi, C., Wilfley, D. E., Taylor, C., Trockel, M. 2023

  Abstract

  The Student Bodies-Eating Disorders intervention (SB-ED), a digital cognitive behavior therapy-guided self-help intervention for college women with an eating disorder, is effective for reducing eating disorder psychopathology. The purpose of this study was to evaluate moderators and mediators of the SB-ED intervention. To our knowledge, this is the first evaluation of clinical mediators of a digital intervention for women with eating disorders.This is an exploratory secondary analysis of a cluster randomized trial comparing the SB-ED intervention to referral to usual care among 690 women at 27 United States colleges. Moderators included body mass index (BMI), race, ethnicity, weight/shape concerns, eating disorder impairment, thin ideal internalization, depression, anxiety, and motivation for treatment, assessed at baseline. Thin ideal internalization and depressive symptoms were tested as predictors at postintervention and mediators at 2-year follow-up. Outcome was change in global eating disorder psychopathology.BMI moderated the effect of the intervention at follow-up (but not posttreatment), with individuals with a lower BMI experiencing more continued improvements in eating disorder psychopathology following the intervention than individuals with a higher BMI. Thin ideal internalization mediated the effect of the intervention at follow-up, and depression partially mediated the effect of the intervention at follow-up.Results of the mediator analyses suggest that helping college women reduce inflated internalization of the thin ideal and improve depressive symptoms leads to improvements in eating disorder psychopathology. Results also suggest opportunities to optimize the intervention so individuals across the BMI spectrum experience ongoing improvements over time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

  View details for DOI 10.1037/ccp0000786

  View details for Web of Science ID 000912082400001

  View details for PubMedID 36634022

• Brief structured respiration practices enhance mood and reduce physiological arousal. Cell reports. Medicine Balban, M. Y., Neri, E., Kogon, M. M., Weed, L., Nouriani, B., Jo, B., Holl, G., Zeitzer, J. M., Spiegel, D., Huberman, A. D. 2023: 100895

  Abstract

  Controlled breathwork practices have emerged as potential tools for stress management and well-being. Here, we report a remote, randomized, controlled study (NCT05304000) of three different daily 5-min breathwork exercises compared with an equivalent period of mindfulness meditation over 1 month. The breathing conditions are (1) cyclic sighing, which emphasizes prolonged exhalations; (2) box breathing, which is equal duration of inhalations, breath retentions, and exhalations; and (3) cyclic hyperventilation with retention, with longer inhalations and shorter exhalations. The primary endpoints are improvement in mood and anxiety as well as reduced physiological arousal (respiratory rate, heart rate, and heart rate variability). Using a mixed-effects model, we show that breathwork, especially the exhale-focused cyclic sighing, produces greater improvement in mood (p < 0.05) and reduction in respiratory rate (p < 0.05) compared with mindfulness meditation. Daily 5-min cyclic sighing has promise as an effective stress management exercise.

  View details for DOI 10.1016/j.xcrm.2022.100895

  View details for PubMedID 36630953

• Insights about personality traits and cognitive performance and decline in adults 51-59Years old from the Wisconsin longitudinal study. International journal of geriatric psychiatry Beaudreau, S. A., Gould, C. E., Hantke, N. C., Kramer, A. O., Suresh, M., Jo, B., Fairchild, J. K. 2023; 38 (1): e5852

  Abstract

  OBJECTIVES: To delineate midlife personality dimensions of early cognitive change in an age-homogenous sample of U.S. older adults.DESIGN: Longitudinal study of 6133 adults from the Wisconsin Longitudinal Study (WLS).MEASURES: Middle-aged participants (mean age=53.2; SD=0.6) from the WLS completed the 'Big-5' personality assessment in 1992. Mixed effects models examined whether midlife personality traits were associated with change in cognitive performance from participant's mid-60s (2004-2005) to early 70s (2011). The cognitive battery assessed abstract reasoning (AR), category fluency (CF), working memory (WM), and delayed verbal memory (DVM). Models adjusted for sex, education, and subjective health.RESULTS: High Openness was a significant predictor of change in AR, CF, and DVM. These cognitive outcomes declined less among those with high Openness, but the effect sizes for Openness by time were small (R2 s<0.01). AR and CF were characterized by higher overall performance with high Openness, but with relatively parallel change for the highest and lowest Openness quartiles. There was no advantage of Openness to DVM by the second assessment. High Conscientiousness was a predictor of more change for DVM, though the effect size was small (R 2 <0.01).CONCLUSIONS: None of the midlife personality traits were uniformly associated with change in cognitive performance in early older adulthood. High midlife Openness had the most noteworthy impact on cognition. Interventions designed to target Openness have potential to elevate and maintain a higher threshold of performance in some cognitive domains, but may only have a small impact on cognitive change.

  View details for DOI 10.1002/gps.5852

  View details for PubMedID 36495530

• Anosognosia in hoarding disorder is predicted by alterations in cognitive and inhibitory control. Scientific reports van Roessel, P. J., Marzke, C., Varias, A. D., Mukunda, P., Asgari, S., Sanchez, C., Shen, H., Jo, B., Gunaydin, L. A., Williams, L. M., Rodriguez, C. I. 2022; 12 (1): 21752

  Abstract

  Insight impairment contributes significantly to morbidity in psychiatric disorders. The neurologic concept of anosognosia, reflecting deficits in metacognitive awareness of illness, is increasingly understood as relevant to psychopathology, but has been little explored in psychiatric disorders other than schizophrenia. We explored anosognosia as an aspect of insight impairment in n = 71 individuals with DSM-5 hoarding disorder. We used a standardized clutter severity measure to assess whether individuals with hoarding disorder underreport home clutter levels relative to independent examiners. We then explored whether underreporting, as a proxy for anosognosia, is predicted by clinical or neurocognitive behavioral measures. We found that individuals with hoarding disorder underreport their clutter, and that underreporting is predicted by objective severity of clutter. In an n = 53 subset of participants, we found that underreporting is predicted by altered performance on tests of cognitive control and inhibition, specifically Go/No-Go and Stroop tests. The relation of underreporting to objective clutter, the cardinal symptom of hoarding disorder, suggests that anosognosia may reflect core pathophysiology of the disorder. The neurocognitive predictors of clutter underreporting suggest that anosognosia in hoarding disorder shares a neural basis with metacognitive awareness deficits in other neuropsychiatric disorders and that executive anosognosia may be a transdiagnostic manifestation of psychopathology.

  View details for DOI 10.1038/s41598-022-25532-4

  View details for PubMedID 36526652

• Dimensional Assessment of Restricted and Repetitive Behaviors: Development and Preliminary Validation of a New Measure. Journal of the American Academy of Child and Adolescent Psychiatry Uljarević, M., Frazier, T. W., Jo, B., Scahill, L., Youngstrom, E. A., Spackman, E., Phillips, J. M., Billingham, W., Hardan, A. 2022

  Abstract

  This paper provides initial validation of the Dimensional Assessment of Restricted and Repetitive Behaviors (DARB)-a new parent-report measure designed to capture the full range of key of restricted and repetitive behaviors (RRB) subdomains.Parents of 1892 children and adolescents with autism spectrum disorder (ASD) (M= 10.81 years; SD= 4.14) recruited from the Simons Foundation Powering Autism Research for Knowledge (SPARK) research match completed the DARB, several existing RRB instruments, and measures of social and communication impairments and anxiety. A subsample of 450 parents completed the DARB after two weeks to evaluate test-retest stability.Exploratory graph analysis (EGA) conducted in the exploratory subsample identified eight dimensions that were aligned with our hypothesized RRB subdomains: repetitive sensory motor behaviors (RSMB), insistence on sameness (IS), restricted interests (RI), unusual interests (UI), sensory sensitivity (SS), self-injurious behaviors (SIB), obsessions and compulsive behaviors (OCB) and repetitive language (RL). The confirmatory application of the exploratory structural equation modeling conducted in the confirmatory subsample showed that the derived factor structure had a good fit to the data. Derived factors had excellent reliability, convergent and divergent validity, very strong test-retest stability, and showed a distinct pattern of associations with key demographic cognitive and clinical correlates.DARB will be useful in a variety of research and clinical contexts considering the prominence and clinical impact of RRB in ASD. The strong preliminary evidence indicates that the new scale is comprehensive and captures a wide range of distinct RRB subdomains not simultaneously captured by any of the existing instruments.

  View details for DOI 10.1016/j.jaac.2022.07.863

  View details for PubMedID 36526162

• Cognitive Control Predicts Alleviation of OCD Symptoms by Ketamine van Roessel, P., Asgari, S., Jo, B., Williams, L., Rodriguez, C. SPRINGERNATURE. 2022: 302

  View details for Web of Science ID 000897934700573

• Efficacy of Ketamine in Unmedicated Adults With Obsessive-Compulsive Disorder: A Randomized Controlled Trial Rodriguez, C., Chen, C., Glover, G., Jo, B., Spielman, D., Williams, L., Van Roessel, P., DeBattista, C., Flood, P., Ringold, A., Wintermark, M., Anderson, K., Linkovski, O., Lombardi, A., Millen, A., Pinto, A., Raila, H., Valentine, K., Filippou-Frye, M., Hawkins, J., McCarthy, E., Mukunda, P., Varias, A., Wilson, J., Wright, B. SPRINGERNATURE. 2022: 302-303

  View details for Web of Science ID 000929613800574

• Cognitive Control Predicts Alleviation of OCD Symptoms by Ketamine van Roessel, P., Asgari, S., Jo, B., Williams, L., Rodriguez, C. SPRINGERNATURE. 2022: 302

  View details for Web of Science ID 000929613800573

• Efficacy of Ketamine in Unmedicated Adults With Obsessive-Compulsive Disorder: A Randomized Controlled Trial Rodriguez, C., Chen, C., Glover, G., Jo, B., Spielman, D., Williams, L., van Roessel, P., DeBattista, C., Flood, P., Ringold, A., Wintermark, M., Anderson, K., Linkovski, O., Lombardi, A., Millen, A., Pinto, A., Raila, H., Valentine, K., Filippou-Frye, M., Hawkins, J., McCarthy, E., Mukunda, P., Varias, A., Wilson, J., Wright, B. SPRINGERNATURE. 2022: 302-303

  View details for Web of Science ID 000897934700574

• GROUP VS INDIVIDUAL TRAUMA-FOCUSED CBT FOR PARENTS OF PREMATURE INFANTS Shaw, R., Moreyra, A., Simon, S., Wharton, E., Dowtin, L., Armer, E., Goldman, L., Borkovi, T., Neri, E., Jo, B., Hintz, S., Van Meurs, K., Horwitz, S. M. ELSEVIER SCIENCE INC. 2022: S191

  View details for DOI 10.1016/j.jaac.2022.09.171

  View details for Web of Science ID 000873567901017

• Long-term follow-up of telehealth-enabled behavioral treatment for challenging behaviors in boys with fragile X syndrome. Journal of neurodevelopmental disorders Hall, S. S., Rodriguez, A. B., Jo, B., Pollard, J. S. 2022; 14 (1): 53

  Abstract

  BACKGROUND: A significant proportion of boys with fragile X syndrome (FXS), the most common known genetic cause of intellectual disability, exhibit challenging behaviors such as aggression and self-injury that can cause significant distress to families. Recent evidence suggests that coaching caregivers to implement functional communication training (FCT) with their child via telehealth can help to ameliorate these behaviors in FXS. In the present study, we followed families who had participated in our previous randomized controlled trial of FCT to evaluate the longer-term effects of FCT on challenging behaviors in this population.METHODS: In study 1, follow-up emails, phone calls, text messages, and letters were sent to caregivers of 48 boys with FXS who had completed our previous study conducted between 2016 and 2019. The main outcome measures administered at follow-up were the Aberrant Behavior Checklist-Community (ABC-C) and the Parenting Stress Index, 4th Edition (PSI-4). In study 2, families who had received FCT treatment but whose child exhibited challenging behaviors daily at follow-up received a 1-h parent training booster session to determine whether the intervention effect could be recovered.RESULTS: Sixteen (66.7%) of 24 families who had received FCT treatment and 18 (75.0%) of 24 families who had received treatment as usual were traced and consented between March and August 2021. The mean follow-up time was 3.1 years (range, 1.4 to 4.2 years). Longitudinal mixed effects analyses indicated that boys who had received FCT were more likely to show improvements on the irritability and lethargy/social withdrawal subscales of the ABC-C over the follow-up interval compared to boys who had continued with treatment as usual. Four of the six boys who had received the booster parent training session via telehealth were reported to exhibit fewer forms of challenging behavior at a 4-week follow-up.CONCLUSIONS: Empowering parents to implement behavior analytic treatments with their child in their own home can have durable effects on maintaining low levels of challenging behaviors in boys with FXS. These data further support the need to implement parent-mediated interventions for challenging behaviors in this population at an early age.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03510156 . Registered 27 April 2018.

  View details for DOI 10.1186/s11689-022-09463-9

  View details for PubMedID 36180840

• A Pilot randomized trial to examine effects of a hybrid closed-loop insulin delivery system on neurodevelopmental and cognitive outcomes in adolescents with type 1 diabetes. Nature communications Reiss, A. L., Jo, B., Arbelaez, A. M., Tsalikian, E., Buckingham, B., Weinzimer, S. A., Fox, L. A., Cato, A., White, N. H., Tansey, M., Aye, T., Tamborlane, W., Englert, K., Lum, J., Mazaika, P., Foland-Ross, L., Marzelli, M., Mauras, N. 2022; 13 (1): 4940

  Abstract

  Type 1 diabetes (T1D) is associated with lower scores on tests of cognitive and neuropsychological function and alterations in brain structure and function in children. This proof-of-concept pilot study (ClinicalTrials.gov Identifier NCT03428932) examined whether MRI-derived indices of brain development and function and standardized IQ scores in adolescents with T1D could be improved with better diabetes control using a hybrid closed-loop insulin delivery system. Eligibility criteria for participation in the study included age between 14 and 17 years and a diagnosis of T1D before 8 years of age. Randomization to either a hybrid closed-loop or standard diabetes care group was performed after pre-qualification, consent, enrollment, and collection of medical background information. Of 46 participants assessed for eligibility, 44 met criteria and were randomized. Two randomized participants failed to complete baseline assessments and were excluded from final analyses. Participant data were collected across five academic medical centers in the United States. Research staff scoring the cognitive assessments as well as those processing imaging data were blinded to group status though participants and their families were not. Forty-two adolescents, 21 per group, underwent cognitive assessment and multi-modal brain imaging before and after the six month study duration. HbA1c and sensor glucose downloads were obtained quarterly. Primary outcomes included metrics of gray matter (total and regional volumes, cortical surface area and thickness), white matter volume, and fractional anisotropy. Estimated power to detect the predicted treatment effect was 0.83 with two-tailed, α = 0.05. Adolescents in the hybrid closed-loop group showed significantly greater improvement in several primary outcomes indicative of neurotypical development during adolescence compared to the standard care group including cortical surface area, regional gray volumes, and fractional anisotropy. The two groups were not significantly different on total gray and white matter volumes or cortical thickness. The hybrid closed loop group also showed higher Perceptual Reasoning Index IQ scores and functional brain activity more indicative of neurotypical development relative to the standard care group (both secondary outcomes). No adverse effects associated with study participation were observed. These results suggest that alterations to the developing brain in T1D might be preventable or reversible with rigorous glucose control. Long term research in this area is needed.

  View details for DOI 10.1038/s41467-022-32289-x

  View details for PubMedID 36042217

• A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder. Journal of personalized medicine Honeycutt, D. C., DelBello, M. P., Strawn, J. R., Ramsey, L. B., Patino, L. R., Hinman, K., Welge, J., Miklowitz, D. J., Jo, B., Blom, T. J., Bruns, K. M., Hamill Skoch, S. K., Starace, N., Tallman, M. J., Singh, M. K. 2022; 12 (6)

  Abstract

  Antidepressants are standardly used to treat moderate to severe symptoms of depression and/or anxiety in youth but may also be associated with rare but serious psychiatric adverse events such as irritability, agitation, aggression, or suicidal ideation. Adverse events are especially common in youth with a family history of bipolar disorder (BD) who are at heightened risk for dysfunction in neurobiological systems that regulate emotion and arousal. To further understand this phenomenon, this study will examine (a) baseline risk factors associated with dysfunctional arousal in a sample of youth at high-risk for BD treated with or without an antidepressant, (b) whether antidepressant-related changes in arousal are mediated by changes in prefrontal-limbic circuitry, and (c) whether pharmacogenetic factors influence antidepressant-related changes in arousal. High-risk youth (aged 12-17 years with moderate to severe depressive and/or anxiety symptoms and at least one first-degree relative with bipolar I disorder) will be randomized to receive psychotherapy plus escitalopram or psychotherapy plus placebo. Neuroimaging and behavioral measures of arousal will be collected prior to randomization and at 4 weeks. Samples for pharmacogenetic analysis (serum escitalopram concentration, CYP2C19 metabolizer phenotype, and HTR2A and SLC6A4 genotypes) will be collected at 8 weeks. Youth will be followed for up to 16 weeks to assess change in arousal measures.

  View details for DOI 10.3390/jpm12061006

  View details for PubMedID 35743790

• Handling parametric assumptions in principal causal effect estimation using Gaussian mixtures. Statistics in medicine Jo, B. 2022

  Abstract

  Given the latent stratum membership, principal stratification models with continuous outcomes naturally fit in the parametric estimation framework of Gaussian mixtures. However, with models that are not nonparametrically identified, relying on parametric mixture modeling has been mostly discouraged as a way of identifying principal effects. This study revisits this rather deserted use of parametric mixture modeling, which may open up various possibilities in principal stratification modeling. The main problem with using the parametric mixture modeling approach is that it is hard to assess the quality of principal effect estimates given its reliance on parametric conditions. As a way of assessing the estimation quality in this situation, this study proposes that we use parametric mixture modeling in two different ways, with and without the assurance of nonparametric identification. The key identifying assumption employed in this study is the moving exclusion restriction, a flexible version of the standard exclusion restriction assumption. This assumption is used as a temporary vehicle to help assess the quality of principal effect estimates obtained relying on parametric mixture modeling. The study presents promising results, showing the possibility of using parametric mixture modeling as an accessible tool for causal inference.

  View details for DOI 10.1002/sim.9401

  View details for PubMedID 35611438

• A randomized controlled trial of Everolimus for neurocognitive symptoms in PTEN hamartoma tumor syndrome. Human molecular genetics Srivastava, S., Jo, B., Zhang, B., Frazier, T., Gallagher, A. S., Peck, F., Levin, A. R., Mondal, S., Li, Z., Filip-Dhima, R., Geisel, G., Dies, K. A., Diplock, A., Eng, C., Hanna, R., Sahin, M., Hardan, A. 2022

  Abstract

  PTEN hamartoma tumor syndrome (PHTS) is a complex neurodevelopmental disorder characterized by mTOR (mechanistic target of rapamycin) overactivity. Limited data suggest that mTOR inhibitors may be therapeutic. No placebo-controlled studies have examined mTOR inhibition on cognition and behavior in humans with PHTS with/without autism.We conducted a 6-month phase II, randomized, double-blinded, placebo-controlled trial to examine the safety profile and efficacy of everolimus (4.5 mg/m2) in individuals (5-45 years) with PHTS. We measured several cognitive and behavioral outcomes, and electroencephalography (EEG) biomarkers. The primary endpoint was a neurocognitive composite derived from Stanford Binet-5 (SB-5) nonverbal working memory score, SB-5 verbal working memory, Conners' Continuous Performance Test hit reaction time, and Purdue Pegboard Test score.Forty-six participants underwent 1:1 randomization: n = 24 (everolimus) and n = 22 (placebo). Gastrointestinal adverse events were more common in the everolimus group (p < 0.001). Changes in the primary endpoint between groups from baseline to month 6 were not apparent (Cohen's d = -0.10, p = 0.518). However, several measures were associated with modest effect sizes (≥0.2) in the direction of improvement, including measures of nonverbal IQ, verbal learning, autism symptoms, motor skills, adaptive behavior, and global improvement. There was a significant difference in EEG central alpha power (p = 0.049) and central beta power (p = 0.039) six months after everolimus treatment.Everolimus is well tolerated in PHTS; adverse events were similar to previous reports. The primary efficacy endpoint did not reveal improvement. Several secondary efficacy endpoints moved in the direction of improvement. EEG measurements indicate target engagement following 6 months of daily oral everolimus. Trial Registration Information: ClinicalTrials.gov NCT02991807 Classification of Evidence: I.

  View details for DOI 10.1093/hmg/ddac111

  View details for PubMedID 35594551

• PREDICTIVE ENRICHMENT TO IDENTIFY RESPONSE TO SLEEP INTERVENTION IN CANCER SURVIVORS WITH HEADACHE - A PRECISION MEDICINE STUDY Woldeamanuel, Y. W., Kushida, C. A., Kesler, S., Jo, B., Neri, E., Edwards, K. S., Gore-Felton, C., Blayney, D. W., Cowan, R. P., Palesh, O. OXFORD UNIV PRESS INC. 2022: S523

  View details for Web of Science ID 000788118601467

• Big Data Approach to Characterize Restricted and Repetitive Behaviors in Autism JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Uljarevic, M., Frazier, T. W., Jo, B., Billingham, W. D., Cooper, M. N., Youngstrom, E. A., Scahill, L., Hardan, A. Y. 2022; 61 (3): 446-457

  View details for Web of Science ID 000760602800015

• Posttraumatic Stress Disorder Does Not Compromise Behavioral Pain Treatment: Secondary Analysis of a Randomized Clinical Trial Among Veterans. Global advances in health and medicine Schulz-Heik, R. J., Avery, T. J., Jo, B., Mahoney, L., Bayley, P. J. 2022; 11: 21649561221075578

  Abstract

  Background: Individuals with posttraumatic stress disorder (PTSD) and chronic pain evince different presentations, coping strategies, and treatment utilization patterns than individuals with chronic pain alone. Theorists have suggested that comorbid PTSD may complicate chronic pain treatment, and that integrated pain and PTSD treatment may be preferable to pain treatment alone.Objective: Assess whether comorbid PTSD moderates Veterans' response to yoga and/or cognitive behavioral therapy (CBT) for pain.Methods: Veterans with Gulf War illness (n = 75) were assessed using the Brief Pain Inventory at baseline and posttreatment as part of a randomized clinical trial. PTSD status was abstracted from participants' medical records.Results: PTSD+ participants (n = 41) reported more pain at baseline than PTSD- participants (n = 34; d = .66, p < .01). PTSD+ participants experienced more improvement in pain from baseline to posttreatment than PTSD- participants by a small to moderate, marginally statistically significant amount (d = .39, p = .07). The relationship between PTSD and treatment outcome was not moderated by treatment type (yoga vs CBT; p = .99). Observation of treatment responses across PTSD status (+ vs -) and treatment (yoga vs CBT) revealed that PTSD+ participants responded well to yoga.Conclusion: PTSD is not associated with reduced effectiveness of behavioral chronic pain treatment among Veterans with Gulf War illness. Therefore behavioral pain treatment should be made readily available to Veterans with pain and PTSD. Yoga deserves further consideration as a treatment for pain among individuals with PTSD.

  View details for DOI 10.1177/21649561221075578

  View details for PubMedID 35186445

• Region-specific associations between gamma-aminobutyric acid A receptor binding and cortical thickness in high-functioning autistic adults. Autism research : official journal of the International Society for Autism Research James, D., Lam, V. T., Jo, B., Fung, L. K. 2022

  Abstract

  The neurobiology of autism has been shown to involve alterations in cortical morphology and gamma-aminobutyric acid A (GABAA ) receptor density. We hypothesized that GABAA receptor binding potential (GABAA R BPND ) would correlate with cortical thickness, but their correlations would differ between autistic adults and typically developing (TD) controls. We studied 50 adults (23 autism, 27 TD, mean age of 27 years) using magnetic resonance imaging to measure cortical thickness, and [18 F]flumazenil positron emission tomography imaging to measure GABAA R BPND . We determined the correlations between cortical thickness and GABAA R BPND by cortical lobe, region-of-interest, and diagnosis of autism spectrum disorder (ASD). We also explored potential sex differences in the relationship between cortical thickness and autism characteristics, as measured by autism spectrum quotient (AQ) scores. Comparing autism and TD groups, no significant differences were found in cortical thickness or GABAA R BPND . In both autism and TD groups, a negative relationship between cortical thickness and GABAA R BPND was observed in the frontal and occipital cortices, but no relationship was found in the temporal or limbic cortices. A positive correlation was seen in the parietal cortex that was only significant for the autism group. Interestingly, in an exploratory analysis, we found sex differences in the relationships between cortical thickness and GABAA R BPND , and cortical thickness and AQ scores in the left postcentral gyrus. LAY SUMMARY: The thickness of the brain cortex and the density of the receptors associated with inhibitory neurotransmitter GABA have been hypothesized to underlie the neurobiology of autism. In this study, we found that these biomarkers correlate positively in the parietal cortex, but negatively in the frontal and occipital cortical regions of the brain. Furthermore, we collected preliminary evidence that the correlations between cortical thickness and GABA receptor density are sexdependent in a brain region where sensory inputs are registered.

  View details for DOI 10.1002/aur.2703

  View details for PubMedID 35261207

• Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. The American journal of psychiatry Cole, E. J., Phillips, A. L., Bentzley, B. S., Stimpson, K. H., Nejad, R., Barmak, F., Veerapal, C., Khan, N., Cherian, K., Felber, E., Brown, R., Choi, E., King, S., Pankow, H., Bishop, J. H., Azeez, A., Coetzee, J., Rapier, R., Odenwald, N., Carreon, D., Hawkins, J., Chang, M., Keller, J., Raj, K., DeBattista, C., Jo, B., Espil, F. M., Schatzberg, A. F., Sudheimer, K. D., Williams, N. R. 2021: appiajp202120101429

  Abstract

  OBJECTIVE: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of 90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression.METHODS: Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Asberg Depression Rating Scale (MADRS) 4 weeks after treatment.RESULTS: At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group.CONCLUSIONS: SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.

  View details for DOI 10.1176/appi.ajp.2021.20101429

  View details for PubMedID 34711062

• Effect of sex chromosome number variation on attention-deficit/hyperactivity disorder symptoms, executive function, and processing speed. Developmental medicine and child neurology Green, T., Flash, S., Shankar, G., Bade Shrestha, S., Jo, B., Klabunde, M., Hong, D. S., Reiss, A. L. 2021

  Abstract

  AIM: To study sex differences in attention-deficit/hyperactivity disorder (ADHD) symptoms, we explored whether X chromosome absence or excess is independently associated with deficits in attention and hyperactivity, executive function, and processing speed.METHOD: We assessed 116 children (ages 3y 10mo-11y 11mo, mean 8y 5mo, SD 1y 11mo) with a variable number of sex chromosomes: 36 females with Turner syndrome (45, X0), 20 males with Klinefelter syndrome (47, XXY), 37 typically developing females (XX), and 23 typically developing males (XY).RESULTS: X chromosome absence was associated with increased attention problems, hyperactivity, and deficits in inhibitory control, compared with female children with XX (all p<0.003). Conversely, X chromosome excess was associated with weakness in working memory (p=0.018) and approached significance for attention problems (p=0.071) but not with hyperactivity, or weakness in inhibitory control relative to male children with XY. Using non-parametric effect size to quantify the clinical effect revealed that X chromosome absence affected attention, hyperactivity, executive function, and processing speed (all r>0.4), while X excess affected in-laboratory as well as parent-reported working memory (all r>0.4).INTERPRETATION: Our observations provide compelling evidence that the absence or excess of an X chromosome distinctly affects cognition and behaviors associated with ADHD.

  View details for DOI 10.1111/dmcn.15020

  View details for PubMedID 34431088

• Big Data Approach to Characterize Restricted and Repetitive Behaviors in Autism. Journal of the American Academy of Child and Adolescent Psychiatry Uljarevic, M., Frazier, T. W., Jo, B., Billingham, W. D., Cooper, M. N., Youngstrom, E. A., Scahill, L., Hardan, A. Y. 2021

  Abstract

  OBJECTIVE: Despite being a core diagnostic feature of autism spectrum disorder (ASD), developmental and clinical correlates of restricted and repetitive behaviors and interests (RRB) remain poorly characterized. This study aimed to utilize the largest available RRB data set to date to provide a comprehensive characterization of how distinct RRB domains vary according to a range of individual characteristics.METHOD: Data were obtained from 17,581 children and adolescents with ASD (Mage= 8.24 years, SDage= 4.06) from the Simons Foundation Powering Autism Research for Knowledge cohort. Caregivers completed the Repetitive Behavior Scale-Revised questionnaire as a measure of repetitive motor behaviors, self-injurious behaviors, compulsions, insistence on sameness and circumscribed interests RRB domains. Caregivers also provided information on children's cognitive functioning, language ability and social and communication impairments.RESULTS: Male sex was associated with higher severity of repetitive motor behaviors and restricted interests and lower severity of compulsions and self-injurious behaviors; no sex differences were found for insistence on sameness domain. While repetitive motor behaviors showed a mostly linear (negative) association with age, other RRB domains showed more complex and non-linear associations. Higher severity of social and communication impairments provided significant independent contribution in predicting higher severity of all RRB domains at the p< .001, however, these effects were small (d< .25). The strongest of these effects was observed for Ritualistic/Sameness (d=.24), followed by Stereotypy (d=.21), Compulsions (d=.17), Restricted Interests (d=.14) and SIB (d=.12).CONCLUSION: Findings reported here provide further evidence that RRB subdomains show a somewhat distinct pattern of associations with demographic, developmental and clinical variables with a key implication that separate consideration of these domains can help to facilitate efforts to understand diverse ASD etiology and inform the design of future interventions.

  View details for DOI 10.1016/j.jaac.2021.08.006

  View details for PubMedID 34391858

• Headache outcomes of a sleep behavioral intervention in breast cancer survivors: Secondary analysis of a randomized clinical trial. Cancer Woldeamanuel, Y. W., Blayney, D. W., Jo, B., Fisher, S. E., Benedict, C., Oakley-Girvan, I., Kesler, S. R., Palesh, O. 2021

  Abstract

  BACKGROUND: Breast cancer survivors often have persisting headache. In a secondary analysis of the Brief Behavioral Therapy for Cancer-Related Insomnia (BBT-CI) clinical trial (ClinicalTrials.gov identifier NCT02165839), the authors examined the effects of BBT-CI on headache outcomes in patients with breast cancer.METHODS: Patients with breast cancer who were receiving chemotherapy were randomly assigned to receive either the BBT-CI intervention or the Healthy EAting Education Learning for healthy sleep (HEAL) control intervention, and both were delivered over 6 weeks by trained staff. Headache outcomes and heart rate variability (HRV) were measured at baseline, 6 weeks, 6 months, and 12 months. Mixed-effects models were used to examine longitudinal headache outcomes in the groups according to the intention to treat. Principal component analysis and agglomerative hierarchical clustering were conducted to reduce 16 variables for data-driven phenotyping.RESULTS: Patients in the BBT-CI arm (n = 73) exhibited a significant reduction in headache burden over time (P = .02; effect size [Cohen d] = 0.43), whereas the reduction was not significant among those in the HEAL arm (n = 66). The first principal component was positively loaded by headache, sleep, fatigue, and nausea/vomiting and was negatively loaded by cognitive, physical, and emotional functioning. Agglomerative hierarchical clustering revealed 3 natural clusters. Cluster I (n = 58) featured the highest burden of headache, insomnia, and nausea/vomiting; cluster II (n = 50) featured the lowest HRV despite a low burden of headache and insomnia; and cluster III (n = 31) showed an inverse relation between HRV and headache-insomnia, signifying autonomic dysfunction.CONCLUSIONS: BBT-CI is efficacious in reducing headache burden in breast cancer survivors. Patient phenotyping demonstrates a headache type featuring sleep disturbance, nausea/vomiting, and low physical functioning-revealing similarities to migraine.LAY SUMMARY: Breast cancer survivors often have persisting headache symptoms. In patients with cancer, treatment of chronic headache disorders using daily medications may be challenging because of drug interactions with chemotherapy and other cancer therapies as well as patients' reluctance to add more drugs to their medicine list. Headache and sleep disorders are closely related to each other. This study demonstrates that a sleep behavioral therapy reduced headache burden in breast cancer survivors. In addition, the majority of headache sufferers had a headache type with similarities to migraine-featuring sleep disturbance, nausea/vomiting, and low physical functioning.

  View details for DOI 10.1002/cncr.33844

  View details for PubMedID 34357593

• Sustainment of Integrated Care in Addiction Treatment Settings: Primary Outcomes From a Cluster-Randomized Controlled Trial. Psychiatric services (Washington, D.C.) Chokron Garneau, H., Assefa, M. T., Jo, B., Ford, J. H., Saldana, L., McGovern, M. P. 2021: appips202000293

  Abstract

  OBJECTIVE: Integrated treatment services are the gold standard for addressing co-occurring mental and substance use disorders, yet they are not readily available. The Network for the Improvement of Addiction Treatment (NIATx) was hypothesized to be an effective strategy to implement and sustain integrated mental health and substance use care in addiction treatment programs. This study examined sustainment of integrated services for up to 2 years after the active implementation phase.METHODS: The effectiveness of NIATx strategies to implement and sustain integrated services was evaluated by using a cluster-randomized, waitlist control group design. Forty-nine addiction treatment organizations were randomly assigned to either NIATx1 (active implementation strategy) or NIATx2 (waitlist control). The Dual Diagnosis Capability in Addiction Treatment Index was used to evaluate organizations' capability to provide integrated care. The NIATx Stages of Implementation Completion scale was used to assess participation in and adherence to the NIATx implementation process. Linear mixed-effects modeling was used to evaluate changes from baseline to end of the sustainment period.RESULTS: Both cohorts sustained their capability to provide integrated treatment services. Both groups achieved successful implementation and sustained integrated services to a similar degree, regardless of sustainment year. Sustainment did not vary as a function of NIATx adherence.CONCLUSIONS: The delivery of integrated treatment services was sustained for 2 years after receipt of active implementation support. Future research should consider how contextual factors may predict, mediate, and moderate sustainment outcomes.

  View details for DOI 10.1176/appi.ps.202000293

  View details for PubMedID 34346729

• Maintenance of Training Effects of Two Models for Implementing Evidence-Based Psychological Treatment. Psychiatric services (Washington, D.C.) Fitzsimmons-Craft, E. E., Bohon, C., Wilson, G. T., Jo, B., Mondal, S., Laing, O., Welch, R. R., Raghavan, R., Proctor, E. K., Agras, W. S., Wilfley, D. E. 2021: appips202000702

  Abstract

  OBJECTIVE: The authors compared maintenance of training outcomes for two approaches to training college therapists in interpersonal psychotherapy (IPT): train the trainer versus expert training.METHODS: A cluster-randomized trial was conducted in 24 college counseling centers. Therapists were recruited from enrolled centers, and the therapists enrolled students with depression and eating disorder symptoms. The therapists (N=184) provided data during baseline, posttraining (during the 12 months of expert consultation offered to the expert training group), and maintenance (approximately 7 months after the expert consultation ended). Outcomes were therapist fidelity (i.e., adherence and competence) and IPT knowledge.RESULTS: Both groups showed within-group improvement from baseline to the maintenance period for adherence, competence, and IPT knowledge; however, the train-the-trainer group had greater improvement over time in adherence and competence.CONCLUSIONS: Given that the effects of the train-the-trainer approach were better maintained, and this model's potential to train more therapists over time, the train-the-trainer approach may help increase dissemination of evidence-based treatments such as IPT.

  View details for DOI 10.1176/appi.ps.202000702

  View details for PubMedID 34189934

• Prevalence and correlates of current suicide risk in an international sample of OCD adults: A report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network and Obsessive Compulsive and Related Disorders Network (OCRN) of the European College of Neuropsychopharmacology. Journal of psychiatric research Benatti, B., Dell'Osso, B., Shen, H., Filippou-Frye, M., Varias, A., Sanchez, C., Jo, B., Hollander, E., Fineberg, N. A., Stein, D. J., Nicolini, H., Lanzagorta, N., Marazziti, D., Pallanti, S., Van Ameringen, M., Lochner, C., Karamustafalioglu, O., Hranov, L., Figee, M., Drummond, L., Grant, J. E., Denys, D., Fontenelle, L. F., Menchon, J. M., Zohar, J., Pellegrini, L., Rodriguez, C. I. 2021; 140: 357-363

  Abstract

  INTRODUCTION: Obsessive-compulsive disorder (OCD), characterized by repetitive anxiety-inducing intrusive thoughts and compulsive behaviors, is associated with higher suicide ideation and suicide attempts than the general population. This study investigates the prevalence and the correlates of current suicide risk in adult outpatients in an international multisite cross-sectional sample of OCD outpatients.METHODS: Data were derived from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network's cross-sectional data set (N=409). Current suicide risk (assessed by Item C of the MINI) and diagnoses of psychiatric disorders were based on DSM-IV. Chi-squared test for categorical variables and t-test for continuous variables were used to make statistical inferences about main features associated with current suicide risk. P<.05 was considered as statistically significant.RESULTS: The prevalence of current suicidal risk was 15.9%, with equal likelihood in sociodemographic variables, including age and gender. Increased rates of major depression and generalized anxiety disorder were associated to higher current suicide risk. Current suicide risk was also associated with higher severity of OCD, depressive comorbidity, and higher levels of disability. There were no significant differences in treatment correlates-including type of treatment and psychiatric hospitalizations-between the groups of individuals with and without current suicide risk.CONCLUSION: Our findings suggest that current suicide risk is common in patients with OCD and associated with various forms of pathology. Our work also provides further empirical data to support what is already known clinically: a worse clinical picture characterized by a high severity of OCD, high distress related to obsessions and compulsions, and the presence of comorbidities such as major depression and generalized anxiety disorder should be considered as relevant risk factors for suicide risk.

  View details for DOI 10.1016/j.jpsychires.2021.05.054

  View details for PubMedID 34139458

• Relationship Between Social Motivation in Children With Autism Spectrum Disorder and Their Parents FRONTIERS IN NEUROSCIENCE Uljarevic, M., Frazier, T. W., Jo, B., Phillips, J. M., Billingham, W., Cooper, M. N., Hardan, A. Y. 2021; 15: 660330

  Abstract

  Impairment in social motivation (SM) has been suggested as a key mechanism underlying social communication deficits observed in autism spectrum disorder (ASD). However, the factors accounting for variability in SM remain poorly described and understood. The current study aimed to characterize the relationship between parental and proband SM. Data from 2,759 children with ASD (M age = 9.03 years, SD age = 3.57, 375 females) and their parents from the Simons Simplex Collection (SSC) project was included in this study. Parental and proband SM was assessed using previously identified item sets from the Social Responsiveness Scale (SRS). Children who had parents with low SM scores (less impairments) showed significantly lower impairments in SM compared to children who had either one or both parents with elevated SM scores. No parent-of-origin effect was identified. No significant interactions were found involving proband sex or intellectual disability (ID) status (presence/absence of ID) with paternal or maternal SM. This study establishes that low SM in children with ASD may be driven, in part, by lower SM in one or both parents. Future investigations should utilize larger family pedigrees, including simplex and multiplex families, evaluate other measures of SM, and include other related, yet distinct constructs, such as social inhibition and anhedonia. This will help to gain finer-grained insights into the factors and mechanisms accounting for individual differences in sociability among typically developing children as well as those with, or at risk, for developing ASD.

  View details for DOI 10.3389/fnins.2021.660330

  View details for Web of Science ID 000658890500001

  View details for PubMedID 34121990

  View details for PubMedCentralID PMC8187582

• Quantitative Measurement of Macromolecular Tissue Properties in White and Gray Matter in Healthy Aging and Amnestic MCI. NeuroImage Gozdas, E., Fingerhut, H., Wu, H., Bruno, J. L., Dacorro, L., Jo, B., O'Hara, R., Reiss, A. L., Hosseini, S. M. 2021: 118161

  Abstract

  Healthy and pathological aging influence brain microstructure via complex processes. Discerning these processes require measurements that are sensitive to specific biological properties of brain tissue. We integrated a novel quantitative R1 measure with multi-shell diffusion weighted imaging to map age-associated changes in macromolecular tissue volume (MTV) along major white matter tracts in healthy older adults and patients with amnestic Mild Cognitive Impairment (aMCI). Reduced MTV in association tracts was associated with older age in healthy aging, was correlated with memory performance, and distinguished aMCI from controls. We also mapped changes in gray matter tissue properties using quantitative R1 measurements. We documented a widespread decrease in R1 with advancing age across cortex and decreased R1 in aMCI compared with controls in regions implicated in episodic memory. Our data are the first to characterize MTV loss along major white matter tracts in aMCI and suggest that qMRI is a sensitive measure for detecting subtle degeneration of white and gray matter tissue that cannot be detected by conventional MRI and diffusion measures.

  View details for DOI 10.1016/j.neuroimage.2021.118161

  View details for PubMedID 34000394

• Novel Effects of Ras-MAPK Activating Mutations on Brain Development and Neuropsychiatry Rai, B., Naylor, P., Jo, B., Reiss, A., Green, T. ELSEVIER SCIENCE INC. 2021: S371

  View details for Web of Science ID 000645683800891

• Changes in Brain Volume Associated with Trauma-Focused Cognitive Behavioral Therapy Among Youth with Posttraumatic Stress Disorder. Journal of traumatic stress Garrett, A. S., Abazid, L., Cohen, J. A., van der Kooij, A., Carrion, V., Zhang, W., Jo, B., Franklin, C., Blader, J., Zack, S., Reiss, A. L., Agras, W. S. 2021

  Abstract

  This study investigated group differences and longitudinal changes in brain volume before and after trauma-focused cognitive behavioral therapy (TF-CBT) in 20 unmedicated youth with maltreatment-related posttraumatic stress disorder (PTSD) and 20 non-trauma-exposed healthy control (HC) participants. We collected MRI scans of brain anatomy before and after 5 months of TF-CBT or the same time interval for the HC group. FreeSurfer software was used to segment brain images into 95 cortical and subcortical volumes, which were submitted to optimal scaling regression with lasso variable selection. The resulting model of group differences at baseline included larger right medial orbital frontal and left posterior cingulate corticies and smaller right midcingulate and right precuneus corticies in the PTSD relative to the HC group, R2 = .67. The model of group differences in pre- to posttreatment change included greater longitudinal changes in right rostral middle frontal, left pars triangularis, right entorhinal, and left cuneus corticies in the PTSD relative to the HC group, R2 = .69. Within the PTSD group, pre- to posttreatment symptom improvement was modeled by longitudinal decreases in the left posterior cingulate cortex, R2 = .45, and predicted by baseline measures of a smaller right isthmus (retrosplenial) cingulate and larger left caudate, R2 = .77. In sum, treatment was associated with longitudinal changes in brain regions that support executive functioning but not those that discriminated PTSD from HC participants at baseline. Additionally, results confirm a role for the posterior/retrosplenial cingulate as a correlate of PTSD symptom improvement and predictor of treatment outcome.

  View details for DOI 10.1002/jts.22678

  View details for PubMedID 33881197

• EFFICACY OF BRIEF BEHAVIORAL THERAPY FOR HEADACHE MANAGEMENT IN BREAST CANCER PATIENTS RECEIVING CHEMOTHERAPY Woldeamanuel, Y., Blayney, D. W., Jo, B., Fisher, S., Benedict, C., Kesler, S., Oakley-Girvan, I., Palesh, O. OXFORD UNIV PRESS INC. 2021: S182

  View details for Web of Science ID 000648922700370

• Effects of X Chromosome Monosomy and Genomic Imprinting on Observational Markers of Social Anxiety in Prepubertal Girls with Turner Syndrome. Journal of autism and developmental disorders Hall, S. S., Riley, M. J., Weston, R. N., Lepage, J., Hong, D. S., Jo, B., Hallmayer, J., Reiss, A. L. 2021

  Abstract

  Previous studies have suggested that girls with Turner syndrome (TS) exhibit symptoms of social anxiety during interactions with others. However, few studies have quantified these behaviors during naturalistic face-to-face social encounters. In this study, we coded observational markers of social anxiety in prepubertal girls with TS and age-matched controls during a 10-min social encounter with an unfamiliar examiner. Results showed that girls with TS exhibited significantly higher levels of gaze avoidance compared to controls. Impairments in social gaze were particularly increased in girls with a maternally retained X chromosome (Xm), suggesting a genomic imprinting effect. These data indicate that social gaze avoidance may be a critical behavioral marker for identifying early social dysfunction in young girls with TS.

  View details for DOI 10.1007/s10803-021-04896-y

  View details for PubMedID 33751331

• A randomized double-blind controlled trial of everolimus in individuals with PTEN mutations: Study design and statistical considerations. Contemporary clinical trials communications Hardan, A. Y., Jo, B., Frazier, T. W., Klaas, P., Busch, R. M., Dies, K. A., Filip-Dhima, R., Snow, A. V., Eng, C., Hanna, R., Zhang, B., Sahin, M. 2021; 21: 100733

  Abstract

  This randomized, double-blind controlled trial of everolimus in individuals with germline phosphatase and tensin homolog mutations (PTEN) was designed to evaluate the safety of everolimus compared with placebo and to evaluate the efficacy of everolimus on neurocognition and behavior compared to placebo as measured by standardized neurocognitive and motor measures as well as behavioral questionnaires. The safety profile of everolimus is characterized by manageable adverse events that are generally reversible and non-cumulative. The primary safety endpoint of this study was drop-out rate due to side effects, comparing everolimus versus placebo. We also sought to determine the frequency of adverse events by type and severity. The main efficacy endpoint was a neurocognitive composite computed in two ways: 1) an average for working memory, processing speed, and fine motor subtests; and 2) the same average as above except weighted 2/3, and an additional average based on all other available neurocognitive testing measures assessing the additional domains of nonverbal ability, visuomotor skills, verbal learning, and receptive and expressive language, weighted 1/3. Secondary efficacy endpoints examined the effect of everolimus on overall global clinical improvement, autism symptoms, behavioral problems, and adaptive abilities as measured by validated, standardized instruments. We predicted that the rate of adverse events would be no more than 10% higher in the everolimus group compared to placebo, and overall severity of side effects would be minimal. We also expected that individuals receiving everolimus would show more improvement, relative to those taking placebo, on the composite neurocognitive index.

  View details for DOI 10.1016/j.conctc.2021.100733

  View details for PubMedID 33644493

• Impact of Type 1 Diabetes in the Developing Brain in Children: A Longitudinal Study. Diabetes care Mauras, N., Buckingham, B., White, N. H., Tsalikian, E., Weinzimer, S. A., Jo, B., Cato, A., Fox, L. A., Aye, T., Arbelaez, A. M., Hershey, T., Tansey, M., Tamborlane, W., Foland-Ross, L. C., Shen, H., Englert, K., Mazaika, P., Marzelli, M., Reiss, A. L., Diabetes Research in Children Network (DirecNet) 2021

  Abstract

  OBJECTIVE: To assess whether previously observed brain and cognitive differences between children with type 1 diabetes and control subjects without diabetes persist, worsen, or improve as children grow into puberty and whether differences are associated with hyperglycemia.RESEARCH DESIGN AND METHODS: One hundred forty-four children with type 1 diabetes and 72 age-matched control subjects without diabetes (mean ± SD age at baseline 7.0 ± 1.7 years, 46% female) had unsedated MRI and cognitive testing up to four times over 6.4 ± 0.4 (range 5.3-7.8) years; HbA1c and continuous glucose monitoring were done quarterly. FreeSurfer-derived brain volumes and cognitive metrics assessed longitudinally were compared between groups using mixed-effects models at 6, 8, 10, and 12 years. Correlations with glycemia were performed.RESULTS: Total brain, gray, and white matter volumes and full-scale and verbal intelligence quotients (IQs) were lower in the diabetes group at 6, 8, 10, and 12 years, with estimated group differences in full-scale IQ of -4.15, -3.81, -3.46, -3.11, respectively (P < 0.05), and total brain volume differences of -15,410, -21,159, -25,548, -28,577 mm3 * 103 at 6, 8, 10, and 12 years, respectively (P < 0.05). Differences at baseline persisted or increased over time, and brain volumes and cognitive scores negatively correlated with a life-long HbA1c index and higher sensor glucose in diabetes.CONCLUSIONS: Detectable changes in brain volumes and cognitive scores persist over time in children with early-onset type 1 diabetes followed longitudinally; these differences are associated with metrics of hyperglycemia. Whether these changes can be reversed with scrupulous diabetes control requires further study. These longitudinal data support the hypothesis that the brain is a target of diabetes complications in young children.

  View details for DOI 10.2337/dc20-2125

  View details for PubMedID 33568403

• Accelerated Neuromodulation Therapy for Obsessive-Compulsive Disorder. Brain stimulation Williams, N. R., Sudheimer, K. D., Cole, E. J., Varias, A. D., Goldstein-Piekarski, A. N., Stetz, P. n., Lombardi, A. n., Filippou-Frye, M. n., van Roessel, P. n., Anderson, K. n., McCarthy, E. A., Wright, B. n., Sandhu, T. n., Menon, S. n., Jo, B. n., Koran, L. n., Williams, L. M., Rodriguez, C. I. 2021

  Abstract

  The open-label trial of Williams, Sudheimer, Cole, et al., suggests safety, feasibility, and high efficacy for treatment-refractory OCD of an accelerated, fMRI-guided, high-dose, cTBSmod protocol targeting the right frontal pole. Larger, randomized, controlled trials are needed to test the promising results of this pilot study. CLINICALTRIALS.GOV REGISTRY NUMBERS: NCT03404609.

  View details for DOI 10.1016/j.brs.2021.02.013

  View details for PubMedID 33631349

• Fine Particulate Air Pollution, Early Life Stress, and Their Interactive Effects on Adolescent Structural Brain Development: A Longitudinal Tensor-Based Morphometry Study. Cerebral cortex (New York, N.Y. : 1991) Miller, J. G., Dennis, E. L., Heft-Neal, S., Jo, B., Gotlib, I. H. 2021

  Abstract

  Air pollution is a major environmental threat to public health; we know little, however, about its effects on adolescent brain development. Exposure to air pollution co-occurs, and may interact, with social factors that also affect brain development, such as early life stress (ELS). Here, we show that severity of ELS and fine particulate air pollution (PM2.5) are associated with volumetric changes in distinct brain regions, but also uncover regions in which ELS moderates the effects of PM2.5. We interviewed adolescents about ELS events, used satellite-derived estimates of ambient PM2.5 concentrations, and conducted longitudinal tensor-based morphometry to assess regional changes in brain volume over an approximately 2-year period (N = 115, ages 9-13 years at Time 1). For adolescents who had experienced less severe ELS, PM2.5 was associated with volumetric changes across several gray and white matter regions. Fewer effects of PM2.5 were observed for adolescents who had experienced more severe ELS, although occasionally they were in the opposite direction. This pattern of results suggests that for many brain regions, moderate to severe ELS largely constrains the effects of PM2.5 on structural development. Further theory and research is needed on the joint effects of ELS and air pollution on the brain.

  View details for DOI 10.1093/cercor/bhab346

  View details for PubMedID 34607342

• Using the big data approach to clarify the structure of restricted and repetitive behaviors across the most commonly used autism spectrum disorder measures. Molecular autism Uljarević, M., Jo, B., Frazier, T. W., Scahill, L., Youngstrom, E. A., Hardan, A. Y. 2021; 12 (1): 39

  Abstract

  Restricted and repetitive behaviors (RRB) in autism spectrum disorder (ASD) encompass several distinct domains. However, commonly used general ASD measures provide broad RRB scores rather than assessing separate RRB domains. The main objective of the current investigation was to conduct a psychometric evaluation of the ability of the Social Responsiveness Scale (SRS-2), the Social Communication Questionnaire (SCQ), the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) to capture different RRB constructs.Exploratory Structural Equation Modeling (ESEM) was conducted using individual item-level data from the SRS-2, SCQ, ADI-R and the ADOS. Data were obtained from five existing publicly available databases. For the SRS-2, the final sample consisted of N = 16,761 individuals (Mage = 9.43, SD = 3.73; 18.5% female); for the SCQ, of N = 15,840 (Mage = 7.99, SD = 4.06; 18.1% female); for the ADI-R, of N = 8985 (Mage = 8.86, SD = 4.68; 19.4% female); and for the ADOS, of N = 6314 (Mage = 12.29, SD = 6.79; 17.7% female).The three-factor structure provided the most optimal and interpretable fit to data for all measures (comparative fit index ≥ .983, Tucker Lewis index ≥ .966, root mean square error of approximation ≤ .028). Repetitive-motor behaviors, insistence on sameness and unusual or circumscribed interests factors emerged across all instruments. No acceptable fit was identified for the ADOS.The five datasets used here afforded a large as well as wide distribution of the RRB item scores. However, measures used for establishing convergent and divergent validity were only available for a portion of the sample.Reported findings offer promise for capturing important RRB domains using general ASD measures and highlight the need for measurement development.

  View details for DOI 10.1186/s13229-021-00419-9

  View details for PubMedID 34044873

• Thalamocortical connectivity is associated with autism symptoms in high-functioning adults with autism and typically developing adults. Translational psychiatry Ayub, R. n., Sun, K. L., Flores, R. E., Lam, V. T., Jo, B. n., Saggar, M. n., Fung, L. K. 2021; 11 (1): 93

  Abstract

  Alterations in sensorimotor functions are common in individuals with autism spectrum disorder (ASD). Such aberrations suggest the involvement of the thalamus due to its key role in modulating sensorimotor signaling in the cortex. Although previous research has linked atypical thalamocortical connectivity with ASD, investigations of this association in high-functioning adults with autism spectrum disorder (HFASD) are lacking. Here, for the first time, we investigated the resting-state functional connectivity of the thalamus, medial prefrontal, posterior cingulate, and left dorsolateral prefrontal cortices and its association with symptom severity in two matched cohorts of HFASD. The principal cohort consisted of 23 HFASD (mean[SD] 27.1[8.9] years, 39.1% female) and 20 age- and sex-matched typically developing controls (25.1[7.2] years, 30.0% female). The secondary cohort was a subset of the ABIDE database consisting of 58 HFASD (25.4[7.8] years, 37.9% female) and 51 typically developing controls (24.4[6.7] years, 39.2% female). Using seed-based connectivity analysis, between-group differences were revealed as hyperconnectivity in HFASD in the principal cohort between the right thalamus and bilateral precentral/postcentral gyri and between the right thalamus and the right superior parietal lobule. The former was associated with autism-spectrum quotient in a sex-specific manner, and was further validated in the secondary ABIDE cohort. Altogether, we present converging evidence for thalamocortical hyperconnectivity in HFASD that is associated with symptom severity. Our results fill an important knowledge gap regarding atypical thalamocortical connectivity in HFASD, previously only reported in younger cohorts.

  View details for DOI 10.1038/s41398-021-01221-0

  View details for PubMedID 33536431

• Amygdala and Insula Connectivity Changes Following Psychotherapy for Posttraumatic Stress Disorder: A Randomized Clinical Trial. Biological psychiatry Fonzo, G. A., Goodkind, M. S., Oathes, D. J., Zaiko, Y. V., Harvey, M., Peng, K. K., Weiss, M. E., Thompson, A. L., Zack, S. E., Lindley, S. E., Arnow, B. A., Jo, B., Rothbaum, B. O., Etkin, A. 2020

  Abstract

  BACKGROUND: Exposure-based psychotherapy is a first-line treatment for posttraumatic stress disorder (PTSD), but its mechanisms are poorly understood. Functional brain connectivity is a promising metric for identifying treatment mechanisms and biosignatures of therapeutic response. To this end, we assessed amygdala and insula treatment-related connectivity changes and their relationship to PTSD symptom improvements.METHODS: Individuals with a primary PTSD diagnosis (N= 66) participated in a randomized clinical trial of prolonged exposure therapy (n= 36) versus treatment waiting list (n= 30). Task-free functional magnetic resonance imaging was completed prior to randomization and 1 month following cessation of treatment/waiting list. Whole-brain blood oxygenation level-dependent responses were acquired. Intrinsic connectivity was assessed by subregion in the amygdala and insula, limbic structures key to the disorder pathophysiology. Dynamic causal modeling assessed evidence for effective connectivity changes in select nodes informed by intrinsic connectivity findings.RESULTS: The amygdala and insula displayed widespread patterns of primarily subregion-uniform intrinsic connectivity change, including increased connectivity between the amygdala and insula; increased connectivity of both regions with the ventral prefrontal cortex and frontopolar and sensory cortices; and decreased connectivity of both regions with the left frontoparietal nodes of the executive control network. Larger decreases in amygdala-frontal connectivity and insula-parietal connectivity were associated with larger PTSD symptom reductions. Dynamic causal modeling evidence suggested that treatment decreased left frontal inhibition of the left amygdala, and larger decreases were associated with larger symptom reductions.CONCLUSIONS: PTSD psychotherapy adaptively attenuates functional interactions between frontoparietal and limbic brain circuitry at rest, which may reflect a potential mechanism or biosignature of recovery.

  View details for DOI 10.1016/j.biopsych.2020.11.021

  View details for PubMedID 33516458

• Telehealth-enabled behavioral treatment for problem behaviors in boys with fragile X syndrome: a randomized controlled trial. Journal of neurodevelopmental disorders Hall, S. S., Monlux, K. D., Rodriguez, A. B., Jo, B., Pollard, J. S. 2020; 12 (1): 31

  Abstract

  BACKGROUND: Children with fragile X syndrome (FXS) are at increased risk for exhibiting problem behaviors such as aggression and self-injury. However, many children with FXS have limited access to behavioral treatments that have known efficacy due to the low availability of treatment providers and the wide geographical dispersion of families with FXS across the country. Telehealth may offer a cost-effective and practical solution to overcome these significant barriers. We examined the effect of administering an established behavior analytic intervention called functional communication training (FCT) via telehealth on levels of problem behaviors exhibited by boys with FXS. We also examined treatment acceptability, as well as the effect of the treatment on levels of parenting stress.METHODS: Boys with FXS, aged 3 to 10years, who displayed problem behaviors daily, were randomized to receive FCT via telehealth (n = 30) or treatment as usual (n = 27) over 12weeks. Outcome measures included in-session observations of problem behavior, the Aberrant Behavior Checklist-Community (ABC-C), the Treatment Acceptability Rating Form-Revised (TARF-R), and the Parenting Stress Index, 4th edition (PSI-4).RESULTS: Intention-to-treat analyses indicated that scores on the irritability subscale of the ABC-C, our primary outcome measure, decreased significantly for boys who received FCT via telehealth compared to boys who received treatment as usual (p < .001, Cohen's d = 0.65). In-session observations conducted for those who received treatment showed that levels of problem behavior decreased by 91% from baseline. Levels of parenting stress related to child behavioral problems were also lower following FCT treatment, and caregivers reported that the intervention was acceptable.CONCLUSIONS: These findings support telehealth-enabled FCT as a framework for expanding access to behavioral treatments for problem behaviors in children with FXS. Expanded delivery of behavior analytic treatment via telehealth also has the potential to lower healthcare costs, improve child and family quality of life, and lead to advances in the treatment of problem behavior in the broader population of individuals with neurodevelopmental disorders.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03510156 . Registered 27 April 2018.

  View details for DOI 10.1186/s11689-020-09331-4

  View details for PubMedID 33218305

• Yoga is effective in treating symptoms of Gulf War illness: A randomized clinical trial. Journal of psychiatric research Bayley, P. J., Schulz-Heik, R. J., Cho, R., Mathersul, D., Collery, L., Shankar, K., Ashford, J. W., Jennings, J. S., Tang, J., Wong, M. S., Avery, T. J., Stanton, M. V., Meyer, H., Friedman, M., Kim, S., Jo, B., Younger, J., Mathews, B., Majmundar, M., Mahoney, L. 2020

  Abstract

  Many Veterans of the 1990-1991 Gulf War report symptoms of Gulf War Illness, a condition involving numerous chronic symptoms including pain, fatigue, and mood/cognition symptoms. Little is known about this condition's etiology and treatment. This study reports outcomes from a randomized controlled single-blind trial comparing yoga to cognitive behavioral therapy for chronic pain and other symptoms of Gulf War Illness. Participants were Veterans with symptoms of GWI: chronic pain, fatigue and cognition-mood symptoms. Seventy-five Veterans were randomized to treatment via selection of envelopes from a bag (39 yoga, 36 cognitive behavioral therapy), which consisted of ten weekly group sessions. The primary outcomes of pain severity and interference (Brief Pain Inventory- Short Form) improved in the yoga condition (Cohen's d=.35, p=0.002 and d=0.69, p<0.001, respectively) but not in the CBT condition (d=0.10, p=0.59 and d=0.25 p=0.23). However, the differences between groups were not statistically significant (d=0.25, p=0.25; d=0.43, p=0.076), though the difference in an a-priori-defined experimental outcome variable which combines these two variables into a total pain variable (d=0.47, p=0.047) was significant. Fatigue, as indicated by a measure of functional exercise capacity (6-min walk test) was reduced significantly more in the yoga group than in the CBT group (between-group d=.27, p=0.044). Other secondary outcomes of depression, wellbeing, and self-reported autonomic nervous system symptoms did not differ between groups. No adverse events due to treatment were reported. Yoga may be an effective treatment for core Gulf War Illness symptoms of pain and fatigue, making it one of few treatments with empirical support for GWI. Results support further evaluation of yoga for treating veterans with Gulf War Illness. CLINICAL TRIAL REGISTRY: clinicaltrials.gov Registration Number NCT02378025.

  View details for DOI 10.1016/j.jpsychires.2020.11.024

  View details for PubMedID 33218747

• Association of serum allopregnanolone with restricted and repetitive behaviors in adult males with autism. Psychoneuroendocrinology Chew, L., Sun, K. L., Sun, W., Wang, Z., Rajadas, J., Flores, R. E., Arnold, E., Jo, B., Fung, L. K. 2020; 123: 105039

  Abstract

  Autism spectrum disorder (ASD) has been associated with imbalance between excitatory and inhibitory (E/I) neurotransmission systems, as well as with neuroinflammation. Sitting at the crossroads between E/I imbalance and neuroinflammation is a class of endogenous hormones known as neurosteroids. Current literature points to dysregulated steroid metabolism and atypical neurosteroid levels in ASD as early as in utero. However, due to the complexity of neurosteroid metabolomics, including possible sex differences, the impact of neurosteroids on ASD symptomatology remains unclear. In this study, we assessed neurosteroid levels and ASD symptom severity of 21 males with ASD and 20 full-scale-IQ-matched typically developing (TD) males, all aged 18-39. Using liquid chromatography-tandem mass spectrometry, concentrations of allopregnanolone, cortisol, dehydroepiandrosterone, progesterone, and testosterone were measured in saliva and serum. With the exception of cortisol's, all neurosteroids' concentrations were found to have ASD vs. TD group differences in distribution, where one group was normally distributed and the other non-normally distributed. Serum allopregnanolone levels in males with ASD were found to negatively correlate with clinician-rated measures of restricted and repetitive behavior measures (ADOS-2 RRB and ADI-R RRSB domain scores). Additionally, lower serum allopregnanolone levels were found to predict more negative camouflaging scores, which represent greater differences in self- and clinician-rated symptom severity, of both ASD symptomatology overall and repetitive behaviors in particular. Taken together, our findings demonstrate that in adult males with ASD, decreased serum allopregnanolone levels are associated with more severe restricted and repetitive behaviors and with less insight into the severity of these behaviors.

  View details for DOI 10.1016/j.psyneuen.2020.105039

  View details for PubMedID 33161257

• Sex differences in the effects of gonadal hormones on white matter microstructure development in adolescence. Developmental cognitive neuroscience Ho, T. C., Colich, N. L., Sisk, L. M., Oskirko, K., Jo, B., Gotlib, I. H. 2020; 42: 100773

  Abstract

  Adolescence is characterized by rapid brain development in white matter (WM) that is attributed in part to surges in gonadal hormones. To date, however, there have been few longitudinal investigations relating changes in gonadal hormones and WM development in adolescents. We acquired diffusion-weighted MRI to estimate mean fractional anisotropy (FA) from 10 WM tracts and salivary testosterone from 51 females and 29 males (ages 9-14 years) who were matched on pubertal stage and followed, on average, for 2 years. We tested whether interactions between sex and changes in testosterone levels significantly explained changes in FA. We found positive associations between changes in testosterone and changes in FA within the corpus callosum, cingulum cingulate, and corticospinal tract in females (all ps<0.05, corrected) and non-significant associations in males. We also collected salivary estradiol from females and found that increases in estradiol were associated with increases in FA in the left uncinate fasciculus (p=0.04, uncorrected); however, this effect was no longer significant after accounting for changes in testosterone. Our findings indicate there are sex differences in how changes in testosterone relate to changes in WM microstructure of tracts that support impulse control and emotion regulation across the pubertal transition.

  View details for DOI 10.1016/j.dcn.2020.100773

  View details for PubMedID 32452463

• Thalamic and prefrontal GABA concentrations but not GABAA receptor densities are altered in high-functioning adults with autism spectrum disorder. Molecular psychiatry Fung, L. K., Flores, R. E., Gu, M. n., Sun, K. L., James, D. n., Schuck, R. K., Jo, B. n., Park, J. H., Lee, B. C., Jung, J. H., Kim, S. E., Saggar, M. n., Sacchet, M. D., Warnock, G. n., Khalighi, M. M., Spielman, D. n., Chin, F. T., Hardan, A. Y. 2020

  Abstract

  The gamma aminobutyric acid (GABA) neurotransmission system has been implicated in autism spectrum disorder (ASD). Molecular neuroimaging studies incorporating simultaneous acquisitions of GABA concentrations and GABAA receptor densities can identify objective molecular markers in ASD. We measured both total GABAA receptor densities by using [18F]flumazenil positron emission tomography ([18F]FMZ-PET) and GABA concentrations by using proton magnetic resonance spectroscopy (1H-MRS) in 28 adults with ASD and 29 age-matched typically developing (TD) individuals. Focusing on the bilateral thalami and the left dorsolateral prefrontal cortex (DLPFC) as our regions of interest, we found no differences in GABAA receptor densities between ASD and TD groups. However, 1H-MRS measurements revealed significantly higher GABA/Water (GABA normalized by water signal) in the left DLPFC of individuals with ASD than that of TD controls. Furthermore, a significant gender effect was observed in the thalami, with higher GABA/Water in males than in females. Hypothesizing that thalamic GABA correlates with ASD symptom severity in gender-specific ways, we stratified by diagnosis and investigated the interaction between gender and thalamic GABA/Water in predicting Autism-Spectrum Quotient (AQ) and Ritvo Autism Asperger's Diagnostic Scale-Revised (RAADS-R) total scores. We found that gender is a significant effect modifier of thalamic GABA/Water's relationship with AQ and RAADS-R scores for individuals with ASD, but not for TD controls. When we separated the ASD participants by gender, a negative correlation between thalamic GABA/Water and AQ was observed in male ASD participants. Remarkably, in female ASD participants, a positive correlation between thalamic GABA/Water and AQ was found.

  View details for DOI 10.1038/s41380-020-0756-y

  View details for PubMedID 32376999

• Quantifying Research Domain Criteria Social Communication Subconstructs Using the Social Communication Questionnaire in Youth. Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53 Uljarević, M. n., Frazier, T. W., Phillips, J. M., Jo, B. n., Littlefield, S. n., Hardan, A. Y. 2020: 1–11

  Abstract

  Research Domain Criteria (RDoC) has posited a set of social dimensions that could be useful in identifying sources of individual variation in social impairments across neurodevelopmental disorders. The current investigation aimed to derive estimates of the RDoC social constructs from the Social Communication Questionnaire (SCQ) and examine whether RDoC social processes, as captured by the SCQ, are best represented by a dimensional, categorical, or hybrid model. Individual SCQ items from 4 databases were combined resulting in a total of 26,407 individuals (Mage = 8.13 years, SDage = 4.19; 69.1% male). The sample consisted of 60.0% of individuals with autism spectrum disorder (ASD), 6.8% with a range of neurodevelopmental disorders and 33.2% of siblings of individuals with ASD. Comparison of a range of factor solutions through the use of exploratory structural equation modeling and confirmatory factor analysis indicated that a 3-factor structure with separate attachment and affiliation, production of nonfacial and facial communication factors provided excellent fit to the data (comparative fit index = .989, Tucker-Lewis index = .984, root mean square error of approximation = .045). and robustness across clinical groups, age, sex, and verbal status. Comparison between the best-fitting factor analysis, latent class analysis, and factor mixture analysis solutions demonstrated that the RDoC social processes domain is best represented as dimensional. Our findings show promise for capturing some of the important RDoC social constructs using the SCQ but also highlight crucial areas for the development of new, dedicated dimensional measures.

  View details for DOI 10.1080/15374416.2019.1669156

  View details for PubMedID 31922427

• Pilot Study of a Novel Approach Management of Sleep Associated Problems in Breast Cancer Patients (MOSAIC) During Chemotherapy. Sleep Palesh, O. n., Solomon, N. n., Hofmeister, E. n., Jo, B. n., Shen, H. n., Cassidy-Eagle, E. n., Innominato, P. F., Mustian, K. n., Kesler, S. n. 2020

  Abstract

  This pilot RCT was conducted to assess the preliminary effects of Brief Behavioral Therapy for Cancer-Related Insomnia (BBT-CI) delivered by trained research staff in comparison to a sleep hygiene pamphlet control, and to assess moderators of treatment effect in breast cancer patients undergoing chemotherapy.Of 74 participants recruited, 37 were randomized to BBT-CI and 37 were randomized to the control condition. Trained staff members delivered the intervention during chemotherapy treatments to reduce burden on the patients. Insomnia was assessed with the Insomnia Severity Index (ISI), anxiety was assessed with the Spielberger State-Trait Anxiety Inventory (STAI), symptom burden was assessed with the Symptom Inventory (SI), and study staff recorded previous treatments and surgeries received by patients.Patients randomized to BBT-CI showed significantly greater improvements in their ISI scores than the sleep hygiene group. Additionally, several treatment moderators were identified. The effect of BBT-CI was greater among individuals with lower baseline state-trait anxiety, with previous surgery for cancer, and with higher baseline somatic symptom severity.BBT-CI shows preliminary efficacy compared to the sleep hygiene handout on insomnia in cancer patients undergoing chemotherapy. A large phase III RCT needs to be conducted to replicate the preliminary findings.

  View details for DOI 10.1093/sleep/zsaa070

  View details for PubMedID 32274500

• Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. The American journal of psychiatry Cole, E. J., Stimpson, K. H., Bentzley, B. S., Gulser, M. n., Cherian, K. n., Tischler, C. n., Nejad, R. n., Pankow, H. n., Choi, E. n., Aaron, H. n., Espil, F. M., Pannu, J. n., Xiao, X. n., Duvio, D. n., Solvason, H. B., Hawkins, J. n., Guerra, A. n., Jo, B. n., Raj, K. S., Phillips, A. L., Barmak, F. n., Bishop, J. H., Coetzee, J. P., DeBattista, C. n., Keller, J. n., Schatzberg, A. F., Sudheimer, K. D., Williams, N. R. 2020: appiajp201919070720

  Abstract

  New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression.Twenty-two participants with treatment-resistant depression received open-label SAINT. fcMRI was used to individually target the region of the left DLPFC most anticorrelated with sgACC in each participant. Fifty iTBS sessions (1,800 pulses per session, 50-minute intersession interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT.One participant withdrew, leaving a sample size of 21. Nineteen of 21 participants (90.5%) met remission criteria (defined as a score <11 on the Montgomery-Åsberg Depression Rating Scale). In the intent-to-treat analysis, 19 of 22 participants (86.4%) met remission criteria. Neuropsychological testing demonstrated no negative cognitive side effects.SAINT, an accelerated, high-dose, iTBS protocol with fcMRI-guided targeting, was well tolerated and safe. Double-blinded sham-controlled trials are needed to confirm the remission rate observed in this initial study.

  View details for DOI 10.1176/appi.ajp.2019.19070720

  View details for PubMedID 32252538

• Effectiveness of a Digital Cognitive Behavior Therapy-Guided Self-Help Intervention for Eating Disorders in College Women: A Cluster Randomized Clinical Trial. JAMA network open Fitzsimmons-Craft, E. E., Taylor, C. B., Graham, A. K., Sadeh-Sharvit, S. n., Balantekin, K. N., Eichen, D. M., Monterubio, G. E., Goel, N. J., Flatt, R. E., Karam, A. M., Firebaugh, M. L., Jacobi, C. n., Jo, B. n., Trockel, M. T., Wilfley, D. E. 2020; 3 (8): e2015633

  Abstract

  Eating disorders (EDs) are common, serious psychiatric disorders on college campuses, yet most affected individuals do not receive treatment. Digital interventions have the potential to bridge this gap.To determine whether a coached, digital, cognitive behavior therapy (CBT) intervention improves outcomes for college women with EDs compared with referral to usual care.This cluster randomized trial was conducted from 2014 to 2018 at 27 US universities. Women with binge-purge EDs (with both threshold and subthreshold presentations) were recruited from enrolled universities. The 690 participants were followed up for up to 2 years after the intervention. Data analysis was performed from February to September 2019.Universities were randomized to the intervention, Student Bodies-Eating Disorders, a digital CBT-guided self-help program, or to referral to usual care.The main outcome was change in overall ED psychopathology. Secondary outcomes were abstinence from binge eating and compensatory behaviors, as well as ED behavior frequencies, depression, anxiety, clinical impairment, academic impairment, and realized treatment access.A total of 690 women with EDs (mean [SD] age, 22.12 [4.85] years; 414 [60.0%] White; 120 [17.4%] Hispanic; 512 [74.2%] undergraduates) were included in the analyses. For ED psychopathology, there was a significantly greater reduction in the intervention group compared with the control group at the postintervention assessment (β [SE], -0.44 [0.10]; d = -0.40; t1387 = -4.23; P < .001), as well as over the follow-up period (β [SE], -0.39 [0.12]; d = -0.35; t1387 = -3.30; P < .001). There was not a significant difference in abstinence from any ED behaviors at the postintervention assessment (odds ratio, 1.48; 95% CI, 0.48-4.62; P = .50) or at follow-up (odds ratio, 1.51; 95% CI, 0.63-3.58; P = .36). Compared with the control group, the intervention group had significantly greater reductions in binge eating (rate ratio, 0.82; 95% CI, 0.70-0.96; P = .02), compensatory behaviors (rate ratio, 0.68; 95% CI, 0.54-0.86; P < .001), depression (β [SE], -1.34 [0.53]; d = -0.22; t1387 = -2.52; P = .01), and clinical impairment (β [SE], -2.33 [0.94]; d = -0.21; t1387 = -2.49; P = .01) at the postintervention assessment, with these gains sustained through follow-up for all outcomes except binge eating. Groups did not differ in terms of academic impairment. The majority of intervention participants (318 of 385 participants [83%]) began the intervention, whereas only 28% of control participants (76 of 271 participants with follow-up data available) sought treatment for their ED (odds ratio, 12.36; 95% CI, 8.73-17.51; P < .001).In this cluster randomized clinical trial comparing a coached, digital CBT intervention with referral to usual care, the intervention was effective in reducing ED psychopathology, compensatory behaviors, depression, and clinical impairment through long-term follow-up, as well as realizing treatment access. No difference was found between the intervention and control groups for abstinence for all ED behaviors or academic impairment. Given its scalability, a coached, digital, CBT intervention for college women with EDs has the potential to address the wide treatment gap for these disorders.ClinicalTrials.gov Identifier: NCT02076464.

  View details for DOI 10.1001/jamanetworkopen.2020.15633

  View details for PubMedID 32865576

• Neurocognitive Correlates of Insight in Hoarding Disorder van Roessel, P., Varias, A., Sanchez, C., Sandhu, T., Shen, H., Jo, B., Rodriguez, C. NATURE PUBLISHING GROUP. 2019: 159

  View details for Web of Science ID 000509665600307

• On the relationship between mathematics and visuospatial processing in Turner syndrome. Journal of psychiatric research Baker, J. M., Klabunde, M., Jo, B., Green, T., Reiss, A. L. 2019; 121: 135–42

  Abstract

  A common neurocognitive phenotype of Turner syndrome (TS) includes coincident deficits in math and visuospatial reasoning while overall IQ remains intact. However, research has highlighted disparities in the relationship between these properties in women with TS, suggesting that not all visuospatial domains are equally related to mathematics in this group. Here, we present findings from a longitudinal investigation of visuospatial processing and its relationship to math performance in adolescent girls with TS and age-matched healthy controls. Participants completed a standardized battery of math and visuospatial tests once a year for 4 years. Linear mixed effects modeling was used to examine the relationship between mathematics and each visuospatial domain over time. Our results indicate that math performance was related to visual tracking, visual-motor coordination, and figure-ground processing. Such visuospatial domains appear to be uniquely affected by TS and could contribute to their deficits in math performance. Furthermore, differences in math and visuospatial test performance between girls with TS and healthy controls remain stable over time. Our results have important implications for the role of visuospatial processing in early math performance and may inform the development of effective interventions aimed at improving math education in children with TS.

  View details for DOI 10.1016/j.jpsychires.2019.11.004

  View details for PubMedID 31812933

• Training Models For Implementing Evidence-Based Psychological Treatment: A Cluster-Randomized Trial in College Counseling Centers. JAMA psychiatry Wilfley, D. E., Agras, W. S., Fitzsimmons-Craft, E. E., Bohon, C., Eichen, D. M., Welch, R. R., Jo, B., Raghavan, R., Proctor, E. K., Wilson, G. T. 2019

  Abstract

  Importance: Progress has been made in establishing evidence-based treatments for psychiatric disorders, but these are not often delivered in routine settings. A scalable solution for training clinicians in evidence-based treatments is needed.Objective: To compare 2 methods of training college (university) counseling center therapists to treat psychiatric disorders using interpersonal psychotherapy. The hypothesis was that the train-the-trainer condition would demonstrate superior implementation outcomes vs the expert condition. Moderating factors were also explored.Design, Setting, and Participants: This cluster-randomized trial was conducted from October 2012 to December 2017 in 24 college counseling centers across the United States. Therapist participants were recruited from enrolled centers, and student patients with symptoms of depression and eating disorders were recruited by therapists. Data were analyzed from 184 enrolled therapists.Interventions: Counseling centers were randomized to the expert condition, which involved a workshop and 12 months of follow-up consultation, or the train-the-trainer condition, in which a staff member from the counseling center was coached to train other staff members.Main Outcomes and Measures: The main outcome was therapist fidelity (adherence and competence) to interpersonal psychotherapy, as assessed via audio recordings of therapy sessions. Therapist knowledge of interpersonal psychotherapy was a secondary outcome.Result: A total of 184 therapists (mean [SD] age, 41.9 [10.6] years; 140 female [76.1%]; 142 white [77.2%]) were included. Both the train-the-trainer-condition and expert-condition groups showed significant within-group improvement for adherence to interpersonal psychotherapy (change: 0.233 [95% CI, 0.192-0.274] and 0.190 [0.145-0.235], respectively; both P<.001), with large effect sizes (1.64 [95% CI, 1.35-1.93] and 1.34 [95% CI, 1.02-1.66], respectively) and no significant difference between conditions. Both groups also showed significant within-group improvement in interpersonal therapy competence (change: 0.179 [95% CI, 0.132-0.226] and 0.106 [0.059-0.153], respectively; both P<.001), with a large effect size for the train-the-trainer condition (1.16 [95% CI, 0.85-1.46]; P<.001) and a significant difference between groups favoring the train-the-trainer condition (effect size, 0.47 [95% CI, 0.05-0.89]; P=.03). Knowledge of interpersonal psychotherapy improved significantly within both groups (effect sizes: train-the-trainer, 0.64 [95% CI, 0.28-0.99]; P=.005; expert, 0.69 [95% CI, 0.38-1.01]; P<.001), with no significant difference between groups. The significant moderating factors were job satisfaction for adherence (b, 0.120 [95% CI, 0.001-0.24]; P=.048) and competence (b, 0.133 [95% CI, 0.001-0.27]; P=.048), and frequency of clinical supervision for competence (b, 0.05 [95% CI, 0.004-0.09]; P=.03).Conclusions and Relevance: Results demonstrate that the train-the-trainer model produced training outcomes comparable with the expert model for adherence and was superior on competence. Given its potential capability to train more therapists over time, it has the potential to facilitate widespread dissemination of evidence-based treatments.Trial Registration: ClinicalTrials.gov Identifier: NCT02079142.

  View details for DOI 10.1001/jamapsychiatry.2019.3483

  View details for PubMedID 31693069

• Implementing integrated services in routine behavioral health care: primary outcomes from a cluster randomized controlled trial. BMC health services research Assefa, M. T., Ford, J. H., Osborne, E., McIlvaine, A., King, A., Campbell, K., Jo, B., McGovern, M. P. 2019; 19 (1): 749

  Abstract

  BACKGROUND: An estimated 8.2 million adults in the United States live with co-occurring mental health and substance use disorders. Although the benefits of integrated treatment services for persons with co-occurring disorders has been well-established, gaps in access to integrated care persist. Implementation research can address this gap. We evaluated if the Network for the Improvement of Addiction Treatment (NIATx) implementation strategy was effective in increasing integrated services capacity among organizations treating persons with co-occurring disorders.METHODS: This study employed a cluster randomized waitlist control group design. Forty-nine addiction treatment organizations from the State of Washington were randomized into one of two study arms: (1) NIATx strategy (active implementation strategy), or (2) waitlist (control). The primary outcome was a standardized organizational measure of integrated service capability: the Dual Diagnosis in Addiction Treatment (DDCAT) Index. Intent-to-treat analyses and per-protocol analyses were conducted to address the following questions: (1) Is NIATx effective in increasing integrated service capacity? and (2) Are there differences in organizations that actually use NIATx per-protocol versus those that do not?RESULTS: From baseline to one-year post active implementation, both the NIATx strategy and waitlist arms demonstrated improvements over time in DDCAT Index total and DDCAT dimension scores. In intent-to-treat analyses, a moderate but statistically significant difference in improvement between study arms was seen only in the Program Milieu dimension (p=0.020, Cohen's d=0.54). In per-protocol analyses, moderate-to-large effects in Program Milieu (p=0.002, Cohen's d=0.91) and Continuity of Care (p=0.026, Cohen's d=0.63) dimensions, and in total DDCAT Index (p=0.046, Cohen's d=0.51) were found.CONCLUSIONS: Overall, organizations in both study arms improved DDCAT Index scores over time. Organizations in the NIATx strategy arm with full adherence to the NIATx protocol had significantly greater improvements in the primary outcome measure of integrated service capacity for persons with co-occurring disorders.TRAIL REGISTRATION: ClinicalTrials.gov, NCT03007940 . Retrospectively registered January 2017.

  View details for DOI 10.1186/s12913-019-4624-x

  View details for PubMedID 31651302

• MAPPING THE RESEARCH DOMAIN CRITERIA (RDOC) SOCIAL COMMUNICATION SUB-CONSTRUCTS TO THE SOCIAL RESPONSIVENESS SCALE Hardan, A., Uljarevic, M., Frazier, T., Phillips, J. M., Jo, B., Littlefield, S. ELSEVIER SCIENCE INC. 2019: S311

  View details for DOI 10.1016/j.jaac.2019.07.713

  View details for Web of Science ID 000518857302334

• Longitudinal changes in brain function associated with symptom improvement in youth with PTSD JOURNAL OF PSYCHIATRIC RESEARCH Garrett, A., Cohen, J. A., Zack, S., Carrion, V., Jo, B., Blader, J., Rodriguez, A., Vanasse, T. J., Reiss, A. L., Agras, W. 2019; 114: 161–69

  View details for DOI 10.1016/j.jpsychires.2019.04.021

  View details for Web of Science ID 000472127300024

• Longitudinal changes in brain function associated with symptom improvement in youth with PTSD. Journal of psychiatric research Garrett, A., Cohen, J. A., Zack, S., Carrion, V., Jo, B., Blader, J., Rodriguez, A., Vanasse, T. J., Reiss, A. L., Agras, W. S. 2019; 114: 161–69

  Abstract

  BACKGROUND: Previous studies indicate that youth with posttraumatic stress disorder (PTSD) have abnormal activation in brain regions important for emotion processing. It is unknown whether symptom improvement is accompanied by normative changes in these regions. This study identified neural changes associated with symptom improvement with the long-term goal of identifying malleable targets for interventions.METHODS: A total of 80 functional magnetic resonance imaging (fMRI) scans were collected, including 20 adolescents with PTSD (ages 9-17) and 20 age- and sex-matched healthy control subjects, each scanned before and after a 5-month period. Trauma-focused cognitive behavioral therapy was provided to the PTSD group to ensure improvement in symptoms. Whole brain voxel-wise activation and region of interest analyses of facial expression task data were conducted to identify abnormalities in the PTSD group versus HC at baseline (BL), and neural changes correlated with symptom improvement from BL to EOS of study (EOS).RESULTS: At BL, the PTSD group had abnormally elevated activation in the cingulate cortex, hippocampus, amygdala, and medial frontal cortex compared to HC. From BL to EOS, PTSD symptoms improved an average of 39%. Longitudinal improvement in symptoms of PTSD was associated with decreasing activation in posterior cingulate, mid-cingulate, and hippocampus, while improvement in dissociative symptoms was correlated with decreasing activation in the amygdala.CONCLUSIONS: Abnormalities in emotion-processing brain networks in youth with PTSD normalize when symptoms improve, demonstrating neural plasticity of these regions in young patients and the importance of early intervention.

  View details for PubMedID 31082658

• When meta-analyses get it wrong: response to 'treatment outcomes for anorexia nervosa: a systematic review and meta-analysis of randomized controlled trials' PSYCHOLOGICAL MEDICINE Lock, J., Kraemer, H., Jo, B., Couturier, J. 2019; 49 (4): 697–98

  View details for DOI 10.1017/S003329171800329X

  View details for Web of Science ID 000458753100018

• Brain and behavioral correlates of insulin resistance in youth with depression and obesity HORMONES AND BEHAVIOR Singh, M. K., Leslie, S. M., Packer, M., Zaiko, Y. V., Phillips, O. R., Weisman, E. F., Wall, D. M., Jo, B., Rasgon, N. 2019; 108: 73–83

  View details for DOI 10.1016/j.yhbeh.2018.03.009

  View details for Web of Science ID 000460189100008

• "Not just another meta-analysis": Sources of heterogeneity in psychosocial treatment effect on cancer survival. Cancer medicine Mirosevic, S., Jo, B., Kraemer, H. C., Ershadi, M., Neri, E., Spiegel, D. 2019

  Abstract

  BACKGROUND: Currently, there are eight meta-analyses that address the question whether psychosocial intervention can prolong survival with widely disparate conclusions. One reason for inconsistent findings may be the methods by which previous meta-analyses were conducted.METHODS: Databases were searched to identify valid randomized controlled trials that compared psychosocial intervention with usual care. Hazard ratios (HRs) and their confidence intervals were pooled to estimate the strength of the treatment effect on survival time, and z-tests were performed to assess possible heterogeneity of effect sizes associated with different patient and treatment characteristics.RESULTS: Twelve trials involving 2439 cancer patients that met screening criteria were included. The overall effect favored the treatment group with a HR of 0.71 (95% Cl 0.58-0.88; P=0.002). An effect size favoring treatment group was observed in studies sampling lower vs higher percentage of married patients' (NNT=4.3 vs NNT=15.4), when Cognitive-Behavioral Therapy was applied at early vs late cancer stage (NNT=2.3 vs NNT=-28.6), and among patients' older vs younger than 50 (NNT=4.2 vs NNT=-20.5).CONCLUSIONS: Psychosocial interventions may have an important effect on survival. Reviewed interventions appear to be more effective in unmarried patients, patients who are older, and those with an early cancer stage who attend CBT. Limitations of previous meta-analysis are discussed.

  View details for PubMedID 30600642

• "Not just another meta-analysis": Sources of heterogeneity in psychosocial treatment effect on cancer survival CANCER MEDICINE Mirosevic, S., Jo, B., Kraemer, H. C., Ershadi, M., Neri, E., Spiegel, D. 2019; 8 (1): 363-373

  View details for DOI 10.1002/cam4.1895

  View details for Web of Science ID 000456858100036

• Mapping the Research Domain Criteria Social Processes Constructs to the Social Responsiveness Scale. Journal of the American Academy of Child and Adolescent Psychiatry Uljarević, M. n., Frazier, T. W., Phillips, J. M., Jo, B. n., Littlefield, S. n., Hardan, A. Y. 2019

  Abstract

  Research Domain Criteria (RDoC) operationalizes a set of basic social dimensions that can be used to deconstruct sources of variation in social impairments across affected individuals, regardless of their diagnostic status. This is a necessary step toward the development of etiologically based and individualized treatments. The main objective of this investigation was to derive estimations of the RDoC social constructs from the Social Responsiveness Scale (SRS-2).Exploratory structural equation modeling and confirmatory factor analysis were conducted using individual SRS-2 items from six distinct databases ( N = 27,953; mean age = 9.55 years, SD = 3.79; 71.7% male participants) spanning normative (33.8%) and atypical (66.2%) development. The following models were estimated: a one-factor model; a three-factor model with separate Attachment and Affiliation , Social Communication , and Understanding of Mental States factors; and a four-factor model where Social Communication was further split into Production of Facial and Non-Facial Communication.The one-factor solution showed poor fit. The three-factor solution had adequate fit (comparative fit index = 0.952, Tucker Lewis Index = 0.937, root mean square error of approximation = 0.054). However, the four-factor solution had superior fit (comparative fit index = 0.973, Tucker Lewis Index = 0.961, root mean square error of approximation = 0.042) and was robust across age, sex, and clinical status.To our knowledge, this is the first study examining estimations of the RDoC social constructs from an existing measure. Reported findings show promise for capturing important RDoC social constructs using the SRS-2 and highlight crucial areas for the development of novel dimensional social processing measures.

  View details for DOI 10.1016/j.jaac.2019.07.938

  View details for PubMedID 31376500

  View details for PubMedCentralID PMC7470629

• Therapist adherence to family-based treatment for adolescents with anorexia nervosa: A multi-site exploratory study. European eating disorders review : the journal of the Eating Disorders Association Dimitropoulos, G. n., Lock, J. D., Agras, W. S., Brandt, H. n., Halmi, K. A., Jo, B. n., Kaye, W. H., Pinhas, L. n., Wilfley, D. E., Woodside, D. B. 2019

  Abstract

  This exploratory study is the first to examine family-based treatment (FBT) adherence and association to treatment outcome in the context of a large-scale, multi-centre study for the treatment of adolescents with anorexia nervosa.One hundred and ninety recorded FBT sessions from 68 adolescents with anorexia nervosa and their families were recruited across multiple sites (N = 6). Each site provided 1-4 tapes per family over four treatment time points, and each was independently rated for therapist adherence.There were differences in adherence scores within and between sites. ANOVA produced a main effect for site, F(5, 46) = 8.6, p < .001, and phase, F(3, 42) = 12.7, p < .001, with adherence decreasing in later phases. Adherence was not associated to end of treatment percent ideal body weight after controlling for baseline percent ideal body weight (r = .088, p = .48).Results suggest that FBT can be delivered with adherence in phase one of treatment. Adherence was not associated with treatment outcome as determined using percent ideal body weight.

  View details for DOI 10.1002/erv.2695

  View details for PubMedID 31297906

• Brain Development in School-Age and Adolescent Girls: Effects of Turner Syndrome, Estrogen Therapy, and Genomic Imprinting. Biological psychiatry O'Donoghue, S. n., Green, T. n., Ross, J. L., Hallmayer, J. n., Lin, X. n., Jo, B. n., Huffman, L. C., Hong, D. S., Reiss, A. L. 2019

  Abstract

  The study of Turner syndrome (TS) offers a unique window of opportunity for advancing scientific knowledge of how X chromosome gene imprinting, epigenetic factors, hormonal milieu, and chronologic age affect brain development in females.We described brain growth trajectories in 55 girls with TS and 53 typically developing girls (258 magnetic resonance imaging datasets) spanning 5 years. Using novel nonparametric and mixed effects analytic approaches, we evaluated influences of X chromosome genomic imprinting and hormone replacement therapy on brain development.Parieto-occipital gray and white matter regions showed slower growth during typical pubertal timing in girls with TS relative to typically developing girls. In contrast, some basal ganglia, cerebellar, and limited cortical areas showed enhanced volume growth with peaks around 10 years of age.The parieto-occipital finding suggests that girls with TS may be particularly vulnerable to altered brain development during adolescence. Basal ganglia regions may be relatively preserved in TS owing to their maturational growth before or early in typical pubertal years. Taken together, our findings indicate that particular brain regions are more vulnerable to TS genetic and hormonal effects during puberty. These specific alterations in neurodevelopment may be more likely to affect long-term cognitive behavioral outcomes in young girls with this common genetic condition.

  View details for DOI 10.1016/j.biopsych.2019.07.032

  View details for PubMedID 31561860

• When meta-analyses get it wrong: response to 'treatment outcomes for anorexia nervosa: a systematic review and meta-analysis of randomized controlled trials'. Psychological medicine Lock, J., Kraemer, H. C., Jo, B., Couturier, J. 2018: 1–2

  View details for PubMedID 30514406

• Clutter Blindness as an Insight Proxy in Hoarding Disorder: A Hypothesis-Generating Study van Roessel, P., Sanchez, C., Linkovski, O., Sandhu, T., Wright, B., McCarthy, E., Varias, A., Filippou-Frye, M., Shen, H., Jo, B., Rodriguez, C. NATURE PUBLISHING GROUP. 2018: S387–S388

  View details for Web of Science ID 000509546600710

• Augmenting Buried in Treasures with in-home uncluttering practice: Pilot study in hoarding disorder JOURNAL OF PSYCHIATRIC RESEARCH Linkovski, O., Zwerling, J., Cordell, E., Sonnenfeld, D., Willis, H., La Lima, C. N., Baker, C., Ghazzaoui, R., Girson, R., Sanchez, C., Wright, B., Alford, M., Varias, A., Filippou-Frye, M., Shen, H., Jo, B., Shuer, L., Frost, R. O., Rodriguez, C. I. 2018; 107: 145-150

  View details for DOI 10.1016/j.jpsychires.2018.10.001

  View details for Web of Science ID 000451490800021

• Augmenting Buried in Treasures with in-home uncluttering practice: Pilot study in hoarding disorder. Journal of psychiatric research Linkovski, O., Zwerling, J., Cordell, E., Sonnenfeld, D., Willis, H., La Lima, C. N., Baker, C., Ghazzaoui, R., Girson, R., Sanchez, C., Wright, B., Alford, M., Varias, A., Filippou-Frye, M., Shen, H., Jo, B., Shuer, L., Frost, R. O., Rodriguez, C. I. 2018; 107: 145–50

  Abstract

  Hoarding disorder is characterized by difficulty parting with possessions and by clutter that impairs the functionality of living spaces. Cognitive behavioral therapy conducted by a therapist (individual or in a group) for hoarding symptoms has shown promise. For those who cannot afford or access the services of a therapist, one alternative is an evidence-based, highly structured, short-term, skills-based group using CBT principles but led by non-professional facilitators (the Buried in Treasures [BIT] Workshop). BIT has achieved improvement rates similar to those of psychologist-led CBT. Regardless of modality, however, clinically relevant symptoms remain after treatment, and new approaches to augment existing treatments are needed. Based on two recent studies - one reporting that personalized care and accountability made treatments more acceptable to individuals with hoarding disorder and another reporting that greater number of home sessions were associated with better clinical outcomes, we tested the feasibility and effectiveness of adding personalized, in-home uncluttering sessions to the final weeks of BIT. Participants (n = 5) had 15 sessions of BIT and up to 20 hours of in-home uncluttering. Reductions in hoarding symptoms, clutter, and impairment of daily activities were observed. Treatment response rate was comparable to rates in other BIT studies, with continued improvement in clutter level after in-home uncluttering sessions. This small study suggests that adding in-home uncluttering sessions to BIT is feasible and effective.

  View details for PubMedID 30419524

• BOOK REVIEW. Biometrics Jo, B. 2018; 74 (3): 1134–36

  View details for DOI 10.1111/biom.12949

  View details for PubMedID 30256400

• Construction of longitudinal prediction targets using semisupervised learning STATISTICAL METHODS IN MEDICAL RESEARCH Jo, B., Findling, R. L., Hastie, T. J., Youngstrom, E. A., Wang, C., Arnold, L., Fristad, M. A., Frazier, T. W., Birmaher, B., Gill, M. K., Horwitz, S. 2018; 27 (9): 2674–93

  View details for DOI 10.1177/0962280216684163

  View details for Web of Science ID 000441728200008

• Training models for implementing evidence-based psychological treatment for college mental health: A cluster randomized trial study protocol CONTEMPORARY CLINICAL TRIALS Wilfley, D. E., Fitzsimmons-Craft, E. E., Eichen, D. M., Van Buren, D. J., Welch, R., Robinson, A. H., Jo, B., Raghavan, R., Proctor, E. K., Wilson, G., Agras, W. 2018; 72: 117–25

  Abstract

  Mental disorders often emerge in adolescence and young adulthood, and these disorders can have lasting effects on students' health, social functioning, and education. Although evidence-based treatments have been established for many mental disorders, few community therapists use such treatments. What is needed is a practical, economically feasible means of training clinicians to implement evidence-based treatments suitable for widespread use. This cluster randomized trial will randomize 26 college counseling centers to one of two implementation strategies for training counselors to use interpersonal psychotherapy (IPT), an evidence-based treatment for depression and eating disorders: 1) an external expert consultation model comprising a workshop, therapy manual, and expert follow-up consultation (n = 13); or 2) a train-the-trainer model in which a staff member from the counseling center is coached to train other staff members to implement IPT (n = 13). The primary outcome is therapist adherence to IPT, with secondary outcomes of therapist competence in IPT and client outcomes for depression and eating disorders. Therapist and organizational characteristics will be explored as potential moderators and mediators of implementation outcomes. Implementation costs for each of the training methods will also be assessed. The present study involves partnering with college counseling centers to determine the most effective method to implement IPT for depression and eating disorders in these settings. The results of this study will inform future large-scale dissemination of clinical interventions to mental health service providers by providing evidence for the selection of training methods when an agency chooses to adopt new interventions.

  View details for PubMedID 30146493

• Persistence of abnormalities in white matter in children with type 1 diabetes DIABETOLOGIA Fox, L. A., Hershey, T., Mauras, N., Arbelaez, A., Tamborlane, W. V., Buckingham, B., Tsalikian, E., Englert, K., Raman, M., Jo, B., Shen, H., Reiss, A., Mazaika, P., Diabet Res Children Network Direct 2018; 61 (7): 1538–47

  Abstract

  Prior studies suggest white matter growth is reduced and white matter microstructure is altered in the brains of young children with type 1 diabetes when compared with brains of non-diabetic children, due in part to adverse effects of hyperglycaemia. This longitudinal observational study examines whether dysglycaemia alters the developmental trajectory of white matter microstructure over time in young children with type 1 diabetes.One hundred and eighteen children, aged 4 to <10 years old with type 1 diabetes and 58 age-matched, non-diabetic children were studied at baseline and 18 months, at five Diabetes Research in Children Network clinical centres. We analysed longitudinal trajectories of white matter using diffusion tensor imaging. Continuous glucose monitoring profiles and HbA1c levels were obtained every 3 months.Axial diffusivity was lower in children with diabetes at baseline (p = 0.022) and at 18 months (p = 0.015), indicating that differences in white matter microstructure persist over time in children with diabetes. Within the diabetes group, lower exposure to hyperglycaemia, averaged over the time since diagnosis, was associated with higher fractional anisotropy (p = 0.037). Fractional anisotropy was positively correlated with performance (p < 0.002) and full-scale IQ (p < 0.02).These results suggest that hyperglycaemia is associated with altered white matter development, which may contribute to the mild cognitive deficits in this population.

  View details for PubMedID 29654376

  View details for PubMedCentralID PMC5991628

• Leveraging routine clinical materials and mobile technology to assess CBT fidelity: the Innovative Methods to Assess Psychotherapy Practices (imAPP) study IMPLEMENTATION SCIENCE Stirman, S., Marques, L., Creed, T. A., Gutner, C. A., DeRubeis, R., Barnett, P. G., Kuhn, E., Suvak, M., Owen, J., Vogt, D., Jo, B., Schoenwald, S., Johnson, C., Mallard, K., Beristianos, M., La Bash, H. 2018; 13: 69

  Abstract

  Identifying scalable strategies for assessing fidelity is a key challenge in implementation science. However, for psychosocial interventions, the existing, reliable ways to test treatment fidelity quality are often labor intensive, and less burdensome strategies may not reflect actual clinical practice. Cognitive behavioral therapies (CBTs) provide clinicians with a set of effective core elements to help treat a multitude of disorders, which, evidence suggests, need to be delivered with fidelity to maximize potential client impact. The current "gold standard" for rating CBTs is rating recordings of therapy sessions, which is extremely time-consuming and requires a substantial amount of initial training. Although CBTs can vary based on the target disorder, one common element employed in most CBTs is the use of worksheets to identify specific behaviors and thoughts that affect a client's ability to recover. The present study will develop and evaluate an innovative new approach to rate CBT fidelity, by developing a universal CBT scoring system based on worksheets completed in therapy sessions.To develop a scoring system for CBT worksheets, we will compile common CBT elements from a variety of CBT worksheets for a range of psychiatric disorders and create adherence and competence measures. We will collect archival worksheets from past studies to test the scoring system and assess test-retest reliability. To evaluate whether CBT worksheet scoring accurately reflects clinician fidelity, we will recruit clinicians who are engaged in a CBT for depression, anxiety, and/or posttraumatic stress disorder. Clinicians and clients will transmit routine therapy materials produced in session (e.g., worksheets, clinical notes, session recordings) to the study team after each session. We will compare observer-rated fidelity, clinical notes, and fidelity-rated worksheets to identify the most effective and efficient method to assess clinician fidelity. Clients will also be randomly assigned to either complete the CBT worksheets on paper forms or on a mobile application (app) to learn if worksheet format influences clinician and client experience or differs in terms of reflecting fidelity.Scoring fidelity using CBT worksheets may allow clinics to test fidelity in a short and effective manner, enhancing continuous quality improvement in the workplace. Clinicians and clinics can use such data to improve clinician fidelity in real time, leading to improved patient outcomes.ClinicalTrials.gov NCT03479398 . Retrospectively registered March 20, 2018.

  View details for PubMedID 29789017

• Brain Responses During Implicit Regulation of Emotional Salience Moderate Antidepressant Treatment Response in Major Depression: Findings From the EMBARC Study Fonzo, G., Cooper, C., Fatt, C., Jo, B., Trivedi, M., Etkin, A. ELSEVIER SCIENCE INC. 2018: S177

  View details for Web of Science ID 000432466300440

• Brain and behavioral correlates of insulin resistance in youth with depression and obesity. Hormones and behavior Singh, M. K., Leslie, S. M., Packer, M. M., Zaiko, Y. V., Phillips, O. R., Weisman, E., Wall, D., Jo, B., Rasgon, N. L. 2018

  Abstract

  Depression, together with insulin resistance, is increasingly prevalent among youth. These conditions have traditionally been compartmentalized, but recent evidence suggests that a shared brain motivational network underlies their co-occurrence. We posit that, in the context of depressive symptoms, insulin resistance is associated with aberrant structure and functional connectivity in the Anterior Cingulate Cortex (ACC) and hippocampus. This motivational neural circuit underlies dysfunctional behavioral responses and increased sensitivity to rewarding aspects of ingesting high calorie food that lead to disinhibition of eating even when satiated. To investigate this shared mechanism, we evaluated a sample of forty-two depressed and overweight (BMI > 85th%) youth aged 9 to 17. Using ACC and hippocampus structural and seed-based regions of interest, we investigated associations between insulin resistance, depression, structure (ACC thickness, and ACC and hippocampal area), and resting-state functional connectivity (RSFC). We predicted that aberrant associations among these neural and behavioral characteristics would be stronger in insulin resistant compared to insulin sensitive youth. We found that youth with greater insulin resistance had higher levels of anhedonia and more food seeking behaviors, reduced hippocampal and ACC volumes, and greater levels of ACC and hippocampal dysconnectivity to fronto-limbic reward networks at rest. For youth with high levels of insulin resistance, thinner ACC and smaller hippocampal volumes were associated with more severe depressive symptoms, whereas the opposite was true for youth with low levels of insulin resistance. The ACC-hippocampal motivational network that subserves depression and insulin resistance separately, may represent a critical neural interaction that link these syndromes together.

  View details for PubMedID 29596854

• Are parental self-efficacy and family flexibility mediators of treatment for anorexia nervosa? INTERNATIONAL JOURNAL OF EATING DISORDERS Sadeh-Sharvit, S., Arnow, K. D., Osipov, L., Lock, J. D., Jo, B., Pajarito, S., Brandt, H., Dodge, E., Halmi, K. A., Johnson, C., Kaye, W., Wilfley, D., Agras, W. 2018; 51 (3): 275–80

  Abstract

  Family-based treatment (FBT) for adolescent anorexia nervosa (AN) promotes faster weight restoration when compared to other treatments. However, the mechanisms through which this occurs are not clarified. This study explored the trajectories of parental self-efficacy and perceived family flexibility during FBT and systemic family therapy (SyFT). We also explored whether parental self-efficacy mediates the effects of treatment on weight gain early in treatment.158 adolescents (12-18 years old; 89% girls) and their parents were randomized to FBT or SyFT. Parental self-efficacy as well as adolescents' and parental perceptions of the family's flexibility were collected at baseline and at sessions 2, 4, 6, and 8.Over time, only parents in FBT reported significantly greater self-efficacy. The change in maternal self-efficacy over the first 8 weeks of treatment was a significant mediator of session 10 weight gain. There were no significant group differences in perceived flexibility by session 8.Both parents in FBT and mothers in SyFT understand early the need to change their family's rules and roles. However, the specific strategies of FBT appear to mediate early weight gain in AN.

  View details for PubMedID 29314160

• Effects of Rapastinel (Formerly GLYX-13) on Serum Brain-Derived Neurotrophic Factor in Obsessive-Compulsive Disorder JOURNAL OF CLINICAL PSYCHIATRY Linkovski, O., Shen, H., Zwerling, J., Filippou-Frye, M., Jo, B., Cordell, E., Cooper, T. B., Simpson, H., Burch, R. M., Moskal, J. R., Lee, F., Rodriguez, C. I. 2018; 79 (1)

  View details for DOI 10.4088/JCP.17l11824

  View details for Web of Science ID 000436389500011

• Feasibility Study Combining Art Therapy or Cognitive Remediation Therapy with Family-based Treatment for Adolescent Anorexia Nervosa EUROPEAN EATING DISORDERS REVIEW Lock, J., Fitzpatrick, K., Agras, W. S., Weinbach, N., Jo, B. 2018; 26 (1): 62–68

  Abstract

  Adolescents with anorexia nervosa who have obsessive-compulsive (OC) features respond poorly to family-based treatment (FBT). This study evaluated the feasibility of combining FBT with either cognitive remediation therapy (CRT) or art therapy (AT) to improve treatment response in this at-risk group. Thirty adolescents with anorexia nervosa and OC features were randomized to 15 sessions of FBT + CRT or AT. Recruitment rate was 1 per month, and treatment attrition was 16.6% with no differences between groups. Suitability, expectancy and therapeutic relationships were acceptable for both combinations. Correlations between changes in OC traits and changes in cognitive inefficiencies were found for both combinations. Moderate changes in cognitive inefficiencies were found in both groups but were larger in the FBT + AT combination. This study suggests that an RCT for poor responders to FBT because of OC traits combining FBT with either CRT or AT is feasible to conduct. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

  View details for PubMedID 29152825

  View details for PubMedCentralID PMC5732028

• Effects of Rapastinel (Formerly GLYX-13) on Serum Brain-Derived Neurotrophic Factor in Obsessive-Compulsive Disorder. The Journal of clinical psychiatry Linkovski, O., Shen, H., Zwerling, J., Filippou-Frye, M., Jo, B., Cordell, E., Cooper, T. B., Simpson, H. B., Burch, R. M., Moskal, J. R., Lee, F., Rodriguez, C. I. 2018; 79 (1)

  View details for PubMedID 29505186

• Impact of Early Diabetic Ketoacidosis on the Developing Brain. Diabetes care Aye, T. n., Mazaika, P. K., Mauras, N. n., Marzelli, M. J., Shen, H. n., Hershey, T. n., Cato, A. n., Weinzimer, S. A., White, N. H., Tsalikian, E. n., Jo, B. n., Reiss, A. L. 2018

  Abstract

  This study examined whether a history of diabetic ketoacidosis (DKA) is associated with changes in longitudinal cognitive and brain development in young children with type 1 diabetes.Cognitive and brain imaging data were analyzed from 144 children with type 1 diabetes, ages 4 to <10 years, who participated in an observational study of the Diabetes Research in Children Network (DirecNet). Participants were grouped according to history of DKA severity (none/mild or moderate/severe). Each participant had unsedated MRI scans and cognitive testing at baseline and 18 months.In 48 of 51 subjects, the DKA event occurred at the time of onset, at an average of 2.9 years before study entry. The moderate/severe DKA group gained more total and regional white and gray matter volume over the observed 18 months compared with the none/mild group. When matched by age at time of enrollment and average HbA1c during the 18-month interval, participants who had a history of moderate/severe DKA compared with none/mild DKA were observed to have significantly lower Full Scale Intelligence Quotient scores, cognitive performance on the Detectability and Commission subtests of the Conners' Continuous Performance Test II, and the Dot Locations subtest of the Children's Memory Scale.A single episode of moderate/severe DKA in young children at diagnosis is associated with lower cognitive scores and altered brain growth. Further studies are needed to assess whether earlier diagnosis of type 1 diabetes and prevention of DKA may reduce the long-term effect of ketoacidosis on the developing brain.

  View details for DOI 10.2337/dc18-1405

  View details for PubMedID 30573652

• PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation AMERICAN JOURNAL OF PSYCHIATRY Fonzo, G. A., Goodkind, M. S., Oathes, D. J., Zaiko, Y. V., Harvey, M., Peng, K. K., Weiss, M., Thompson, A. L., Zack, S. E., Lindley, S. E., Arnow, B. A., Jo, B., Gross, J. J., Rothbaum, B. O., Etkin, A. 2017; 174 (12): 1163–74

  View details for DOI 10.1176/appi.ajp.2017.16091072

  View details for Web of Science ID 000417355900010

• Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD. The American journal of psychiatry Fonzo, G. A., Goodkind, M. S., Oathes, D. J., Zaiko, Y. V., Harvey, M., Peng, K. K., Weiss, M. E., Thompson, A. L., Zack, S. E., Mills-Finnerty, C. E., Rosenberg, B. M., Edelstein, R., Wright, R. N., Kole, C. A., Lindley, S. E., Arnow, B. A., Jo, B., Gross, J. J., Rothbaum, B. O., Etkin, A. 2017; 174 (12): 1175-1184

  Abstract

  Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms.Individuals with PTSD underwent functional MRI (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30) and underwent a second scan approximately 4 weeks after the last treatment session or a comparable waiting period, respectively.Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayed a greater variety of temporal resting-state signal pattern changes after treatment. Concurrent transcranial magnetic stimulation and fMRI in healthy participants demonstrated that the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum.Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy and that the frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works, and they identify a promising target for stimulation-based therapeutics.

  View details for DOI 10.1176/appi.ajp.2017.16091073

  View details for PubMedID 28715907

  View details for PubMedCentralID PMC5711612

• PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation. The American journal of psychiatry Fonzo, G. A., Goodkind, M. S., Oathes, D. J., Zaiko, Y. V., Harvey, M., Peng, K. K., Weiss, M. E., Thompson, A. L., Zack, S. E., Lindley, S. E., Arnow, B. A., Jo, B., Gross, J. J., Rothbaum, B. O., Etkin, A. 2017; 174 (12): 1163-1174

  Abstract

  Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients do not respond. Brain functions governing treatment outcome are not well characterized. The authors examined brain systems relevant to emotional reactivity and regulation, constructs that are thought to be central to PTSD and exposure therapy effects, to identify the functional traits of individuals most likely to benefit from treatment.Individuals with PTSD underwent functional MRI (fMRI) while completing three tasks assessing emotional reactivity and regulation. Participants were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30). A random subset of the prolonged exposure group (N=17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with fMRI to examine whether predictive activation patterns reflect causal influence within circuits. Linear mixed-effects modeling in line with the intent-to-treat principle was used to examine how baseline brain function moderated the effect of treatment on PTSD symptoms.At baseline, individuals with larger treatment-related symptom reductions (compared with the waiting list condition) demonstrated 1) greater dorsal prefrontal activation and 2) less left amygdala activation, both during emotion reactivity; 3) better inhibition of the left amygdala induced by single TMS pulses to the right dorsolateral prefrontal cortex; and 4) greater ventromedial prefrontal/ventral striatal activation during emotional conflict regulation. Reappraisal-related activation was not a significant moderator of the treatment effect.Capacity to benefit from prolonged exposure in PTSD is gated by the degree to which prefrontal resources are spontaneously engaged when superficially processing threat and adaptively mitigating emotional interference, but not when deliberately reducing negative emotionality.

  View details for DOI 10.1176/appi.ajp.2017.16091072

  View details for PubMedID 28715908

  View details for PubMedCentralID PMC5711543

• Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD AMERICAN JOURNAL OF PSYCHIATRY Fonzo, G. A., Goodkind, M. S., Oathes, D. J., Zaiko, Y. V., Harvey, M., Peng, K. K., Weiss, M., Thompson, A. L., Zack, S. E., Mills-Finnerty, C. E., Rosenberg, B. M., Edelstein, R., Wright, R. N., Kole, C. A., Lindley, S. E., Arnow, B. A., Jo, B., Gross, J. J., Rothbaum, B. O., Etkin, A. 2017; 174 (12): 1175–84

  View details for DOI 10.1176/appi.ajp.2017.16091073

  View details for Web of Science ID 000417355900011

• Modulation of the Neural Circuitry Underlying Trait Hypnotizability With Spaced Continuous Theta-Burst Stimulation Williams, N., Sudheimer, K., Stimpson, K., Duvio, D., Chung, C., DeSouza, D., Jo, B., Williams, L., Yeomans, D., Spiegel, D. NATURE PUBLISHING GROUP. 2017: S508–S509

  View details for Web of Science ID 000416846303052

• Meta-Analysis of Psychosocial Treatment Effects on Cancer Survival and Sources of Heterogeneity Spiegel, D., Krizanec, S., Kraemer, H., Jo, B., Ershadi, M., Neri, E., Nouriani, B., Aasly, L. NATURE PUBLISHING GROUP. 2017: S331

  View details for Web of Science ID 000416846302058

• Anomalous prefrontal-limbic activation and connectivity in youth at high risk for bipolar disorder JOURNAL OF AFFECTIVE DISORDERS Chang, K., Garrett, A., Kelley, R., Howe, M., Sanders, E., Acquaye, T., Bararpour, L., Li, S., Singh, M., Jo, B., Hallmayer, J., Reiss, A. 2017; 222: 7–13

  Abstract

  Abnormal prefrontal-limbic brain activation in response to facial expressions has been reported in pediatric bipolar disorder (BD). However, it is less clear whether these abnormalities exist prior to onset of mania, thus representing a biomarker predicting development of BD.We examined brain activation in 50 youth at high risk for BD (HR-BD), compared with 29 age- and gender-matched healthy control (HC) subjects. HR-BD was defined as having a parent with BD, as well as current mood or attentiondeficit/ hyperactivity disorder (ADHD) symptoms, or a history of at least one depressive episode. FMRI data were collected during an implicit emotion perception task using facial expression stimuli. Activation to fearful faces versus calm faces was compared between HR-BD and HC groups, including analyses of functional connectivity, and comparison of allele subgroups of the serotonin transporter (5-HTTLPR) gene.While viewing fearful versus calm faces, HR-BD youth had significantly greater activation than HC youth in the right amygdala, ventrolateral prefrontal cortex (VLPFC), superior frontal cortex, cerebellum, and lingual gyrus. HR-BD youth, relative to HC youth, had greater functional connectivity between the right amygdala and the VLPFC as well as visual cortical regions Within the HR-BD group, youth with the s-allele had a trend for greater activation in the right amygdala and subgenual cingulate cortex CONCLUSIONS: Similar to youth with BD, youth at high risk for BD have greater activation than healthy controls in the amygdala and ventrolateral prefrontal cortex in response to fearful faces, as well greater functional connectivity between these regions. HR-BD youth with the s-allele of the 5-HTTLPR gene may be at greatest risk for developing BD.

  View details for PubMedID 28667891

• Improving preschoolers' mathematics achievement with tablets: a randomized controlled trial MATHEMATICS EDUCATION RESEARCH JOURNAL Schacter, J., Jo, B. 2017; 29 (3): 313-327

  View details for DOI 10.1007/s13394-017-0203-9

  View details for Web of Science ID 000413682700003

• Effect of a Novel NMDA Receptor Modulator, Rapastinel (formerly GLYX-13) in OCD: Proof-Of-Concept Rodriguez, C., Zwerling, J., Kalanthroff, E., Shen, H., Filippou, M., Jo, B., Simpson, H., Burch, R., Moskal, J. ELSEVIER SCIENCE INC. 2017: S345–S346

  View details for DOI 10.1016/j.biopsych.2017.02.578

  View details for Web of Science ID 000400348700850

• Differential effects of metformin on age related comorbidities in older men with type 2 diabetes JOURNAL OF DIABETES AND ITS COMPLICATIONS Wang, C., Lorenzo, C., Habib, S. L., Jo, B., Espinoza, S. E. 2017; 31 (4): 679-686

  Abstract

  To identify distinct temporal likelihoods of age-related comorbidity (ARC) diagnoses: cardiovascular diseases (CVD), cancer, depression, dementia, and frailty-related diseases (FRD) in older men with type 2 diabetes (T2D) but ARC naïve initially, and assess the heterogeneous effects of metformin on ARCs and mortality.We identified a clinical cohort of male veterans in the United States who were ≥65years old with T2D and free from ARCs during 2002-2003. ARC diagnoses during 2004-2012 were analyzed using latent class modeling adjusted for confounders.The cohort consisted of 41,204 T2D men with age 74.6±5.8years, HbA1c 6.5±0.97%, and 8393 (20.4%) metformin users. Four ARC classes were identified. 'Healthy Class' (53.6%): metformin reduced likelihoods of all ARCs (from 0.14% in dementia to 6.1% in CVD). 'High Cancer Risk Class' (11.6%): metformin reduced likelihoods of CVD (13.3%), cancer (45.5%), depression (5.0%), and FRD (13.7%). 'High CVD Risk Class' (17.4%): metformin reduced likelihoods of CVD (48.6%), cancer (3.2%), depression (2.8%), and FRD (6.3%). 'High Frailty Risk Class' (17.2%): metformin reduced likelihoods of CVD (18.8%), cancer (3.9%), dementia (3.8%), depression (15.6%), and FRD (23.8%).Metformin slowed ARC development in old men with T2D, and these effects varied by ARC phenotype.

  View details for DOI 10.1016/jjdiacomp.2017.01.013

  View details for PubMedID 28190681

• Targeted use of growth mixture modeling: a learning perspective STATISTICS IN MEDICINE Jo, B., Findling, R. L., Wang, C., Hastie, T. J., Youngstrom, E. A., Arnold, L. E., Fristad, M. A., Horwitz, S. M. 2017; 36 (4): 671-686

  Abstract

  From the statistical learning perspective, this paper shows a new direction for the use of growth mixture modeling (GMM), a method of identifying latent subpopulations that manifest heterogeneous outcome trajectories. In the proposed approach, we utilize the benefits of the conventional use of GMM for the purpose of generating potential candidate models based on empirical model fitting, which can be viewed as unsupervised learning. We then evaluate candidate GMM models on the basis of a direct measure of success; how well the trajectory types are predicted by clinically and demographically relevant baseline features, which can be viewed as supervised learning. We examine the proposed approach focusing on a particular utility of latent trajectory classes, as outcomes that can be used as valid prediction targets in clinical prognostic models. Our approach is illustrated using data from the Longitudinal Assessment of Manic Symptoms study. Copyright © 2016 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/sim.7152

  View details for Web of Science ID 000393304400008

  View details for PubMedCentralID PMC5217165

• Learning in Generalized Anxiety Disorder Benefits From Neither the Carrot Nor the Stick. American journal of psychiatry Etkin, A., Fonzo, G. A. 2017; 174 (2): 87-88

  View details for DOI 10.1176/appi.ajp.2016.16111267

  View details for PubMedID 28142268

• Effects of childhood trauma exposure and cortisol levels on cognitive functioning among breast cancer survivors. Child abuse & neglect Kamen, C. n., Scheiber, C. n., Janelsins, M. n., Jo, B. n., Shen, H. n., Palesh, O. n. 2017; 72: 163–71

  Abstract

  Cognitive functioning difficultiesin breast cancer patients receiving chemotherapy are common, but not all women experience these impairments. Exposure to childhood trauma may impair cognitive functioning following chemotherapy, and these impairments may be mediated by dysregulation of hypothalamic-pituitary-adrenal (HPA) axis function and cortisol slope. This study evaluated the association between childhood trauma exposure, cortisol, and cognition in a sample of breast cancer survivors. 56 women completed measures of trauma exposure (the Traumatic Events Survey), salivary cortisol, and self-reported cognitive functioning (the Functional Assessment of Cancer Therapy - Cognitive). We examined correlations between childhood trauma exposure and cognitive functioning, then used linear regression to control for factors associated with cognition (age, education, time since chemotherapy, depression, anxiety, and insomnia), and the MacArthur approach to test whether cortisol levels mediated the relationship between trauma and cognitive functioning. 57.1% of the sample had experienced at least one traumatic event in childhood, with 19.6% of the sample witnessing a serious injury, 17.9% experiencing physical abuse, and 14.3% experiencing sexual abuse. Childhood trauma exposure and cognitive functioning were moderately associated (r=-0.29). This association remained even when controlling for other factors associated with cognition; the final model explained 47% of the variance in cognitive functioning. The association between childhood trauma and cognitive functioning was mediated by steeper cortisol slope (partial r=0.35, p=0.02). Childhood trauma exposure is associated with self-reported cognitive functioning among breast cancer survivors and is mediated by cortisol dysregulation. Trauma should be considered, among other factors, in programs aiming to address cognition in this population.

  View details for PubMedID 28818733

  View details for PubMedCentralID PMC5659913

• A Longitudinal Pilot Study of Behavioral Abnormalities in Children with Autism. Journal of psychiatry and psychiatric disorders Libove, R. A., Frazier, T. W., O'Hara, R. n., Phillips, J. M., Jo, B. n., Hardan, A. Y. 2017; 1 (4): 215–23

  Abstract

  This longitudinal investigation examined the development of emotional and behavioral functioning in school-age children with autism. The Child Behavior Checklist was obtained at baseline and after an average interval of 28.5 months from 13 boys with autism and 14 age- and gender-matched controls between the ages of 7 and 12 years at baseline. Children with autism demonstrated clinically significant elevations in several domains including Social, Thought, and Attention Problems. Children with autism exhibited significant improvements over time in Total, Externalizing, Social, and Oppositional Defiant Problems and Aggressive Behavior, while there were no changes over time in the controls. These findings suggest that children with autism may demonstrate improvements over time in some clinical domains such as social and behavioral functioning.

  View details for DOI 10.26502/jppd.2572-519X0022

  View details for PubMedID 32587950

  View details for PubMedCentralID PMC7316392

• Brain Mechanisms and Predictors of Response to Prolonged Exposure Therapy in PTSD Fonzo, G., Goodkind, M., Oathes, D., Zaiko, Y., Harvey, M., Peng, K., Weiss, E., Mills-Finnerty, C., Thompson, A., Zack, S., Lindley, S., Arnow, B., Jo, B., Gross, J., Rothbaum, B., Etkin, A. NATURE PUBLISHING GROUP. 2016: S291–S292

  View details for Web of Science ID 000440365600493

• Effect of a Novel NMDA Receptor Modulator, Rapastinel (Formerly GLYX-13) in OCD: Proof-of-Concept Rodriguez, C., Zwerling, J., Kalanthroff, E., Shen, H., Filippou, M., Jo, B., Simpson, H., Burch, R., Moskal, J. NATURE PUBLISHING GROUP. 2016: S334–S335

  View details for Web of Science ID 000440365600566

• The cognitive developmental profile associated with fragile X syndrome: A longitudinal investigation of cognitive strengths and weaknesses through childhood and adolescence. Development and psychopathology Quintin, E., Jo, B., Hall, S. S., Bruno, J. L., Chromik, L. C., Raman, M. M., Lightbody, A. A., Martin, A., Reiss, A. L. 2016; 28 (4): 1457-1469

  Abstract

  Few studies have investigated developmental strengths and weaknesses within the cognitive profile of children and adolescents with fragile X syndrome (FXS), a single-gene cause of inherited intellectual impairment. With a prospective longitudinal design and using normalized raw scores (Z scores) to circumvent floor effects, we measured cognitive functioning of 184 children and adolescents with FXS (ages 6 to 16) using the Wechsler Scale of Intelligence for Children on one to three occasions for each participant. Participants with FXS received lower raw scores relative to the Wechsler Scale of Intelligence for Children normative sample across the developmental period. Verbal comprehension, perceptual organization, and processing speed Z scores were marked by a widening gap from the normative sample, while freedom from distractibility Z scores showed a narrowing gap. Key findings include a relative strength for verbal skills in comparison with visuospatial-constructive skills arising in adolescence and a discrepancy between working memory (weakness) and processing speed (strength) in childhood that diminishes in adolescence. Results suggest that the cognitive profile associated with FXS develops dynamically from childhood to adolescence. Findings are discussed within the context of aberrant brain morphology in childhood and maturation in adolescence. We argue that assessing disorder-specific cognitive developmental profiles will benefit future disorder-specific treatment research.

  View details for PubMedID 26648140

• Does family-based treatment reduce the need for hospitalization in adolescent anorexia nervosa? International journal of eating disorders Lock, J., Agras, W. S., Bryson, S. W., Brandt, H., Halmi, K. A., Kaye, W., Wilfley, D., Woodside, B., Pajarito, S., Jo, B. 2016; 49 (9): 891-894

  Abstract

  We examined the timing and number of days of hospitalization during the course of treatment, hospitalization effects on outcome, and predictors and moderators of the use of hospitalization in adolescents with anorexia nervosa (AN).Data used in this study were collected from 158 adolescents (ages 12 to 18 years of age) who met DSM-IVTR criteria for AN (exclusive of the amenorrhea criteria) randomized to receive either Family Based Treatment (FBT) or Systemic Family Therapy (SyFT) in a 7 site study.The trajectory of hospital day use is similar in the first 5 weeks irrespective of treatment allocation. However, days of hospitalization continued to increase throughout SyFT but leveled off in FBT after ∼5 weeks of treatment. Early hospitalization was a negative predictor for improvements in percent weight change for both treatment groups (t(1)=2.6, p = 0.011). Co-morbid psychopathology predicted early hospital use in both treatments. Higher levels of eating related obsessions and depression moderated hospitalization rates suggesting that FBT reduces early hospitalization rates compared to SyFT for these subgroups.These data support and extend findings from previous studies by identifying patterns of hospital use, and predictors and moderators of treatment effect for early hospitalization use in adolescent AN. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:891-894).

  View details for DOI 10.1002/eat.22536

  View details for PubMedID 27062400

• Aberrant nocturnal cortisol and disease progression in women with breast cancer BREAST CANCER RESEARCH AND TREATMENT Zeitzer, J. M., Nouriani, B., Rissling, M. B., Sledge, G. W., Kaplan, K. A., Aasly, L., Palesh, O., Jo, B., Neri, E., Dhabhar, F. S., Spiegel, D. 2016; 158 (1): 43-50

  Abstract

  While a relationship between disruption of circadian rhythms and the progression of cancer has been hypothesized in field and epidemiologic studies, it has never been unequivocally demonstrated. We determined the circadian rhythm of cortisol and sleep in women with advanced breast cancer (ABC) under the conditions necessary to allow for the precise measurement of these variables. Women with ABC (n = 97) and age-matched controls (n = 24) took part in a 24-h intensive physiological monitoring study involving polysomnographic sleep measures and high-density plasma sampling. Sleep was scored using both standard clinical metrics and power spectral analysis. Three-harmonic regression analysis and functional data analysis were used to assess the 24-h and sleep-associated patterns of plasma cortisol, respectively. The circadian pattern of plasma cortisol as described by its timing, timing relative to sleep, or amplitude was indistinguishable between women with ABC and age-matched controls (p's > 0.11, t-tests). There was, however, an aberrant spike of cortisol during the sleep of a subset of women, during which there was an eightfold increase in the amount of objectively measured wake time (p < 0.004, Wilcoxon Signed-Rank). This cortisol aberration was associated with cancer progression such that the larger the aberration, the shorter the disease-free interval (time from initial diagnosis to metastasis; r = -0.30, p = 0.004; linear regression). The same aberrant spike was present in a similar percent of women without ABC and associated with concomitant sleep disruption. A greater understanding of this sleep-related cortisol abnormality, possibly a vulnerability trait, is likely important in our understanding of individual variation in the progression of cancer.

  View details for DOI 10.1007/s10549-016-3864-2

  View details for Web of Science ID 000379494200005

  View details for PubMedID 27314577

  View details for PubMedCentralID PMC4938753

• Using Complier Average Causal Effect Estimation to Determine the Impacts of the Good Behavior Game Preventive Intervention on Teacher Implementers. Administration and policy in mental health Berg, J. K., Bradshaw, C. P., Jo, B., Ialongo, N. S. 2016: -?

  Abstract

  Complier average causal effect (CACE) analysis is a causal inference approach that accounts for levels of teacher implementation compliance. In the current study, CACE was used to examine one-year impacts of PAX good behavior game (PAX GBG) and promoting alternative thinking strategies (PATHS) on teacher efficacy and burnout. Teachers in 27 elementary schools were randomized to PAX GBG, an integration of PAX GBG and PATHS, or a control condition. There were positive overall effects on teachers' efficacy beliefs, but high implementing teachers also reported increases in burnout across the school year. The CACE approach may offer new information not captured using a traditional intent-to-treat approach.

  View details for PubMedID 27207372

• Improving low-income preschoolers mathematics achievement with Math Shelf, a preschool tablet computer curriculum COMPUTERS IN HUMAN BEHAVIOR Schacter, J., Jo, B. 2016; 55: 223-229

  View details for DOI 10.1016/j.chb.2015.09.013

  View details for Web of Science ID 000367755400024

• Pharmacologic Treatment of Severe Irritability and Problem Behaviors in Autism: A Systematic Review and Meta-analysis. Pediatrics Fung, L. K., Mahajan, R., Nozzolillo, A., Bernal, P., Krasner, A., Jo, B., Coury, D., Whitaker, A., Veenstra-VanderWeele, J., Hardan, A. Y. 2016; 137: S124-35

  Abstract

  Autism spectrum disorder (ASD) is increasingly recognized as a public health issue. Irritability and aggression (IA) often negatively affect the lives of people with ASD and their families. Although many medications have been tested for IA in ASDs in randomized controlled trials (RCTs), critical quantitative analyses of these trials are lacking in the literature.To systematically review and quantitatively analyze the efficacy and safety of pharmacologic treatments for IA in youth with ASD.Studies were identified from Medline, PsycINFO, Embase, and review articles.Original articles on placebo-controlled RCTs of pharmacologic treatments of IA in youth age 2 to 17 years with ASD were included. Data items included study design, study goals, details of study participants, details of intervention, study results, statistical methods, side effects, and risks of bias. The primary study outcome measure was the effect size of reduction in the Aberrant Behavioral Checklist-Irritability (ABC-I) scores in the medication group, as compared with placebo, in RCTs using parallel groups design.Forty-six RCTs were identified. Compared with placebo, 3 compounds resulted in significant improvement in ABC-I at the end of treatment. Risperidone and aripiprazole were found to be the most effective, with the largest effect sizes. Sedation, extrapyramidal sides effects, and weight gain were assessed quantitatively.Although risperidone and aripiprazole have the strongest evidence in reducing ABC-I in youth with ASD, a few other compounds also showed significant efficacy with fewer potential side effects and adverse reactions in single studies.

  View details for DOI 10.1542/peds.2015-2851K

  View details for PubMedID 26908468

• Math Shelf: A Randomized Trial of a Prekindergarten Tablet Number Sense Curriculum EARLY EDUCATION AND DEVELOPMENT Schacter, J., Shih, J., Allen, C. M., DeVaul, L., Adkins, A. B., Ito, T., Jo, B. 2016; 27 (1): 74-88

  View details for DOI 10.1080/10409289.2015.1057462

  View details for Web of Science ID 000366613700005

• Construction of longitudinal prediction targets using semisupervised learning. Statistical methods in medical research Jo, B., Findling, R. L., Hastie, T. J., Youngstrom, E. A., Wang, C., Arnold, L. E., Fristad, M. A., Frazier, T. W., Birmaher, B., Gill, M. K., Horwitz, S. M. 2016: 962280216684163-?

  Abstract

  In establishing prognostic models, often aided by machine learning methods, much effort is concentrated in identifying good predictors. However, the same level of rigor is often absent in improving the outcome side of the models. In this study, we focus on this rather neglected aspect of model development. We are particularly interested in the use of longitudinal information as a way of improving the outcome side of prognostic models. This involves optimally characterizing individuals' outcome status, classifying them, and validating the formulated prediction targets. None of these tasks are straightforward, which may explain why longitudinal prediction targets are not commonly used in practice despite their compelling benefits. As a way of improving this situation, we explore the joint use of empirical model fitting, clinical insights, and cross-validation based on how well formulated targets are predicted by clinically relevant baseline characteristics (antecedent validators). The idea here is that all these methods are imperfect but can be used together to triangulate valid prediction targets. The proposed approach is illustrated using data from the longitudinal assessment of manic symptoms study.

  View details for DOI 10.1177/0962280216684163

  View details for PubMedID 28067113

• Effect of a Novel NMDA Receptor Modulator, Rapastinel (Formerly GLYX-13), in OCD: Proof of Concept. The American journal of psychiatry Rodriguez, C. I., Zwerling, J. n., Kalanthroff, E. n., Shen, H. n., Filippou, M. n., Jo, B. n., Simpson, H. B., Burch, R. M., Moskal, J. R. 2016; 173 (12): 1239–41

  View details for PubMedID 27903098

• Assessing the sensitivity of methods for estimating principal causal effects. Statistical methods in medical research Stuart, E. A., Jo, B. 2015; 24 (6): 657-674

  Abstract

  The framework of principal stratification provides a way to think about treatment effects conditional on post-randomization variables, such as level of compliance. In particular, the complier average causal effect (CACE) - the effect of the treatment for those individuals who would comply with their treatment assignment under either treatment condition - is often of substantive interest. However, estimation of the CACE is not always straightforward, with a variety of estimation procedures and underlying assumptions, but little advice to help researchers select between methods. In this article, we discuss and examine two methods that rely on very different assumptions to estimate the CACE: a maximum likelihood ('joint') method that assumes the 'exclusion restriction,' (ER) and a propensity score-based method that relies on 'principal ignorability.' We detail the assumptions underlying each approach, and assess each methods' sensitivity to both its own assumptions and those of the other method using both simulated data and a motivating example. We find that the ER-based joint approach appears somewhat less sensitive to its assumptions, and that the performance of both methods is significantly improved when there are strong predictors of compliance. Interestingly, we also find that each method performs particularly well when the assumptions of the other approach are violated. These results highlight the importance of carefully selecting an estimation procedure whose assumptions are likely to be satisfied in practice and of having strong predictors of principal stratum membership.

  View details for DOI 10.1177/0962280211421840

  View details for PubMedID 21971481

  View details for PubMedCentralID PMC3253203

• Aberrant Nocturnal Cortisol as a Vulnerability Trait for More Rapid Progression of Advanced Breast Cancer Zeitzer, J., Nouriani, B., Rissling, M., Sledge, G., Palesh, O., Jo, B., Neri, E., Spiegel, D. NATURE PUBLISHING GROUP. 2015: S194–S195

  View details for Web of Science ID 000366597700347

• Randomized Clinical Trial of Family-Based Treatment and Cognitive-Behavioral Therapy for Adolescent Bulimia Nervosa. Journal of the American Academy of Child and Adolescent Psychiatry Le Grange, D., Lock, J., Agras, W. S., Bryson, S. W., Jo, B. 2015; 54 (11): 886-894 e2

  View details for DOI 10.1016/j.jaac.2015.08.008

  View details for PubMedID 26506579

• Can adaptive treatment improve outcomes in family-based therapy for adolescents with anorexia nervosa? Feasibility and treatment effects of a multi-site treatment study. Behaviour research and therapy Lock, J., Le Grange, D., Agras, W. S., Fitzpatrick, K. K., Jo, B., Accurso, E., Forsberg, S., Anderson, K., Arnow, K., Stainer, M. 2015; 73: 90-95

  Abstract

  Adolescents with Anorexia Nervosa (AN), treated with family-based treatment (FBT) who fail to gain 2.3 kg by the fourth week of treatment have a 40-50% lower chance of recovery than those who do. Because of the high risk of developing enduring AN, improving outcomes in this group of poor responders is essential. This study examines the feasibility and effects of a novel adaptive treatment (i.e., Intensive Parental Coaching-IPC) aimed at enhancing parental self-efficacy related to re-feeding skills in poor early responders to FBT.45 adolescents (12-18 years of age) meeting DSM TR IV criteria for AN were randomized in an unbalanced design (10 to standard FBT; 35 to the adaptive arm). Attrition, suitability, expectancy rates, weight change, and psychopathology were compared between groups.There were no differences in rates of attrition, suitability, expectancy ratings, or most clinical outcomes between randomized groups. However, the group of poor early responders that received IPC achieved full weight restoration (>95% of expected mean BMI) by EOT at similar rates as those who had responded early.The results of this study suggest that it is feasible to use an adaptive design to study the treatment effect of IPC for those who do not gain adequate weight by session 4 of FBT. The results also suggest that using IPC for poor early responders significantly improves weight recovery rates to levels comparable to those who respond early. A sufficiently powered study is needed to confirm these promising findings.

  View details for DOI 10.1016/j.brat.2015.07.015

  View details for PubMedID 26276704

  View details for PubMedCentralID PMC4573312

• DOES AN INTERVENTION TO REDUCE MATERNAL ANXIETY, DEPRESSION AND TRAUMA ALSO IMPROVE MOTHERS' PERCEPTIONS OF THEIR PRETERM INFANTS' VULNERABILITY? (vol 36, pg 42, 2015) INFANT MENTAL HEALTH JOURNAL Horwitz, S., Leibovitz, A., Lilo, E., Jo, B., Debattista, A., St John, N., Shaw, R. J. 2015; 36 (3): 352

  View details for DOI 10.1002/imhj.21517

  View details for Web of Science ID 000354487800011

• DOES AN INTERVENTION TO REDUCE MATERNAL ANXIETY, DEPRESSION AND TRAUMA ALSO IMPROVE MOTHERS' PERCEPTIONS OF THEIR PRETERM INFANTS' VULNERABILITY? INFANT MENTAL HEALTH JOURNAL Horwitz, S. M., Leibovitz, A., Lilo, E., Jo, B., DeBattista, A., St John, N., Shaw, R. J. 2015; 36 (1): 42-52

  Abstract

  To determine if an intervention to reduce maternal distress and address maternal perceptions of infants' vulnerability also reduces perceptions of vulnerability, 105 mothers of premature infants (25- to 34-weeks' gestational age; >600 g) with depression, anxiety, or trauma were randomized to a six- or nine-session intervention or a comparison condition. The outcome was changes in a measure of perception of infant vulnerability between 4 to 5 weeks' and 6 months' postdelivery, the Vulnerability Baby Scale (VBS; B. Forsyth, S. Horwitz, J. Leventhal, & J. Burger, 1996; N. Kerruish, K. Settle, P. Campbell-Stokes, & B. Taylor, 2005). High scores on the VBS were indicative of high levels of perceived infant vulnerability. The perceptions of infants' vulnerability showed significant declines, with no differences across groups or in rate of change. Mothers reporting prior trauma at entry to the study showed much lower perceptions of infants' vulnerability scores under the intervention, Cohen's d = -0.86, p = .01. Given that women with prior trauma are very likely to view their premature infants as vulnerable, this intervention may have important implications for subsequent parenting behaviors and child development.

  View details for DOI 10.1002/imhj.21484

  View details for Web of Science ID 000348421800006

  View details for PubMedID 25452159

• A randomized controlled trial of in-patient treatment for anorexia nervosa in medically unstable adolescents PSYCHOLOGICAL MEDICINE Madden, S., Miskovic-Wheatley, J., Wallis, A., Kohn, M., Lock, J., le Grange, D., Jo, B., Clarke, S., Rhodes, P., Hay, P., Touyz, S. 2015; 45 (2): 415-427

  View details for DOI 10.1017/S0033291714001573

  View details for Web of Science ID 000349617100016

• Longitudinal trajectories of aberrant behavior in fragile X syndrome. Research in developmental disabilities Hustyi, K. M., Hall, S. S., Jo, B., Lightbody, A. A., Reiss, A. L. 2014; 35 (11): 2691-2701

  Abstract

  The Aberrant Behavior Checklist-Community (ABC-C; Aman et al., 1995) has been increasingly adopted as a primary tool for measuring behavioral change in clinical trials for individuals with fragile X syndrome (FXS). To our knowledge, however, no study has documented the longitudinal trajectory of aberrant behaviors in individuals with FXS using the ABC-C. As part of a larger longitudinal study, we examined scores obtained on the ABC-C subscales for 124 children and adolescents (64 males, 60 females) with FXS who had two or more assessments (average interval between assessments was approximately 4 years). Concomitant changes in age-equivalent scores on the Vineland Adaptive Behavior Scales (VABS) were also examined. As expected for an X-linked genetic disorder, males with FXS obtained significantly higher scores on all subscales of the ABC-C and significantly lower age-equivalent scores on the VABS than females with FXS. In both males and females with FXS, scores on the Irritability/Agitation and Hyperactivity/Noncompliance subscales of the ABC-C decreased significantly with age, with little to no change occurring over time on the Lethargy/Social Withdrawal, Stereotypic Behavior, and Inappropriate Speech subscales. The decrease in scores on the Hyperactivity/Noncompliance domain was significantly greater for males than for females. In both males and females, age-equivalent scores on the VABS increased significantly over this developmental period. These results establish a basis upon which to evaluate long-term outcomes from intervention-based research. However, longitudinal direct observational studies are needed to establish whether the severity of problem behavior actually decreases over time in this population.

  View details for DOI 10.1016/j.ridd.2014.07.003

  View details for PubMedID 25129200

• Comparison of 2 family therapies for adolescent anorexia nervosa: a randomized parallel trial. JAMA psychiatry Agras, W. S., Lock, J., Brandt, H., Bryson, S. W., Dodge, E., Halmi, K. A., Jo, B., Johnson, C., Kaye, W., Wilfley, D., Woodside, B. 2014; 71 (11): 1279-1286

  Abstract

  Anorexia nervosa (AN) is a serious disorder with high rates of morbidity and mortality. Family-based treatment (FBT) is an evidence-based therapy for adolescent AN, but less than half of those who receive this approach recover. Hence, it is important to identify other approaches to prevent the development of the chronic form of AN for which there is no known evidence-based treatment.To compare FBT with systemic family therapy (SyFT) for the treatment of adolescent-onset AN.Research in Anorexia Nervosa (RIAN) is a 2-group (FBT and SyFT) randomized trial conducted between September 2005 and April 2012. Interviewers were blinded to the treatment condition. A total of 564 adolescents receiving care at 6 outpatient clinics experienced in the treatment of AN were screened. Of these, 262 adolescents did not meet the inclusion criteria and 138 declined to participate; hence, 164 adolescents (aged 12-18 years) of both sexes meeting the criteria for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, AN (except for amenorrhea) were enrolled. Three participants were withdrawn from FBT and 7 were withdrawn from SyFT after serious adverse events occurred.Two manualized family therapies with 16 one-hour sessions during 9 months. Family-based therapy focuses on the facilitation of weight gain, whereas SyFT addresses general family processes.The primary outcomes were percentage of ideal body weight (IBW) and remission (≥95% of IBW). The a priori hypothesis was that FBT would result in faster weight gain early in treatment and at the end of treatment (EOT).There were no statistically significant differences between treatment groups for the primary outcome, for eating disorder symptoms or comorbid psychiatric disorders at the EOT or follow-up. Remission rates included FBT, 33.1% at the EOT and 40.7% at follow-up and SyFT, 25.3% and 39.0%, respectively. Family-based therapy led to significantly faster weight gain early in treatment, significantly fewer days in the hospital, and lower treatment costs per patient in remission at the EOT (FBT, $8963; SyFT, $18 005). An exploratory moderator analysis found that SyFT led to greater weight gain than did FBT for participants with more severe obsessive-compulsive symptoms.The findings of this study suggest that FBT is the preferred treatment for adolescent AN because it is not significantly different from SyFT and leads to similar outcomes at a lower cost than SyFT. Adolescents with more severe obsessive-compulsive symptoms may receive more benefits with SyFT.clinicaltrials.gov Identifier NCT00610753.

  View details for DOI 10.1001/jamapsychiatry.2014.1025

  View details for PubMedID 25250660

• Comparison of 2 Family Therapies for Adolescent Anorexia Nervosa A Randomized Parallel Trial JAMA PSYCHIATRY Agras, W. S., Lock, J., Brandt, H., Bryson, S. W., Dodge, E., Halmi, K. A., Jo, B., Johnson, C., Kaye, W., Wilfley, D., Woodside, B. 2014; 71 (11): 1279-1286

  Abstract

  Anorexia nervosa (AN) is a serious disorder with high rates of morbidity and mortality. Family-based treatment (FBT) is an evidence-based therapy for adolescent AN, but less than half of those who receive this approach recover. Hence, it is important to identify other approaches to prevent the development of the chronic form of AN for which there is no known evidence-based treatment.To compare FBT with systemic family therapy (SyFT) for the treatment of adolescent-onset AN.Research in Anorexia Nervosa (RIAN) is a 2-group (FBT and SyFT) randomized trial conducted between September 2005 and April 2012. Interviewers were blinded to the treatment condition. A total of 564 adolescents receiving care at 6 outpatient clinics experienced in the treatment of AN were screened. Of these, 262 adolescents did not meet the inclusion criteria and 138 declined to participate; hence, 164 adolescents (aged 12-18 years) of both sexes meeting the criteria for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, AN (except for amenorrhea) were enrolled. Three participants were withdrawn from FBT and 7 were withdrawn from SyFT after serious adverse events occurred.Two manualized family therapies with 16 one-hour sessions during 9 months. Family-based therapy focuses on the facilitation of weight gain, whereas SyFT addresses general family processes.The primary outcomes were percentage of ideal body weight (IBW) and remission (≥95% of IBW). The a priori hypothesis was that FBT would result in faster weight gain early in treatment and at the end of treatment (EOT).There were no statistically significant differences between treatment groups for the primary outcome, for eating disorder symptoms or comorbid psychiatric disorders at the EOT or follow-up. Remission rates included FBT, 33.1% at the EOT and 40.7% at follow-up and SyFT, 25.3% and 39.0%, respectively. Family-based therapy led to significantly faster weight gain early in treatment, significantly fewer days in the hospital, and lower treatment costs per patient in remission at the EOT (FBT, $8963; SyFT, $18 005). An exploratory moderator analysis found that SyFT led to greater weight gain than did FBT for participants with more severe obsessive-compulsive symptoms.The findings of this study suggest that FBT is the preferred treatment for adolescent AN because it is not significantly different from SyFT and leads to similar outcomes at a lower cost than SyFT. Adolescents with more severe obsessive-compulsive symptoms may receive more benefits with SyFT.clinicaltrials.gov Identifier NCT00610753.

  View details for DOI 10.1001/jamapsychiatry.2014.1025

  View details for Web of Science ID 000344989100010

• Causal inference in longitudinal comparative effectiveness studies with repeated measures of a continuous intermediate variable STATISTICS IN MEDICINE Wang, C., Jo, B., Brown, C. H. 2014; 33 (20): 3509-3527

  Abstract

  We propose a principal stratification approach to assess causal effects in nonrandomized longitudinal comparative effectiveness studies with a binary endpoint outcome and repeated measures of a continuous intermediate variable. Our method is an extension of the principal stratification approach originally proposed for the longitudinal randomized study "Prevention of Suicide in Primary Care Elderly: Collaborative Trial" to assess the treatment effect on the continuous Hamilton depression score adjusting for the heterogeneity of repeatedly measured binary compliance status. Our motivation for this work comes from a comparison of the effect of two glucose-lowering medications on a clinical cohort of patients with type 2 diabetes. Here, we consider a causal inference problem assessing how well the two medications work relative to one another on two binary endpoint outcomes: cardiovascular disease-related hospitalization and all-cause mortality. Clinically, these glucose-lowering medications can have differential effects on the intermediate outcome, glucose level over time. Ultimately, we want to compare medication effects on the endpoint outcomes among individuals in the same glucose trajectory stratum while accounting for the heterogeneity in baseline covariates (i.e., to obtain 'principal effects' on the endpoint outcomes). The proposed method involves a three-step model estimation procedure. Step 1 identifies principal strata associated with the intermediate variable using hybrid growth mixture modeling analyses. Step 2 obtains the stratum membership using the pseudoclass technique and derives propensity scores for treatment assignment. Step 3 obtains the stratum-specific treatment effect on the endpoint outcome weighted by inverse propensity probabilities derived from Step 2.

  View details for DOI 10.1002/sim.6120

  View details for Web of Science ID 000340423200006

  View details for PubMedID 24577715

  View details for PubMedCentralID PMC4122661

• Longitudinal profiles of adaptive behavior in fragile x syndrome. Pediatrics Klaiman, C., Quintin, E., Jo, B., Lightbody, A. A., Hazlett, H. C., Piven, J., Hall, S. S., Reiss, A. L. 2014; 134 (2): 315-324

  Abstract

  To examine longitudinally the adaptive behavior patterns in fragile X syndrome.Caregivers of 275 children and adolescents with fragile X syndrome and 225 typically developing children and adolescents (2-18 years) were interviewed with the Vineland Adaptive Behavior Scales every 2 to 4 years as part of a prospective longitudinal study.Standard scores of adaptive behavior in people with fragile X syndrome are marked by a significant decline over time in all domains for males and in communication for females. Socialization skills are a relative strength as compared with the other domains for males with fragile X syndrome. Females with fragile X syndrome did not show a discernible pattern of developmental strengths and weaknesses.This is the first large-scale longitudinal study to show that the acquisition of adaptive behavior slows as individuals with fragile X syndrome age. It is imperative to ensure that assessments of adaptive behavior skills are part of intervention programs focusing on childhood and adolescence in this condition.

  View details for DOI 10.1542/peds.2013-3990

  View details for PubMedID 25070318

• Prevention of traumatic stress in mothers of preterms: 6-month outcomes. Pediatrics Shaw, R. J., St John, N., Lilo, E., Jo, B., Benitz, W., Stevenson, D. K., Horwitz, S. M. 2014; 134 (2): e481-8

  View details for DOI 10.1542/peds.2014-0529

  View details for PubMedID 25049338

• Prevention of Problem Behavior Through Annual Family Check-Ups in Early Childhood: Intervention Effects From Home to Early Elementary School JOURNAL OF ABNORMAL CHILD PSYCHOLOGY Dishion, T. J., Brennan, L. M., Shaw, D. S., McEachern, A. D., Wilson, M. N., Jo, B. 2014; 42 (3): 343-354

  Abstract

  This randomized intervention trial examined the effects of yearly Family Check-Ups (FCUs) and tailored parent management training on parent report of problem behavior from age 2 to 5 years and teacher report of oppositional behavior at age 7.5. A multiethnic risk sample of 731 families in 3 distinct geographical settings who were receiving assistance from the Women, Infants, and Children Nutritional Supplement (WIC) program were randomly assigned to a yearly FCU. Intention to treat (ITT) analyses were used to examine overall intervention effects, and complier average causal effect (CACE) modeling was used to examine the effects of annual intervention engagement in the FCU on parent reports of child problem behavior from age 2 to 5 and teacher reports of problem behavior at age 7.5. ITT intervention effects were found regarding parent report at ages 2 to 5 and teacher report at age 7.5, indicating less growth in problem behavior for children in the intervention group than for those in the control group. CACE modeling of intervention engagement revealed that the effect sizes on parent- and teacher-reported problem behavior increased as a function of the number of yearly FCUs caregivers participated in. Findings suggest that embedding yearly FCU services within the context of social, health, and educational services in early childhood can potentially prevent early-onset trajectories of antisocial behavior. The increases in effect size with successive FCU engagement underscores the importance of a motivational approach to parenting support among high-risk families.

  View details for DOI 10.1007/s10802-013-9768-2

  View details for Web of Science ID 000332323700002

  View details for PubMedCentralID PMC3952033

• Bedtime misalignment and progression of breast cancer. Chronobiology international Hahm, B., Jo, B., Dhabhar, F. S., Palesh, O., Aldridge-Gerry, A., Bajestan, S. N., Neri, E., Nouriani, B., Spiegel, D., Zeitzer, J. M. 2014; 31 (2): 214-221

  Abstract

  Disruption of circadian rhythms, which frequently occurs during night shift work, may be associated with cancer progression. The effect of chronotype (preference for behaviors such as sleep, work, or exercise to occur at particular times of day, with an associated difference in circadian physiology) and alignment of bedtime (preferred vs. habitual), however, have not yet been studied in the context of cancer progression in women with breast cancer. Chronotype and alignment of actual bedtime with preferred chronotype were examined using the Morningness-Eveningness Scale (MEQ) and sleep-wake log among 85 women with metastatic breast cancer. Their association with disease-free interval (DFI) was retrospectively examined using the Cox proportional hazards model. Median DFI was 81.9 months for women with aligned bedtimes ("going to bed at preferred bedtime") (n = 72), and 46.9 months for women with misaligned bedtimes ("going to bed later or earlier than the preferred bedtime") (n = 13) (log rank p = 0.001). In a multivariate Cox proportional hazard model, after controlling for other significant predictors of DFI, including chronotype (morning type/longer DFI; HR = 0.539, 95% CI = 0.320-0.906, p = 0.021), estrogen receptor (ER) status at initial diagnosis (negative/shorter DFI; HR = 2.169, 95% CI = 1.124-4.187, p = 0.028) and level of natural-killer cell count (lower levels/shorter DFI; HR = 1.641, 95% CI = 1.000-2.695, p = 0.050), misaligned bedtimes was associated with shorter DFI, compared to aligned bedtimes (HR = 3.180, 95% CI = 1.327-7.616, p = 0.018). Our data indicate that a misalignment of bedtime on a daily basis, an indication of circadian disruption, is associated with more rapid breast cancer progression as measured by DFI. Considering the limitations of small sample size and study design, a prospective study with a larger sample is necessary to explore their causal relationship and underlying mechanisms.

  View details for DOI 10.3109/07420528.2013.842575

  View details for PubMedID 24156520

• Actigraphy-Measured Sleep Disruption as a Predictor of Survival among Women with Advanced Breast Cancer. Sleep Palesh, O., Aldridge-Gerry, A., Zeitzer, J. M., Koopman, C., Neri, E., Giese-Davis, J., Jo, B., Kraemer, H., Nouriani, B., Spiegel, D. 2014; 37 (5): 837-842

  Abstract

  Poor sleep, prevalent among cancer survivors, is associated with disrupted hormonal circadian rhythms and poor quality of life. Using a prospective research design, this study aimed to clarify the relationship between objective measures of sleep efficiency and sleep disruption with survival among women with advanced breast cancer.We examined sleep quality and duration via wrist-worn actigraphy and sleep diaries for 3 days among 97 women in whom advanced breast cancer was diagnosed (age = 54.6 ± 9.8 years). Sleep efficiency was operationalized using actigraphy as the ratio of total sleep time to total sleep time plus wake after sleep onset.As hypothesized, better sleep efficiency was found to predict a significant reduction in overall mortality (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94-0.98; P < 0.001) at median 6 y follow-up. This relationship remained significant (HR, 0.94; 95% CI, 0.91-0.97; P < 0.001) even after adjusting for other known prognostic factors (age, estrogen receptor status, cancer treatment, metastatic spread, cortisol levels, and depression). Secondary hypotheses were also supported (after adjusting for baseline prognostic factors) showing that less wake after sleep onset (HR, 0.41; 95% CI, 0.25-0.67; P < 0.001), fewer wake episodes, (HR, 0.93; 95% CI, 0.88-0.98; P = 0.007); and shorter wake episode duration (HR, 0.29; 95% CI, 0.14-0.58; P < 0.001) also contributed to reductions in overall mortality.These findings show that better sleep efficiency and less sleep disruption are significant independent prognostic factors in women with advanced breast cancer. Further research is needed to determine whether treating sleep disruption with cognitive behavioral and/or pharmacologic therapy could improve survival in women with advanced breast cancer.

  View details for DOI 10.5665/sleep.3642

  View details for PubMedID 24790261

  View details for PubMedCentralID PMC3985107

• Actigraphy Measured Sleep Disruption as a Predictor of Survival Among Women with Advanced Breast Cancer Spiegel, D., Palesh, O., Aldridge-Gerry, A., Zeitzer, J., Koopman, C., Giese-Davis, J., Jo, B., Kraemer, H., Neri, E., Nouriani, B. NATURE PUBLISHING GROUP. 2013: S352–S353

  View details for Web of Science ID 000209477100572

• Prospective neurochemical characterization of child offspring of parents with bipolar disorder. Psychiatry research Singh, M. K., Jo, B., Adleman, N. E., Howe, M., Bararpour, L., Kelley, R. G., Spielman, D., Chang, K. D. 2013; 214 (2): 153-160

  Abstract

  We wished to determine whether decreases in N-acetyl aspartate (NAA) and increases in myoinositol (mI) concentrations as a ratio of creatine (Cr) occurred in the dorsolateral prefrontal cortex (DLPFC) of pediatric offspring of parents with bipolar disorder (BD) and a healthy comparison group (HC) over a 5-year period using proton magnetic resonance spectroscopy ((1)H-MRS). Paticipants comprised 64 offspring (9-18 years old) of parents with BD (36 with established BD, and 28 offspring with symptoms subsyndromal to mania) and 28 HCs, who were examined for group differences in NAA/Cr and mI/Cr in the DLPFC at baseline and follow-up at either 8, 10, 12, 52, 104, 156, 208, or 260 weeks. No significant group differences were found in metabolite concentrations at baseline or over time. At baseline, BD offspring had trends for higher mI/Cr concentrations in the right DLPFC than the HC group. mI/Cr concentrations increased with age, but no statistically significant group differences were found between groups on follow-up. It may be the case that with intervention youth at risk for BD are normalizing otherwise potentially aberrant neurochemical trajectories in the DLPFC. A longer period of follow-up may be required before observing any group differences.

  View details for DOI 10.1016/j.pscychresns.2013.05.005

  View details for PubMedID 24028795

• Psychosocial correlates of sleep quality and architecture in women with metastatic breast cancer SLEEP MEDICINE Aldridge-Gerry, A., Zeitzer, J. M., Palesh, O. G., Jo, B., Nouriani, B., Neri, E., Spiegel, D. 2013; 14 (11): 1178-1186

  Abstract

  Sleep disturbance is prevalent among women with metastatic breast cancer (MBC). Our study examined the relationship of depression and marital status to sleep assessed over three nights of polysomnography (PSG).Women with MBC (N=103) were recruited; they were predominately white (88.2%) and 57.8±7.7 years of age. Linear regression analyses assessed relationships among depression, marital status, and sleep parameters.Women with MBC who reported more depressive symptoms had lighter sleep (e.g., stage 1 sleep; P<.05), less slow-wave sleep (SWS) (P<.05), and less rapid eye movement (REM) sleep (P<.05). Single women had less total sleep time (TST) (P<.01), more wake after sleep onset (WASO) (P<.05), worse sleep efficiency (SE) (P<.05), lighter sleep (e.g., stage 1; P<.05), and less REM sleep (P<.05) than married women. Significant interactions indicated that depressed and single women had worse sleep quality than partnered women or those who were not depressed.Women with MBC and greater symptoms of depression had increased light sleep and reduced SWS and REM sleep, and single women had worse sleep quality and greater light sleep than married counterparts. Marriage was related to improved sleep for women with more depressive symptoms.

  View details for DOI 10.1016/j.sleep.2013.07.012

  View details for Web of Science ID 000326625400021

  View details for PubMedID 24074694

• Psychosocial correlates of sleep quality and architecture in women with metastatic breast cancer. Sleep medicine Aldridge-Gerry, A., Zeitzer, J. M., Palesh, O. G., Jo, B., Nouriani, B., Neri, E., Spiegel, D. 2013; 14 (11): 1178-1186

  Abstract

  Sleep disturbance is prevalent among women with metastatic breast cancer (MBC). Our study examined the relationship of depression and marital status to sleep assessed over three nights of polysomnography (PSG).Women with MBC (N=103) were recruited; they were predominately white (88.2%) and 57.8±7.7 years of age. Linear regression analyses assessed relationships among depression, marital status, and sleep parameters.Women with MBC who reported more depressive symptoms had lighter sleep (e.g., stage 1 sleep; P<.05), less slow-wave sleep (SWS) (P<.05), and less rapid eye movement (REM) sleep (P<.05). Single women had less total sleep time (TST) (P<.01), more wake after sleep onset (WASO) (P<.05), worse sleep efficiency (SE) (P<.05), lighter sleep (e.g., stage 1; P<.05), and less REM sleep (P<.05) than married women. Significant interactions indicated that depressed and single women had worse sleep quality than partnered women or those who were not depressed.Women with MBC and greater symptoms of depression had increased light sleep and reduced SWS and REM sleep, and single women had worse sleep quality and greater light sleep than married counterparts. Marriage was related to improved sleep for women with more depressive symptoms.

  View details for DOI 10.1016/j.sleep.2013.07.012

  View details for PubMedID 24074694

• Prevention of traumatic stress in mothers with preterm infants: a randomized controlled trial. Pediatrics Shaw, R. J., St John, N., Lilo, E. A., Jo, B., Benitz, W., Stevenson, D. K., Horwitz, S. M. 2013; 132 (4): e886-94

  Abstract

  The current study evaluates a treatment intervention developed with the goal of reducing symptoms of posttraumatic stress, depression, and anxiety in parents of premature infants.A total of 105 mothers of preterm infants (25-34 weeks' gestational age; >600 g) were randomized to receive a 6-session intervention developed to target parental trauma as well as facilitate infant redefinition (n = 62) or to an active comparison group (n = 43). Mothers in the intervention group received a combination of trauma-focused treatments, including psychoeducation, cognitive restructuring, progressive muscle relaxation, and development of their trauma narrative. The intervention also incorporated material targeting infant redefinition, defined as the process of changing the mother's negative perceptions of her infant and the parenting experience.Mothers in the intervention group reported a greater reduction in both trauma symptoms (Cohen's d = 0.41, P = .023) and depression (Cohen's d = 0.59, P < .001) compared with the comparison group. Patients under both conditions improved significantly in terms of anxiety, with no differences between groups. Results of the moderator analysis showed that mothers with higher ratings of baseline NICU stress benefited more from the intervention compared with mothers who had lower ratings (P = .036).This short, highly manualized intervention for mothers of preterm infants statistically significantly reduced symptoms of trauma and depression. The intervention is feasible, can be delivered with fidelity, and has high ratings of maternal satisfaction. Given that improvements in mothers' distress may lead to improved infant outcomes, this intervention has the potential for a high public health impact.

  View details for DOI 10.1542/peds.2013-1331

  View details for PubMedID 23999956

• Applications of a Kullback-Leibler divergence for comparing non-nested models STATISTICAL MODELLING Wang, C., Jo, B. 2013; 13 (5-6): 409-429

  Abstract

  Wang and Ghosh (2011) proposed a Kullback-Leibler divergence (KLD) which is asymptotically equivalent to the KLD by Goutis and Robert (1998) when the reference model (in comparison with a competing fitted model) is correctly specified and when certain regularity conditions hold true. While properties of the KLD by Wang and Ghosh (2011) have been investigated in the Bayesian framework, this paper further explores the property of this KLD in the frequentist framework using four application examples, each fitted by two competing non-nested models.

  View details for DOI 10.1177/1471082X13494610

  View details for Web of Science ID 000327195400004

  View details for PubMedCentralID PMC4006220

• Is outpatient cognitive remediation therapy feasible to use in randomized clinical trials for anorexia nervosa? International journal of eating disorders Lock, J., Agras, W. S., Fitzpatrick, K. K., Bryson, S. W., Jo, B., Tchanturia, K. 2013; 46 (6): 567-575

  Abstract

  OBJECTIVE: There are limited data supporting specific treatments for adults with anorexia nervosa (AN). Randomized clinical trials (RCTs) for adults with AN are characterized by high attrition limiting the feasibility of conducting and interpreting existing studies. High dropout rates may be related to the inflexible and obsessional cognitive style of patients with AN. This study evaluated the feasibility of using cognitive remediation therapy (CRT) to reduce attrition in RCTs for AN. METHOD: Forty-six participants (mean age of 22.7 years and mean duration of AN of 6.4 years) were randomized to receive eight sessions of either CRT or cognitive behavioral therapy (CBT) over 2 months followed by 16 sessions of CBT for 4 months. RESULTS: During the 2-month CRT vs. CBT treatment, rates of attrition were lower in CRT (13%) compared with that of CBT (33%). There were greater improvements in cognitive inefficiencies in the CRT compared with that of the CBT group at the end of 2 months. There were no differences in other outcomes. DISCUSSION: These results suggest that CRT is acceptable and feasible for use in RCTs for outpatient treatment of AN. CRT may reduce attrition in the short term. Adequately powered future studies are needed to examine CRT as an outpatient treatment for AN.

  View details for DOI 10.1002/eat.22134

  View details for PubMedID 23625628

• The 24-month course of manic symptoms in children BIPOLAR DISORDERS Findling, R. L., Jo, B., Frazier, T. W., Youngstrom, E. A., Demeter, C. A., Fristad, M. A., Birmaher, B., Kowatch, R. A., Arnold, E., Axelson, D. A., Ryan, N., Hauser, J. C., Brace, D. J., Marsh, L. E., Gill, M. K., Depew, J., Rowles, B. M., Horwitz, S. M. 2013; 15 (6): 669-679

  Abstract

  The Longitudinal Assessment of Manic Symptoms (LAMS) study was designed to investigate phenomenology and establish predictors of functional outcomes in children with elevated manic symptoms. The purpose of this series of analyses was to determine whether the participants demonstrated different trajectories of parent-reported manic and biphasic symptoms over the first 24 months of follow-up and to describe the clinical characteristics of the trajectories.The 707 participants were initially aged 6-12 years and ascertained from outpatient clinics associated with the four university-affiliated LAMS sites. There were 621 children whose parents/guardians' ratings scored ≥ 12 on the Parent General Behavior Inventory-10-item Mania Form (PGBI-10M) and a matched random sample of 86 children whose parents/guardians' ratings scored ≤ 11 on the PGBI-10M. Participants were seen every six months after the baseline and their parents completed the PGBI-10M at each visit.For the whole sample, manic symptoms decreased over 24 months (linear effect B = -1.15, standard error = 0.32, t = -3.66, p < 0.001). Growth mixture modeling revealed four unique trajectories of manic symptoms. Approximately 85% of the cohort belonged to two classes in which manic symptoms decreased. The remaining ~15% formed two classes (high and rising and unstable) characterized by the highest rates of diagnostic conversion to a bipolar disorder (all p-values < 0.001).Outcomes are not uniform among children with symptoms of mania or at high risk for mania. A substantial minority of clinically referred children shows unstable or steadily increasing manic symptoms, and these patterns have distinct clinical correlates.

  View details for DOI 10.1111/bdi.12100

  View details for Web of Science ID 000323783600005

  View details for PubMedID 23799945

• Prevention of Postpartum Traumatic Stress in Mothers with Preterm Infants: Manual Development and Evaluation. Issues in mental health nursing Shaw, R. J., Sweester, C. J., St John, N., Lilo, E., Corcoran, J. B., Jo, B., Howell, S. H., Benitz, W. E., Feinstein, N., Melnyk, B., Horwitz, S. M. 2013; 34 (8): 578-586

  Abstract

  Premature birth has been associated with multiple adverse maternal psychological outcomes that include depression, anxiety, and trauma as well as adverse effects on maternal coping ability and parenting style. Infants who are premature are more likely to have poorer cognitive and developmental functioning and, thus, may be harder to parent, both as infants and as they get older. In response to these findings, a number of educational and behavioral interventions have been developed that target maternal psychological functioning, parenting, and aspects of the parent-infant relationship. The current study aimed to both develop and evaluate a treatment that integrates, for the first time, effective interventions for reducing symptoms of posttraumatic stress disorder (PTSD) and enhancing maternal-infant interactions. Conclusions from the study indicate that the intervention is feasible, able to be implemented with a high level of fidelity, and is rated as highly satisfactory by participants. Though encouraging, these findings are preliminary, and future studies should strive to reproduce these findings with a larger sample size and a comparison group.

  View details for DOI 10.3109/01612840.2013.789943

  View details for PubMedID 23909669

• Actigraphy measured sleep disruption as a predictor of survival in advanced breast cancer Palesh, O., Gerry, A., Zeitzer, J. M., Koopman, C., Jo, B., Neri, E., Nouriani, B., Spiegel, D. AMER SOC CLINICAL ONCOLOGY. 2013

  View details for Web of Science ID 000335419603015

• Losing sleep over cancer: Relationships with negative affect, blood pressure, and disease-free interval among women with metastatic breast cancer. Gerry, A., Palesh, O., Rissling, M., Zeitzer, J. M., Dhabhar, F. S., Jo, B., Neri, E., Nouriani, B., Spiegel, D. AMER SOC CLINICAL ONCOLOGY. 2013

  View details for Web of Science ID 000335419602808

• CANCER PROGRESSION AND ALTERATIONS OF SLEEP ARCHITECTURE IN WOMEN WITH METASTATIC BREAST CANCER Aldridge-Gerry, A., Zeitzer, J., Palesh, O., Dhabhar, F., Jo, B., Neri, E., Nouriani, B., Spiegel, D. SPRINGER. 2013: S159

  View details for Web of Science ID 000209928001199

• NATURAL KILLER (NK) CELL DIURNAL RHYTHMS AND SLEEP DISRUPTION IN METASTATIC BREAST CANCER Dhabhar, F. S., Jo, B., Neri, E., Zeitzer, J., Bricker, N. M., Nouriani, B., Aldridge-Gerry, A., Spiegel, D. SPRINGER. 2013: S160

  View details for Web of Science ID 000209928001201

• COGNITIVE TRAJECTORY IN MALES AND FEMALES WITH FRAGILE X SYNDROME 20th Annual Meeting of the Cognitive-Neuroscience-Society Quintin, E., Hall, S., Jo, B., Bruno, J., Chromik, L., Raman, M., Linghtbody, A., Reiss, A. MIT PRESS. 2013: 251–251

  View details for Web of Science ID 000317030501371

• Modeling the effects of obstructive sleep apnea and hypertension in Vietnam veterans with PTSD SLEEP AND BREATHING Kinoshita, L. M., Yesavage, J. A., Noda, A., Jo, B., Hernandez, B., Taylor, J., Zeitzer, J. M., Friedman, L., Fairchild, J. K., Cheng, J., Kuschner, W., O'Hara, R., Holty, J. C., Scanlon, B. K. 2012; 16 (4): 1201-1209

  Abstract

  The present work aimed to extend models suggesting that obstructive sleep apnea (OSA) is associated with worse cognitive performance in community-dwelling older adults. We hypothesized that in addition to indices of OSA severity, hypertension is associated with worse cognitive performance in such adults.The PTSD Apnea Clinical Study recruited 120 community-dwelling, male veterans diagnosed with PTSD, ages 55 and older. The Rey Auditory Verbal Learning Test (RAVLT) and Color-Word Interference Test (CWIT) were measures of auditory verbal memory and executive function, respectively. Apnea-hypopnea index (AHI), minimum and mean pulse oximeter oxygen saturation (min SpO(2), mean SpO(2)) indicators were determined during standard overnight polysomnography. Multivariate linear regression and receiver operating characteristic (ROC) curve analyses were performed.In regression models, AHI (β = -4.099; p < 0.01) and hypertension (β = -4.500; p < 0.05) predicted RAVLT; hypertension alone (β = 9.146; p < 0.01) predicted CWIT. ROC analyses selected min SpO(2) cut-points of 85% for RAVLT (κ = 0.27; χ² = 8.23, p < 0.01) and 80% for CWIT (κ = 0.25; χ² = 12.65, p < 0.01). Min SpO(2) cut-points and hypertension were significant when added simultaneously in a regression model for RAVLT (min SpO(2), β = 4.452; p < 0.05; hypertension, β = -4.332; p < 0.05), and in separate models for CWIT (min SpO(2), β = -8.286; p < 0.05; hypertension, β = -8.993; p < 0.01).OSA severity and presence of self-reported hypertension are associated with poor auditory verbal memory and executive function in older adults.

  View details for DOI 10.1007/s11325-011-0632-8

  View details for Web of Science ID 000311301700038

  View details for PubMedID 22193972

• Psychosocial correlates of sleep architecture in women with advanced breast cancer. 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Gerry, A. A., Jo, B., Palesh, O., Zeitzer, J., Neri, E., Spiegel, D. AMER SOC CLINICAL ONCOLOGY. 2012

  View details for Web of Science ID 000318009800188

• Moderators and mediators of remission in family-based treatment and adolescent focused therapy for anorexia nervosa BEHAVIOUR RESEARCH AND THERAPY le Grange, D., Lock, J., Agras, W. S., Moye, A., Bryson, S. W., Jo, B., Kraemer, H. C. 2012; 50 (2): 85-92

  Abstract

  Few of the limited randomized controlled trails (RCTs) for adolescent anorexia nervosa (AN) have explored the effects of moderators and mediators on outcome. This study aimed to identify treatment moderators and mediators of remission at end of treatment (EOT) and 6- and 12-month follow-up (FU) for adolescents with AN (N = 121) who participated in a multi-center RCT of family-based treatment (FBT) and individual adolescent focused therapy (AFT). Mixed effects modeling were utilized and included all available outcome data at all time points. Remission was defined as ≥ 95% IBW plus within 1 SD of the Eating Disorder Examination (EDE) norms. Eating related obsessionality (Yale-Brown-Cornell Eating Disorder Total Scale) and eating disorder specific psychopathology (EDE-Global) emerged as moderators at EOT. Subjects with higher baseline scores on these measures benefited more from FBT than AFT. AN type emerged as a moderator at FU with binge-eating/purging type responding less well than restricting type. No mediators of treatment outcome were identified. Prior hospitalization, older age and duration of illness were identified as non-specific predictors of outcome. Taken together, these results indicate that patients with more severe eating related psychopathology have better outcomes in a behaviorally targeted family treatment (FBT) than an individually focused approach (AFT).

  View details for DOI 10.1016/j.brat.2011.11.003

  View details for Web of Science ID 000301019200001

  View details for PubMedID 22172564

  View details for PubMedCentralID PMC3260378

• Comments: Causal Interpretations of Mediation Effects JOURNAL OF RESEARCH ON EDUCATIONAL EFFECTIVENESS Jo, B., Stuart, E. A. 2012; 5 (3): 250-253

  View details for DOI 10.1080/19345747.2012.688414

  View details for Web of Science ID 000323947800004

• GROWTH MIXTURE MODELING AND CAUSAL INFERENCE ADVANCES IN LONGITUDINAL METHODS IN THE SOCIAL AND BEHAVIORAL SCIENCES Jo, B., Harring, Hancock, G. R. 2012: 193-214

  View details for Web of Science ID 000312227400008

• Lower peak numbers, blunted diurnal rhythms of immune cell distribution, and sleep disruption in metastatic breast cancer Dhabhar, F. S., Jo, B., Neri, E., Zeitzer, J., Tillie, J. M., Bricker, N. M., Nouriani, B., Spiegel, D. CO-ACTION PUBLISHING. 2012

  View details for DOI 10.3402/ejpt.v3i0.19487

  View details for Web of Science ID 000208868500013

• Aberrant Frontal Lobe Maturation in Adolescents with Fragile X Syndrome is Related to Delayed Cognitive Maturation BIOLOGICAL PSYCHIATRY Bray, S., Hirt, M., Jo, B., Hall, S. S., Lightbody, A. A., Walter, E., Chen, K., Patnaik, S., Reiss, A. L. 2011; 70 (9): 852-858

  Abstract

  Fragile X syndrome (FXS) is the most common known heritable cause of intellectual disability. Prior studies in FXS have observed a plateau in cognitive and adaptive behavioral development in early adolescence, suggesting that brain development in FXS may diverge from typical development during this period.In this study, we examined adolescent brain development using structural magnetic resonance imaging data acquired from 59 individuals with FXS and 83 typically developing control subjects aged 9 to 22, a subset of whom were followed up longitudinally (1-5 years; typically developing: 17, FXS: 19). Regional volumes were modeled to obtain estimates of age-related change.We found that while structures such as the caudate showed consistent volume differences from control subjects across adolescence, prefrontal cortex (PFC) gyri showed significantly aberrant maturation. Furthermore, we found that PFC-related measures of cognitive functioning followed a similarly aberrant developmental trajectory in FXS.Our findings suggest that aberrant maturation of the PFC during adolescence may contribute to persistent or increasing intellectual deficits in FXS.

  View details for DOI 10.1016/j.biopsych.2011.05.038

  View details for Web of Science ID 000296228000012

  View details for PubMedID 21802660

  View details for PubMedCentralID PMC3191299

• PERFORMANCE OF APPOINTMENT TASKS SCALE (PATS): A STAFF-RATED INSTRUMENT FOR ASSESSING OLDER ADULTS' PERFORMANCE OF EVERYDAY TASKS Holland, J. M., Anker, L., Jo, B., Kesler, S., Marquett, R., O'Hara, R., Pritchard-Berman, M., Gallagher-Thompson, D. OXFORD UNIV PRESS INC. 2011: 55–55

  View details for Web of Science ID 000303602000252

• Using Potential Outcomes to Understand Causal Mediation Analysis: Comment on. Multivariate behavioral research Imai, K., Jo, B., Stuart, E. A. 2011; 46 (5): 861-873

  Abstract

  In this commentary, we demonstrate how the potential outcomes framework can help understand the key identification assumptions underlying causal mediation analysis. We show that this framework can lead to the development of alternative research design and statistical analysis strategies applicable to the longitudinal data settings considered by Maxwell, Cole, and Mitchell (2011).

  View details for PubMedID 23788819

• Sensitivity Analysis and Bounding of Causal Effects With Alternative Identifying Assumptions JOURNAL OF EDUCATIONAL AND BEHAVIORAL STATISTICS Jo, B., Vinokur, A. D. 2011; 36 (4): 415-440

  Abstract

  When identification of causal effects relies on untestable assumptions regarding nonidentified parameters, sensitivity of causal effect estimates is often questioned. For proper interpretation of causal effect estimates in this situation, deriving bounds on causal parameters or exploring the sensitivity of estimates to scientifically plausible alternative assumptions can be critical. In this paper, we propose a practical way of bounding and sensitivity analysis, where multiple identifying assumptions are combined to construct tighter common bounds. In particular, we focus on the use of competing identifying assumptions that impose different restrictions on the same non-identified parameter. Since these assumptions are connected through the same parameter, direct translation across them is possible. Based on this cross-translatability, various information in the data, carried by alternative assumptions, can be effectively combined to construct tighter bounds on causal effects. Flexibility of the suggested approach is demonstrated focusing on the estimation of the complier average causal effect (CACE) in a randomized job search intervention trial that suffers from noncompliance and subsequent missing outcomes.

  View details for DOI 10.3102/1076998610383985

  View details for Web of Science ID 000293142600001

  View details for PubMedCentralID PMC3150587

• Initial Cognitive Performance Predicts Longitudinal Aviator Performance JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES Yesavage, J. A., Jo, B., Adamson, M. M., Kennedy, Q., Noda, A., Hernandez, B., Zeitzer, J. M., Friedman, L. F., Fairchild, K., Scanlon, B. K., Murphy, G. M., Taylor, J. L. 2011; 66 (4): 444-453

  Abstract

  The goal of the study was to improve prediction of longitudinal flight simulator performance by studying cognitive factors that may moderate the influence of chronological age.We examined age-related change in aviation performance in aircraft pilots in relation to baseline cognitive ability measures and aviation expertise. Participants were aircraft pilots (N = 276) aged 40-77.9. Flight simulator performance and cognition were tested yearly; there were an average of 4.3 (± 2.7; range 1-13) data points per participant. Each participant was classified into one of the three levels of aviation expertise based on Federal Aviation Administration pilot proficiency ratings: least, moderate, or high expertise.Addition of measures of cognitive processing speed and executive function to a model of age-related change in aviation performance significantly improved the model. Processing speed and executive function performance interacted such that the slowest rate of decline in flight simulator performance was found in aviators with the highest scores on tests of these abilities. Expertise was beneficial to pilots across the age range studied; however, expertise did not show evidence of reducing the effect of age.These data suggest that longitudinal performance on an important real-world activity can be predicted by initial assessment of relevant cognitive abilities.

  View details for DOI 10.1093/geronb/gbr031

  View details for Web of Science ID 000293251900007

  View details for PubMedID 21586627

  View details for PubMedCentralID PMC3132267

• The Use of Propensity Scores in Mediation Analysis MULTIVARIATE BEHAVIORAL RESEARCH Jo, B., Stuart, E. A., MacKinnon, D. P., Vinokur, A. D. 2011; 46 (3): 425-452

  Abstract

  Mediation analysis uses measures of hypothesized mediating variables to test theory for how a treatment achieves effects on outcomes and to improve subsequent treatments by identifying the most efficient treatment components. Most current mediation analysis methods rely on untested distributional and functional form assumptions for valid conclusions, especially regarding the relation between the mediator and outcome variables. Propensity score methods offer an alternative whereby the propensity score is used to compare individuals in the treatment and control groups who would have had the same value of the mediator had they been assigned to the same treatment condition. This article describes the use of propensity score weighting for mediation with a focus on explicating the underlying assumptions. Propensity scores have the potential to offer an alternative estimation procedure for mediation analysis with alternative assumptions from those of standard mediation analysis. The methods are illustrated investigating the mediational effects of an intervention to improve sense of mastery to reduce depression using data from the Job Search Intervention Study (JOBS II). We find significant treatment effects for those individuals who would have improved sense of mastery when in the treatment condition but no effects for those who would not have improved sense of mastery under treatment.

  View details for DOI 10.1080/00273171.2011.576624

  View details for Web of Science ID 000291533400003

  View details for PubMedCentralID PMC3293166

• A pilot study of an online cognitive rehabilitation program for executive function skills in children with cancer-related brain injury BRAIN INJURY Kesler, S. R., Lacayo, N. J., Jo, B. 2011; 25 (1): 101-112

  Abstract

  Children with a history of cancer are at increased risk for cognitive impairments, particularly in executive and memory domains. Traditional, in-person cognitive rehabilitation strategies may be unavailable and/or impractical for many of these children given difficulties related to resources and health status. The feasibility and efficacy of implementing a computerized, home-based cognitive rehabilitation curriculum designed to improve executive function skills was examined in these children.A one-arm open trial pilot study of an original executive function cognitive rehabilitation curriculum was conducted with 23 paediatric cancer survivors aged 7-19.Compliance with the cognitive rehabilitation program was 83%, similar to that of many traditional programs. Following the cognitive intervention, participants showed significantly increased processing speed, cognitive flexibility, verbal and visual declarative memory scores as well as significantly increased pre-frontal cortex activation compared to baseline.These results suggest that a program of computerized cognitive exercises can be successfully implemented at home in young children with cancer. These exercises may be effective for improving executive and memory skills in this group, with concurrent changes in neurobiologic status.

  View details for DOI 10.3109/02699052.2010.536194

  View details for PubMedID 21142826

  View details for PubMedCentralID PMC3050575

• Commentary: Using Potential Outcomes to Understand Causal Mediation Analysis MULTIVARIATE BEHAVIORAL RESEARCH Imai, K., Jo, B., Stuart, E. A. 2011; 46 (5): 861-873

  Abstract

  In this commentary, we demonstrate how the potential outcomes framework can help understand the key identification assumptions underlying causal mediation analysis. We show that this framework can lead to the development of alternative research design and statistical analysis strategies applicable to the longitudinal data settings considered by Maxwell, Cole, and Mitchell (2011).

  View details for DOI 10.1080/00273171.2011.606743

  View details for Web of Science ID 000299256600008

  View details for PubMedCentralID PMC3685497

• Handling Missing Data in Randomized Experiments with Noncompliance PREVENTION SCIENCE Jo, B., Ginexi, E. M., Ialongo, N. S. 2010; 11 (4): 384-396

  Abstract

  Treatment noncompliance and missing outcomes at posttreatment assessments are common problems in field experiments in naturalistic settings. Although the two complications often occur simultaneously, statistical methods that address both complications have not been routinely considered in data analysis practice in the prevention research field. This paper shows that identification and estimation of causal treatment effects considering both noncompliance and missing outcomes can be relatively easily conducted under various missing data assumptions. We review a few assumptions on missing data in the presence of noncompliance, including the latent ignorability proposed by Frangakis and Rubin (Biometrika 86:365-379, 1999), and show how these assumptions can be used in the parametric complier average causal effect (CACE) estimation framework. As an easy way of sensitivity analysis, we propose the use of alternative missing data assumptions, which will provide a range of causal effect estimates. In this way, we are less likely to settle with a possibly biased causal effect estimate based on a single assumption. We demonstrate how alternative missing data assumptions affect identification of causal effects, focusing on the CACE. The data from the Johns Hopkins School Intervention Study (Ialongo et al., Am J Community Psychol 27:599-642, 1999) will be used as an example.

  View details for DOI 10.1007/s11121-010-0175-4

  View details for Web of Science ID 000284668800005

  View details for PubMedID 20379779

  View details for PubMedCentralID PMC2912956

• Randomized Clinical Trial Comparing Family-Based Treatment With Adolescent-Focused Individual Therapy for Adolescents With Anorexia Nervosa ARCHIVES OF GENERAL PSYCHIATRY Lock, J., Le Grange, D., Agras, S., Moye, A., Bryson, S. W., Jo, B. 2010; 67 (10): 1025-1032

  Abstract

  Evidence-based treatment trials for adolescents with anorexia nervosa are few.To evaluate the relative efficacy of family-based treatment (FBT) and adolescent-focused individual therapy (AFT) for adolescents with anorexia nervosa in full remission.Randomized controlled trial.Stanford University and The University of Chicago (April 2005 until March 2009).One hundred twenty-one participants, aged 12 through 18 years, with DSM-IV diagnosis of anorexia nervosa excluding the amenorrhea requirement. Intervention Twenty-four outpatient hours of treatment over 12 months of FBT or AFT. Participants were assessed at baseline, end of treatment (EOT), and 6 months' and 12 months' follow-up posttreatment.Full remission from anorexia nervosa defined as normal weight (≥95% of expected for sex, age, and height) and mean global Eating Disorder Examination score within 1 SD of published means. Secondary outcome measures included partial remission rates (>85% of expected weight for height plus those who were in full remission) and changes in body mass index percentile and eating-related psychopathology.There were no differences in full remission between treatments at EOT. However, at both the 6- and 12-month follow-up, FBT was significantly superior to AFT on this measure. Family-based treatment was significantly superior for partial remission at EOT but not at follow-up. In addition, body mass index percentile at EOT was significantly superior for FBT, but this effect was not found at follow-up. Participants in FBT also had greater changes in Eating Disorder Examination score at EOT than those in AFT, but there were no differences at follow-up.Although both treatments led to considerable improvement and were similarly effective in producing full remission at EOT, FBT was more effective in facilitating full remission at both follow-up points.clinicaltrials.gov Identifier: NCT00149786.

  View details for Web of Science ID 000282917400005

  View details for PubMedID 20921118

• Outcome From a Randomized Controlled Trial of Group Therapy for Binge Eating Disorder: Comparing Dialectical Behavior Therapy Adapted for Binge Eating to an Active Comparison Group Therapy (vol 41, pg 106, 2010) BEHAVIOR THERAPY Safer, D. L., Robinson, A. H., Jo, B. 2010; 41 (3): 432-432

  View details for Web of Science ID 000278892500016

• Outcome From a Randomized Controlled Trial of Group Therapy for Binge Eating Disorder: Comparing Dialectical Behavior Therapy Adapted for Binge Eating to an Active Comparison Group Therapy BEHAVIOR THERAPY Safer, D. L., Robinson, A. H., Jo, B. 2010; 41 (1): 106-120

  Abstract

  Dialectical Behavior Therapy for Binge Eating Disorder (DBT-BED) aims to reduce binge eating by improving adaptive emotion-regulation skills. Preliminary findings have been promising but have only compared DBT-BED to a wait-list. To control for the hypothesized specific effects of DBT-BED, the present study compared DBT-BED to an active comparison group therapy (ACGT). Men and women (n=101) meeting DSM-IV BED research criteria were randomly assigned to 20 group sessions of DBT-BED (n=50) or ACGT (n=51). DBT-BED had a significantly lower dropout rate (4%) than ACGT (33.3%). Linear Mixed Models revealed that posttreatment binge abstinence and reductions in binge frequency were achieved more quickly for DBT-BED than for ACGT (posttreatment abstinence rate=64% for DBT-BED vs. 36% for ACGT) though differences did not persist over the 3-, 6-, and 12-month follow-up assessments (e.g., 12-month follow-up abstinence rate=64% for DBT-BED vs. 56% for ACGT). Secondary outcome measures revealed no sustained impact on emotion regulation. Although both DBT-BED and ACGT reduced binge eating, DBT-BED showed significantly fewer dropouts and greater initial efficacy (e.g., at posttreatment) than ACGT. The lack of differential findings over follow-up suggests that the hypothesized specific effects of DBT-BED do not show long-term impact beyond those attributable to nonspecific common therapeutic factors.

  View details for Web of Science ID 000275349100010

  View details for PubMedID 20171332

• On the use of propensity scores in principal causal effect estimation STATISTICS IN MEDICINE Jo, B., Stuart, E. A. 2009; 28 (23): 2857-2875

  Abstract

  We examine the practicality of propensity score methods for estimating causal treatment effects conditional on intermediate posttreatment outcomes (principal effects) in the context of randomized experiments. In particular, we focus on the sensitivity of principal causal effect estimates to violation of principal ignorability, which is the primary assumption that underlies the use of propensity score methods to estimate principal effects. Under principal ignorability (PI), principal strata membership is conditionally independent of the potential outcome under control given the pre-treatment covariates; i.e. there are no differences in the potential outcomes under control across principal strata given the observed pretreatment covariates. Under this assumption, principal scores modeling principal strata membership can be estimated based solely on the observed covariates and used to predict strata membership and estimate principal effects. While this assumption underlies the use of propensity scores in this setting, sensitivity to violations of it has not been studied rigorously. In this paper, we explicitly define PI using the outcome model (although we do not actually use this outcome model in estimating principal scores) and systematically examine how deviations from the assumption affect estimates, including how the strength of association between principal stratum membership and covariates modifies the performance. We find that when PI is violated, very strong covariate predictors of stratum membership are needed to yield accurate estimates of principal effects.

  View details for DOI 10.1002/sim.3669

  View details for Web of Science ID 000270833000002

  View details for PubMedID 19610131

  View details for PubMedCentralID PMC2757143

• Using latent outcome trajectory classes in causal inference STATISTICS AND ITS INTERFACE Jo, B., Wang, C., Ialongo, N. S. 2009; 2 (4): 403-412

  Abstract

  In longitudinal studies, outcome trajectories can provide important information about substantively and clinically meaningful underlying subpopulations who may also respond differently to treatments or interventions. Growth mixture analysis is an efficient way of identifying heterogeneous trajectory classes. However, given its exploratory nature, it is unclear how involvement of latent classes should be handled in the analysis when estimating causal treatment effects. In this paper, we propose a 2-step approach, where formulation of trajectory strata and identification of causal effects are separated. In Step 1, we stratify individuals in one of the assignment conditions (reference condition) into trajectory strata on the basis of growth mixture analysis. In Step 2, we estimate treatment effects for different trajectory strata, treating the stratum membership as partly known (known for individuals assigned to the reference condition and missing for the rest). The results can be interpreted as how subpopulations that differ in terms of outcome prognosis under one treatment condition would change their prognosis differently when exposed to another treatment condition. Causal effect estimation in Step 2 is consistent with that in the principal stratification approach (Frangakis and Rubin, 2002) in the sense that clarified identifying assumptions can be employed and therefore systematic sensitivity analyses are possible. Longitudinal development of attention deficit among children from the Johns Hopkins School Intervention Trial (Ialongo et al., 1999) will be presented as an example.

  View details for Web of Science ID 000282651000003

  View details for PubMedCentralID PMC2863041

• Adaptive Designs for Randomized Trials in Public Health ANNUAL REVIEW OF PUBLIC HEALTH Brown, C. H., Ten Have, T. R., Jo, B., Dagne, G., Wyman, P. A., Muthen, B., Gibbons, R. D. 2009; 30: 1-25

  Abstract

  In this article, we present a discussion of two general ways in which the traditional randomized trial can be modified or adapted in response to the data being collected. We use the term adaptive design to refer to a trial in which characteristics of the study itself, such as the proportion assigned to active intervention versus control, change during the trial in response to data being collected. The term adaptive sequence of trials refers to a decision-making process that fundamentally informs the conceptualization and conduct of each new trial with the results of previous trials. Our discussion below investigates the utility of these two types of adaptations for public health evaluations. Examples are provided to illustrate how adaptation can be used in practice. From these case studies, we discuss whether such evaluations can or should be analyzed as if they were formal randomized trials, and we discuss practical as well as ethical issues arising in the conduct of these new-generation trials.

  View details for DOI 10.1146/annurev.publhealth.031308.100223

  View details for Web of Science ID 000268071900002

  View details for PubMedID 19296774

  View details for PubMedCentralID PMC2778326

• Causal Inference in Randomized Experiments With Mediational Processes PSYCHOLOGICAL METHODS Jo, B. 2008; 13 (4): 314-336

  Abstract

  This article links the structural equation modeling (SEM) approach with the principal stratification (PS) approach, both of which have been widely used to study the role of intermediate posttreatment outcomes in randomized experiments. Despite the potential benefit of such integration, the 2 approaches have been developed in parallel with little interaction. This article proposes the cross-model translation (CMT) approach, in which parameter estimates are translated back and forth between the PS and SEM models. First, without involving any particular identifying assumptions, translation between PS and SEM parameters is carried out on the basis of their close conceptual connection. Monte Carlo simulations are used to further clarify the relation between the 2 approaches under particular identifying assumptions. The study concludes that, under the common goal of causal inference, what makes a practical difference is the choice of identifying assumptions, not the modeling framework itself. The CMT approach provides a common ground in which the PS and SEM approaches can be jointly considered, focusing on their common inferential problems.

  View details for DOI 10.1037/a0014207

  View details for Web of Science ID 000261604000002

  View details for PubMedID 19071997

  View details for PubMedCentralID PMC2927874

• Intention-to-treat analysis in cluster randomized trials with noncompliance STATISTICS IN MEDICINE Jo, B., Asparouhov, T., Muthen, B. O. 2008; 27 (27): 5565-5577

  Abstract

  In cluster randomized trials (CRTs), individuals belonging to the same cluster are very likely to resemble one another, not only in terms of outcomes but also in terms of treatment compliance behavior. Although the impact of resemblance in outcomes is well acknowledged, little attention has been given to the possible impact of resemblance in compliance behavior. This study defines compliance intraclass correlation as the level of resemblance in compliance behavior among individuals within clusters. On the basis of Monte Carlo simulations, it is demonstrated how compliance intraclass correlation affects power to detect intention-to-treat (ITT) effect in the CRT setting. As a way of improving power to detect ITT effect in CRTs accompanied by noncompliance, this study employs an estimation method, where ITT effect estimates are obtained based on compliance-type-specific treatment effect estimates. A multilevel mixture analysis using an ML-EM estimation method is used for this estimation.

  View details for DOI 10.1002/sim.3370

  View details for Web of Science ID 000260906000001

  View details for PubMedID 18623608

  View details for PubMedCentralID PMC2907896

• An MRI and proton spectroscopy study of the thalamus in children with autism PSYCHIATRY RESEARCH-NEUROIMAGING Hardan, A. Y., Minshew, N. J., Melhem, N. M., Srihari, S., Jo, B., Bansal, R., Keshavan, M. S., Stanley, J. A. 2008; 163 (2): 97-105

  Abstract

  Thalamic alterations have been reported in autism, but the relationships between these abnormalities and clinical symptoms, specifically sensory features, have not been elucidated. The goal of this investigation is to combine two neuroimaging methods to examine further the pathophysiology of thalamic anomalies in autism and to identify any association with sensory deficits. Structural MRI and multi-voxel, short echo-time proton magnetic resonance spectroscopy ((1)H MRS) measurements were collected from 18 male children with autism and 16 healthy children. Anatomical measurements of thalamic nuclei and absolute concentration levels of key (1)H MRS metabolites were obtained. Sensory abnormalities were assessed using a sensory profile questionnaire. Lower levels of N-acetylaspartate (NAA), phosphocreatine and creatine, and choline-containing metabolites were observed on the left side in the autism group compared with controls. No differences in thalamic volumes were observed between the two groups. Relationships, although limited, were observed between measures of sensory abnormalities and (1)H MRS metabolites. Findings from this study support the role of the thalamus in the pathophysiology of autism and more specifically in the sensory abnormalities observed in this disorder. Further investigations of this structure are warranted, since it plays an important role in information processing as part of the cortico-thalamo-cortical pathways.

  View details for DOI 10.1016/j.pscychresns.2007.12.002

  View details for Web of Science ID 000257581200001

  View details for PubMedID 18508243

  View details for PubMedCentralID PMC2467447

• Bias mechanisms in intention-to-treat analysis with data subject to treatment noncompliance and missing outcomes JOURNAL OF EDUCATIONAL AND BEHAVIORAL STATISTICS Jo, B. 2008; 33 (2): 158-185

  Abstract

  An analytical approach was employed to compare sensitivity of causal effect estimates with different assumptions on treatment noncompliance and non-response behaviors. The core of this approach is to fully clarify bias mechanisms of considered models and to connect these models based on common parameters. Focusing on intention-to-treat analysis, systematic model comparisons are performed on the basis of explicit bias mechanisms and connectivity between models. The method is applied to the Johns Hopkins school intervention trial, where assessment of the intention-to-treat effect on school children's mental health is likely to be affected by assumptions about intervention noncompliance and nonresponse at follow-up assessments. The example calls attention to the importance of focusing on each case in investigating relative sensitivity of causal effect estimates with different identifying assumptions, instead of pursuing a general conclusion that applies to every occasion.

  View details for DOI 10.3102/1076998607302635

  View details for Web of Science ID 000256029200002

  View details for PubMedCentralID PMC2916202

• Cluster Randomized trials with treatment noncompliance PSYCHOLOGICAL METHODS Jo, B., Asparouhov, T., Muthen, B. O., Ialongo, N. S., Brown, C. H. 2008; 13 (1): 1-18

  Abstract

  Cluster randomized trials (CRTs) have been widely used in field experiments treating a cluster of individuals as the unit of randomization. This study focused particularly on situations where CRTs are accompanied by a common complication, namely, treatment noncompliance or, more generally, intervention nonadherence. In CRTs, compliance may be related not only to individual characteristics but also to the environment of clusters individuals belong to. Therefore, analyses ignoring the connection between compliance and clustering may not provide valid results. Although randomized field experiments often suffer from both noncompliance and clustering of the data, these features have been studied as separate rather than concurrent problems. On the basis of Monte Carlo simulations, this study demonstrated how clustering and noncompliance may affect statistical inferences and how these two complications can be accounted for simultaneously. In particular, the effect of the intervention on individuals who not only were assigned to active intervention but also abided by this intervention assignment (complier average causal effect) was the focus. For estimation of intervention effects considering noncompliance and data clustering, an ML-EM estimation method was employed.

  View details for DOI 10.1037/1082-989X.13.1.1

  View details for Web of Science ID 000253926900001

  View details for PubMedID 18331150

  View details for PubMedCentralID PMC2917590

• State and trait emotions in delinquent adolescents CHILD PSYCHIATRY & HUMAN DEVELOPMENT Plattner, B., Karnik, N., Jo, B., Hall, R. E., Schallauer, A., Carrion, V., Feucht, M., Steiner, H. 2007; 38 (2): 155-169

  Abstract

  To examine the structure of emotions and affective dysregulation in juvenile delinquents.Fifty-six juvenile delinquents from a local juvenile hall and 169 subjects from a local high school were recruited for this study. All participants completed psychometric testing for trait emotions followed by measurements of state emotions under two conditions (free association and stress condition). Finally, delinquent participants completed a detailed assessment of past trauma using the Childhood Trauma Interview (CTI).Delinquents exhibit significantly higher levels of negative state and trait emotions when compared to a high school sample. In the delinquent sample chronicity of physical trauma affects the longstanding variable of trait emotionality and severity of trauma, specifically emotional abuse and witnessing violence, shapes negative emotional outcomes in state emotionality. In addition, delinquents appear to experience a wider range of emotions than the comparison sample and were more likely to experience a confluence of state emotions of sadness and anger under stressed conditions.Adolescent delinquents appear to have a different experience of negative emotions than comparison adolescents. The experience of emotions appears to differ in state and trait conditions. These emotions may be related to childhood experiences of trauma.

  View details for Web of Science ID 000247265400006

  View details for PubMedID 17417724

• Prediction of children's reading skills using behavioral, functional, and structural neuroimaging measures BEHAVIORAL NEUROSCIENCE Hoeft, F., Ueno, T., Reiss, A. L., Meyler, A., Whitfield-Gabrieli, S., Glover, G. H., Keller, T. A., Kobayashi, N., Mazaika, P., Jo, B., Just, M. A., Gabrieli, J. D. 2007; 121 (3): 602-613

  Abstract

  The ability to decode letters into language sounds is essential for reading success, and accurate identification of children at high risk for decoding impairment is critical for reducing the frequency and severity of reading impairment. We examined the utility of behavioral (standardized tests), and functional and structural neuroimaging measures taken with children at the beginning of a school year for predicting their decoding ability at the end of that school year. Specific patterns of brain activation during phonological processing and morphology, as revealed by voxel-based morphometry (VBM) of gray and white matter densities, predicted later decoding ability. Further, a model combining behavioral and neuroimaging measures predicted decoding outcome significantly better than either behavioral or neuroimaging models alone. Results were validated using cross-validation methods. These findings suggest that neuroimaging methods may be useful in enhancing the early identification of children at risk for poor decoding and reading skills.

  View details for DOI 10.1037/0735-7044.121.3.602

  View details for Web of Science ID 000247359300017

  View details for PubMedID 17592952

• Bias Mechanisms in Intention-to-Treat Analysis With Data Subject to Treatment Noncompliance and Missing Outcomes. Journal of educational and behavioral statistics : a quarterly publication sponsored by the American Educational Research Association and the American Statistical Association Jo, B. 2007; 33 (2): 158-185

  Abstract

  An analytical approach was employed to compare sensitivity of causal effect estimates with different assumptions on treatment noncompliance and non-response behaviors. The core of this approach is to fully clarify bias mechanisms of considered models and to connect these models based on common parameters. Focusing on intention-to-treat analysis, systematic model comparisons are performed on the basis of explicit bias mechanisms and connectivity between models. The method is applied to the Johns Hopkins school intervention trial, where assessment of the intention-to-treat effect on school children's mental health is likely to be affected by assumptions about intervention noncompliance and nonresponse at follow-up assessments. The example calls attention to the importance of focusing on each case in investigating relative sensitivity of causal effect estimates with different identifying assumptions, instead of pursuing a general conclusion that applies to every occasion.

  View details for DOI 10.3102/1076998607302635

  View details for PubMedID 20689663

  View details for PubMedCentralID PMC2916202

• Sex differences in brain activation elicited by humor PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Azim, E., Mobbs, D., Jo, B., Menon, V., Reiss, A. L. 2005; 102 (45): 16496-16501

  Abstract

  With recent investigation beginning to reveal the cortical and subcortical neuroanatomical correlates of humor appreciation, the present event-related functional MRI (fMRI) study was designed to elucidate sex-specific recruitment of these humor related networks. Twenty healthy subjects (10 females) underwent fMRI scanning while subjectively rating 70 verbal and nonverbal achromatic cartoons as funny or unfunny. Data were analyzed by comparing blood oxygenation-level-dependent signal activation during funny and unfunny stimuli. Males and females share an extensive humor-response strategy as indicated by recruitment of similar brain regions: both activate the temporal-occipital junction and temporal pole, structures implicated in semantic knowledge and juxtaposition, and the inferior frontal gyrus, likely to be involved in language processing. Females, however, activate the left prefrontal cortex more than males, suggesting a greater degree of executive processing and language-based decoding. Females also exhibit greater activation of mesolimbic regions, including the nucleus accumbens, implying greater reward network response and possibly less reward expectation. These results indicate sex-specific differences in neural response to humor with implications for sex-based disparities in the integration of cognition and emotion.

  View details for DOI 10.1073/pnas.0408456102

  View details for Web of Science ID 000233283700066

  View details for PubMedID 16275931

  View details for PubMedCentralID PMC1277963

• COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome NATURE NEUROSCIENCE Gothelf, D., Eliez, S., Thompson, T., Hinard, C., Penniman, L., Feinstein, C., Kwon, H., Jin, S. T., Jo, B., Antonarakis, S. E., Morris, M. A., Reiss, A. L. 2005; 8 (11): 1500-1502

  Abstract

  Although schizophrenia is strongly hereditary, there are limited data regarding biological risk factors and pathophysiological processes. In this longitudinal study of adolescents with 22q11.2 deletion syndrome, we identified the catechol-O-methyltransferase low-activity allele (COMT(L)) as a risk factor for decline in prefrontal cortical volume and cognition, as well as for the consequent development of psychotic symptoms during adolescence. The 22q11.2 deletion syndrome is a promising model for identifying biomarkers related to the development of schizophrenia.

  View details for DOI 10.1038/nn1572

  View details for Web of Science ID 000232966600023

  View details for PubMedID 16234808

• Learning when school is not in session: a reading summer day-camp intervention to improve the achievement of exiting First-Grade students who are economically disadvantaged JOURNAL OF RESEARCH IN READING Schacter, J., Jo, B. 2005; 28 (2): 158-169

  View details for Web of Science ID 000229450100006

• Discussion on ?A principal stratification to broken randomized experiments? by Barnard, Frangakis, Hill, and Rubin. Journal of American Statistical Association Association Muthén BO, Jo B, Brown CH 2003; 98 (462): 311-314
• General growth mixture modeling for randomized preventive interventions BIOSTATISTICS Muthen, B., Brown, C. H., Masyn, K., Jo, B., Khoo, S. T., Yang, C. C., Wang, C. P., Kellam, S. G., Carlin, J. B., Liao, J. 2002; 3 (4): 459-475

  Abstract

  This paper proposes growth mixture modeling to assess intervention effects in longitudinal randomized trials. Growth mixture modeling represents unobserved heterogeneity among the subjects using a finite-mixture random effects model. The methodology allows one to examine the impact of an intervention on subgroups characterized by different types of growth trajectories. Such modeling is informative when examining effects on populations that contain individuals who have normative growth as well as non-normative growth. The analysis identifies subgroup membership and allows theory-based modeling of intervention effects in the different subgroups. An example is presented concerning a randomized intervention in Baltimore public schools aimed at reducing aggressive classroom behavior, where only students who were initially more aggressive showed benefits from the intervention.

  View details for Web of Science ID 000182894700002

  View details for PubMedID 12933592

• Model misspecification sensitivity analysis in estimating causal effects of interventions with non-compliance STATISTICS IN MEDICINE Jo, B. 2002; 21 (21): 3161-3181

  Abstract

  Randomized trials often face complications in assessing the effect of treatment because of study participants' non-compliance. If compliance type is observed in both the treatment and control conditions, the causal effect of treatment can be estimated for a targeted subpopulation of interest based on compliance type. However, in practice, compliance type is not observed completely. Given this missing compliance information, the complier average causal effect (CACE) estimation approach provides a way to estimate differential effects of treatments by imposing the exclusion restriction for non-compliers. Under the exclusion restriction, the CACE approach estimates the effect of treatment assignment for compliers, but disallows the effect of treatment assignment for non-compliers. The exclusion restriction plays a key role in separating outcome distributions based on compliance type. However, the CACE estimate can be substantially biased if the assumption is violated. This study examines the bias mechanism in the estimation of CACE when the assumption of the exclusion restriction is violated. How covariate information affects the sensitivity of the CACE estimate to violation of the exclusion restriction assumption is also examined.

  View details for DOI 10.1002/sim.1267

  View details for Web of Science ID 000178814200002

  View details for PubMedID 12375297

• Statistical power in randomized intervention studies with noncompliance PSYCHOLOGICAL METHODS Jo, B. 2002; 7 (2): 178-193

  Abstract

  This study examined various factors that affect statistical power in randomized intervention studies with noncompliance. On the basis of Monte Carlo simulations, this study demonstrates how statistical power changes depending on compliance rate, study design, outcome distributions, and covariate information. It also examines how these factors influence power in different methods of estimating intervention effects. Intent-to-treat analysis and complier average causal effect estimation are compared as 2 alternative ways of estimating intervention effects under noncompliance. The results of this investigation provide practical implications in designing and evaluating intervention studies taking into account noncompliance.

  View details for DOI 10.1037//1082-989X.7.2.178

  View details for Web of Science ID 000176079500002

  View details for PubMedID 12090409

• Estimation of Intervention Effects with Noncompliance: Alternative Model Specifications (With comment and rejoinder) Journal of Educational and Behavioral Statistics Jo B 2002; 27 (4): 385-415
• OPPORTUNITY-TO-LEARN EFFECTS ON ACHIEVEMENT - ANALYTICAL ASPECTS Special Symposium on Sleepless in Woodland Hills - The Leigh Burstein Legacy, at the 1995 Annual Meeting of the American-Educational-Research-Association Muthen, B., Huang, L. C., Jo, B., Khoo, S. T., GOFF, G. N., Novak, J. R., Shih, J. C. AMER EDUCATIONAL RESEARCH ASSOC. 1995: 371–403

  View details for Web of Science ID A1995RW98500009