Victoria Cosgrove

All Publications

• From Tummy Troubles To Tranquil Thoughts: A Meta Analytic Investigation Of Cbt's Role In Treating Disorders Of Gut-Brain Interaction And Anxiety Korte, C., Cordova, M., Cosgrove, V. E., Friedberg, R. D. OXFORD UNIV PRESS INC. 2024: 76

  View details for Web of Science ID 001271423400155

• Post-Traumatic Stress Symptom Prevention in Pediatric Cancer Patients: Communication and Uncertainty Siciliano, S., Hull, M., Fox, H. L., Macias, M. R., Borge, O., Cosgrove, V. OXFORD UNIV PRESS INC. 2024: 105-106

  View details for Web of Science ID 001271423400216

• Chemotherapy and Cognition in Pediatric Cancer Fox, H. L., Donner, M., Hull, M., Aufderheide-Palk, C., Macias, M. R., Siciliano, S., Cosgrove, V., Borge, O. OXFORD UNIV PRESS INC. 2024: 106

  View details for Web of Science ID 001271423400217

• Covid-19-Related Anxiety In Latinx Parents Of Children With Asthma Cassar, M., Friedberg, R. D., Cordova, M., Cosgrove, V. E. OXFORD UNIV PRESS INC. 2024: 152

  View details for Web of Science ID 001271423400310

• A prospective study of social competence in survivors of pediatric brain and solid tumors. Pediatric blood & cancer Albee, M., Allende, S., Cosgrove, V., Hocking, M. C. 2022: e29670

  Abstract

  BACKGROUND/OBJECTIVES: Survivors of pediatric brain tumors are at increased risk for difficulties with social competence, including poor social information processing (SIP) and peer relationships. Improved survival rates heighten the need to better understand these challenges and if they are specific to survivors of pediatric brain tumors versus survivors of other childhood cancers.METHODS: Fifty-one survivors of pediatric brain tumors and 34 survivors of pediatric solid tumors completed evaluations of SIP and peer relationship quality within six months of completing treatment and one year later. Caregivers completed a measure of social skills. Linear mixed models evaluated differences between survivors of pediatric brain and solid tumors on SIP and social skills and how indices of SIP were associated with peer relationships over time.RESULTS: The two groups did not differ on indices of SIP or social skills over time. A three-way interaction between measures of SIP, group, and time predicted peer relationships. Survivors of pediatric solid tumors showed a positive association between baseline social skills and theory of mind and peer relationships over time, whereas survivors of pediatric brain tumors showed an inverse association between baseline social skills and theory of mind and peer relationships over time.CONCLUSION: Findings revealed unanticipated associations between baseline SIP and social skills and peer relationships over time among survivors of pediatric brain tumors. Additional research is needed to elucidate the factors most influential on peer relationships in this group to inform interventions.

  View details for DOI 10.1002/pbc.29670

  View details for PubMedID 35312152

• A pilot trial of quetiapine, lithium, or placebo added to divalproex sodium for hypomanic or manic episodes in ambulatory adults with bipolar I disorder. International journal of bipolar disorders Cosgrove, V. E., Allende, S., Gwizdowski, I., Grace Fischer, E., Ostacher, M., Suppes, T. 2022; 10 (1): 7

  Abstract

  BACKGROUND: Many patients with bipolar I disorder do not respond to monotherapy treatment with mood-stabilizing medications, and combination regimens are commonly used in both inpatient and outpatient settings for the acute and maintenance treatment of bipolar disorder. We studied whether combination therapy is more effective than monotherapy for the acute treatment of subjects with bipolar I disorder currently experiencing manic symptoms. The primary hypothesis was that combination treatments would be associated with greater reductions in symptoms of mania and hypomania than monotherapy alone. The secondary hypothesis was that combination therapies would be associated with lower depression levels than monotherapy alone. Last, a post-hoc exploratory aim was used to examine whether the effect of side effect severity on risk-of-dropout would be greater in combination therapies than in monotherapy alone.RESULTS: In this 12-week, double-blind, placebo-controlled ambulatory pilot trial, participants (n=75) with bipolar I disorder were randomly assigned to: (1) monotherapy divalproex plus placebo (DVP+PBO), (2) combination therapy of divalproex plus blinded lithium (DVP+Li) or (3) divalproex plus blinded quetiapine (DVP+QTP). Combination therapies (vs. monotherapy) were not associated with improved symptoms of mania, hypomania or depression. The effect of side effect severity on study retention did not differ between combination therapies and monotherapy. However, the risk-of-dropout was significantly greater in the DVP+Li arm versus the DVP+PBO arm.CONCLUSIONS: No longitudinal differences in mania, hypomania or depression were found between combination therapies and monotherapy. The effect of side effect severity on study retention did not differ between groups. Due to the small sample size and differential rates of attrition between treatment arms, results of this pilot trial must be interpreted with caution. Trial registration ClinicalTrials.gov identifier: NCT00183443.

  View details for DOI 10.1186/s40345-022-00252-w

  View details for PubMedID 35235061

• Aberrant Neural Response to Social Exclusion Without Significantly Greater Distress in Youth With Bipolar Disorder: Preliminary Findings. Frontiers in psychiatry Roybal, D. J., Cosgrove, V. E., Kelley, R., Smallwood Shoukry, R., Larios, R. M., Novy, B., Chang, K. D., Garrett, A. S. 2022; 13: 687052

  Abstract

  Background: Little is known about the effects of social exclusion on youth with bipolar disorder (BD). Understanding these effects and the functional neural correlates of social exclusion in youth with BD may establish differences from healthy youth and help identify areas of intervention.Methods: We investigated brain function in 19 youth with BD and 14 age and gender matched healthy control (HC) participants while performing Cyberball, an fMRI social exclusion task. Whole brain activation, region-of-interest, and functional connectivity were compared between groups and examined with behavioral measures.Results: Compared with the HC group, youth with BD exhibited greater activation in the left fusiform gyrus (FFG) during social exclusion. Functional connectivity between the left FFG and the posterior cingulate/precuneus was significantly greater in the HC compared with the BD group. For the HC group only, age and subjective distress during Cyberball significantly predicted mean FFG activation. No significant differences in distress during social exclusion were found between groups.Conclusion: Although preliminary due to small sample size, these data suggest that youth with BD process social exclusion in a manner that focuses on basic visual information while healthy youth make use of past experiences to interpret current social encounters. This difference may account for the social cognitive issues experienced by youth with BD, which can lead to more severe anxiety and mood symptoms.

  View details for DOI 10.3389/fpsyt.2022.687052

  View details for PubMedID 35432046

• Peripheral Inflammatory Biomarkers Define Biotypes of Bipolar Depression Lee, Y., Mansur, R. B., Brietzke, E., Kapogiannis, D., Delgado-Peraza, F., Boutilier, J. J., Chan, T. Y., Carmona, N. E., Rosenblat, J., Lee, J., Maletic, V., Vinberg, M., Suppes, T., Goldstein, B. I., Ravindran, A., Taylor, V., Cosgrove, V., Kramer, N. E., Ho, R., Raison, C., McIntyre, R. S. ELSEVIER SCIENCE INC. 2021: S156

  View details for Web of Science ID 000645683800376

• All in the Family: How Parental Criticism Impacts Depressive Symptoms in Youth. Research on child and adolescent psychopathology Berla, N., Peisch, V., Thacher, A., Pearlstein, J., Dowdle, C., Geraghty, S., Cosgrove, V. 2021

  Abstract

  Despite a strong connection between family environment and mood symptoms in youth, little research to date has examined potential underlying mechanisms. We propose an etiological model investigating how parenting (i.e., expressed emotion, or EE) affects youth depression by shaping their emotion regulation abilities. Forty-six youth and caregivers participated in this cross-sectional study. Family environment was assessed using the Five-Minute Speech Sample (FMSS) and the Levels of Expressed Emotion Scale (LEE). The Difficulties in Emotion Regulation Scale (DERS) and the Children's Depression Rating Scale-Revised (CDRS-R) were used to assess youth emotion regulation and depressive symptoms, respectively. Analyses demonstrated no significant relationships between type of reporter (i.e., independent rater, parent, youth) of parental EE and criticism. Mediation analyses suggested that youth-reported parental EE predicted greater levels of youth depressive symptoms, and that this association was mediated by emotion regulation. This study has direct clinical implications, elucidating the importance of strengthening positive parent-child communication to support the development of emotion regulation skills and psychological well-being for youth.

  View details for DOI 10.1007/s10802-021-00809-w

  View details for PubMedID 33743095

• Peripheral inflammatory biomarkers define biotypes of bipolar depression. Molecular psychiatry Lee, Y. n., Mansur, R. B., Brietzke, E. n., Kapogiannis, D. n., Delgado-Peraza, F. n., Boutilier, J. J., Chan, T. C., Carmona, N. E., Rosenblat, J. D., Lee, J. n., Maletic, V. n., Vinberg, M. n., Suppes, T. n., Goldstein, B. I., Ravindran, A. V., Taylor, V. H., Chawla, S. n., Nogueras-Ortiz, C. n., Cosgrove, V. E., Kramer, N. E., Ho, R. n., Raison, C. A., McIntyre, R. S. 2021

  Abstract

  We identified biologically relevant moderators of response to tumor necrosis factor (TNF)-α inhibitor, infliximab, among 60 individuals with bipolar depression. Data were derived from a 12-week, randomized, placebo-controlled clinical trial secondarily evaluating the efficacy of infliximab on a measure of anhedonia (i.e., Snaith-Hamilton Pleasure Scale). Three inflammatory biotypes were derived from peripheral cytokine measurements using an iterative, machine learning-based approach. Infliximab-randomized participants classified as biotype 3 exhibited lower baseline concentrations of pro- and anti-inflammatory cytokines and soluble TNF receptor-1 and reported greater pro-hedonic improvements, relative to those classified as biotype 1 or 2. Pretreatment biotypes also moderated changes in neuroinflammatory substrates relevant to infliximab's hypothesized mechanism of action. Neuronal origin-enriched extracellular vesicle (NEV) protein concentrations were reduced to two factors using principal axis factoring: phosphorylated nuclear factorκB (p-NFκB), Fas-associated death domain (p-FADD), and IκB kinase (p-IKKα/β) and TNF receptor-1 (TNFR1) comprised factor "NEV1," whereas phosphorylated insulin receptor substrate-1 (p-IRS1), p38 mitogen-activated protein kinase (p-p38), and c-Jun N-terminal kinase (p-JNK) constituted "NEV2". Among infliximab-randomized subjects classified as biotype 3, NEV1 scores were decreased at weeks 2 and 6 and increased at week 12, relative to baseline, and NEV2 scores increased over time. Decreases in NEV1 scores and increases in NEV2 scores were associated with greater reductions in anhedonic symptoms in our classification and regression tree model (r2 = 0.22, RMSE = 0.08). Our findings provide preliminary evidence supporting the hypothesis that the pro-hedonic effects of infliximab require modulation of multiple TNF-α signaling pathways, including NF-κB, IRS1, and MAPK.

  View details for DOI 10.1038/s41380-021-01051-y

  View details for PubMedID 33658605

• Effects of infliximab on brain neurochemistry of adults with bipolar depression. Journal of affective disorders Mansur, R. B., Subramaniapillai, M., Lee, Y., Pan, Z., Carmona, N. E., Shekotikhina, M., Iacobucci, M., Rodrigues, N., Nasri, F., Rosenblat, J. D., Brietzke, E., Cosgrove, V. E., Kramer, N. E., Suppes, T., Newport, J., Hajek, T., McIntyre, R. S. 2020; 281: 61–66

  Abstract

  OBJECTIVES: To explore the relationship between inflammation and neuronal metabolism in bipolar disorder (BD) by evaluating the neurochemical effects of the tumor necrosis factor-alpha (TNF-alpha) antagonist infliximab among individuals with bipolar depression METHODS: This is a post-hoc, exploratory analysis from a 12-week, randomized, double-blind, placebo-controlled trial with infliximab for adults with bipolar depression. We assessed the effects of infliximab on concentration of metabolites in the prefrontal cortex, using proton-magnetic resonance spectroscopy (1H-MRS), as well as its association with clinical outcomes (i.e. depressive symptom severity and cognitive function).RESULTS: Eighteen participants in the placebo and 15 in the infliximab group were included in this analysis. In the pre-specified primary outcome, there were no significant effects of treatment on prefrontal concentrations of N-acetylaspartate (NAA; p=0.712). In the secondary analyses, there was a significant treatment by time interaction for glutamate (Glx; p=0.018), indicating that Glx levels decreased in infliximab-treated patients, relative to placebo. Treatment group significantly moderated the association between changes in Glx levels and changes in a neurocognitive test (i.e. Digit Symbol Substitution Test; p=0.014), indicating that in infliximab-treated participants reductions in Glx were associated with cognitive improvement.CONCLUSIONS: Treatment with infliximab did not affect prefrontal NAA concentration in adults with BD. Exploratory analysis suggested a potential effect of treatment on the glutamate system, a finding that should be confirmed and validated by additional studies.

  View details for DOI 10.1016/j.jad.2020.11.128

  View details for PubMedID 33296798

• Extracellular Vesicle Biomarkers Reveal Inhibition of Neuroinflammation by Infliximab in Association with Antidepressant Response in Adults with Bipolar Depression. Cells Mansur, R. B., Delgado-Peraza, F., Subramaniapillai, M., Lee, Y., Iacobucci, M., Rodrigues, N., Rosenblat, J. D., Brietzke, E., Cosgrove, V. E., Kramer, N. E., Suppes, T., Raison, C. L., Chawla, S., Nogueras-Ortiz, C., McIntyre, R. S., Kapogiannis, D. 2020; 9 (4)

  Abstract

  Accumulating evidence suggests that neuroinflammation is involved in bipolar disorder (BD) pathogenesis. The tumor necrosis factor-alpha (TNF-alpha) antagonist infliximab was recently reported to improve depressive symptoms in a subpopulation of individuals with BD and history of childhood maltreatment. To explore the mechanistic mediators of infliximab's effects, we investigated its engagement with biomarkers of cellular response to inflammation derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We hypothesized that infliximab, compared to placebo, would decrease TNF-alpha receptors (TNFRs) and nuclear factor-kappa B (NF-kappaB) pathway signaling biomarkers, and that history of childhood abuse would moderate infliximab's effects. We immunocaptured NEVs from plasma samples collected at baseline and at weeks 2, 6, and 12 (endpoint) from 55 participants of this clinical trial and measured NEV biomarkers using immunoassays. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging at baseline and endpoint. Childhood physical abuse moderated treatment by time interactions for TNFR1 (chi2 = 9.275, p = 0.026), NF-kappaB (chi2 = 13.825, p = 0.003), and inhibitor of NF-kappaB (IkappaBalpha) (chi2 = 7.990, p = 0.046), indicating that higher levels of physical abuse were associated with larger biomarker decreases over time. Moreover, the antidepressant response to infliximab was moderated by TNFR1 (chi2 = 7.997, p = 0.046). In infliximab-treated participants, reductions in TNFR1 levels were associated with improvement of depressive symptoms, an effect not detected in the placebo group. Conversely, reductions in TNFR1 levels were associated with increased global cortical thickness in infliximab- (r = -0.581, p = 0.029), but not placebo-treated, patients (r = 0.196, p = 0.501). In conclusion, we report that NEVs revealed that infliximab engaged the TNFR/NF-kappaB neuro-inflammatory pathway in individuals with BD, in a childhood trauma-dependent manner, which was associated with clinical response and brain structural changes.

  View details for DOI 10.3390/cells9040895

  View details for PubMedID 32268604

• Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin. Journal of psychiatric research Mansur, R. B., Delgado-Peraza, F. n., Subramaniapillai, M. n., Lee, Y. n., Iacobucci, M. n., Nasri, F. n., Rodrigues, N. n., Rosenblat, J. D., Brietzke, E. n., Cosgrove, V. E., Kramer, N. E., Suppes, T. n., Raison, C. L., Fagiolini, A. n., Rasgon, N. n., Chawla, S. n., Nogueras-Ortiz, C. n., Kapogiannis, D. n., McIntyre, R. S. 2020; 133: 82–92

  Abstract

  Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations.

  View details for DOI 10.1016/j.jpsychires.2020.12.007

  View details for PubMedID 33316649

• Personality and pediatric bipolar disorder: Toward personalizing psychosocial intervention. Journal of affective disorders Kelman, J. n., Thacher, A. n., Hossepian, K. n., Pearlstein, J. n., Geraghty, S. n., Cosgrove, V. E. 2020; 275: 311–18

  Abstract

  Previous research suggests that challenging temperament characteristics (i.e., low mood, irritability and rigidity) are associated with risk for the development of Pediatric Bipolar Disorder (PBD). This study aimed to investigate the connection between PBD and discrete dimensions of the Five Factor Model (FFM) of personality.Youth diagnosed with PBD I, II, or NOS, at high risk for the disorder (BD-HR) and healthy controls were recruited from the Child and Adolescent Psychiatry Outpatient Clinic at Stanford University School of Medicine. Researchers administered a personality inventory and evaluated current mood state.BD and BD-HR youth scored lower in Emotional Regulation than did HC youth (F (3, 70) = 10.75, p < .001). Within the BD and BD-HR groups, youth with high depression scores scored lower on Extraversion (F (3, 70) = 8.62, p < .001) and Conscientiousness (F (3, 70) = 4.53, p < .01).A major limitation of this study is its cross-sectional design, precluding analysis of whether certain traits or clusters of traits predict PBD or other mood disorders.Low Emotional Regulation, Conscientiousness, and Agreeableness were associated with PBD; this personality profile clinically corresponds with youth diagnosed with PBD who present with difficulty regulating their emotions, vulnerability to stress, and emotional reactivity. Future research examining personality characteristics in PBD may elucidate further a specific profile to aid clinicians in developing psychosocial interventions for youth with and at high risk of developing PBD.

  View details for DOI 10.1016/j.jad.2020.07.007

  View details for PubMedID 32734924

• Leptin mediates improvements in cognitive function following treatment with infliximab in adults with bipolar depression. Psychoneuroendocrinology Mansur, R. B., Subramaniapillai, M. n., Lee, Y. n., Pan, Z. n., Carmona, N. E., Shekotikhina, M. n., Iacobucci, M. n., Rodrigues, N. n., Nasri, F. n., Rashidian, H. n., Rosenblat, J. D., Brietzke, E. n., Cosgrove, V. E., Kramer, N. E., Suppes, T. n., McIntyre, R. S. 2020; 120: 104779

  Abstract

  A potential role for leptin in the pathophysiology of bipolar disorder (BD) has been proposed. We recently investigated the effects of the tumor necrosis factor-alpha (TNF-α) antagonist infliximab in individuals with bipolar depression. Leptin is known to interact with the TNF-α system. Herein, we aimed to explore infliximab's effects on leptin and its relationship with brain structure and function. Sixty adults with bipolar depression were enrolled in this randomized, double-blind, 12-week clinical trial of adjunctive infliximab (n = 29) and saline control (n = 31), which were administered intravenously at weeks 0, 2, and 6. Plasma concentrations of leptin, TNF-α and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. We observed a significant decrease in leptin levels in infliximab-treated patients, relative to placebo. Infliximab treatment also significantly reduced TNF-α and sTNFR2, but not sTNFR1 levels. Changes in sTNR2 levels at week 6 significantly determined changes in leptin at week 12 in infliximab-, but not placebo-treated participants. Improvements in verbal memory and increases in global cortical volume were associated with reduction in leptin levels in the treatment group. Mediation analysis indicated that cognitive improvement in infliximab-treated patients was mediated by reductions in leptin levels, which in its turn were determined by decreases in sTNR2 levels. In conclusion, infliximab treatment reduced plasma leptin levels in individuals with BD, through modulation of sTNFR2. Decreases in leptin signaling were associated with an increase in global cortical volume and better performance in a verbal memory task.

  View details for DOI 10.1016/j.psyneuen.2020.104779

  View details for PubMedID 32603956

• Efficacy of Adjunctive Infliximab vs. Placebo in the Treatment of Anhedonia in Bipolar I/II Depression. Brain, behavior, and immunity Lee, Y. n., Mansur, R. B., Brietzke, E. n., Carmona, N. E., Subramaniapillai, M. n., Pan, Z. n., Shekotikhina, M. n., Rosenblat, J. D., Suppes, T. n., Cosgrove, V. E., Kramer, N. E., McIntyre, R. S. 2020

  Abstract

  We investigated the efficacy of tumour necrosis factor (TNF)-α antagonist infliximab on a measure of anhedonia amongst individuals with bipolar I/II depression (ClinicalTrials.gov identifier NCT02363738). Adults (ages 18-65) with bipolar I/II disorder currently experiencing a major depressive episode with a higher probability of inflammatory activity (i.e., meeting one or more of the following inflammatory/metabolic criteria: obesity and dyslipidemia/hypertension, daily cigarette smoking, diabetes mellitus, migraine, inflammatory bowel disease, and/or C-reactive protein level of ⩾5 mg/L) were enrolled in a double-blind, 12-week clinical trial of adjunctive infliximab (5 mg/kg) and saline control, which were administered at weeks 0, 2, and 6. The primary outcome measure for the present secondary analysis was change in the Snaith-Hamilton Pleasure Scale (SHAPS) total score between placebo- and infliximab-treated subjects from baseline to weeks 6 and 12. Plasma concentrations of TNF-α and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. Sixty eligible adults received treatment with infliximab (n=29) or placebo (n=31); 48 subjects completed the study (infliximab: n=21, placebo: n=26). Overall, infliximab-randomized subjects exhibited significantly larger increases in SHAPS total score, denoting greater reductions in anhedonic symptoms, when compared to placebo-randomized subjects (treatment × time interaction effect: χ2=7.15,df=2,p=0.03). Anti-anhedonic efficacy was moderated by baseline plasma levels of TNF-α and sTNFR1, but not by changes in TNF-α or sTNFR1 concentrations. Baseline and changes in sTNFR2 concentrations did not moderate anti-anhedonic efficacy. Infliximab significantly improved a measure of anhedonia relative to placebo in adults with bipolar I/II depression at week 6; intervention efficacy was not sustained 6 weeks after the final infusion.

  View details for DOI 10.1016/j.bbi.2020.04.063

  View details for PubMedID 32380271

• Immune response to stress induction as a predictor of cognitive-behavioral therapy outcomes in adolescent mood disorders: A pilot study. Journal of psychiatric research Pearlstein, J. G., Staudenmaier, P. J., West, A. E., Geraghty, S., Cosgrove, V. E. 2019; 120: 56–63

  Abstract

  Cognitive-behavioral therapy (CBT) alleviates symptoms of depression in youth with bipolar disorder (BD) and major depressive disorder (MDD). Empirical research has linked inflammatory markers to depressive symptoms and acute psychosocial stress; however, a gap remains as to whether immune response to stress may serve as a putative mechanism of treatment. This preliminary pilot study determined the modest feasibility of assessing psychobiological response to stress as a predictor of CBT outcomes for youth with mood disorders. We evaluated whether participation in a 10-session group-CBT intervention for mood disorders altered inflammatory response to a laboratory psychosocial stress induction and if this alteration in immune stress responsivity was related to a decrease in depressive symptoms. Thirty-four youth (age M = 15.03, SD = 1.91) diagnosed with BD or MDD participated in a 10-session CBT group and pre- and post-group assessments; twenty-eight participants who completed the group had usable cytokine data. Pre- and post-group assessments included stress induction with the Trier Social Stress Test (TSST) during which inflammatory cytokines were measured at baseline (time 0) and after the TSST at 30, 60, and 90 min. Results suggest it is modestly feasible to measure immune response to stress alongside CBT treatment for adolescent mood disorders. Our findings were mixed; across seven cytokines, hierarchical linear models indicated two cytokines, IL6 and IL12, were sensitive to acute laboratory stress. We also found significant correlations between life stress, inflammation, and depression both pre- and post- CBT group. Inflammation pre-group, as measured by IL12 and IL1 beta predicted depressive symptoms following treatment. Although we did not find significant within-subject reductions in inflammation, chronic stress predicted changes in IL beta, signaling the central role of chronic stress. This study offers preliminary evidence that immune responsivity to stress induction could serve as a mechanism of treatment for mood disorders in youth, indicating a potential marker for more personalized model of healthcare.

  View details for DOI 10.1016/j.jpsychires.2019.10.012

  View details for PubMedID 31634750

• Editorial: The Impact of Parental Psychopathology on Family Functioning: Prioritizing Transdiagnostic Interventions With Parents and Families JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY West, A. E., Cosgrove, V. E. 2019; 58 (10): 940–42

  View details for DOI 10.1016/j.jaac.2019.04.005

  View details for Web of Science ID 000518532500005

• Efficacy of Adjunctive Infliximab vs Placebo in the Treatment of Adults With Bipolar I/II Depression: A Randomized Clinical Trial JAMA PSYCHIATRY McIntyre, R. S., Subramaniapillai, M., Lee, Y., Pan, Z., Carmona, N. E., Shekotikhina, M., Rosenblat, J. D., Brietzke, E., Soczynska, J. K., Cosgrove, V. E., Miller, S., Fischer, E., Kramer, N. E., Dunlap, K., Suppes, T., Mansur, R. B. 2019; 76 (8): 783–90

  View details for DOI 10.1001/jamapsychiatry.2019.0779

  View details for Web of Science ID 000480298500005

• A clinical model for identifying an inflammatory phenotype in mood disorders JOURNAL OF PSYCHIATRIC RESEARCH Kramer, N. E., Cosgrove, V. E., Dunlap, K., Subramaniapillai, M., McIntyre, R. S., Suppes, T. 2019; 113: 148–58

  View details for DOI 10.1016/j.jpsychires.2019.02.005

  View details for Web of Science ID 000467670000022

• A randomized controlled trial of MoodSwings 2.0: An internet-based self-management program for bipolar disorder BIPOLAR DISORDERS Gliddon, E., Cosgrove, V., Berk, L., Lauder, S., Mohebbi, M., Grimm, D., Dodd, S., Coulson, C., Raju, K., Suppes, T., Berk, M. 2019; 21 (1): 28–39

  Abstract

  Bipolar disorder is a complex illness often requiring combinations of therapies to successfully treat symptoms. In recent years, there have been significant advancements in a number of therapies for bipolar disorder. It is therefore timely to provide an overview of current adjunctive therapeutic options to help treating clinicians to inform their patients and work towards optimal outcomes.Publications were identified from PubMed searches on bipolar disorder and pharmacotherapy, nutraceuticals, hormone therapy, psychoeducation, interpersonal and social rhythm therapy, cognitive remediation, mindfulness, e-Health and brain stimulation techniques. Relevant articles in these areas were selected for further review. This paper provides a narrative review of adjunctive treatment options and is not a systematic review of the literature.A number of pharmacotherapeutic, psychological and neuromodulation treatment options are available. These have varying efficacy but all have shown benefit to people with bipolar disorder. Due to the complex nature of treating the disorder, combination treatments are often required. Adjunctive treatments to traditional pharmacological and psychological therapies are proving useful in closing the gap between initial symptom remission and full functional recovery.Given that response to monotherapy is often inadequate, combination regimens for bipolar disorder are typical. Correspondingly, psychiatric research is working towards a better understanding of the disorder's underlying biology. Therefore, treatment options are changing and adjunctive therapies are being increasingly recognized as providing significant tools to improve patient outcomes. Towards this end, this paper provides an overview of novel treatments that may improve clinical outcomes for people with bipolar disorder.

  View details for DOI 10.1111/bdi.12669

  View details for Web of Science ID 000459791000005

  View details for PubMedID 29369487

• Overhauling technology-based interventions for young people with bipolar disorder: Lessons learned from adults BIPOLAR DISORDERS Van Meter, A., Cosgrove, V. E. 2019; 21 (1): 86-87

  View details for DOI 10.1111/bdi.12716

  View details for Web of Science ID 000459791000011

• Overhauling technology-based interventions for young people with bipolar disorder: lessons learned from adults. Bipolar disorders Van Meter, A., Cosgrove, V. E. 2018

  Abstract

  Gliddon etal.1 adds to a compelling evidence base suggesting that digital interventions like MoodSwings 2.0 have the potential to contribute to long-lasting, clinically meaningful reductions in depression for adults with bipolar disorder (BD). Like MoodSwings, most digital interventions are essentially evidence-based psychosocial programs adapted for online delivery. Some include interaction with a clinician, whereas others are entirely self-guided. From a public health perspective, the allure of empirically-valid digital interventions for BD is considerable; a majority of psychosocial interventions with an evidence base in BD have not been disseminated widely and are principally available at research institutions where they were developed. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30387928

• Online ethics: where will the interface of mental health and the internet lead us? International journal of bipolar disorders Cosgrove, V., Gliddon, E., Berk, L., Grimm, D., Lauder, S., Dodd, S., Berk, M., Suppes, T. 2017; 5 (1): 26-?

  Abstract

  While e-health initiatives are poised to revolutionize delivery and access to mental health care, conducting clinical research online involves specific contextual and ethical considerations. Face-to-face psychosocial interventions can at times entail risk and have adverse psychoactive effects, something true for online mental health programs too. Risks associated with and specific to internet psychosocial interventions include potential breaches of confidentiality related to online communications (such as unencrypted email), data privacy and security, risks of self-selection and self-diagnosis as well as the shortcomings of receiving psychoeducation and treatment at distance from an impersonal website. Such ethical issues need to be recognized and proactively managed in website and study design as well as treatment implementation. In order for online interventions to succeed, risks and expectations of all involved need to be carefully considered with a focus on ethical integrity.

  View details for DOI 10.1186/s40345-017-0095-3

  View details for PubMedID 28480484

• Progressing MoodSwings. The upgrade and evaluation of MoodSwings 2.0: An online intervention for bipolar disorder. Contemporary clinical trials Lauder, S., Cosgrove, V. E., Gliddon, E., Grimm, D., Dodd, S., Berk, L., Castle, D., Suppes, T. S., Berk, M. 2017

  Abstract

  MoodSwings 2.0 is a self-guided online intervention for bipolar disorder. The intervention incorporates technological improvements on an earlier validated version of the intervention (MoodSwings 1.0). The previous MoodSwings trial provides this study with a unique opportunity to progress previous work, whilst being able to take into consideration lesson learnt, and technological enhancements. The structure and technology of MoodSwings 2.0 are described and the relevance to other online health interventions is highlighted. An international team from Australia and the US updated and improved the programs content pursuant to changes in DSM-5, added multimedia components and included larger numbers of participants in the group discussion boards. Greater methodological rigour in this trial includes an attention control condition, quarterly telephone assessments, and red flag alerts for significant clinical change. This paper outlines these improvements, including additional security and safety measures. A 3 arm RCT is currently evaluating the enhanced program to assess the efficacy of MS 2.0; the primary outcome is change in depressive and manic symptoms. To our knowledge this is the first randomized controlled online bipolar study with a discussion board attention control and meets the key methodological criteria for online interventions.

  View details for DOI 10.1016/j.cct.2017.02.008

  View details for PubMedID 28257919

• TEACHING THERAPY: A CO-THERAPY MODEL Vasan, N., Kishore, A., Isaac, S., Stubbe, D. E., Lotspeich, L. J., Dobry, Y., Zalpuri, I., Reichert, E., Cosgrove, V. ELSEVIER SCIENCE INC. 2016: S352

  View details for DOI 10.1016/j.jaac.2016.07.097

  View details for Web of Science ID 000541964302260

• Toward a Valid Animal Model of Bipolar Disorder: How the Research Domain Criteria Help Bridge the Clinical-Basic Science Divide. Biological psychiatry Cosgrove, V. E., Kelsoe, J. R., Suppes, T. 2016; 79 (1): 62-70

  Abstract

  Bipolar disorder is a diagnostically heterogeneous disorder, although mania emerges as a distinct phenotype characterized by elevated mood and increased activity or energy. While bipolar disorder's cyclicity is difficult to represent in animals, models of mania have begun to decode its fundamental underlying neurobiology. When psychostimulants such as amphetamine or cocaine are administered to rodents, a resulting upsurge of motor activity is thought to share face and predictive validity with mania in humans. Studying black Swiss mice, which inherently exhibit proclivity for reward seeking and risk taking, also has yielded some insight. Further, translating the biology of bipolar disorder in humans into animal models has led to greater understanding of roles for candidate biological systems such as the GRIK2 and CLOCK genes, as well as the extracellular signal-related kinase pathway involved in the pathophysiology of the illness. The National Institute of Mental Health Research Domain Criteria initiative seeks to identify building blocks of complex illnesses like bipolar disorder in hopes of uncovering the neurobiology of each, as well as how each fits together to produce syndromes like bipolar disorder or why so many mental illnesses co-occur together. Research Domain Criteria-driven preclinical models of isolated behaviors and domains involved in mania and bipolar disorder will ultimately inform movement toward nosology supported by neurobiology.

  View details for DOI 10.1016/j.biopsych.2015.09.002

  View details for PubMedID 26531027

• Evaluating discussion board engagement in the MoodSwings online self-help program for bipolar disorder: protocol for an observational prospective cohort study BMC PSYCHIATRY Gliddon, E., Lauder, S., Berk, L., Cosgrove, V., Grimm, D., Dodd, S., Suppes, T., Berk, M. 2015; 15

  Abstract

  Online, self-guided programs exist for a wide range of mental health conditions, including bipolar disorder, and discussion boards are often part of these interventions. The impact engagement with these discussion boards has on the psychosocial well-being of users is largely unknown. More specifically we need to clarify the influence of the type and level of engagement on outcomes. The primary aim of this exploratory study is to determine if there is a relationship between different types (active, passive or none) and levels (high, mid and low) of discussion board engagement and improvement in outcome measures from baseline to follow up, with a focus on self-reported social support, stigma, quality of life and levels of depression and mania. The secondary aim of this study is to identify any differences in demographic variables among discussion users.The present study is a sub-study of the MoodSwings 2.0 3-arm randomised controlled trial (discussion board only (arm 1), discussion board plus psychoeducation (arm 2), discussion board, psychoeducation plus cognitive behavioural therapy-based tools (arm 3)). Discussion engagement will be measured via online participant activity monitoring. Assessments include online self-report as well as blinded phone interviews at baseline, 3, 6, 9 and 12 months follow up.The results of this study will help to inform future programs about whether or not discussion boards are a beneficial inclusion in online self-help interventions. It will also help to determine if motivating users to actively engage in online discussion is necessary, and if so, what level of engagement is optimal to produce the most benefit. Future programs may benefit through being able to identify those most likely to poorly engage, based on demographic variables, so motivational strategies can be targeted accordingly.ClinicalTrials.gov NCT02118623 registered April 15 2014 and NCT02106078 registered May 16 2013.

  View details for DOI 10.1186/s12888-015-0630-7

  View details for Web of Science ID 000363120700001

  View details for PubMedID 26462799

  View details for PubMedCentralID PMC4604761

• Evaluating discussion board engagement in the MoodSwings online self-help program for bipolar disorder: protocol for an observational prospective cohort study. BMC psychiatry Gliddon, E., Lauder, S., Berk, L., Cosgrove, V., Grimm, D., Dodd, S., Suppes, T., Berk, M. 2015; 15: 243-?

  Abstract

  Online, self-guided programs exist for a wide range of mental health conditions, including bipolar disorder, and discussion boards are often part of these interventions. The impact engagement with these discussion boards has on the psychosocial well-being of users is largely unknown. More specifically we need to clarify the influence of the type and level of engagement on outcomes. The primary aim of this exploratory study is to determine if there is a relationship between different types (active, passive or none) and levels (high, mid and low) of discussion board engagement and improvement in outcome measures from baseline to follow up, with a focus on self-reported social support, stigma, quality of life and levels of depression and mania. The secondary aim of this study is to identify any differences in demographic variables among discussion users.The present study is a sub-study of the MoodSwings 2.0 3-arm randomised controlled trial (discussion board only (arm 1), discussion board plus psychoeducation (arm 2), discussion board, psychoeducation plus cognitive behavioural therapy-based tools (arm 3)). Discussion engagement will be measured via online participant activity monitoring. Assessments include online self-report as well as blinded phone interviews at baseline, 3, 6, 9 and 12 months follow up.The results of this study will help to inform future programs about whether or not discussion boards are a beneficial inclusion in online self-help interventions. It will also help to determine if motivating users to actively engage in online discussion is necessary, and if so, what level of engagement is optimal to produce the most benefit. Future programs may benefit through being able to identify those most likely to poorly engage, based on demographic variables, so motivational strategies can be targeted accordingly.ClinicalTrials.gov NCT02118623 registered April 15 2014 and NCT02106078 registered May 16 2013.

  View details for DOI 10.1186/s12888-015-0630-7

  View details for PubMedID 26462799

  View details for PubMedCentralID PMC4604761

• A randomized, double-blind, placebo-controlled study of ziprasidone monotherapy in bipolar disorder with co-occurring lifetime panic or generalized anxiety disorder. journal of clinical psychiatry Suppes, T., McElroy, S. L., Sheehan, D. V., Hidalgo, R. B., Cosgrove, V. E., Gwizdowski, I. S., Feldman, N. S. 2014; 75 (1): 77-84

  Abstract

  Bipolar disorder often co-occurs with anxiety disorders. Evidence suggests that second-generation antipsychotics (SGAs) may be useful in treating both conditions. This study examined the efficacy of ziprasidone in the treatment of these disorders.This 3-site, randomized, double-blind, placebo-controlled, parallel group, 8-week trial of ziprasidone monotherapy examined 49 subjects with bipolar disorder and lifetime panic disorder (with or without agoraphobia) or generalized anxiety disorder (GAD) experiencing moderately severe anxiety symptoms at entrance into the study. Both bipolar disorder and anxiety diagnoses were based on DSM-IV-TR criteria. Patients were screened and randomized from June 25, 2010, through August 23, 2011. Primary outcome measures were the Clinical Global Impressions-21 Anxiety Scale (CGI-21 Anxiety) and the Sheehan Disability Scale (SDS), with secondary measures monitoring anxiety and mood symptoms.Last-observation-carried-forward analyses demonstrated that patients in the ziprasidone group did not improve significantly more than those in the placebo group on the CGI-21 Anxiety (F1 = 0.34; P = .564) or SDS (F1 = 0.26; P = .611). Secondary analysis using hierarchical linear modeling found similar results (CGI-21 Anxiety: F1 = 1.82; P = .178; and SDS: F1 = 0.70; P = .408). Regardless of group, time in the study was associated with significant decrease in anxiety (F1 = 11.08; P = .001) and total disability (F1 = 26.16; P < .001). Patients in the ziprasidone group showed a greater increase in abnormal involuntary movement, and 81.8% (n = 9) of the subjects who withdrew from the study due to adverse events, serious adverse events, or side effects were in the ziprasidone group.Results suggest that ziprasidone monotherapy was not associated with a clinically significant improvement in anxiety symptoms or improved function for patients with bipolar disorder, lifetime panic disorder or GAD, and concurrent moderately severe anxiety symptoms, and it was associated with a more negative side-effect profile relative to placebo.ClinicalTrials.gov identifier: NCT01172652.

  View details for DOI 10.4088/JCP.12m08297

  View details for PubMedID 24345758

• First controlled treatment trial of bipolar II hypomania with mixed symptoms: Quetiapine versus placebo. Journal of affective disorders Suppes, T., Ketter, T. A., Gwizdowski, I. S., Dennehy, E. B., Hill, S. J., Fischer, E. G., Snow, D. E., Gonzalez, R., Sureddi, S., Shivakumar, G., Cosgrove, V. E. 2013; 150 (1): 37-43

  Abstract

  OBJECTIVES: To compare the efficacy and safety of adjunctive quetiapine (QTP) versus placebo (PBO) for patients with bipolar II disorder (BDII) currently experiencing mixed hypomanic symptoms in a 2-site, randomized, placebo-controlled, double-blind, 8-week investigation. METHODS: Participants included 55 adults (age 18-65 years) who met criteria for BDII on the Structured Clinical Interview for DSM-IV-TR (SCID). Entrance criteria included a stable medication regimen for ≥2 weeks and hypomania with mixed symptoms (>12 on the Young Mania Rating Scale [YMRS] and >15 on the Montgomery Asberg Depression Rating Scale [MADRS] at two consecutive visits 1-3 days apart). Participants were randomly assigned to receive adjunctive quetiapine (n=30) or placebo (n=25). RESULTS: Adjunctive quetiapine demonstrated significantly greater improvement than placebo in Clinical Global Impression for Bipolar Disorder Overall Severity scores (F(1)=10.12, p=.002) and MADRS scores (F(1)=6.93, p=.0138), but no significant differences were observed for YMRS scores (F(1)=3.68, p=.069). Side effects of quetiapine were consistent with those observed in previous clinical trials, with sedation/somnolence being the most common, occurring in 53.3% with QTP and 20.0% with PBO. CONCLUSIONS: While QTP was significantly more effective than PBO for overall and depressive symptoms of BDII, there was no significant difference between groups in reducing symptoms of hypomania. Hypomania improved across both groups throughout the study.

  View details for DOI 10.1016/j.jad.2013.02.031

  View details for PubMedID 23521871

• Inflammation in Response to Stress as a Potential Risk Factor for Pediatric Bipolar Disorder Cosgrove, V., Staudenmaier, P., Pearlstein, J., Li, S., Sanders, E., Dhabhar, F., Chang, K. ELSEVIER SCIENCE INC. 2013: 43S

  View details for Web of Science ID 000318671800133

• Bipolar depression in pediatric populations : epidemiology and management. Paediatric drugs Cosgrove, V. E., Roybal, D., Chang, K. D. 2013; 15 (2): 83-91

  Abstract

  Depression in children and adolescents with bipolar disorder is more commonly observed than mania or hypomania, and is associated with significant functional disability in multiple environmental realms. Optimal management of pediatric bipolar depression is often defined by its multimodal nature with emphasis on both psychopharmacological and psychosocial treatment. This article provides a brief overview of the epidemiology and clinical course of pediatric bipolar depression, a clinically-oriented guide to the evidence-based psychopharmacological and psychosocial management of bipolar depression in youth, and suggestions on how best to integrate medication and therapy. Recommended treatment for bipolar depression in pediatric populations usually includes both medication and psychosocial interventions given a paucity of double-blind, placebo-controlled psychopharmacological studies. Lithium and lamotrigine are feasible and tentatively efficacious options; however, treatment with quetiapine monotherapy may be no better than placebo. Furthermore, some youth may be at heightened risk for developing manic symptoms after treatment with selective serotonin reuptake inhibitors (SSRIs). Psychotherapy, either alone or adjunctively with medications, provides practitioners with a safe and feasible alternative. Interpersonal and Social Rhythm Therapy for Adolescents (IPSRT-A), Child- and Family-Focused Cognitive Behavioral Therapy (CFF-CBT), Dialectical Behavior Therapy for Adolescents (DBT-A), family psychoeducation, and Family Focused Therapy for Adolescents (FFT-A) are evidence-based treatments available to clinicians treating youth with bipolar depression.

  View details for DOI 10.1007/s40272-013-0022-8

  View details for PubMedID 23529869

• Characteristics of responders and non-responders to risperidone monotherapy or placebo in co-occurring bipolar disorder and anxiety disorder EUROPEAN PSYCHIATRY Seo, J. S., Jamieson, K., Cosgrove, V., Gwizdowski, I. S., Yang, H., Sheehan, D. V., McElroy, S. L., Suppes, T. 2013; 28 (3): 190-196

  Abstract

  Clinical characteristics predicting response and remission to psychopharmacological treatment of bipolar disorder (BD) and co-occurring anxiety disorders have been understudied. We hypothesized that non-response to risperidone or placebo in individuals with co-occurring BD and anxiety symptoms would be associated with a more severe clinical course of BD, and certain demographic variables. This study was a secondary analysis of a randomized, double-blind, parallel, 8-week study comparing risperidone monotherapy and placebo in individuals with BD plus current panic disorder, current generalized anxiety disorder (GAD), or lifetime panic disorder (n=111) [31]. We compared clinical characteristics of responders (50% improvement on the Hamilton Anxiety Scale [HAM-A]) and non-responders as well as remitters (HAM-A<7) and non-remitters in risperidone treatment (n=54) and placebo (n=57) groups. For non-responders in the risperidone group, co-occurring lifetime panic disorder was significantly more common than for non-responders in the placebo group. Apart from this, no significant differences in course of illness or demographics were found either between or across groups for patients with BD and co-occurring anxiety symptoms receiving risperidone or placebo in this acute phase study.

  View details for DOI 10.1016/j.eurpsy.2011.08.001

  View details for PubMedID 22130178

• Early Intervention for Symptomatic Youth at Risk for Bipolar Disorder: A Randomized Trial of Family-Focused Therapy JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Miklowitz, D. J., Schneck, C. D., Singh, M. K., Taylor, D. O., George, E. L., Cosgrove, V. E., Howe, M. E., Dickinson, L. M., Garber, J., Chang, K. D. 2013; 52 (2): 121-131

  Abstract

  Depression and brief periods of (hypo)mania are linked to an increased risk of progression to bipolar I or II disorder (BD) in children of bipolar parents. This randomized trial examined the effects of a 4-month family-focused therapy (FFT) program on the 1-year course of mood symptoms in youth at high familial risk for BD, and explored its comparative benefits among youth in families with high versus low expressed emotion (EE).Participants were 40 youth (mean 12.3±2.8 years, range 9-17) with BD not otherwise specified, major depressive disorder, or cyclothymic disorder who had a first-degree relative with BD I or II and active mood symptoms (Young Mania Rating Scale [YMRS]>11 or Child Depression Rating Scale>29). Participants were randomly allocated to FFT-High Risk version (FFT-HR; 12 sessions of psychoeducation and training in communication and problem-solving skills) or an education control (EC; 1-2 family sessions).Youth in FFT-HR had more rapid recovery from their initial mood symptoms (hazard ratio = 2.69, p = .047), more weeks in remission, and a more favorable trajectory of YMRS scores over 1 year than youth in EC. The magnitude of treatment effect was greater among youth in high-EE (versus low-EE) families.FFT-HR may hasten and help sustain recovery from mood symptoms among youth at high risk for BD. Longer follow-up will be necessary to determine whether early family intervention has downstream effects that contribute to the delay or prevention of full manic episodes in vulnerable youth.

  View details for DOI 10.1016/j.jaac.2012.10.007

  View details for Web of Science ID 000314430000004

  View details for PubMedID 23357439

  View details for PubMedCentralID PMC3558946

• Informing DSM-5: biological boundaries between bipolar I disorder, schizoaffective disorder, and schizophrenia. BMC medicine Cosgrove, V. E., Suppes, T. 2013; 11: 127-?

  Abstract

  The fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) opted to retain existing diagnostic boundaries between bipolar I disorder, schizoaffective disorder, and schizophrenia. The debate preceding this decision focused on understanding the biologic basis of these major mental illnesses. Evidence from genetics, neuroscience, and pharmacotherapeutics informed the DSM-5 development process. The following discussion will emphasize some of the key factors at the forefront of the debate.Family studies suggest a clear genetic link between bipolar I disorder, schizoaffective disorder, and schizophrenia. However, large-scale genome-wide association studies have not been successful in identifying susceptibility genes that make substantial etiological contributions. Boundaries between psychotic disorders are not further clarified by looking at brain morphology. The fact that symptoms of bipolar I disorder, but not schizophrenia, are often responsive to medications such as lithium and other anticonvulsants must be interpreted within a larger framework of biological research.For DSM-5, existing nosological boundaries between bipolar I disorder and schizophrenia were retained and schizoaffective disorder preserved as an independent diagnosis since the biological data are not yet compelling enough to justify a move to a more neurodevelopmentally continuous model of psychosis.

  View details for DOI 10.1186/1741-7015-11-127

  View details for PubMedID 23672587

  View details for PubMedCentralID PMC3653750

• Association between 5HTT, DAT1, and DRD4 and bipolar disorder in youth PSYCHIATRIC GENETICS Cosgrove, V. E., Miklowitz, D. J., Rhee, S. H., Hawkey, C., Corley, R., Haberstick, B., Smolen, A. 2012; 22 (6): 304-304

  View details for DOI 10.1097/YPG.0b013e3283539517

  View details for Web of Science ID 000310756500008

  View details for PubMedID 22668826

  View details for PubMedCentralID PMC3437239

• Biological evidence for a neurodevelopmental model of pediatric bipolar disorder. The Israel journal of psychiatry and related sciences Roybal, D. J., Singh, M. K., Cosgrove, V. E., Howe, M., Kelley, R., Barnea-Goraly, N., Chang, K. D. 2012; 49 (1): 28-43

  Abstract

  Bipolar disorder (BD) is a chronic illness with high morbidity and mortality. Pediatric onset BD has a more severe course of illness with higher rates of relapse and psychosocial impairment. Discovering interventions early in the course of BD in youth is paramount to preventing full illness expression and improve functioning in these individuals throughout the lifespan. It is therefore important to understand the mechanisms involved in the development of BD in order to determine which youth are at most risk and provide biological targets for early intervention. To serve this cause, we propose a neurodevelopmental model of BD, based on the existing data that implicate prefrontal-subcortical network dysfunction, caused by pre-existing genetic susceptibility and triggered by pathological reactions to stress and chronic inflammatory processes.

  View details for PubMedID 22652927

• Biological Evidence for a Neurodevelopmental Model of Pediatric Bipolar Disorder ISRAEL JOURNAL OF PSYCHIATRY AND RELATED SCIENCES Roybal, D. J., Singh, M. K., Cosgrove, V. E., Howe, M., Kelley, R., Barnea-Goraly, N., Chang, K. D. 2012; 49 (1): 28-43

  Abstract

  Bipolar disorder (BD) is a chronic illness with high morbidity and mortality. Pediatric onset BD has a more severe course of illness with higher rates of relapse and psychosocial impairment. Discovering interventions early in the course of BD in youth is paramount to preventing full illness expression and improve functioning in these individuals throughout the lifespan. It is therefore important to understand the mechanisms involved in the development of BD in order to determine which youth are at most risk and provide biological targets for early intervention. To serve this cause, we propose a neurodevelopmental model of BD, based on the existing data that implicate prefrontal-subcortical network dysfunction, caused by pre-existing genetic susceptibility and triggered by pathological reactions to stress and chronic inflammatory processes.

  View details for Web of Science ID 000308697600004

• Family Support and Depressive Symptoms: A 23-Year Follow-Up JOURNAL OF CLINICAL PSYCHOLOGY Kamen, C., Cosgrove, V., McKellar, J., Cronkite, R., Moos, R. 2011; 67 (3): 215-223

  Abstract

  We examined change in family support and depressive symptoms over the course of 23 years and included the potential moderators of gender and participation in treatment. A sample of 373 depressed individuals provided data in five waves, with baseline, 1-year, 4-year, 10-year, and 23-year follow-ups. Multilevel modeling was used to evaluate longitudinal relationships between variables. Higher family support was associated with less depression at baseline and predicted a steeper trajectory of recovery from depression over 23 years. This relationship was moderated by gender, such that women with supportive families reported the most rapid recovery from depression. Evaluating family context may be clinically relevant when beginning treatment with a depressed patient, particularly for female patients.

  View details for DOI 10.1002/jclp.20765

  View details for Web of Science ID 000286693800001

  View details for PubMedID 21254050

• Structure and Etiology of Co-occurring Internalizing and Externalizing Disorders in Adolescents JOURNAL OF ABNORMAL CHILD PSYCHOLOGY Cosgrove, V. E., Rhee, S. H., Gelhorn, H. L., Boeldt, D., Corley, R. C., Ehringer, M. A., Young, S. E., Hewitt, J. K. 2011; 39 (1): 109-123

  Abstract

  Several studies suggest that a two-factor model positing internalizing and externalizing factors explains the interrelationships among psychiatric disorders. However, it is unclear whether the covariation between internalizing and externalizing disorders is due to common genetic or environmental influences. We examined whether a model positing two latent factors, internalizing and externalizing, explained the interrelationships among six psychiatric disorders (major depressive disorder, generalized anxiety disorder, separation anxiety disorder, attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder) in adolescents, and whether there are common genetic and environmental influences on internalizing and externalizing latent factors. Multivariate behavior genetic analyses of data from 1162 twin pairs and 426 siblings ascertained from the general population via the Colorado Center for Antisocial Drug Dependence (CADD) were conducted. We found support for a model positing two latent factors (internalizing and externalizing). These factors were moderately heritable and influenced by significant common genetic and nonshared environmental influences. These findings suggest that co-occurrence of internalizing and externalizing psychopathology in adolescents results from both genetic and environmental influences.

  View details for DOI 10.1007/s10802-010-9444-8

  View details for Web of Science ID 000287149500010

  View details for PubMedID 20683651

• Suicidal ideation and depressive symptoms among bipolar patients as predictors of the health and well-being of caregivers BIPOLAR DISORDERS Chessick, C. A., Perlick, D. A., Miklowitz, D. J., Dickinson, L. M., Allen, M. H., Morris, C. D., Gonzalez, J. M., Marangell, L. B., Cosgrove, V., Ostacher, M. 2009; 11 (8): 876-884

  Abstract

  Few studies have addressed the physical and mental health effects of caring for a family member with bipolar disorder. This study examined whether caregivers' health is associated with changes in suicidal ideation and depressive symptoms among bipolar patients observed over one year.Patients (N = 500) participating in the Systematic Treatment Enhancement Program for Bipolar Disorder and their primary caregivers (N = 500, including 188 parental and 182 spousal caregivers) were evaluated for up to one year as part of a naturalistic observational study. Caregivers' perceptions of their own physical health were evaluated using the general health scale from the Medical Outcomes Study 36-item Short-Form Health Survey. Caregivers' depression was evaluated using the Center for Epidemiological Studies of Depression Scale.Caregivers of patients who had increasing suicidal ideation over time reported worsening health over time compared to caregivers of patients whose suicidal ideation decreased or stayed the same. Caregivers of patients who had more suicidal ideation and depressive symptoms reported more depressed mood over a one-year reporting period than caregivers of patients with less suicidal ideation or depression. The pattern of findings was consistent across parent caregivers and spousal caregivers.Caregivers, rightly concerned about patients becoming suicidal or depressed, may try to care for the patient at the expense of their own health and well-being. Treatments that focus on the health of caregivers must be developed and tested.

  View details for Web of Science ID 000271899700008

  View details for PubMedID 19922556

  View details for PubMedCentralID PMC2796426

• Early childhood temperament and the covariation between internalizing and externalizing behavior in school-aged children TWIN RESEARCH AND HUMAN GENETICS Rhee, S. H., Cosgrove, V. E., Schmitz, S., Haberstick, B. C., Corley, R. C., Hewitt, J. K. 2007; 10 (1): 33-44

  Abstract

  There is significant covariation between internalizing and externalizing behavior, although there is also evidence that internalizing behavior is a protective factor against externalizing behavior. Several researchers have posited that the examination of the relationship between temperament or personality and behavior problems may help explain these seemingly contradictory results. Specifically, negative emotionality or neuroticism has been cited as a temperament characteristic that internalizing and externalizing behavior share in common, whereas behavioral inhibition may be related only to internalizing behavior. We examined the degree to which the covariation between internalizing and externalizing behavior assessed from age 4 to 12 years can be explained by temperament characteristics assessed from age 14 to 36 months. Additionally, we assessed the extent to which this relationship is due to genetic or environmental factors, analyzing data from 225 monozygotic and 185 dizygotic twin pairs assessed by the Colorado Longitudinal Twin Study. In males, a portion of the covariation between internalizing and externalizing behavior was explained by shared environmental influences in common with emotionality and shared environmental influences in common with shyness. In females, most of the covariation between internalizing and externalizing behavior was explained by shared environmental influences in common with emotionality. A possible limitation of this study is that the covariation between temperament and behavior problems may be due to shared measurement variance, as parent ratings were used to assess both temperament and behavior problems.

  View details for Web of Science ID 000244823800005

  View details for PubMedID 17539363

• Bipolar disorder: current treatments and new strategies. Cleveland Clinic journal of medicine Sachs, G. S., Cosgrove, V. E. 1998; 65: SI31-7

  View details for PubMedID 12033204