John Leikauf

All Publications

• Pediatric Long COVID Subphenotypes: An EHR-based study from the RECOVER program. medRxiv : the preprint server for health sciences Lorman, V., Bailey, L. C., Song, X., Rao, S., Hornig, M., Utidjian, L., Razzaghi, H., Mejias, A., Leikauf, J. E., Brill, S. B., Allen, A., Bunnell, H. T., Reedy, C., Mosa, A. S., Horne, B. D., Geary, C. R., Chuang, C. H., Williams, D. A., Christakis, D. A., Chrischilles, E. A., Mendonca, E. A., Cowell, L. G., McCorkell, L., Liu, M., Cummins, M. R., Jhaveri, R., Blecker, S., Forrest, C. B. 2024

  Abstract

  Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients' clinical histories to then identify groups of patients with similar presentations. The results indicate that cardiorespiratory presentations are most common (present in 54% of patients) followed by subphenotypes marked (in decreasing order of frequency) by musculoskeletal pain, neuropsychiatric conditions, gastrointestinal symptoms, headache, and fatigue.

  View details for DOI 10.1101/2024.09.17.24313742

  View details for PubMedID 39371163

  View details for PubMedCentralID PMC11451761

• Psychiatric Symptoms, Cognition, and Symptom Severity in Children. JAMA psychiatry Pines, A., Tozzi, L., Bertrand, C., Keller, A. S., Zhang, X., Whitfield-Gabrieli, S., Hastie, T., Larsen, B., Leikauf, J., Williams, L. M. 2024

  Abstract

  Mental illnesses are a leading cause of disability globally, and functional disability is often in part caused by cognitive impairments across psychiatric disorders. However, studies have consistently reported seemingly opposite findings regarding the association between cognition and psychiatric symptoms.To determine if the association between general cognition and mental health symptoms diverges at different symptom severities in children.A total of 5175 children with complete data at 2 time points assessed 2 years apart (aged 9 to 11 years at the first assessment) from the ongoing Adolescent Brain and Cognitive Development (ABCD) study were evaluated for a general cognition factor and mental health symptoms from September 2016 to August 2020 at 21 sites across the US. Polynomial and generalized additive models afforded derivation of continuous associations between cognition and psychiatric symptoms across different ranges of symptom severity. Data were analyzed from December 2022 to April 2024.Aggregate cognitive test scores (general cognition) were primarily evaluated in relation to total and subscale-specific symptoms reported from the Child Behavioral Checklist.The sample included 5175 children (2713 male [52.4%] and 2462 female [47.6%]; mean [SD] age, 10.9 [1.18] years). Previously reported mixed findings regarding the association between general cognition and symptoms may consist of several underlying, opposed associations that depend on the class and severity of symptoms. Linear models recovered differing associations between general cognition and mental health symptoms, depending on the range of symptom severities queried. Nonlinear models confirm that internalizing symptoms were significantly positively associated with cognition at low symptom burdens higher cognition = more symptoms) and significantly negatively associated with cognition at high symptom burdens.The association between mental health symptoms and general cognition in this study was nonlinear. Internalizing symptoms were both positively and negatively associated with general cognition at a significant level, depending on the range of symptom severities queried in the analysis sample. These results appear to reconcile mixed findings in prior studies, which implicitly assume that symptom severity tracks linearly with cognitive ability across the entire spectrum of mental health. As the association between cognition and symptoms may be opposite in low vs high symptom severity samples, these results reveal the necessity of clinical enrichment in studies of cognitive impairment.

  View details for DOI 10.1001/jamapsychiatry.2024.2399

  View details for PubMedID 39196567

• Precision Psychiatry Implementation in Child and Adolescent Psychiatric Clinical Practice: Opportunities and Challenges PSYCHIATRIC ANNALS Leikauf, J. E. 2024; 54 (4): e108-e112

  View details for DOI 10.3928/00485713-20240314-01

  View details for Web of Science ID 001209479600007

• Classroom Function is Critical to the Relationship Between the G Factor and P Factor Pines, A., Leikauf, J., Keller, A., Larsen, B., Williams, L. ELSEVIER SCIENCE INC. 2023: S274

  View details for Web of Science ID 000993018500663

• Neurodevelopmental Effects of Cannabis Use in Adolescents and Emerging Adults with ADHD: A Systematic Review. Harvard review of psychiatry Cawkwell, P. B., Hong, D. S., Leikauf, J. E. 2021

  Abstract

  OBJECTIVE: Systematically review the scientific literature to characterize the effects of cannabis use on brain structure, function, and neurodevelopmental outcomes in adolescents and young adults with ADHD.METHOD: Systematic review following PRISMA guidelines utilizing PubMed, Embase, PsycINFO, and Cochrane CENTRAL trials register from inception until 1 January 2020. Articles that examined the impact of cannabis use on youth with ADHD were included.RESULTS: Eleven studies were identified that compared outcomes for individuals with ADHD who used cannabis or synthetic cannabinoids against those with ADHD who did not. Seven of these studies used neuroimaging techniques, including fMRI, structural MRI, and SPECT. Differential regions of activation were identified, including the right hippocampus and cerebellar vermis, and bilateral temporal lobes. Morphological differences were identified in the right precentral and postcentral gyri, left nucleus accumbens, right superior frontal and postcentral gyri. No study identified any additive or ADHD * cannabis use interaction on neuropsychological tasks of executive function. Two studies found adverse differential impacts of early-onset cannabis use in this population.CONCLUSION: A dearth of evidence is available on the impact of cannabis use on the developing brain and functioning for individuals with ADHD, despite the elevated risk for substance use in this population. The limited, potentially underpowered evidence does not support the hypothesis that cannabis use has a deleterious impact on neuropsychological tasks in transitional age youth with ADHD. Larger and longer-term studies are needed, however, to better inform clinicians and patients as to the impacts of cannabis use in youth with ADHD.

  View details for DOI 10.1097/HRP.0000000000000303

  View details for PubMedID 34138796

• StopWatch: Pilot study for an Apple Watch application for youth with ADHD. Digital health Leikauf, J. E., Correa, C., Bueno, A. N., Sempere, V. P., Williams, L. M. 2021; 7: 20552076211001215

  Abstract

  Introduction: To address the need for non-pharmacologic, scalable approaches for managing attention-deficit and hyperactivity disorder (ADHD) in young people, we report the results of a study of an application developed for a wearable device (Apple Watch) that was designed to track movement and provide visual and haptic feedback for ADHD.Methods: Six-week, open label pilot study with structured rating scales ADHD and semi-structured qualitative interview. Apple Watch software application given to users that uses actigraphy and graphic interface as well as haptic feedback to provide feedback to users about level of movement during periods of intentional focus. Linear mixed models to estimate trajectories.Results: Thirty-two participants entered the study. This application was associated with improvement in ADHD symptoms over the 6weeks of the study. We observed an ADHD-Rating Scale change of beta=-1.2 units/week (95% CI=-0.56 to -1.88, F=13.4, P=.0004).Conclusions: These positive clinical outcomes highlight the promise of such wearable applications for ADHD and the need to pursue their further development.

  View details for DOI 10.1177/20552076211001215

  View details for PubMedID 33868703

• Medical Students' Experiences of Unplanned Leaves of Absence MEDICAL SCIENCE EDUCATOR Fallar, R., Leikauf, J., Dokun, O., Anand, S., Gliatto, P., Mellman, L., Autenrieth, S., Katz, C. 2019; 29 (4): 1003–11

  View details for DOI 10.1007/s40670-019-00792-4

  View details for Web of Science ID 000624419300018

• APPLE WATCH PILOT FOR YOUTH WITH ADHD Leikauf, J. E., Bueno, A. N., Correa, C., Sempere, V., Williams, L. M. ELSEVIER SCIENCE INC. 2019: S289–S290

  View details for DOI 10.1016/j.jaac.2019.08.450

  View details for Web of Science ID 000518857302270

• A Signature of Attention-Elicited Electrocortical Activity Distinguishes Response From Non-Response to the Non-Stimulant Atomoxetine in Children and Adolescents With ADHD JOURNAL OF ATTENTION DISORDERS Griffiths, K. R., Jurigova, B. G., Leikauf, J. E., Palmer, D., Clarke, S. D., Tsang, T. W., Teber, E. T., Kohn, M. R., Williams, L. M. 2019; 23 (7): 744–53

  View details for DOI 10.1177/1087054717733044

  View details for Web of Science ID 000465015800010

• Paying attention to attention in depression. Translational psychiatry Keller, A. S., Leikauf, J. E., Holt-Gosselin, B. n., Staveland, B. R., Williams, L. M. 2019; 9 (1): 279

  Abstract

  Attention is the gate through which sensory information enters our conscious experiences. Oftentimes, patients with major depressive disorder (MDD) complain of concentration difficulties that negatively impact their day-to-day function, and these attention problems are not alleviated by current first-line treatments. In spite of attention's influence on many aspects of cognitive and emotional functioning, and the inclusion of concentration difficulties in the diagnostic criteria for MDD, the focus of depression as a disease is typically on mood features, with attentional features considered less of an imperative for investigation. Here, we summarize the breadth and depth of findings from the cognitive neurosciences regarding the neural mechanisms supporting goal-directed attention in order to better understand how these might go awry in depression. First, we characterize behavioral impairments in selective, sustained, and divided attention in depressed individuals. We then discuss interactions between goal-directed attention and other aspects of cognition (cognitive control, perception, and decision-making) and emotional functioning (negative biases, internally-focused attention, and interactions of mood and attention). We then review evidence for neurobiological mechanisms supporting attention, including the organization of large-scale neural networks and electrophysiological synchrony. Finally, we discuss the failure of current first-line treatments to alleviate attention impairments in MDD and review evidence for more targeted pharmacological, brain stimulation, and behavioral interventions. By synthesizing findings across disciplines and delineating avenues for future research, we aim to provide a clearer outline of how attention impairments may arise in the context of MDD and how, mechanistically, they may negatively impact daily functioning across various domains.

  View details for DOI 10.1038/s41398-019-0616-1

  View details for PubMedID 31699968

• Response inhibition and emotional cognition improved by atomoxetine in children and adolescents with ADHD: The ACTION randomized controlled trial JOURNAL OF PSYCHIATRIC RESEARCH Griffiths, K. R., Leikauf, J. E., Tsang, T. W., Clarke, S., Hermens, D. F., Efron, D., Williams, L. M., Kohn, M. R. 2018; 102: 57–64

  View details for DOI 10.1016/j.jpsychires.2018.03.009

  View details for Web of Science ID 000438660500010

• INDIVIDUAL COGNITIVE SUBTYPE STATUS CAN BE PREDICTED IN YOUTH WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD) Leikauf, J., Sacchet, M. D., Griffiths, K., Kohn, M. R., Williams, L. M. ELSEVIER SCIENCE INC. 2017: S285

  View details for DOI 10.1016/j.jaac.2017.09.371

  View details for Web of Science ID 000544086202103

• A TALE OF TWO DEPARTMENTS: HOW IMPLICIT BIAS DIVIDES US AND CAN UNITE US Kishore, A., Silverman, M. A., Alleyne, S. D., Benoit, M. B., Leikauf, J., Martin, A., Mayes, L. C., Miller, S., Post, M., Stubbe, D. E., Zalpuri, I. ELSEVIER SCIENCE INC. 2017: S82

  View details for DOI 10.1016/j.jaac.2017.07.321

  View details for Web of Science ID 000544086200280

• Identification of biotypes in Attention-Deficit/Hyperactivity Disorder, a report from a randomized, controlled trial. Personalized medicine in psychiatry Leikauf, J. E., Griffiths, K. R., Saggar, M., Hong, D. S., Clarke, S., Efron, D., Tsang, T. W., Hermens, D. F., Kohn, M. R., Williams, L. M. 2017; 3: 8-17

  Abstract

  Attention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous disorder. Current subtypes lack longitudinal stability or prognostic utility. We aimed to identify data-driven biotypes using multiple cognitive measures, then to validate these biotypes using EEG, ECG, and clinical response to atomoxetine as external validators. Study design was a double-blind, randomized, placebo-controlled crossover trial of atomoxetine including 116 subjects ages 6 through 17 with diagnosis of ADHD and 56 typically developing controls. Initial features for unsupervised machine learning included a cognitive battery with 20 measures affected in ADHD. External validators included baseline mechanistic validators (using electroencephalogram/EEG and electrocardiogram/ECG) and clinical response (ADHD Rating Scale and correlation with cognitive change). One biotype, labeled impulsive cognition, was characterized by increased errors of commission and shorter reaction time, had greater EEG slow wave (theta/delta) power and greater resting heart rate. The second biotype, labeled inattentive cognition, was characterized by longer/more variable reaction time and errors of omission, had lower EEG fast wave (beta) power, resting heart rate that did not differ from controls, and a strong correlation (r = -0.447, p < 0.001) between clinical response to atomoxetine and improvement in verbal memory immediate recall. ADHD comprises at least two biotypes that cut across current subtype criteria and that may reflect distinct arousal mechanisms. The findings provide evidence that further investigation of cognitive subtypes may be at least as fruitful as symptom checklist-based subtypes for development of biologically-based diagnostics and interventions for ADHD.

  View details for DOI 10.1016/j.pmip.2017.02.001

  View details for PubMedID 35637915

  View details for PubMedCentralID PMC9148272

• Sluggish Cognitive Tempo, Internalizing Symptoms, and Executive Function in Adults With ADHD JOURNAL OF ATTENTION DISORDERS Leikauf, J. E., Solanto, M. V. 2017; 21 (8): 701-711

  Abstract

  We sought to characterize relationships between sluggish cognitive tempo (SCT) and both internalizing symptoms and executive functioning in adults with ADHD.A total of 102 adults with ADHD completed clinical interviews and clinical rating scales. Hierarchical regression analyses were conducted to ascertain the independent predictive power of SCT symptoms for deficits in executive function (EF) after considering severity of ADHD inattentive and hyperactive-impulsive symptoms and internalizing symptoms.SCT correlated with ADHD inattentive symptoms and dimensional measures of depression and anxiety but not with clinical diagnosis of depression or anxiety. SCT predicted EF deficits over and above the effects of internalizing and ADHD symptoms. This relationship between SCT and EF was limited to the subset of participants ( n = 48) receiving stimulant treatment.SCT in adults with ADHD is associated with internalizing symptoms, ADHD inattentive symptoms, and, independently, with EF deficits. Further research is needed to ascertain why this relationship occurred primarily in adults concurrently receiving stimulants.

  View details for DOI 10.1177/1087054716682337

  View details for Web of Science ID 000400911100010

• The Need for Infant Mental Health Training for All Child and Adolescent Psychiatrists. Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry Benham, A. L., Leikauf, J. E., Romanowicz, M. n. 2017

  View details for PubMedID 28842856

• Identification of biotypes in Attention-Deficit/Hyperactivity Disorder, a report from a randomized, controlled trial Personalized Medicine in Psychiatry Leikauf, J. E., Griffiths, K. R., Saggar, M., Hong, D. S., Clarke, S., Efron, D., Tsang, T. W., Hermens, D. F., Michael, K. R., M Leanne 2017; 3: 8-17
• Patient-Clinician Agreement on Treatment Type and Helpfulness: Results From a WTC Rescue and Recovery Worker Cohort PSYCHIATRIC SERVICES Leikauf, J., Schechter, C. B., Marrone, K., Ozbay, F., Rapoport, A., Sharma, V., Katz, C. L. 2013; 64 (11): 1173-1176

  Abstract

  This study assessed patient and clinician agreement about treatment type and its association with treatment helpfulness among World Trade Center rescue and recovery workers.A total of 187 outpatients and 280 clinicians completed a survey, which gathered information on patient characteristics, treatment types, and treatment helpfulness. Kappa statistics and sensitivity and specificity analyses were used, and the association between patient-clinician agreement and reported treatment benefit was determined.Patient-clinician agreement was highest for group therapy, medication management, eye movement desensitization and reprocessing, and couples therapy. Agreement about medication management, individual psychotherapy, and workers' compensation evaluation was associated with higher reported treatment benefits.Findings support the hypothesis that agreement regarding treatment type is associated with higher reported benefit and extend findings of previous studies to a linguistically diverse, naturalistic sample exposed to a disaster trauma. Results also highlight the need for better understanding of eclectic therapies offered in real-world clinical practice.

  View details for DOI 10.1176/appi.ps.201200402

  View details for Web of Science ID 000327303800017

  View details for PubMedID 24185541

• A Young Man with History of ADHD and Methamphetamine Use PSYCHIATRIC ANNALS Leikauf, J., Ivanov, I. 2013; 43 (1): 26-29

  View details for DOI 10.3928/00485713-20130109-06

  View details for Web of Science ID 000315630000006

• Comparisons of Self-Reported and Chart-Identified Chronic Diseases in Inner-City Seniors JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Leikauf, J., Federman, A. D. 2009; 57 (7): 1219-1225

  Abstract

  To examine agreement between self-report of chronic disease and medical record data for inner-city seniors, their sensitivity and specificity, and the association between patient characteristics and accuracy of self-reports.Cross-sectional analysis.Two hospital-based primary care practices serving a low-income inner-city population.Adults aged 65 and older (n=323).Data on self-reported asthma, depression, diabetes mellitus, and hypertension were collected through interviewer-administered surveys (in English and Spanish) and chart abstraction. Chart-based disease was defined in two ways: physician documentation and physician documentation plus use of a medication to treat that condition. Sensitivity, specificity, and agreement were calculated. Univariate and multivariable regression analyses were used to determine the associations between patient characteristics and patient-chart agreement.Agreement between self-report and chart data was high for diabetes mellitus (kappa=0.94) intermediate for asthma (kappa=0.66), and hypertension (kappa=0.54) and low for depression (kappa=0.4). Sensitivity and specificity were high for diabetes mellitus (0.99 and 0.96, respectively) and low for depression (0.74 and 0.72, respectively). Specificity for hypertension was lowest (0.67). Age, education, health literacy, and other patient characteristics did not have clear associations across conditions.Self-reports may be most reliable for diabetes mellitus and least reliable for depression for surveys involving older, inner-city adults. Survey research with older adults should include confirmatory data when assessing presence of depression, hypertension, and asthma.

  View details for DOI 10.1111/j.1532-5415.2009.02313.x

  View details for Web of Science ID 000267539800011

  View details for PubMedID 19486197

  View details for PubMedCentralID PMC2768322