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  • Identifying Adolescents at Risk for Depression: A Prediction Score Performance in Cohorts Based in Three Different Continents
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2020-01-15
    Thiago Botter-Maio Rocha; Helen L. Fisher; Arthur Caye; Luciana Anselmi; Louise Arseneault; Fernando C. Barros; Avshalom Caspi; Andrea Danese; Helen Gonçalves; HonaLee Harrington; Renate Houts; Ana M.B. Menezes; Terrie E. Moffitt; Valeria Mondelli; Richie Poulton; Luis Augusto Rohde; Fernando Wehrmeister; Christian Kieling

    Objective Prediction models have become frequent in the medical literature, but most published studies are conducted in a single setting. Heterogeneity between development and validation samples has been posited as a major obstacle for the generalization of models. We aimed to develop a multivariable prognostic model using sociodemographic variables easily obtainable from adolescents at age 15 to predict a depressive disorder diagnosis at age 18, and to evaluate its generalizability in two samples from diverse socioeconomic and cultural settings. Method Data from the 1993 Pelotas Birth Cohort were used to develop the prediction model, and its generalizability was evaluated in two representative cohort studies: the Environmental Risk (E-Risk) Longitudinal Twin Study and the Dunedin Multidisciplinary Health and Development Study. Results At age 15, 2,192 adolescents with no evidence of current or previous depression were included (44.6% male). The apparent C-statistic of the models derived in Pelotas ranged from 0.76 to 0.79, and the model obtained from a penalized logistic regression was selected for subsequent external evaluation. Major discrepancies between the samples were identified, impacting the external prognostic performance of the model (Dunedin and E-Risk C-statistics of 0.63 and 0.59, respectively). The implementation of recommended strategies to account for this heterogeneity among samples improved the model’s calibration in both samples. Conclusion An adolescent depression risk score comprising easily obtainable predictors was developed with good prognostic performance in a Brazilian sample. Heterogeneity among settings was not trivial, but strategies to deal with sample diversity were identified as pivotal for providing better risk stratification across samples. Future efforts should focus on developing better methodological approaches for incorporating heterogeneity in prognostic research.

  • Systematic Review and Meta-Analysis: Mental Health in Children With Neurogenetic Disorders Associated With Intellectual Disability
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2020-01-13
    Emma J. Glasson; Nicholas Buckley; Wai Chen; Helen Leonard; Amy Epstein; Rachel Skoss; Peter Jacoby; A. Marie Blackmore; Jenny Bourke; Jenny Downs

    Objective The behavioral phenotype of neurogenetic disorders associated with intellectual disability often includes psychiatric comorbidity. The objectives of this systematic review and meta-analysis were to systematically review the prevalence of psychiatric disorders and symptoms in children and adolescents with these disorders and compare phenotypic signatures between syndromes. Method MEDLINE and PsycINFO databases were searched for articles from inception to December 2018. Eligible articles were peer reviewed, published in English and reported prevalence data for psychiatric disorders and symptoms in children aged four to 21 years, using a formal psychiatric assessment or a standardized assessment of mental health symptomology. Pooled prevalence was determined using a random effects meta-analysis in studies with sufficient data. Prevalence estimates were compared with general population data using a test of binomial proportions. Results Of 2301 studies identified for review, 39 papers were included in the final pool which provided data on 4039 individuals. Ten syndromes were represented and five were predominant: Down syndrome, 22q11.2 deletion syndrome, Fragile X syndrome, Williams syndrome and Prader-Willi syndrome. The Child Behavior Checklist was the most commonly used assessment tool for psychiatric symptoms. The pooled prevalence with total scores above the clinical threshold was lowest for Down syndrome (32%; 95% CI, 19%-44%) and highest for Prader-Willi syndrome (74%; 95% CI, 65%-82%) with each syndrome associated with significantly higher prevalence than in the general population. Parallel trends were observed for the internalizing and externalizing domains and social subscale scores. Conclusion Differential vulnerability for ‘psychiatric phenotype’ expression across the disorders was observed. Syndromes with higher levels of social ability or competence appear to offer relative protection against developing psychopathology, and this preliminary finding merits further exploration.

  • Effectiveness of Brief and Standard School-Based Cognitive-Behavioral Interventions for Adolescents With Anxiety: A Randomized Non-Inferiority Study
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2020-01-08
    Bente Storm Mowatt Haugland; Åshild Tellefsen Haaland; Valborg Baste; Jon Fauskanger Bjaastad; Asle Hoffart; Ronald M. Rapee; Solfrid Raknes; Joseph A. Himle; Elisabeth Husabø; Gro Janne Wergeland

    Objective We examined the effectiveness of targeted school-based cognitive-behavioral therapy (CBT) for adolescents (12-16 years) with anxiety, and tested whether brief-CBT was non-inferior to standard duration CBT. Method A randomized controlled study of 313 adolescents (mean 14.0 years, SD= 0.84, 84% girls) were recruited through school-health services to 10-weeks CBT group-interventions. Groups of 5-8 adolescents were randomly allocated to brief (5 sessions comprising 5.5 hours) or standard-CBT (10 sessions comprising 15 hours), or 10-weeks waitlist (WL). Self-reported and parent-reported youth anxiety symptoms, impairment from anxiety, depressive symptoms and clinical severity were assessed pre- and post-intervention, after WL, and at 1-year follow-up. Results Targeted school based CBT significantly reduced adolescents’ anxiety symptoms with small to moderate effect sizes compared to WL (Cohen’s d= 0.34 for youth report and d=0.53 for parent report). According to the parents, also adolescents’ impairment from anxiety was significantly reduced compared to WL (d=0.51). Pre- to post changes in anxiety symptoms were small to moderate (within-group effect sizes between d=0.41 and 0.67). Although no significant differences in effects were found between brief and standard CBT, brief-CBT was not non-inferior to standard-CBT. Outcomes from both interventions were sustained at 1-year follow-up. Conclusion Targeted school-based CBT-interventions reduce anxiety, impairment and depressive symptoms in adolescents. Both brief- and standard-CBT demonstrate efficacy, but brief-CBT was not non-inferior to standard CBT. By administering school-based CBT to youth with anxiety symptoms we may reach young people with effective interventions at an earlier phase in their life.

  • Systematic Review and Meta-Analysis: Outcomes of Routine Specialist Mental Health Care for Young People With Depression and/or Anxiety
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-12-24
    Holly Alice Bear; Julian Edbrooke-Childs; Sam Norton; Karolin Rose Krause; Miranda Wolpert

    Objective Depression and anxiety are the most prevalent mental health problems in youth, yet almost nothing is known about what outcomes are to be expected at the individual level following routine treatment. This paper sets out to address this gap by undertaking a systematic review of outcomes following treatment as usual (TAU) with a particular focus on individual-level outcomes. Method MEDLINE, Embase and PsycInfo were searched for articles published between 1980 and January 2019 that assessed TAU outcomes for youth depression and anxiety accessing specialist mental healthcare. Meta-analysis considered change at both group-level pre-post effect size (ES) and individual-level recovery, reliable change and reliable recovery. Temporal analysis considered stability of primary and secondary outcomes over time. Sub-group analysis considered the moderating effect of informant; presenting problem; study design; study year; mean age of youth; use of medication; intervention dosage and type of treatment offered on outcomes. A protocol was pre-registered on PROSPERO (CRD42017063914). Results Initial screening of 6,350 publications resulted in 38 which met the inclusion criteria, and which were subsequently included in meta-analyses. This resulted in a final full pooled sample of 11,739 young people (61% of which were female, mean age 13.8 years). The pre-post ES (Hedges’ g) at first/final outcome (13/ 26 weeks) was -0.74/- 0.87. The individual-level change on measures of self-report was 38% reliable improvement, 44% no reliable change and 6% reliable deterioration. Outcomes varied according to moderators, informant, problem type and dosage. Conclusion Poor data quantity and quality are limitations, but this is the first study that indicates likely rates of reliable improvement for those accessing TAU. We propose the need for improved reporting of both individual-level metrics and details of TAU to enable greater understanding of likely current outcomes from routine care for youth with depression and anxiety in order to allow the potential for further improvement of impact.

  • Meta-Analysis: 13-Year Follow-up of Psychotherapy Effects on Youth Depression
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-04-17
    Dikla Eckshtain; Sofie Kuppens; Ana Ugueto; Mei Yi Ng; Rachel Vaughn-Coaxum; Katherine Corteselli; John R. Weisz

    Objective Youth depression is a debilitating condition that constitutes a major public health concern. A 2006 meta-analysis found modest benefits for psychotherapy versus control. Has 13 more years of research improved that picture? We sought to find out. Method We searched PubMed, PsychINFO, and Dissertation Abstracts International for 1960 to 2017, identifying 655 randomized, English-language psychotherapy trials for individuals aged 4 to 18 years. Of these, 55 assessed psychotherapy versus control for youth depression with outcome measures administered to both treatment and control conditions at post (κ = 53) and/or follow-up (κ = 32). Twelve study and outcome characteristics were extracted, and effect sizes were calculated for all psychotherapy versus control comparisons. Using a three-level random-effects model, we obtained an overall estimate of the psychotherapy versus control difference while accounting for the dependency among effect sizes. We then fitted a three-level mixed-effects model to identify moderators that might explain variation in effect size within and between studies. Results The overall effect size (g) was 0.36 at posttreatment and 0.21 at follow-up (averaging 42 weeks after posttreatment). Three moderator effects were identified: effects were significantly larger for interpersonal therapy than for cognitive behavioral therapy, for youth self-reported outcomes than parent-reports, and for comparisons with inactive control conditions (eg, waitlist) than active controls (eg, usual care). Effects showed specificity, with significantly smaller effects for anxiety and externalizing behavior outcomes than for depression measures. Conclusion Youth depression psychotherapy effects are modest, with no significant change over the past 13 years. The findings highlight the need for treatment development and research to improve both immediate and longer-term benefits.

  • Systematic Review: United States Workforce for Autism-Related Child Healthcare Services
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-05-29
    Ryan K. McBain; Vishnupriya Kareddy; Jonathan H. Cantor; Bradley D. Stein; Hao Yu

    Objective A diversity of health professional disciplines provide services for children with autism spectrum disorder (ASD) in the United States. We conducted a systematic review examining the availability, distribution, and competencies of the US workforce for autism-related child health care services, and assess studies’ strength of evidence. Method We searched PubMed, PsychINFO, Embase, and Google Scholar from 2008 to 2018 for relevant US-based studies. Two investigators independently screened and evaluated studies against a set of prespecified inclusion criteria and evaluated strength of evidence (SOE) using a framework designed to integrate a mixed-methods research. Results Of 754 records identified, 33 studies (24 quantitative, 6 qualitative, and 3 mixed-methods) were included. Strength of evidence associated was low-to-moderate, with only 8 studies (24%) satisfying criteria for strong SOE. Geographies and provider cadres varied considerably. The most common specialties studied were pediatricians (n = 13), occupational therapists (n = 12), speech therapists (n = 11), physical therapists (n = 10), and child psychiatrists (n = 8). Topical areas included the following: provider availability by service area and care delivery model; qualitative assessments of provider availability and competency; role of insurance mandates in increasing access to providers: and disparities in access. Across provider categories, we found that workforce availability for autism-related services was limited in terms of overall numbers, time available, and knowledgeability. The greatest unmet need was observed among minorities and in rural settings. Most studies were short term, were limited in scope, and used convenience samples. Conclusion There is limited evidence to characterize the availability and distribution of the US workforce for autism-related child health care services. Existing evidence to date indicates significantly restricted availability.

  • Telomere Length and Psychopathology: Specificity and Direction of Effects Within the Bucharest Early Intervention Project
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-03-04
    Mark Wade; Nathan A. Fox; Charles H. Zeanah; Charles A. Nelson; Stacy S. Drury

    Objective Telomere length (TL) has been linked to several psychiatric conditions in children and adults. Telomere shortening is accelerated by early adversity, including maltreatment and psychosocial deprivation. These experiences also increase the risk of psychopathology in many domains. Two fundamental issues remain unresolved. The first concerns the specificity of the relations between TL and different dimensions of psychopathology; and the second relates to the direction of association between TL and psychopathology. Method This study addressed these shortcomings in a 2-fold manner. First, the association between TL and statistically independent general, internalizing, and externalizing psychopathology factors was examined to determine the specificity of this relation. Second, a 2-wave longitudinal cross-lagged model was used to explicitly examine the direction of the relation between TL and each psychopathology factor. Data were drawn from the Bucharest Early Intervention Project, a longitudinal study exploring the impact of severe psychosocial deprivation on child health and development (N = 195). At 8 to 10 and 12 to 14 years of age, buccal DNA was collected and teachers and/or caregivers reported on different domains of psychopathology. Results Longitudinal path analyses showed that shorter TL was specifically associated with higher internalizing psychopathology at 8 to 10 years of age. In contrast, at 12 to 14 years, shorter TL was associated with higher general psychopathology. Most telling, internalizing psychopathology at 8 to 10 years predicted shorter TL at 12 to 14 years, with no reciprocal effects. Conclusion Results suggest that telomere erosion could be a consequence of distress-related psychopathology rather than a selection mechanism for later psychiatric problems. Clinical trial registration information The Bucharest Early Intervention Project; https://clinicaltrials.gov/; NCT00747396.

  • Efficacy of Dialectical Behavior Therapy Versus Treatment as Usual for Acute-Care Inpatient Adolescents
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-04-01
    Alison A. Tebbett-Mock; Ema Saito; Madeline McGee; Patricia Woloszyn; Maria Venuti

    Objective Dialectical behavior therapy (DBT) is an evidence-based treatment that targets suicidal behavior and nonsuicidal self-injury (NSSI) and has been adapted for adolescents. Given the seriousness of these behaviors, many adolescents are psychiatrically hospitalized, but minimal research has been conducted on specific interventions during hospitalization. The goal of this study was to evaluate DBT versus treatment as usual (TAU) for adolescents on an acute-care psychiatric inpatient unit. Method We conducted a retrospective chart review for adolescents receiving inpatient DBT (n = 425) and for a historical control group treated on the same unit before DBT (ie, TAU, n = 376). Both χ2 and t tests were conducted as preliminary analyses to examine differences between groups on diagnosis, sex, and age. Mann−Whitney U tests were conducted to examine differences between groups on outcome variables. The potential benefit of cost savings was analyzed. Results Patients who received DBT had significantly fewer constant observation (CO) hours for self-injury; incidents of suicide attempts and self-injury; restraints; and days hospitalized compared to patients who received TAU. Statistically significant differences were not found between DBT and TAU groups for number of CO hours for aggression, incidents of aggression toward patients or staff, seclusions, or readmissions. A cost analysis determined that $251,609 less was spent on staff time for CO hours with DBT compared to TAU. Conclusion Results provide support for the implementation of DBT in an acute-care adolescent psychiatric inpatient unit for adolescents. Clinical implications, study limitations, and future research directions are discussed.

  • A Randomized Controlled Trial of Attention Bias Modification Treatment in Youth With Treatment-Resistant Anxiety Disorders
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-03-13
    Jeremy W. Pettit; Michele Bechor; Yasmin Rey; Michael W. Vasey; Rany Abend; Daniel S. Pine; Yair Bar-Haim; James Jaccard; Wendy K. Silverman

    Objective Randomized clinical trials of augmentation strategies for youth with treatment-resistant anxiety disorders do not exist. This report presents findings from an efficacy trial of attention bias modification treatment (ABMT) as an augment for this population compared with attention control training (ACT). Method Sixty-four youths (34 boys; mean age 11.7 years) who continued to meet for anxiety diagnoses after completing cognitive-behavioral therapy were randomized to ABMT or ACT. ABMT and ACT consisted of dot-probe attention training trials presenting angry and neutral faces; probes appeared in the location of neutral faces on 100% of trials in ABMT and 50% of trials in ACT. Independent evaluators, youths, and parents completed ratings of youth anxiety severity, and youths completed measures of attention bias to threat and attention control at pretreatment, post-treatment, and 2-month follow-up. Results The 2 arms showed significant decreases in anxiety severity, with no differences between arms. Specifically, across informants, anxiety severity was significantly decreased at post-treatment and decreases were maintained at follow-up. Primary anxiety disorder diagnostic recovery combined across arms was 50% at post-treatment and 58% at follow-up. Attention control, but not attention bias to threat, was significantly improved at post-treatment in the 2 arms. Conclusion This is the first study to show anxiety can be decreased in youth who did not respond to cognitive-behaviorial therapy, and that the anxiety-decreasing effect is found using these 2 attention training contingency schedules. These findings and increases in attention control in the 2 arms raise intriguing questions about mechanisms of decreasing anxiety in treatment-resistant youth with attention training that require further research. Clinical trial registration information Attention Bias Modification Training for Child Anxiety CBT Nonresponders; https://clinicaltrials.gov/; NCT01819311.

  • Antipsychotic Use Among Youth in Foster Care Enrolled in a Specialized Managed Care Organization Intervention
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-05-06
    Thomas I. Mackie; Sharon Cook; Stephen Crystal; Mark Olfson; Ayse Akincigil

    Objective Little is known about whether interventions implemented by specialized Medicaid managed care organizations (MMCOs) contributed to recent stabilization of antipsychotic prescribing to youths in foster care. This study examined a multimodal antipsychotic intervention implemented by a specialized MMCO for youths in foster care with routine mental health screening, health passports, elective psychiatric consultation line, and retrospective drug utilization reviews to determine whether this multimodal intervention significantly reduced antipsychotic dispensing for youths with conditions without US Food and Drug Administration (FDA)–approved indications. Method Employing a difference-in-differences design, intervention effectiveness for youths in foster care (age 6–17 years) compared with adopted youthss was examined. Analyses were stratified by FDA-indicated conditions, other externalizing conditions, and other internalizing conditions. Outcomes included predicted annual probabilities of any antipsychotic dispensed, antipsychotic dispensed for ≥90 consecutive days, and glucose and lipid testing. Results Intervention-enrolled youths with FDA-indicated conditions, relative to comparison youths, experienced a 0.6% reduction in any antipsychotic dispensed and 3.1% increase for ≥90 consecutive days dispensed in the 2 years following implementation, both nonsignificant differences. Youths with other externalizing disorders experienced significant reductions, relative to comparison youths, in any antipsychotic dispensed (−6.3%, p < .001) and in ≥90 consecutive days dispensed (−5.5%, p < .001). Youths with other internalizing disorders experienced a significant reduction, relative to comparison youths, in any antipsychotic dispensed (−7.6%, p < .001) and in ≥90 consecutive days dispensed (−5.1%, p < .001). Glucose and lipid testing increased at statistically comparable rates for both groups. Conclusion MMCO implementation significantly reduced antipsychotic medications without FDA-indicated conditions prescribed to youths, while not significantly affecting antipsychotic medications prescribed to youths with FDA-indicated conditions.

  • Internalizing and Externalizing Symptoms Are Associated With Different Trajectories of Cortical Development During Late Childhood
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-04-29
    Sarah Whittle; Nandita Vijayakumar; Julian G. Simmons; Nicholas B. Allen

    Objective Investigation of neurobiological differences between internalizing and externalizing symptoms in children is needed to better understand the unique pathophysiology of each, which may ultimately better target treatments and interventions. Longitudinal studies are critical, given the marked brain development that occurs in childhood; however, few such studies exist, and results are inconsistent. The aim of this study was to longitudinally investigate associations between internalizing and externalizing symptoms, and cortical thinning during late childhood. Method Participants were 105 children (49 male) from the community, who underwent magnetic resonance imaging (MRI) brain scans, and completed questionnaire measures of depressive and anxiety symptoms at two time points (mean age: 8.4 years at baseline, 10.0 years at follow-up); and, mothers, who reported on child internalizing and externalizing symptoms at both time points. Whole-brain vertex-wise regression analyses were performed to assess associations between change in cortical thickness and symptoms between baseline and follow-up. Results Increases in internalizing symptoms over time were associated with reduced thinning in the orbitofrontal cortex, whereas increases in externalizing symptoms were associated with reduced thinning in the postcentral gyrus. The interaction between internalizing and externalizing symptom change was not associated with cortical thinning. Conclusion Results suggest that the development of internalizing and externalizing symptoms are associated with unique neurodevelopmental patterns in late childhood, potentially implicating differential deficits in affective reactivity, emotion regulation, and social cognition. Further research is required to elucidate the implications of these patterns for ongoing brain development, psychopathology, and behavior.

  • Validation of the UCLA PTSD Reaction Index for DSM-5: A Developmentally Informed Assessment Tool for Youth
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-04-03
    Julie B. Kaplow; Benjamin Rolon-Arroyo; Christopher M. Layne; Evan Rooney; Benjamin Oosterhoff; Ryan Hill; Alan M. Steinberg; Jennifer Lotterman; Katherine A.S. Gallagher; Robert S. Pynoos

    Objective To describe the test construction procedure and evaluate the internal consistency, criterion-referenced validity, and diagnostic accuracy of the Child/Adolescent Self-Report Version of the UCLA PTSD Reaction Index for DSM-5 (RI-5) across 2 independent samples. Method Study 1 examined the clarity, developmental appropriateness, acceptability of individual RI-5 items, and internal consistency and criterion-referenced validity of the full test. The study 1 sample included 486 youth recruited from 2 major US cities who completed the RI-5 and a measure of depression. Study 2 evaluated the reliability and diagnostic accuracy of the RI-5 in 41 treatment-seeking youth who completed the RI-5 and a “gold standard” structured diagnostic interview, the Clinician-Administered PTSD Scale for DSM-5—Child/Adolescent Version. Results RI-5 total scale scores showed excellent internal consistency in the 2 samples. Study 1 provided evidence of criterion-referenced validity, in that total scale scores correlated positively with depressive symptoms. Study 2 provided evidence of diagnostic accuracy (including discriminant-groups validity). RI-5 total scores discriminated youth with from youth without PTSD as benchmarked against the structured diagnostic interview. Further, receiver operating characteristic analyses using a total score of 35 provided excellent diagnostic classification accuracy (area under the curve 0.94). Conclusion The developmental appropriateness and diagnostic accuracy of the RI-5 support its utility for clinical assessment, case conceptualization, and treatment planning in different child-serving systems, including schools, juvenile justice, child welfare, and mental health.

  • Trajectories in Symptoms of Autism and Cognitive Ability in Autism From Childhood to Adult Life: Findings From a Longitudinal Epidemiological Cohort
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-12-19
    Emily Simonoff; Rachel Kent; Dominic Stringer; Catherine Lord; Jackie Briskman; Steve Lukito; Andrew Pickles; Tony Charman; Gillian Baird

    Objective For the first time, we use a longitudinal population-based autism cohort to chart the trajectories of cognition and autism symptoms from childhood to early adulthood and identify features that predict the level of function and change with development. Method Latent growth curve models were fitted to data from the Special Needs and Autism Project cohort at three timepoints: 12, 16 and 23 years. Outcome measures were IQ and parent-reported Social Responsiveness Scale (SRS) autism symptoms. Of the 158 participants with an autism spectrum disorder at 12 years, 126 (80%) were re-assessed at 23 years. Child, family and contextual characteristics obtained at 12 years predicted intercept and slope of the trajectories. Results Both trajectories showed considerable variability. IQ increased significantly by a mean of 7.48 points from 12 to 23 years while autism symptoms remained unchanged. In multivariate analysis, full-scale IQ was predicted by initial language level and school type (mainstream/specialist). Those with a history of early language regression showed significantly greater IQ gains. Autism symptoms were predicted by Social Communication Questionnaire scores (lifetime version) and emotional and behavioral problems. Those attending mainstream schools showed significantly fewer autism disorder symptoms at 23 than those in specialist settings; this finding was robust to propensity score analysis for confounding. Conclusion Our findings suggest continued cognitive increments for many across the adolescent period, but a lack of improvement in autism symptoms. Our finding of school influences on autism symptoms requires replication in other cohorts and t settings before drawing any implications for mechanisms or policy.

  • Maternal Vitamin D Levels and the Risk of Offspring Attention-Deficit/Hyperactivity Disorder
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-12-19
    Minna Sucksdorff; Alan S. Brown; Roshan Chudal; Heljä-Marja Surcel; Susanna Hinkka-Yli-Salomäki; Keely Cheslack-Postava; David Gyllenberg; Andre Sourander

    Objective Recent evidence has highlighted the importance of vitamin D to the development of the central nervous system. Some studies have shown an association between maternal vitamin D deficiency during pregnancy and offspring Attention-deficit/hyperactivity disorder (ADHD) symptoms based on parent- or teacher ratings. There are no previous studies on early pregnancy 25-hydroxyvitamin D (25(OH)D) levels and the risk of diagnosed offspring ADHD. Our aim was to examine maternal 25(OH)D levels in early pregnancy and offspring ADHD. Method In this nationwide population-based case-control study, 1067 ADHD cases born between 1998 and 1999 and diagnosed according to the International Classification of Diseases and 1067 matched controls, were identified from Finnish registers. Maternal 25(OH)D levels were measured using quantitative immunoassay from maternal sera, collected during the first trimester, and archived in the national biobank. Conditional logistic regression was used to examine the association between maternal 25(OH)D and offspring ADHD. Results There was a significant association between decreasing log-transformed maternal 25(OH)D levels and offspring ADHD both in the unadjusted analyses (OR 1.65, 95% CI 1.33-2.05, P<.001) as well as in the analyses adjusting for maternal socio-economic status and age (OR 1.45, 95% CI 1.15-1.81, P=.002). Analyses by quintiles of maternal 25(OH)D levels in the lowest versus highest quintile revealed an adjusted odds ratio for offspring ADHD of 1.53 (95% CI 1.11-2.12, P=.010). Conclusion This study demonstrated an association between low maternal 25(OH)D during pregnancy and an elevated risk for offspring ADHD. If replicated in independent samples, this finding may have significant public health implications.

  • Five Profiles of Adolescents at Elevated Risk for Suicide Attempts: Differences in Mental Health Service Use
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-12-09
    Cheryl A. King, David Brent, Jacqueline Grupp-Phelan, Rohit Shenoi, Kent Page, E. Melinda Matabele-Gittens, Lauren S. Chernick, Marlene Melzer-Lange, Margaret Rea, Taylor C. McGuire, Andrew Littlefield, T. Charles Casper

    Objective Adolescents at risk for suicide are highly heterogeneous in terms of psychiatric and social risk factors, yet there has been little systematic research on risk profiles, which would facilitate recognition and the matching of patients to services. Our primary study aims were to identify latent class profiles of adolescents with elevated suicide risk, and to examine the association of these profiles with mental health service use (MHSU). Method Participants were 1,609 adolescents from the Emergency Department Screen for Teens at Risk for Suicide (ED-STARS) cohort. Participants completed baseline surveys assessing demographics, MHSU, and suicide risk. Telephone follow-up interviews were conducted at 3-months to assess suicide attempts. Participants met pre-established baseline criteria for suicide risk. Results Using latent class analysis, we derived five profiles of elevated suicide risk with differing patterns of eight risk factors: history of multiple suicide attempts, past-month suicidal ideation, depression, alcohol and drug misuse, impulsive-aggression, and sexual and physical abuse. In comparison to adolescents who did not meet baseline criteria for suicide risk, each profile was associated with increased risk of a suicide attempt within 3 months. MHSU was lowest for adolescents fitting profiles with previous (but no recent) suicidal thoughts and behavior and for adolescents from racial and ethnic minority groups. Conclusion Adolescents at elevated risk for suicide present to EDs with differing profiles of suicide risk. MHSU varies across these profiles and by race/ethnicity, indicating that targeted risk recognition and treatment linkage efforts may be necessary to reach some adolescents at risk.

  • Practice Parameter for the Assessment and Treatment of Psychiatric Disorders in Children and Adolescents With Intellectual Disability (Intellectual Developmental Disorder)
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-11-29
    Matthew Siegel, Kelly McGuire, Jeremy Veenstra-VanderWeele, Katharine Stratigos, Bryan King

    Intellectual Disability (Intellectual Developmental Disorder) (ID/IDD) is both a psychiatric disorder and a risk factor for co-occurring psychiatric disorders in children and adolescents. DSM-5 introduced important changes in the conceptualization and diagnosis of ID/IDD, and current research studies clarify assessment and treatment of co-occurring psychiatric disorders in this population. Optimal assessment and treatment of psychiatric illness in children and adolescents with ID/IDD includes modifications in diagnostic and treatment techniques, appreciation of variations in the clinical presentation of psychiatric disorders, an understanding of the spectrum of etiologies of behavioral disturbance, and knowledge of psychosocial and medical interventions.

  • Increased Functional Segregation Related to the Salience Network in Unaffected Siblings of Youths With Attention-Deficit/Hyperactivity Disorder
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-11-26
    Hsiang-Yuan Lin, Daniel Kessler, Wen-Yih Isaac Tseng, Susan Shur-Fen Gau

    Objective While there are frequent reports of shared neurofunctional and neurostructural alterations among probands with attention-deficit/hyperactivity disorder (ADHD) and their unaffected siblings, there is little knowledge regarding whether abnormalities in the resting-state functional connectivity of ADHD probands is also expressed in unaffected siblings, or if this unaffected (but at-risk) cohort manifests distinct patterns. Method We used a multivariate connectome-wide association study examining intrinsic functional connectivity with resting-state functional MRI in a sample (aged 8-17 years) of medication-naïve ADHD probands (N=56), their unaffected siblings (N=55), and typically developing (TD) youths (N=106). Results ADHD probands showed, relative to TD youths, increased connectivity between the default-mode network (DMN) and task-positive networks. Relative to ADHD and TD groups, respectively, unaffected siblings showed increased connectivity within the salience network and reduced connectivity between the DMN and salience network. No shared alterations in functional connectivity among ADHD probands and their unaffected siblings were identified. These findings were largely confirmed by complementary pairwise connectomic comparisons. However, the main connectivity differences between ADHD and UnSib were not replicated in a tightly age- and sex-matched subsample (20 proband-sibling pairs and 60 TD). Conclusion Our findings suggest that increased functional segregation related to the attention networks, especially the salience (ventral attention) system, may be a potential feature of at-risk siblings who remain unaffected by ADHD expression. Further replications are needed in other larger and sex-matched samples.

  • Systematic Review and Meta-Analysis: The Prevalence of Mental Illness in Child and Adolescent Refugees and Asylum Seekers
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-11-26
    Rebecca Blackmore, Kylie M. Gray, Jacqueline A. Boyle, Mina Fazel, Sanjeeva Ranasinha, Grace Fitzgerald, Marie Misso, Melanie Gibson-Helm

    Objective Over half of the world’s refugee population are under the age of 18 years. This systematic review aims to summarise the current body of evidence for the prevalence of mental illness in child and adolescent refugee populations. Method Eight electronic databases, grey literature, and Google Scholar were searched for articles from 1 January 2003 to 5 February 2018. Strict inclusion criteria regarding the diagnosis of mental illness were imposed. Study quality was assessed using a template according to study design, and study heterogeneity using I2 statistic. Random effects meta-analyses results were presented given heterogeneity among studies. The protocol for this systematic review was registered with PROSPERO (CRD42016046349). Results Eight studies were eligible, involving 779 child and adolescent refugees and asylum seekers, with studies conducted in five countries. The overall prevalence of post-traumatic stress disorder (PTSD) was 22.71% (95% CI 12.79-32.64), depression 13.81% (95% CI 5.96-21.67), and anxiety disorders 15.77% (95% CI 8.04-23.50). Attention-deficit/hyperactivity disorder (ADHD) was 8.6% (1.08-16.12) and oppositional defiant disorder (ODD) was 1.69% (95% CI -0.78 – 4.16). Due to high heterogeneity, further subgroup analyses were conducted. Conclusion Refugee and asylum seeker children have high rates of PTSD, depression, and anxiety. Without the serious commitment by health and resettlement services to provide early support to promote mental health, these findings suggest a high proportion of refugee children are at risk of educational disadvantage and poor social integration in host communities, potentially affecting their life course.

  • Is Treatment Working? Detecting Real Change in the Treatment of Child and Adolescent Depression
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-02-27
    Freda F. Liu, Molly C. Adrian

    Objective Despite advances in evidence-based treatments for youth depression in recent decades, overall treatment effects are modest at best, with 30% to 50% of youth being nonresponders. Practice parameters consistently recommend systematic assessment and routine monitoring of depressive symptoms, or measurement-based care (MBC), to enhance youth depression treatment. However, the literature offers few guidelines on how to use assessment results to inform care decisions or to detect real and clinically meaningful change. Thus the current study produced reliable change indices (RCIs) per Jacobson and Truax for two commonly used standardized assessments of youth depression (ie, Patient Health Questionnaire−9 items, Modified for Adolescents [PHQ-9A], the Short Moods and Feelings Questionnaire [SMFQ]). Method The study sample (N = 1,738) consisted of youths 6 to 18 years old seen in a child and adolescent psychiatry clinic of a regional pediatric medical center who completed at least one of the target depression measures. We examined the factor structure and internal reliability for the PHQ-9A, and calculated RCIs for patients with a depression-related diagnosis for both measures. Results Analyses confirmed a one-factor solution and adequate internal consistency (α = .86) for the PHQ-9A. All measures yielded acceptable test-retest reliabilities (r > 0.75) and RCIs that equate to clinical practice recommendations of using reliable changes scores of 7, 6, and 8 for the PHQ-9A, the SMFQ−Child Report, and the SMFQ−Parent Report, respectively. Conclusion Psychometric validation of the PHQ-9A and these RCIs are timely and significant contributions to the treatment of youth depression, by facilitating effective use of MBC—a critical evidence-based strategy for improving treatment outcomes.

  • Home Visiting and Antenatal Depression Affect the Quality of Mother and Child Interactions in South Africa
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-03-26
    Joan Christodoulou, Mary Jane Rotheram-Borus, Alexandra K. Bradley, Mark Tomlinson

    Objective To examine whether maternal depressed mood at birth moderated the protective effect of a home-visiting intervention on the quality of caregiving for children growing up in a low- and middle-income country. Method Almost all pregnant mothers in 24 Cape Town neighborhoods were recruited into a cluster randomized controlled trial matched by neighborhoods to the Philani home-visiting condition (HVC) or the standard care condition (SC). At 3 years after birth, the quality of mother–child interactions between HVC and SC mothers with and without antenatal depressed mood was assessed in a representative subset by rating videotaped observations of mother–child interactions on 10 dimensions of caregiving. Results As predicted, maternal depressed mood at birth moderated the effect of the HVC on the quality of mother–child interactions. Among nondepressed mothers, mothers and their children in the HVC scored significantly higher on 5 of the 10 dimensions of the maternal–child interaction scale than mothers in the SC: mothers exhibited more maternal sensitivity, talked more, had more harmonious interactions, and had children who paid more attention and exhibited more positive affect. However, being in the HVC did not significantly affect the mother–child interaction scores among mothers with depressed mood. Among HVC children, those with mothers with depressed mood showed significantly less positive affect and talked less with their mothers than children with nondepressed mothers. SC children with mothers with depressed mood were more responsive and paid attention to their mothers than children with nondepressed mothers. Conclusion Home visiting resulted in a better quality of caregiving for mothers without depressive symptoms. Future interventions need to specifically target maternal depression and positive mother–child interactions. Clinical trial registration information Mentor Mothers: A Sustainable Family Intervention in South African Townships; https://clinicaltrials.gov; NCT00972699; Philani Home-based Nutrition Intervention Program; https://clinicaltrials.gov; NCT00995592.

  • Cumulative Prevalence of Onset and Recurrence of Child Maltreatment Reports
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-03-06
    Hyunil Kim, Brett Drake

    Objective We estimated cumulative probabilities of onset and recurrences of child maltreatment reports from birth to age 11 years. Estimates were provided overall and within subcategories of race/ethnicity, sex, and subtype. Method We developed synthetic life tables from national Child Protective Services records (2003−2016) and Census data. Although 28 states and the District of Columbia were used for estimates due to data quality, sensitivity analyses suggest that our estimates may be very similar to national estimates, with very minor underestimation. Results The probability of having at least “X-number” of maltreatment reports by age 12 years was 32.41% for 1 report, 13.71% for 2 reports, 7.57% for 3 reports, 4.50% for reports, 2.80% for 5 reports, and 1.79% for 6 reports. Children with more prior reports were more likely to have future reports. The risk increased from 42.31% when having 1 prior report to 64.01% when having 5 prior reports. Asian/Pacific Islanders showed exceptionally lower onset and recurring rates than others. Individuals of nonwhite ethnicity (African American/black, Native American, and Hispanic) had higher onset rates than white individuals. Once initially reported, however, white persons had generally slightly higher rates of recurrence than nonwhite persons. Neglect was the most frequent subtype in both onset and recurring reports. No practical difference existed in overall onset and recurring rates by sex. Conclusion Many United States children experience reported maltreatment, and many experience repeated or chronic maltreatment. The increased risk of recurring with more prior reports suggests preventive efforts for serially reported children. The large racial disparity at the onset stage disappears at the recurring stages, suggesting interventions prior to the onset.

  • White Matter Microstructure in Youths With Conduct Disorder: Effects of Sex and Variation in Callous Traits
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-04-25
    Jack C. Rogers, Karen Gonzalez-Madruga, Gregor Kohls, Rosalind H. Baker, Roberta L. Clanton, Ruth Pauli, Philippa Birch, Alimul I. Chowdhury, Marietta Kirchner, Jesper L.R. Andersson, Areti Smaragdi, Ignazio Puzzo, Sarah Baumann, Nora M. Raschle, Lynn V. Fehlbaum, Willeke M. Menks, Martin Steppan, Christina Stadler, Stephane A. De Brito

    Objective Studies using diffusion tensor imaging (DTI) to investigate white matter (WM) microstructure in youths with conduct disorder (CD) have reported disparate findings. We investigated WM alterations in a large sample of youths with CD, and examined the influence of sex and callous-unemotional (CU) traits. Method DTI data were acquired from 124 youths with CD (59 female) and 174 typically developing (TD) youths (103 female) 9 to 18 years of age. Tract-based spatial statistics tested for effects of diagnosis and sex-by-diagnosis interactions. Associations with CD symptoms, CU traits, a task measuring impulsivity, and the impact of comorbidity, and age- and puberty-related effects were examined. Results Youths with CD exhibited higher axial diffusivity in the corpus callosum and lower radial diffusivity and mean diffusivity in the anterior thalamic radiation relative to TD youths. Female and male youths with CD exhibited opposite changes in the left hemisphere within the internal capsule, fornix, posterior thalamic radiation, and uncinate fasciculus. Within the CD group, CD symptoms and callous traits exerted opposing influences on corpus callosum axial diffusivity, with callous traits identified as the unique clinical feature predicting higher axial diffusivity and lower radial diffusivity within the corpus callosum and anterior thalamic radiation, respectively. In an exploratory analysis, corpus callosum axial diffusivity partially mediated the association between callous traits and impulsive responses to emotional faces. Results were not influenced by symptoms of comorbid disorders, and no age- or puberty-related interactions were observed. Conclusion WM alterations within the corpus callosum represent a reliable neuroimaging marker of CD. Sex and callous traits are important factors to consider when examining WM in CD.

  • Early Pubertal Timing and Testosterone Associated With Higher Levels of Adolescent Depression in Girls
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-02-14
    William E. Copeland, Carol Worthman, Lilly Shanahan, E. Jane Costello, Adrian Angold

    Objective The prevalence of depression increases dramatically during puberty in girls. Earlier work in this sample reported that the sex steroids estradiol and testosterone were associated with increased depression in girls. Using three additional data waves (983 new observations), we retest the relative contributions of pubertal timing, pubertal status, and sex hormones on the increases in female depression. Method Eight waves of data from the prospective, representative Great Smoky Mountains Study were used covering female participants in the community who were 9 to 16 years of age (3,005 assessments of 630 girls; 1993−2000). Structured interviews assessed depressive disorders. Youth rated their pubertal status using Tanner stage drawings, and sex steroids were assayed from dried blood spots. Results Risk for depression during puberty was associated with both age and Tanner stage in univariate models. In adjusted models accounting for pubertal timing and sex steroids, the apparent effects of age and Tanner stage were attenuated both in terms of statistical significance and effect size. The only significant predictors of change in depression status during puberty were early pubertal timing (odds ratio = 5.8, 95% CI = 1.9−17.9, p = .002 after age 12 years) and higher testosterone levels (odds ratio = 2.0, 95% CI = 1.1−3.8, p = .03 for quartile-split variable). Conclusion The added observations have modified the original conclusions, implicating the following: testosterone only, but not estradiol; and early pubertal timing, but not age or pubertal status per se. These findings argue for multiple pubertal determinants of depression risk, including factors that are socially and biologically mediated.

  • A Role of Oxytocin Receptor Gene Brain Tissue Expression Quantitative Trait Locus rs237895 in the Intergenerational Transmission of the Effects of Maternal Childhood Maltreatment
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-03-09
    Philipp Toepfer, Kieran J. O'Donnell, Sonja Entringer, Christine M. Heim, David T.S. Lin, Julia L. MacIsaac, Michael S. Kobor, Michael J. Meaney, Nadine Provençal, Elisabeth B. Binder, Pathik D. Wadhwa, Claudia Buss

    Objective Women exposed to childhood maltreatment (CM) are more likely to exhibit insensitive parenting, which may have consequences for their offspring’s development. Variation in the oxytocin-receptor gene (OXTR) moderates risk of CM-associated long-term sequelae associated with mother−child attachment, although functionality of previously investigated single nucleotide polymorphisms (SNPs) remained elusive. Here, we investigated the role of OXTR rs237895, a brain tissue expression quantitative trait locus (eQTL), as a moderator of the relationship between CM and maternal behavior (MB) and the association between MB and offspring attachment security. Method Of 110 women with information on rs237895 genotype (T-allele = 64, CC = 46), 107 had information on CM (CTQ) and 99 on standardized observer-based ratings of MB at 6 months postpartum (responsivity and detachment), which were used in principal component analysis to obtain a latent factor representing MB. Offspring (n = 86) attachment was evaluated at 12 months of age. Analyses predicting MB were adjusted for socioeconomic status, age, postpartum depression, and genotype-based ethnicity. Analyses predicting child attachment were adjusted for infant sex, socioeconomic status, and postpartum depression. Results rs237895 significantly moderated the relationship between CM and MB (F1;66 = 7.99, p < .01), indicating that CM was associated with maternal insensitivity only in high−OXTR-expressing T-allele carriers but not in low−OXTR-expressing CC homozygotes. Moreover, maternal insensitivity predicted offspring insecure attachment (B = –0.551; p < .05). Conclusion Women with a high OXTR expressing genotype are more susceptible to CM-related impairments in MB that, in turn, predict attachment security in their children, supporting the role of the OT system in the intergenerational transmission of risk associated with maternal CM.

  • Abnormal Thalamic Functional Connectivity During Light Non–Rapid Eye Movement Sleep in Children With Primary Nocturnal Enuresis
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-06-18
    Bing Yu, Shanshan Xiao, Yi You, Hongwei Ma, Miao Peng, Yang Hou, Qiyong Guo

    Objective To investigate abnormalities of thalamocortical and intrathalamic functional connectivity (FC) in children with primary nocturnal enuresis (PNE) during light non–rapid eye movement (NREM) sleep using a simultaneous EEG–functional magnetic resonance imaging (fMRI) method. Method Polysomnographic and EEG-fMRI data were obtained during sleep from 61 children with PNE (age 10.2 ± 1.7 years, 59% boys) and 61 age-matched controls (age 10.1 ± 1.4 years, 54% boys). All subjects first participated in one overnight video-polysomnographic study. Total sleep time, percentage of total sleep time in each sleep stage, arousal index, and awakening index were calculated. Simultaneous EEG-fMRI studies were then performed using a 3T MRI system with a 32-channel MRI-compatible EEG system. Visual scoring of EEG data permitted sleep staging. Thalamocortical and intrathalamic FCs in the waking state and at different stages of light sleep were calculated and compared. Results Children with PNE had a higher percentage of total sleep time in light sleep and a higher arousal index compared with controls. Abnormal thalamocortical FCs were detected in the lateral prefrontal cortex, medial prefrontal cortex, and inferior parietal lobule during light NREM sleep. Abnormal intrathalamic FCs were also detected during light NREM sleep among the motor, occipital, prefrontal, and temporal subdivisions of the thalamus. Conclusion Abnormal prefrontal and parietal thalamocortical FCs, accompanied by abnormal intrathalamic FCs among the motor, occipital, prefrontal, and temporal subdivision of thalamus during light NREM sleep, may be related to abnormal sleep and enuresis in children with PNE.

  • Stigma and Acceptance of Sierra Leone’s Child Soldiers: A Prospective Longitudinal Study of Adult Mental Health and Social Functioning
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-06-07
    Theresa S. Betancourt, Dana L. Thomson, Robert T. Brennan, Cara M. Antonaccio, Stephen E. Gilman, Tyler J. VanderWeele

    Objective To investigate the associations of war and postconflict factors with mental health among Sierra Leone’s former child soldiers as adults. Method In 2002, we recruited former child soldiers from lists of soldiers (aged 10–17 years) served by Disarmament, Demobilization, Reintegration centers and from a random door-to-door sample in 5 districts of Sierra Leone. In 2004, self-reintegrated child soldiers were recruited in an additional district. At 2016/2017, 323 of the sample of 491 former child soldiers were reassessed. Subjects reported on war exposures and postconflict stigma, family support, community support, anxiety/depression, and posttraumatic stress symptoms. Results Of the subjects, 72% were male, with a mean age of 28 years. In all, 26% reported killing or injuring others; 67% reported being victims of life-threatening violence; 45% of female subjects and 5% of male subjects reported being raped; and 32% reported death of a parent. In 2016/2017 (wave 4), 47% exceeded the threshold for anxiety/depression, and 28% exceeded the likely posttraumatic stress disorder threshold. Latent class growth analysis yielded 3 trajectory groups based on changes in stigma and family/community acceptance; “Improving Social Integration” (n = 77) fared nearly as well as the “Socially Protected” (n = 213). The “Socially Vulnerable” group (n = 33) had increased risk of anxiety/depression above the clinical threshold and possible PTSD, and were around 3 times more likely to attempt suicide. Conclusion Former child soldiers had elevated rates of mental health problems. Postconflict risk and protective factors related to outcomes long after the end of conflict. Targeted social inclusion interventions could benefit the long-term mental health of former child soldiers.

  • Reward-Related Brain Activity Prospectively Predicts Increases in Alcohol Use in Adolescents
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-06-04
    Johnna R. Swartz, David G. Weissman, Emilio Ferrer, Sarah J. Beard, Catherine Fassbender, Richard W. Robins, Paul D. Hastings, Amanda E. Guyer

    Objective Altered activity within reward-related neural regions, including the ventral striatum (VS) and medial prefrontal cortex (mPFC), is associated with concurrent problematic substance use. The aims of the present study were (a) to identify patterns of reward-related neural activity that prospectively predicted changes in alcohol use 2 years after magnetic resonance imaging in a sample of adolescents, and (b) to examine whether these patterns differed by sex. We also tested whether depression symptoms or impulsivity mediated associations between neural activity and future alcohol use. Method Participants were 262 adolescents (129 male and 133 female) of Mexican origin who completed the Monetary Incentive Delay task during a functional magnetic resonance imaging scan at age 16. Participants reported on their alcohol use at ages 16 and 18. Results Results indicated that different patterns of reward-related neural activity predicted future increases in alcohol use for male and female adolescents. In boys, higher VS activity during reward anticipation and average ventral mPFC activity during reward feedback predicted increases in alcohol use from age 16 to 18 years; in girls, higher dorsal mPFC activity and blunted VS activity during reward anticipation predicted increases in alcohol use from age 16 to 18 years. Depression symptoms or impulsivity did not mediate these associations. Conclusion The results suggest that different pathways of risk may lead to problematic alcohol use for adolescent boys and girls. These sex differences in neural risk pathways have important implications for prevention and intervention approaches targeting Mexican-origin youth.

  • Brain Development and Stochastic Processes During Prenatal and Early Life: You Can’t Lose It if You’ve Never Had It; But It’s Better to Have It and Lose It, Than Never to Have Had It at All
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-05-14
    Tonya J.H. White

    Brain development, although largely driven by genetic processes, also is influenced by environmental factors. However, there has been little discussion in the psychiatric literature on the role of stochastic, or chance, events that take place during neurodevelopment. Studies suggest that the brain capitalizes on and regulates the extent of stochastic processes during development. Furthermore, because neurodevelopment is influenced by environmental factors, there is emerging evidence that fostering those positive environmental factors during prenatal and early life could optimize neurodevelopment and provide greater resilience, including those potentially resulting from stochastic processes. Evidence for the role of environmental factors in optimizing early brain development is supported by work in large population-based studies of child development, randomized control trials in high-risk populations, and early-life adoption studies. The public health message is that creating an environment that fosters optimal brain development during prenatal and early life could prevent psychopathology and provide the developing brain the best chance against negative stochastic processes and potential stressors that are inevitable later in life.

  • Neuroimaging Evidence for Right Orbitofrontal Cortex Differences in Adolescents With Emotional and Behavioral Dysregulation
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-04-17
    Philip A. Spechler, Bader Chaarani, Catherine Orr, Scott Mackey, Stephen T. Higgins, Tobias Banaschewski, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Erin Burke Quinlan, Patricia J. Conrod, Sylvane Desrivières, Herta Flor, Vincent Frouin, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Gunter Schumann

    Objective To characterize the structural and functional neurobiology of a large group of adolescents exhibiting a behaviorally and emotionally dysregulated phenotype. Method Adolescents aged 14 years from the IMAGEN study were investigated. Latent class analysis (LCA) on the Strengths and Difficulties Questionnaire (SDQ) was used to identify a class of individuals with elevated behavioral and emotional difficulties (“dysregulated”; n = 233) who were compared to a matched sample from a low symptom class (controls, n = 233). Whole-brain gray matter volume (GMV) images were compared using a general linear model with 10,000 random label permutations. Regional GMV findings were then probed for functional differences from three functional magnetic resonance imaging (fMRI) tasks. Significant brain features then informed mediation path models linking the likelihood of psychiatric disorders (DSM-IV) with dysregulation. Results Whole-brain differences were found in the right orbitofrontal cortex (R.OFC; p < .05; k = 48), with dysregulated individuals exhibiting lower GMV. The dysregulated group also exhibited higher activity in this region during successful inhibitory control (F1,429 = 7.53, p < .05). Path analyses indicated significant direct effects between the likelihood of psychopathologies and dysregulation. Modeling the R.OFC as a mediator returned modest partial effects, suggesting that the path linking the likelihood of an anxiety or conduct disorder diagnoses to dysregulation is partially explained by this anatomical feature. Conclusion A large sample of dysregulated adolescents exhibited lower GMV in the R.OFC relative to controls. Dysregulated individuals also exhibited higher regional activations when exercising inhibitory control at performance levels comparable to those of controls. These findings suggest a neurobiological marker of dysregulation and highlight the role of the R.OFC in impaired emotional and behavioral control.

  • Lithium Versus Other Mood-Stabilizing Medications in a Longitudinal Study of Bipolar Youth
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-07-29
    Danella M. Hafeman, Brian Rooks, John Merranko, Fangzi Liao, Mary Kay Gill, Tina R. Goldstein, Rasim Diler, Neal Ryan, Benjamin I. Goldstein, David A. Axelson, Michael Strober, Martin Keller, Jeffrey Hunt, Heather Hower, Lauren M. Weinstock, Shirley Yen, Boris Birmaher

    Objective Lithium is the mainstay for bipolar disorder (BD) treatment in adults, but evidence in youths is limited. We used data from the Course and Outcome of Bipolar Youth (COBY) study to assess whether lithium versus other mood-stabilizing medication (OMS) was associated with improved outcomes, including mood symptoms and suicidality. Method COBY is a naturalistic, longitudinal study of 413 youths, 7 to 17.11 years old at intake, with BD. At each visit, medication exposure, psychiatric symptoms, and psychosocial function over the preceding follow-up period were assessed using the Adolescent Longitudinal Interval Follow-Up Evaluation. Using mixed models, we determined whether participants taking lithium versus OMS (but not lithium) differed regarding mood symptoms, suicidality, psychosocial function, hospitalization, aggression, and substance use. Results A total of 340 participants contributed 2,638 six-month follow-up periods (886 lithium, 1,752 OMS), over a mean follow-up of 10 years. During lithium (versus OMS) follow-up periods, participants were older, less likely to have lifetime anxiety, and less likely to be on antidepressants (p values<.005). After covariate adjustment, the lithium group (versus OMS) had half as many suicide attempts (p = .03), fewer depressive symptoms (p = .004), less psychosocial impairment (p = .003), and less aggression (p = .0004). Similar findings were observed in the subgroup of follow-up periods in which participants were <18 years old. Conclusion Findings are consistent with adult studies, showing that lithium is associated with decreased suicidality, less depression, and better psychosocial functioning. Given the paucity of evidence regarding lithium in children and adolescents, these findings have important clinical implications for the pharmacological management of youths with BD.

  • Neuropsychiatric “Comorbidity” as Causal Influence in Autism
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-07-22
    Zoë W. Hawks, John N. Constantino

    Behavioral comorbidity is the rule rather than the exception in autism spectrum disorder (ASD), and the co-occurrence of autistic traits with subclinical manifestations of other psychiatric syndromes (eg anxiety, developmental coordination disorder) extends to the general population, where there is strong evidence for overlap in the respective genetic causes. An ASD “comorbidity” can have several fundamentally distinct causal origins: it can arise due to shared genetic risk between ASD and non-ASD phenotypes (eg, ASD and microcephaly in the context of the MECP2 mutation), as a “secondary symptom” of ASD when engendered by the same causal influence (eg, epilepsy in channelopathies associated with ASD), due to chance co-occurrence of ASD with a causally independent liability (eg, ASD and diabetes), or as the late manifestation of an independent causal influence on ASD (eg, attention-deficit/hyperactivity disorder). Here, we review evidence for the latter, that is, the role of nonspecific causal influences on the development of ASD itself. The notion that nonspecific insults to neural development, either inherited or acquired, might augment the impact of ASD-specific genetic susceptibilities in contributing to its cause has not been appreciated in the literature on comorbidity, and has significant implications for both personalized intervention and future research. Prior biomarker studies of ASD have typically not accounted for variation in such traits. The statistical power of future studies, particularly in autism genetics and neuroimaging, can be enhanced by more comprehensive attention to the measurement of comorbid behavioral traits that index causal influences on the disorder, among not only cases but (importantly) controls.

  • White Matter Microstructure in Pediatric Bipolar Disorder and Disruptive Mood Dysregulation Disorder
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-07-19
    Julia O. Linke, Nancy E. Adleman, Joelle Sarlls, Andrew Ross, Samantha Perlstein, Heather R. Frank, Kenneth E. Towbin, Daniel S. Pine, Ellen Leibenluft, Melissa A. Brotman

    Objective Disruptive mood dysregulation disorder (DMDD) codifies severe, chronic irritability. Youths with bipolar disorder (BD) also present with irritability, but with an episodic course. To date, it is not clear whether aberrant white matter microstructure—a well-replicated finding in BD—can be observed in DMDD and relates to symptoms of irritability. Method We acquired diffusion tensor imaging data from 118 participants (BD = 36, DMDD = 44, healthy volunteers (HV = 38). Images of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were processed with tract-based spatial statistics controlling for age and sex. The data were also used to train Gaussian process classifiers to predict diagnostic group. Results In BD versus DMDD, FA in the corticospinal tract was reduced. In DMDD versus HV, reductions in FA and AD were confined to the anterior corpus callosum. In BD versus HV, widespread reductions in FA and increased RD were observed. FA in the anterior corpus callosum and corticospinal tract was negatively associated with irritability. The Gaussian process classifier could not discriminate between BD and DMDD, but achieved 68% accuracy in predicting DMDD versus HV and 75% accuracy in predicting BD versus HV. Conclusion Aberrant white matter microstructure was associated with both categorical diagnosis and the dimension of irritability. Alterations in DMDD were regionally discrete and related to reduced AD. In BD, we observed widespread increases in RD, supporting the hypothesis of altered myelination in BD. These findings will contribute to the pathophysiological understanding of DMDD and its differentiation from BD. Clinical trial registration information: Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder; https://clinicaltrials.gov/; NCT00025935; Child & Adolescent Bipolar Disorder Brain Imaging and Treatment Study; https://clinicaltrials.gov/; NCT00006177.

  • Systematic Review: Nonmedical Use of Prescription Stimulants: Risk Factors, Outcomes, and Risk Reduction Strategies
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-07-19
    Stephen V. Faraone, Anthony L. Rostain, C. Brendan Montano, Oren Mason, Kevin M. Antshel, Jeffrey H. Newcorn

    Objective To review all literature on the nonmedical use (NMU) and diversion of prescription stimulants, to better understand the characteristics, risk factors, and outcomes of NMU and to review risk-reduction strategies. Method We systematically searched PubMed, PsycINFO, and SCOPUS from inception to May 2018 for studies containing empirical data about NMU and diversion of prescription stimulants. Additional references identified by the authors were also assessed for inclusion. Results A total of 109 studies met inclusion criteria. NMU and diversion of stimulants are highly prevalent; self-reported rates among population samples range from 2.1% to 58.7% and from 0.7% to 80.0%, respectively. A variety of terms are used to describe NMU, and most studies have examined college students. Although most NMU is oral, non-oral NMU also occurs. The majority of NMU is associated with no, or minor, medical effects; however adverse medical outcomes, including death, occur in some individuals, particularly when administered by non-oral routes. Although academic and occupational performance enhancement are the most commonly cited motivations, there is little evidence that academic performance is improved by NMU in individuals without attention-deficit/hyperactivity disorder. Conclusion NMU of stimulants is a significant public health problem, especially in college students, but variations in the terms used to describe NMU and inconsistencies in the available data limit a better understanding of this problem. Further research is needed to develop methods to detect NMU, identify individuals at greatest risk, study routes of administration, and devise educational and other interventions to help reduce occurrence of NMU. Colleges should consider including NMU in academic integrity policies.

  • Cannabis-Associated Psychotic-like Experiences Are Mediated by Developmental Changes in the Parahippocampal Gyrus
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-07-18
    Tao Yu, Tianye Jia, Liping Zhu, Sylvane Desrivières, Christine Macare, Yan Bi, Arun L.W. Bokde, Erin Burke Quinlan, Andreas Heinz, Bernd Ittermann, ChuanXin Liu, Lei Ji, Tobias Banaschewski, Decheng Ren, Li Du, Binyin Hou, Herta Flor, Vincent Frouin, Gabriel Robert

    Objective Cannabis consumption during adolescence has been reported as a risk factor for psychotic-like experiences (PLEs) and schizophrenia. However, brain developmental processes associated with cannabis-related PLEs are still poorly described. Method A total of 706 adolescents from the general population who were recruited by the IMAGEN consortium had structural magnetic resonance imaging scans at both 14 and 19 years of age. We used deformation-based morphometry to map voxelwise brain changes between the two time points, using the pairwise algorithm in SPM12b. We used an a priori region-of-interest approach focusing on the hippocampus/parahippocampus to perform voxelwise linear regressions. Lifetime cannabis consumption was assessed using the European School Survey Project on Alcohol and other Drugs (ESPAD), and PLEs were assessed with the Comprehensive Assessment Psychotic-like experiences (CAPE) tool. We first tested whether hippocampus/parahippocampus development was associated with PLEs. Then we formulated and tested an a priori simple mediation model in which uncus development mediates the association between lifetime cannabis consumption and PLEs. Results We found that PLEs were associated with reduced expansion within a specific region of the right hippocampus/parahippocampus formation, the uncus (p = .002 at the cluster level, p = .018 at the peak level). The partial simple mediation model revealed a significant total effect from lifetime cannabis consumption to PLEs (b = 0.069, 95% CI = 0.04−0.1, p =2 × 10−16), as well as a small yet significant, indirect effect of right uncus development (0.004; 95% CI = 0.0004−0.01, p = .026). Conclusion We show here that the uncus development is involved in the cerebral basis of PLEs in a population-based sample of healthy adolescents.

  • Borderline Symptoms at Age 12 Signal Risk for Poor Outcomes During the Transition to Adulthood: Findings From a Genetically Sensitive Longitudinal Cohort Study
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-07-17
    Jasmin Wertz, Avshalom Caspi, Antony Ambler, Louise Arseneault, Daniel W. Belsky, Andrea Danese, Helen L. Fisher, Timothy Matthews, Leah Richmond-Rakerd, Terrie E. Moffitt

    Objective Borderline personality disorder in adolescence remains a controversial construct. We addressed concerns about the prognostic significance of adolescent borderline pathology by testing whether borderline symptoms at age 12 years predict functioning during the transition to adulthood, at age 18 years, in areas critical to life-course development. Method We studied members of the Environmental Risk (E-Risk) Longitudinal Twin Study, which tracks the development of a birth cohort of 2,232 British twin children. At age 12, borderline symptoms of study members were measured using mothers’ reports. At age 18, study members’ personality, psychopathology, functional outcomes, and experiences of victimization were measured using self-reports, coinformant reports, and official records. Results At age 18, study members who had more borderline symptoms at age 12 were more likely to have difficult personalities, to struggle with poor mental health, to experience poor functional outcomes, and to have become victims of violence. Reports of poor outcomes were corroborated by coinformants and official records. Borderline symptoms in study members at 12 years old predicted poor outcomes over and above other behavioral and emotional problems during adolescence. Twin analyses showed that borderline symptoms in 12-year-olds were influenced by familial risk, particularly genetic risk, which accounted for associations with most poor outcomes at age 18. Conclusion Borderline symptoms in 12-year-olds signal risk for pervasive poor functioning during the transition to adulthood. This association is driven by genetic influences, suggesting that borderline symptoms and poor outcomes are manifestations of shared genetic risk.

  • Attention-Deficit/Hyperactivity Disorder Medication and Unintentional Injuries in Children and Adolescents
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-07-11
    Laura Ghirardi, Henrik Larsson, Zheng Chang, Qi Chen, Patrick D. Quinn, Kwan Hur, Robert D. Gibbons, Brian M. D’Onofrio

    Objective Our objective was to determine whether attention-deficit/hyperactivity disorder (ADHD) medication is associated with a decreased risk of unintentional injuries in children and adolescents in the United States across sexes, age groups and injury types. Method We used de-identified inpatient, outpatient, and filled prescription claims data from the Truven Health MarketScan Research Databases. Individuals were followed from January 1, 2005, date of first ADHD diagnosis, or medication prescription, or age 6 years, whichever occurred last, until December 31, 2014, first healthcare insurance disenrollment, or the first year at which their age was recorded as 19 years, whichever occurred first. A person was considered on ADHD medication during a given month if a prescription was filled in that month. The outcome was defined as emergency department visits for injuries, including traumatic brain injuries, with unintentional causes. Odds of having the outcome were compared between medicated and unmedicated months at the population-level and in within-individual analyses using logistic regression. Results Among 1,968,146 individuals diagnosed with ADHD or receiving ADHD medication, 87,154 had at least one event. At the population level, medication use was associated a lower risk of injuries, both in boys (odds ratio [OR] = 0.85; 95% CI = 0.84−0.86) and girls (OR = 0.87; 95% CI = 0.85−0.89). Similar results were obtained from within-individual analysis among male (OR = 0.72; 95% CI = 0.70−0.74) and female (OR = 0.72; 95% CI = 0.69−0.75) children, and among male (OR = 0.64; 95% CI = 0.60−0.67) and female (OR = 0.65; 95% CI = 0.60−0.71) adolescents. Similar results were found for traumatic brain injuries. Conclusion ADHD medication use was associated with a reduction of different types of unintentional injuries in children and adolescents of both sexes.

  • Brief Behavioral Therapy for Pediatric Anxiety and Depression in Primary Care: A Follow-Up
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-07-03
    David A. Brent, Giovanna Porta, Michelle S. Rozenman, Araceli Gonzalez, Karen T.G. Schwartz, Frances L. Lynch, John F. Dickerson, Satish Iyengar, V. Robin Weersing

    Objective To report on the 32-week outcome of the Brief Behavioral Therapy (BBT) for Pediatric Anxiety and Depression in Primary Care clinical trial. Method A total of 185 youths aged 8 to 17 years with anxiety and/or depression identified through 9 pediatric primary care (PPC) settings in San Diego and Pittsburgh were randomized to receive Assisted Referral to Care (ARC) or up to 12 sessions of BBT over 16 weeks. The primary outcome was clinical response across anxiety and depression, defined as a Clinical Global Impressions−Improvement Score of ≤2. Secondary outcomes included interview-rated functioning, depression, and anxiety. Here, we report on outcomes at 32 weeks after randomization. All analyses with primary outcomes are corrected for multiple comparisons using the false discovery rate technique. Results At 32 weeks, BBT was superior to ARC with respect to response (67.5% versus 43.1%, q = 0.03, number needed to treat [NNT] = 5) and functioning (d = 0.49, q = 0.04). BBT was superior to ARC with respect to its impact on anxiety (f = 0.21) but not depressive symptoms (f = 0.05). These findings persisted after controlling for the number of sessions received. Ethnicity moderated the impact of BBT on outcome (NNT for Hispanic youths = 2), because of a much lower response rate to ARC in Hispanic than in non-Hispanic youths (16.7% versus 49.2%, p = 0.04). Conclusion BBT is a promising intervention that can be effectively delivered in PPC and may be particularly effective for Hispanic patients. Further work is indicated to improve its impact on depressive symptoms and to test BBT against other treatments delivered in pediatric primary care. Clinical Trial Registration Brief Cognitive Behavioral Therapy (CBT) for Pediatric Anxiety and Depression in Primary Care; http://clinicaltrials.gov; NCT01147614.

  • Systematic Review and Meta-Analysis: Eye-Tracking of Attention to Threat in Child and Adolescent Anxiety
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-06-29
    Stephen Lisk, Ayesha Vaswani, Marian Linetzky, Yair Bar-Haim, Jennifer Y.F. Lau

    Objective Attention biases for threat may reflect an early risk marker for anxiety disorders. Yet questions remain regarding the direction and time-course of anxiety-linked biased attention patterns in youth. A meta-analysis of eye-tracking studies of biased attention for threat was used to compare the presence of an initial vigilance toward threat and a subsequent avoidance in anxious and nonanxious youths. Method PubMed, PsycARTICLES, Medline, PsychINFO, and Embase were searched using anxiety, children and adolescent, and eye-tracking-related key terms. Study inclusion criteria were as follows: studies including participants ≤18 years of age; reported anxiety using standardized measures; measured attention bias using eye tracking with a free-viewing task; comparison of attention toward threatening and neutral stimuli; and available data to allow effect size computation for at least one relevant measure. A random effects model estimated between- and within-group effects of first fixations toward threat and overall dwell time on threat. Results Thirteen eligible studies involving 798 participants showed that neither youths with or without anxiety showed significant bias in first fixation to threat versus neutral stimuli. However anxious youths showed significantly less overall dwell time on threat versus neutral stimuli than nonanxious controls (g = −0.26). Conclusion Contrasting with adult eye-tracking data and child and adolescent data from reaction time indices of attention biases to threat, there was no vigilance bias toward threat in anxious youths. Instead, anxious youths were more avoidant of threat across the time course of stimulus viewing. Developmental differences in brain circuits contributing to attention deployment to emotional stimuli and their relationship with anxiety are discussed.

  • Review: Exteroceptive Sensory Abnormalities in Childhood and Adolescent Anxiety and Obsessive-Compulsive Disorder: A Critical Review
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-06-29
    David C. Houghton, Dan J. Stein, Bernadette M. Cortese

    Objective Childhood anxiety and obsessive-compulsive disorder (OCD) are defined by fear, worry, and uncertainty, but there is also evidence that affected children possess exteroceptive sensory abnormalities. These sensory features may often instigate symptoms and cause significant distress and functional impairment. In addition, a purported class of conditions known as “sensory processing disorders” may significantly overlap with childhood anxiety and OCD, which provides further support for a connection between abnormal sensation and fear-based psychopathology. Method The current review was conducted to synthesize and to critically evaluate the existing research on exteroceptive sensory abnormalities in childhood anxiety and OCD. Because of the paucity of research in this area, studies with adult populations were also briefly reviewed. Results The review found significant support for the notion that sensory abnormalities are common in children with anxiety disorders and OCD, but there are significant limitations to research in this area that prevent firm conclusions. Conclusion Potential avenues for future research on sensory features of pediatric anxiety and OCD are discussed.

  • Sensory-to-Cognitive Systems Integration Is Associated With Clinical Severity in Autism Spectrum Disorder
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-06-28
    Kenia Martínez, Magdalena Martínez-García, Luis Marcos-Vidal, Joost Janssen, Francisco X. Castellanos, Clara Pretus, Óscar Villarroya, Laura Pina-Camacho, Covadonga M. Díaz-Caneja, Mara Parellada, Celso Arango, Manuel Desco, Jorge Sepulcre, Susanna Carmona

    Objective Impaired multisensory integration in autism spectrum disorder (ASD) may arise from functional dysconnectivity among brain systems. Our study examines the functional connectivity integration between primary modal sensory regions and heteromodal processing cortex in ASD, and whether abnormalities in network integration relate to clinical severity. Method We studied a sample of 55 high-functioning ASD and 64 healthy control (HC) male children and adolescents (total n = 119, age range 7−18 years). Stepwise functional connectivity analysis (SFC) was applied to resting state functional magnetic resonance images (rsfMRI) to characterize the connectivity paths that link primary sensory cortices to higher-order brain cognitive functional circuits and to relate alterations in functional connectivity integration with three clinical scales: Social Communication Questionnaire, Social Responsiveness Scale, and Vineland Adaptive Behavior Scales. Results HC displayed typical functional connectivity transitions from primary sensory systems to association areas, but the ASD group showed altered patterns of multimodal sensory integration to heteromodal systems. Specifically, compared to the HC group, the ASD group showed the following: (1) hyperconnectivity in the visual cortex at initial link step distances; (2) hyperconnectivity between sensory unimodal regions and regions of the default mode network; and (3) hypoconnectivity between sensory unimodal regions and areas of the fronto-parietal and attentional networks. These patterns of hyper- and hypoconnectivity were associated with increased clinical severity in ASD. Conclusion Networkwise reorganization in high-functioning ASD individuals affects strategic regions of unimodal-to-heteromodal cortical integration predicting clinical severity. In addition, SFC analysis appears to be a promising approach for studying the neural pathophysiology of multisensory integration deficits in ASD.

  • Mechanisms of Change in the Prevention of Depression: An Indicated School-Based Prevention Trial at the Transition to High School
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-06-20
    Jennifer B. Blossom, Molly C. Adrian, Ann Vander Stoep, Elizabeth McCauley

    Objective Depression represents a major public health concern, and prevalence increases significantly during adolescence. The high school transition may exacerbate the risk of depression for youth with pre-existing vulnerability. The High School Transition Program (HSTP) is a brief, skills-based intervention that has demonstrated efficacy in preventing depression in adolescents. The current study aimed to evaluate the theorized mechanisms of change of the HSTP intervention by testing a multiple mediation model including school attachment (SA) and self-esteem (SE) as two mediators of treatment outcomes. Method Students (N= 497; 61.5% girls) with elevated depressive symptoms, identified for the intervention program via an eighth-grade screening, were randomized to a brief intervention (n = 247) or the HSTP (n = 233) from 2003 to 2008. Participants completed measures at five time points. The first assessment occurred at the start of the second semester of eighth grade and the last assessment occurred at the end of ninth grade. A multiple mediation model tested whether SA and SE contributed to changes in depression for youth in the HSTP. Results The mediation model, including contemporaneously assessed SE and SA, was not supported. There was evidence of sequential mediation, such that students who participated in the HSTP intervention reported higher SA, which in turn predicted improved SE, and in turn contributed to amelioration of depressive symptoms. Conclusion The HSTP intervention ameliorated depressive symptoms by targeting factors specific to the school transition (ie, SA). Results suggest youth at risk for depression may benefit from prevention efforts that enhance students’ capacity to effectively manage identified environmental stressors, such as school transitions. Clinical trial registration information Middle School to High School Transition Project: Depression and Substance Abuse Prevention; https://clinicaltrials.gov/; NCT00071513.

  • Avoidance, Insight, Impairment Recognition Concordance, and Cognitive-Behavioral Therapy Outcomes in Pediatric Obsessive-Compulsive Disorder
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-06-20
    Robert R. Selles, Davið R.M.A. Højgaard, Tord Ivarsson, Per Hove Thomsen, Nicole Michelle McBride, Eric A. Storch, Daniel Geller, Sabine Wilhelm, Lara J. Farrell, Allison M. Waters, Sharna Mathieu, S. Evelyn Stewart

    Objective Insight and avoidance are commonly discussed factors in obsessive-compulsive disorder (OCD) that have demonstrated associations with increased severity as well as reduced treatment response in adults, but these factors have not been sufficiently examined in pediatric OCD. This study examined the impacts of avoidance, insight, and impairment recognition concordance on cognitive-behavioral therapy (CBT) outcomes as well as impacts of CBT on insight and avoidance in a large sample of youths affected by OCD. Method Data from 573 OCD-affected youths enrolled in CBT trials were aggregated. Children’s Yale-Brown Obsessive-Compulsive Scale items measured treatment response, insight, and avoidance. Standardized differences between child and parent ratings of impairment were used to calculate impairment recognition concordance. Binary logistic regression was used to identify variables associated with treatment response. Results Greater avoidance, limited child recognition of impairment, older age, and lower baseline severity predicted reduced likelihood of treatment response, but insight did not. Both insight and avoidance improved significantly following CBT. Response rates were lower when posttreatment insight and avoidance were worse. Conclusion Contrasting with prevailing belief, poor insight does not appear to limit CBT response potential in pediatric OCD. Avoidance and impairment recognition are understudied CBT response predictors and warrant further consideration in pediatric OCD. Clinicians should attend to these factors to optimize outcomes for children affected by this common, debilitating illness.

  • Antidepressant Tolerability in Pediatric Anxiety and Obsessive-Compulsive Disorders: A Bayesian Hierarchical Modeling Meta-Analysis
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-11-01
    Jeffrey A. Mills, Jeffrey R. Strawn

    Objective To compare antidepressant-related adverse events (AEs), suicidality and AE-related discontinuation in double-blind, placebo-controlled trials of pediatric patients with OCD and anxiety disorders treated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Method MEDLINE, PubMed, Web of Science, PsycINFO and Embase were searched for peer-reviewed, English-language articles from inception through March 1, 2019. We identified prospective, randomized, SSRI and SNRI studies in patients <18 years of age with OCD, generalized, separation or social anxiety disorders. AE rates were extracted and antidepressant-placebo differences examined using Bayesian hierarchical models (BHM) then posterior estimates of relative risk (RR) was determined for each AE by medication class and disorder. Results Data were included from 18 trials (2631 patients) and 7 medications (16 SSRI and 4 SNRI trials). Compared to placebo, SSRIs were associated with a greater likelihood of AE-related discontinuation (RR: 3.59, CrI: 0.019 to 0.067, p=0.0003), activation (RR: 2.39, CrI: 0.048 to 0.125, p=0.003), sedation (RR: 1.94, CrI: 0.035 to 0.157, p=0.002), insomnia (RR: 1.93, CrI: 0.040 to 0.149, p=0.001), abdominal pain (RR: 1.53, Credible Interval [CrI]: 0.032 to 0.164, p=0.005) and headache (RR: 1.24, CrI: 0.003 to 0.139, p=0.04). Activation was more common with SSRI (vs. SNRIs, RR: 1.32, CrI: 0.018 to 0.114, p=0.007). Neither SSRIs nor SNRIs were associated with treatment-emergent suicidality. Conclusion In pediatric OCD and anxiety disorders, SSRIs (compared to placebo) are associated with distinct adverse events (AEs) and greater AE-related discontinuation, although their tolerability does not differ between anxiety disorders and OCD. Compared to SNRIs, SSRIs are more likely to produce activation. Class-related AEs are important for clinicians to consider, particularly in light of data suggesting differences in class-related efficacy. While SSRIs are superior to SNRIs and the treatment of choice for anxiety, for youth who become activated on SSRIs, SNRIs might represent a good second choice given their reported efficacy and lower risk of activation.

  • Meta-Analysis: Exposure to Early Life Stress and Risk for Depression in Childhood and Adolescence
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-10-30
    Joelle LeMoult, Kathryn L. Humphreys, Alison Tracy, Jennifer-Ashley Hoffmeister, Eunice Ip, Ian H. Gotlib

    Objective Early life stress (ELS) is associated with increased risk for the development of major depressive disorder (MDD) in adulthood; the degree to which ELS is associated with an early onset of MDD (ie, during childhood or adolescence), however, is not known. In this meta-analysis, we estimated the associations between ELS and the risk for onset of MDD before age 18 years. In addition, we examined the associations between eight specific forms of ELS (ie, sexual abuse, physical abuse, poverty, physical illness/injury, death of a family member, domestic violence, natural disaster, and emotional abuse) and risk for youth-onset MDD. Method We conducted a systematic search in scientific databases for studies that assessed both ELS and the presence or absence of MDD before age 18 years. We identified 62 journal articles with a total of 44,066 unique participants. We assessed study quality using the Newcastle-Ottawa Scale. When heterogeneous effect sizes were detected, we tested whether demographic and/or methodological factors moderated the association between ELS and MDD. Results Using a random-effects meta-analysis, we found that individuals who experienced ELS were more likely to develop MDD before the age of 18 than were individuals without a history of ELS (OR=2.50; 95% CI [2.08, 3.00]). Separate meta-analyses revealed a range of associations with MDD; while some types of ELS (eg, poverty) were not associated with MDD, other types (eg, emotional abuse) were associated more strongly with MDD than was ELS considered more broadly. Conclusion These findings provide important evidence that the adverse effect of ELS on MDD risk manifests early in development, prior to adulthood, and varies by type of ELS.

  • Systematic Review: Anxiety in Children and Adolescents With Chronic Medical Conditions
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-10-30
    Vanessa E. Cobham, Anna Hickling, Hayley Kimball, Hannah J. Thomas, James G. Scott, Christel M. Middeldorp

    Objective Youth with chronic medical conditions (CMCs) have been reported to be at increased risk of developing anxiety disorders. Importantly, suffering from anxiety may also impact their disease-related outcomes. This study set out to systematically review the literature on anxiety and seven CMCs among youth (asthma, congenital heart disease, diabetes, epilepsy, inflammatory bowel disease, juvenile idiopathic arthritis and sickle cell disease). Method A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Searches were conducted across PubMed, PsycNET, Embase, and reference lists of the included studies (1990–2018). Three independent reviewers screened titles and abstracts and conducted full-text assessment. Studies were included if they reported the prevalence of anxiety or the association of anxiety on disease-related outcomes in children and/or adolescents with the focal CMCs. Results Fifty-three studies met the predetermined inclusion criteria. Across the CMCs, the prevalence of anxiety disorder was increased in youth with CMCs compared to the general population. Evidence for a relationship between anxiety and adverse disease-related outcomes was limited. For asthma, inflammatory bowel disease and sickle cell disease, there was some evidence indicating that anxiety was associated with adverse outcomes; supported by two longitudinal studies, one in asthma and one in inflammatory bowel disease. For diabetes, results were inconsistent; with some studies indicating that anxiety was associated with worse and others with better treatment adherence. Conclusion The prevalence of anxiety disorders in youth with CMCs is higher than that of the general population. Anxiety may also be associated with adverse disease-related outcomes for youth, but it is not possible to draw definitive conclusions. Longitudinal studies making use of parent/youth composite anxiety measures and a combination of parent/youth reported and objective measures of disease-related outcomes are needed. Given the burden of disease of anxiety disorders; regardless of the impact on the disease outcomes, screening for and treatment of anxiety is recommended in youth with CMCs.

  • Editorial: Stimulants: Friend or Foe?
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-11-24
    Timothy E Wilens,Tamar Arit Kaminski

    Stimulants remain the treatment of choice for attention-deficit/hyperactivity disorder (ADHD), in part owing to their large effect size within the pharmacotherapeutic repertoire for ADHD-in other words, they are highly effective. When used appropriately, they are also quite safe and actually mitigate the misuse of drugs or alcohol. So, why all the fuss?

  • Editorial: Beyond the Prior Authorization: Multimodal Efforts to Reduce Antipsychotic Medication Prescribing in Foster Care Youth.
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-11-16
    David C Rettew

    When it comes to efforts to reduce the overprescribing of psychiatric medications, the first thing that comes to mind for many clinicians is burdensome prior authorizations or generic letters from insurance companies telling you things you already know. Most psychiatrists and primary care clinicians are well aware of the potential risks associated with drugs such as antipsychotic medications, and many wonder if these intrusions into the doctor-patient relationship go beyond saving money and actually contribute to improved care.

  • Clinical Affective Neuroscience.
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2018-12-14
    Anne E Penner,Joel Stoddard

    Affective neuroscience is a promising young field in neuroscience for understanding the basis of many types of psychopathology. It describes the scientific investigation of the neural basis of affect, emotion, and feelings. These phenomena arise from mental processes that are not always directly observable, which complicates discovering their neural basis. Nevertheless, as it has done for other inferred processes, such as memory and language, neuroscience should transform our emotion-based patient formulations and lead to novel, targeted therapeutics for emotional issues. In this Translations article, we aim to provide a brief introduction to affective neuroscience for clinicians, beginning with defining key terms and then reviewing clinical applications.

  • Mobile Health (mHealth): Building the Case for Adapting Emerging Technologies for Justice-Involved Youth.
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2018-12-14
    Eraka Bath,Marina Tolou-Shams,David Farabee

    The term justice-involved youth encompasses a broad range of youth. It can include youth who have not been detained and have been placed on probation or diversion programs, as well re-entry populations transitioning out of detention facilities or stated custody and placed on probation or parole. There are more than 1.3 million juvenile arrests per year, and on any given day there are 50,821 youth incarcerated in the United States. Of the 716,000 delinquency cases, probation is court-ordered for approximately half.1 Even among these youth who are supervised in the community, rates of mental health and substance use disorders are high, with more than two-thirds reporting substance use problems or other mental health disorders.2 However, these youth often have a hard time connecting to and staying in treatment,3 and recidivism is high-most commonly for failing to satisfy the myriad (and well intentioned) conditions of their probation.4 Dual diagnosis (ie, co-occurring psychiatric and substance use disorders) in justice-involved youth is one of the most significant predictors of recidivism,5 and, as such, closing the gap between need and receipt of substance use and mental health treatment for justice-involved youth could potentially offset rates of re-offending into adulthood.6 Despite high rates of mental health and substance use disorders among justice-involved adolescents, only 15% of detained youth receive mental health treatment for their condition(s); this number falls to 8% once these youth re-enter the community.7 These statistics regarding treatment receipt among justice-involved youth are important to consider not only from a health care perspective but also in terms of public health significance and policy.

  • Co-occurrence of Avoidant/Restrictive Food Intake Disorder and Traditional Eating Psychopathology.
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-11-30
    Kendra R Becker,Lauren Breithaupt,Elizabeth A Lawson,Kamryn T Eddy,Jennifer J Thomas

  • High Viewership of Videos About Teenage Suicide on YouTube.
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-11-05
    Anjali Dagar,Tatiana Falcone

    The recent rise in suicide rate of teenagers has coincided with their increasing use of social media sites. YouTube is the social media platform most commonly used by teenagers. Recent research studies and news reports have highlighted serious concerns about the nature of information available on YouTube and its potential impact. Owing to such concerns, the aim of our study was to analyze videos about teenage suicide on YouTube and viewers' engagement with them. We conducted a comprehensive search and analyzed unique videos in the English language with ≥1,000 views. The videos were categorized and compared based on their source. The tone of top 10 comments, based on viewer engagement, was analyzed as well. Statistical analysis, including Kruskal-Wallis tests to compare the videos, was conducted. The final analysis included 413 videos, with cumulative 482,736,217 views. Close to half (48.6%) of the videos were educational, and almost a third (29.3%) were about awareness/prevention of teenage suicide. Only 8.2% of videos were from academic sources. Among the 2,500 comments analyzed, 29.5% had a positive tone, and 7.5% expressed frank suicidal ideation or explicitly sought help against such thoughts. In conclusion, the extremely high viewership of videos on teenage suicide, which overwhelmingly convey a positive message, speaks to the demand for such content online and therefore reflects an online cry for help by teenagers. On the same note, this high demand also provides us a great opportunity to engage teenagers for suicide prevention through YouTube.

  • 更新日期:2019-11-01
  • Corrigendum.
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2017-06-26

  • 更新日期:2019-11-01
  • Transparency: Disclosure of Financial Interests.
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : null

    In keeping with the Journal's policies,1 we provide a listing of disclosures for all members of the editorial masthead and the ad hoc and guest editors (marked with an asterisk) as of October 3, 2019. This list, based on annually updated signed statements on file in the editorial office, includes all biomedical financial interests and potential conflicts of interest disclosed for the previous 24 months and the foreseeable future.

  • Invisible Allies: Thanking Our Reviewers.
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : null

    Reviewing manuscripts is hard work. We wish to express our heartfelt appreciation to the 493 hard workers listed below, who so diligently served their Journal between July 1, 2018, and June 30, 2019. Our additional gratitude is to our 17 colleagues (Matthew G. Biel, Daniel A. Geller, Mary Margaret Gleason, Michelle S. Horner, Ellen Leibenluft, Bennett L. Leventhal, Christel Middeldorp, Armin Raznahan, Laura Richardson, Neal D. Ryan, Lawrence Scahill, Manpreet K. Singh, Joel S. Stoddard, Argyris Stringaris, Peter Szatmari, Amy E. West, and Bonnie T. Zima) who served as ad hoc and guest editors and helped ensure that all manuscripts, our own included, were treated under the same editorial standards. We also would like to acknowledge the four colleagues who are completing their terms on our Editorial Board (Benjamin I. Goldstein, Guilherme V. Polanczyk, Manpreet K. Singh, and Argyris Stringaris) and the six colleagues who will be joining the Editorial Board in 2020 (Kathryn Regan Cullen, Stefan Ehrlich, Ryan J. Herringa, and Emily A. Simonoff, Assistant Editor Lesha D. Shah, and John F. McDermott, MD, Assistant Editor-in-Residence Anne Baden McBride).

  • "Just Breathe".
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : null
    Julie A Chilton

  • Juvenile Radicalization Into Violent Extremism: Investigative and Research Perspectives.
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : null
    Randy Borum,Terri D Patterson

    At least since the September 11, 2001 (9/11) terrorist attacks on America, Western countries have ranked terrorism as a high-priority security threat. Many Western nations have viewed violent extremism principally as an external threat-committed on or against one's homeland by individuals who have migrated or traveled from a foreign country. More recently, however, concern has accelerated about violent extremism emerging from people who have been born in, or at least spent considerable time as a resident of, the target country. This has been labeled "homegrown violent extremism" (HVE).

  • Considerations for Treating Young People With Comorbid Autism Spectrum Disorder and Substance Use Disorder.
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : null
    Benjamin M Isenberg,Amy M Yule,James W McKowen,Lisa A Nowinski,Gina A Forchelli,Timothy E Wilens

    Although substance use disorder (SUD) and autism spectrum disorder (ASD) are highly comorbid with other mental disorders and commonly have onset during childhood,1 little attention has been paid to their overlap. Despite limited data suggesting that up to 4% of patients with ASD also have substance-related problems,2 there are no existing guidelines, protocols, or tailored resources focused on SUD in young people with co-occurring ASD. This is concerning given that the simultaneous presence of these disorders presents unique challenges that complicate clinical care. In particular, many of the symptoms of ASD can interfere with standard SUD treatment. Thus, when treating patients with this comorbidity, practitioners should consider the following: communication difficulties, diminished capacity for motivation and insight, limited social interactions, and obstacles to treatment engagement.

  • Change in Psychotropic Prescribing Patterns Among Youths in Foster Care Associated With a Peer-to-Peer Physician Consultation Program.
    J. Am. Acad. Child Adolesc. Psychiatry (IF 6.391) Pub Date : 2019-08-03
    Brea Perry,Kelda Harris Walsh,Martin H Plawecki,Jill C Fodstad,Hillary S Blake,Amber Hunt,Carol Ott,Richard Rowlison,William R McConnell,Katlyn Kleimola,Leslie A Hulvershorn

    There has been growing concern about the safety and efficacy of psychotropic prescribing practices for children enrolled in Medicaid and in foster care.1 In response, accreditation organizations and policymakers have developed standards for optimal use of psychotropic medications among children.2 In addition, federal legislation has prompted states to implement monitoring programs to address quality and safety issues among vulnerable pediatric subpopulations.3,4 Here, we report findings from an evaluation of Indiana's program for foster youth, which used outlier case review followed by peer-to-peer consultation between prescribing physicians and child and adolescent psychiatrists. We observed clinically and statistically significant reductions in polypharmacy, off-label prescribing, inpatient hospitalizations, health care costs, and related outcomes among youths randomized to an immediate intervention group compared to no improvements in a waitlist control group.

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