A multi-method and multi-informant approach to assessing post-traumatic stress disorder (PTSD) in children.

Trauma exposure is highly prevalent among children globally, and is associated with elevated rates of PTSD. The goal of this study was to systematically evaluate the effects of multiple informants and multiple screening measures on the identification of specific PTSD symptoms and rates of PTSD diagnoses. Participants in this study included 350 maltreated children from two cohorts, one recruited from Connecticut (n = 130), and the other from Vermont (n = 220). Both cohorts completed the Screen for Child Anxiety-Related Emotional Disorders (SCARED) before a PTSD self-report measure. The KSADS psychiatric interview was also completed with the Connecticut cohort, with best-estimate ratings generated using parent and child interview, child self-report, and teacher questionnaire data. In addition to the SCARED and PTSD self-report scale, parents of the Vermont cohort completed the Child Behavioural Checklist. Significant differences emerged between parent and child report of sleep, nightmares, concentration, and irritability problems, suggesting the need for multiple informants in PTSD screening. Children also under-reported nightmares when asked in the context of a trauma-specific screening tool. As child trauma is associated with a broad range of psychiatric sequelae, comprehensive assessment using both general symptomatology and trauma-specific measures is recommended, since children often shut down when completing trauma measures.

Adverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth.

OBJECTIVE: To determine if measures of adverse childhood experiences and DNA methylation relate to indices of obesity in youth. STUDY DESIGN: Participants were derived from a cohort of 321 8 to 15-year-old children recruited for an investigation examining risk and resilience and psychiatric outcomes in maltreated children. Assessments of obesity were collected as an add-on for a subset of 234 participants (56% female; 52% maltreated). Illumina arrays were used to examine whole genome epigenetic predictors of obesity in saliva DNA. For analytic purposes, the cohort analyzed in the first batch comprised the discovery sample (n = 160), and the cohort analyzed in the second batch the replication sample (n = 74). RESULTS: After controlling for race, sex, age, cell heterogeneity, 3 principal components, and whole genome testing, 10 methylation sites were found to interact with adverse childhood experiences to predict cross-sectional measures of body mass index, and an additional 6 sites were found to exert a main effect in predicting body mass index (P < 5.0 × 10-7, all comparisons). Eight of the methylation sites were in genes previously associated with obesity risk (eg, PCK2, CxCl10, BCAT1, HID1, PRDM16, MADD, PXDN, GALE), with several of the findings from the discovery data set replicated in the second cohort. CONCLUSIONS: This study lays the groundwork for future longitudinal studies to elucidate these mechanisms further and identify novel interventions to alleviate the health burdens associated with early adversity.

Development of Three Web-Based Computerized Versions of the Kiddie Schedule for Affective Disorders and Schizophrenia Child Psychiatric Diagnostic Interview: Preliminary Validity Data.

OBJECTIVE: To present initial validity data on three web-based computerized versions of the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-COMP). METHOD: The sample for evaluating the validity of the clinician-administered KSADS-COMP included 511 youths 6-18 years of age who were participants in the Child Mind Institute Healthy Brain Network. The sample for evaluating the parent and youth self-administered versions of the KSADS-COMP included 158 youths 11-17 years of age recruited from three academic institutions. RESULTS: Average administration time for completing the combined parent and youth clinician-administered KSADS-COMP was less time than previously reported for completing the paper-and-pencil K-SADS with only one informant (91.9 ± 50.1 minutes). Average administration times for the youth and parent self-administered KSADS-COMP were 50.9 ± 28.0 minutes and 63.2 ± 38.3 minutes, respectively, and youths and parents rated their experience using the web-based self-administered KSADS-COMP versions very positively. Diagnoses generated with all three KSADS-COMP versions demonstrated good convergent validity against established clinical rating scales and dimensional diagnostic-specific ratings derived from the KSADS-COMP. When parent and youth self-administered KSADS-COMP data were integrated, good to excellent concordance was also achieved between diagnoses derived using the self-administered and clinician-administered KSADS-COMP versions (area under the curve = 0.89-1.00). CONCLUSION: The three versions of the KSADS-COMP demonstrate promising psychometric properties, while offering efficiency in administration and scoring. The clinician-administered KSADS-COMP shows utility not only for research, but also for implementation in clinical practice, with self-report preinterview ratings that streamline administration. The self-administered KSADS-COMP versions have numerous potential research and clinical applications, including in large-scale epidemiological studies, in schools, in emergency departments, and in telehealth to address the critical shortage of child and adolescent mental health specialists. CLINICAL TRIAL REGISTRATION INFORMATION: Computerized Screening for Comorbidity in Adolescents With Substance or Psychiatric Disorders; https://clinicaltrials.gov/; NCT01866956.

Methylation in OTX2 and related genes, maltreatment, and depression in children.

Through unbiased transcriptomics and multiple molecular tools, transient downregulation of the Orthodenticle homeobox 2 (OTX2) gene was recently causatively associated with the development of depressive-like behaviors in a mouse model of early life stress. The analyses presented in this manuscript test the translational applicability of these findings by examining peripheral markers of methylation of OTX2 and OTX2-regulated genes in relation to measures of depression and resting-state functional connectivity data collected as part of a larger study examining risk and resilience in maltreated children. The sample included 157 children between the ages of 8 and 15 years (χ = 11.4, SD = 1.9). DNA specimens were derived from saliva samples and processed using the Illumina 450 K beadchip. A subset of children (N = 47) with DNA specimens also had resting-state functional MRI data. After controlling for demographic factors, cell heterogeneity, and three principal components, maltreatment history and methylation in OTX2 significantly predicted depression in the children. In terms of the imaging data, increased OTX2 methylation was found to be associated with increased functional connectivity between the right vmPFC and bilateral regions of the medial frontal cortex and the cingulate, including the subcallosal gyrus, frontal pole, and paracingulate gyrus-key structures implicated in depression. Mouse models of early stress hold significant promise in helping to unravel the mechanisms by which child adversity confers risk for psychopathology, with data presented in this manuscript supporting a potential role for OTX2 and OTX2-related (e.g., WNT1, PAX6) genes in the pathophysiology of stress-related depressive disorders in children.