Dimensional profiling of psychopathology in children and adolescents based on the K-SADS-PL and an analysis of the construct validity of two ADHD symptom dimensions.

OBJECTIVES: The traditional view on psychiatric disorders as categorical and distinct is being challenged by perspectives emphasizing the relevance of dimensional and transdiagnostic assessment. However, most diagnostic instruments are based on a categorical view with a threshold-approach to disease classification. METHODS: We here describe algorithms for dimensionalizing the psychopathological ratings of the widely used diagnostic interview for children and adolescents, the Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (K-SADS-PL). We further evaluate the criterion-related construct validity of the dimensionalized attention-deficit/hyperactivity disorder (ADHD) scales using Rasch models in a sample of 590 children (mean age 10.29 (.36), 49% girls). RESULTS: The algorithms generate scores of current symptom load, i.e., the sum of clinician-rated symptoms within each disorder assessed with the interview. We found support for counting symptoms of inattention and hyperactivity/impulsivity, respectively, but not for a single combined ADHD scale. CONCLUSIONS: The algorithms constitute an initial step in creating a framework for clinician-rated dimensional analyses of symptoms derived from the K-SADS-PL, but future studies are needed to further evaluate the construct validity of the remaining scales and the reliability and clinical utility of the method. We believe that our proposed algorithms offer a novel method of dimensional psychopathological assessment, which can be applied in multiple branches of child and adolescent psychiatry.

Predicting individual cases of major adolescent psychiatric conditions with artificial intelligence.

Three-quarters of lifetime mental illness occurs by the age of 24, but relatively little is known about how to robustly identify youth at risk to target intervention efforts known to improve outcomes. Barriers to knowledge have included obtaining robust predictions while simultaneously analyzing large numbers of different types of candidate predictors. In a new, large, transdiagnostic youth sample and multidomain high-dimension data, we used 160 candidate predictors encompassing neural, prenatal, developmental, physiologic, sociocultural, environmental, emotional and cognitive features and leveraged three different machine learning algorithms optimized with a novel artificial intelligence meta-learning technique to predict individual cases of anxiety, depression, attention deficit, disruptive behaviors and post-traumatic stress. Our models tested well in unseen, held-out data (AUC ≥ 0.94). By utilizing a large-scale design and advanced computational approaches, we were able to compare the relative predictive ability of neural versus psychosocial features in a principled manner and found that psychosocial features consistently outperformed neural metrics in their relative ability to deliver robust predictions of individual cases. We found that deep learning with artificial neural networks and tree-based learning with XGBoost outperformed logistic regression with ElasticNet, supporting the conceptualization of mental illnesses as multifactorial disease processes with non-linear relationships among predictors that can be robustly modeled with computational psychiatry techniques. To our knowledge, this is the first study to test the relative predictive ability of these gold-standard algorithms from different classes across multiple mental health conditions in youth within the same study design in multidomain data utilizing >100 candidate predictors. Further research is suggested to explore these findings in longitudinal data and validate results in an external dataset.

Transgenerational Inheritance and Systemic Racism in America.

Objective: It is well established that personal experiences of trauma, adversity, and discrimination can "get under the skin" and increase risk for a whole host of negative mental and physical health outcomes. The aim of this article is to review emerging research on transgenerational epigenetic inheritance which suggests that negative exposures in one generation, can also be passed down to affect the health and well-being of future generations. Method: This paper reviews key concepts in transgenerational epigenetic inheritance research, select animal and human studies examining the role of epigenetic mechanisms in transmitting the impact of ancestral stress and trauma, poor nutrition, and toxicant exposure across generations, and factors that can mitigate the effects of these experiences. Results: The animal studies provide compelling evidence for a role for these mechanisms in the transmission of the negative effects associated with ancestral adversities. Animal and clinical studies also suggest that the negative impact of personal and ancestral traumas can be prevented, with a role for in humans for evidence-based trauma treatments, culturally adapted prevention and intervention programs, and enrichment opportunities strongly indicated. Conclusions: Although comparable definitive data is lacking in multigenerational human cohorts, preliminary data supports a potential role for transgenerational epigenetic mechanisms in explaining persistent health disparities in the absence of personal exposures, and further elucidation of these mechanisms may guide the design of novel interventions. In addressing ancestral traumas, however, true change and healing will require acknowledgement of the harms that were done, and broader systemic policy level changes.

The Coronavirus Impact Scale: Construction, Validation, and Comparisons in Diverse Clinical Samples.

Objective: This report is of the construction and initial psychometric properties of the Coronavirus Impact Scale in multiple large and diverse samples of families with children and adolescents. The scale was established to capture the impact of the coronavirus pandemic during its first wave. Differences in impact between samples and internal structure within samples were assessed. Method: A total of 572 caregivers of children and adolescents or expecting mothers in diverse clinical and research settings completed the Coronavirus Impact Scale. Samples differed in regard to developmental stage, background, inpatient/outpatient status, and primary research or clinical setting. Model free methods were used to measure the scale's internal structure and to determine a scoring method. Differences between samples in specific item responses were measured by multivariate ordinal regression. Results: The Coronavirus Impact Scale demonstrated good internal consistency in a variety of clinical and research populations. Across the groups studied, single, immigrant, predominantly Latinx mothers of young children reported the greatest impact of the pandemic, with noteworthy effects on food access and finances reported. Individuals receiving outpatient or inpatient care reported greater impacts on health care access. Elevated scores on the Coronavirus Impact Scale were positively associated with measures of caregiver anxiety and both caregiver- and child-reported stress at a moderate effect size. Conclusion: The Coronavirus Impact Scale is a publicly available scale with adequate psychometric properties for use in measuring the impact of the coronavirus pandemic in diverse populations.

Financial stress as a mediator of the association between maternal childhood adversity and infant birth weight, gestational age, and NICU admission.

BACKGROUND: To examine whether financial stress during pregnancy mediates the association between maternal exposure to adverse childhood experiences (ACEs) and three birth outcomes (i.e., gestational age, birth weight, and admission to the neonatal intensive care unit [NICU]). METHODS: Data were obtained from a prospective cohort study of pregnant women and their infants in Florida and North Carolina. Mothers (n = 531; Mage at delivery = 29.8 years; 38% Black; 22% Hispanic) self-reported their exposure to childhood adversity and financial stress during pregnancy. Data on infant gestational age at birth, birth weight, and admission to the NICU were obtained from medical records within 7 days of delivery. Mediation analysis was used to test study hypotheses, adjusting for study cohort, maternal race, ethnicity, body mass index, and tobacco use during pregnancy. RESULTS: There was evidence of an indirect association between maternal exposure to childhood adversity and infant gestational age at birth (b = -0.03, 95% CI = -0.06 - -0.01) and infant birth weight (b = -8.85, 95% CI = -18.60 - -1.28) such that higher maternal ACE score was associated with earlier gestational age and lower infant birth weight through increases in financial distress during pregnancy. There was no evidence of an indirect association between maternal exposure to childhood adversity and infant NICU admission (b = 0.01, 95% CI = -0.02-0.08). CONCLUSIONS: Findings demonstrate one pathway linking maternal childhood adversity to a potentially preterm birth or shorter gestational age, in addition to low birth weight at delivery, and present an opportunity for targeted intervention to support expecting mothers who face financial stress.

DNA methylation signatures as biomarkers of socioeconomic position.

This review article provides a framework for the use of deoxyribonucleic acid (DNA) methylation (DNAm) biomarkers to study the biological embedding of socioeconomic position (SEP) and summarizes the latest developments in the area. It presents the emerging literature showing associations between individual- and neighborhood-level SEP exposures and DNAm across the life course. In contrast to questionnaire-based methods of assessing SEP, we suggest that DNAm biomarkers may offer an accessible metric to study questions about SEP and health outcomes, acting as a personal dosimeter of exposure. However, further work remains in standardizing SEP measures across studies and evaluating consistency across domains, tissue types, and time periods. Meta-analyses of epigenetic associations with SEP are offered as one approach to confirm the replication of DNAm loci across studies. The development of DNAm biomarkers of SEP would provide a method for examining its impact on health outcomes in a more robust way, increasing the rigor of epidemiological studies.

KSADS-COMP Perspectives on Child Psychiatric Diagnostic Assessment and Treatment Planning.

Gibbons et al.1 demonstrated the utility of computerized adaptive tests (CATs) based on multidimensional item response theory for the assessment of depression, anxiety, mania/hypomania, attention-deficit/hyperactivity disorder, conduct disorder, oppositional defiant disorder, and suicidality in children and adolescents. The Kiddie-Computerized Adaptive Test (K-CAT) demonstrated good convergent validity, test-retest reliability, and diagnostic concordance with diagnoses derived using the paper-and-pencil Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) child psychiatric interview.

Obsessive-Compulsive Disorder in the Adolescent Brain Cognitive Development Study: Impact of Changes From DSM-IV to DSM-5.

The Diagnostic and Statistical Manual of Mental Disorders (DSM), used to diagnose psychiatric disorders, was revised to DSM-5 in 2013. Changes were made to the criteria for obsessive-compulsive disorder (OCD), a disorder with a lifetime prevalence of 1% to 3% in children.1 Prior revisions to OCD criteria (from DSM-III to DSM-IV) resulted in lower reported prevalence rates,2 but this is not yet clear with DSM-5. In DSM-5, the definition of obsessions was broadened (Table 1), and the requirement that obsessions cause marked anxiety or distress was removed. Thus we examined rates of OCD within the Adolescent Brain Cognitive Development (ABCD) study3 using both DSM-IV and DSM-5 criteria.

Challenges and Opportunities in China's Health Aid to Africa: Findings from Qualitative Interviews in Tanzania and Malawi.

BACKGROUND: China has played an increasing role in development aid across Africa. Most recently, China has increased its external investments through the Belt and Road Initiative, China's signature infrastructure and trade drive to link China to Asia and Africa. This is likely to result in continuing growth of China's investment in health in sub Saharan Africa. While conflicting opinions have been raised regarding the motivation and value of these investments, few data have been solicited from those directly involved in China-Africa health aid. We conducted a qualitative study to collect information on perceptions and opinions regarding Chinese-supported health related activities in Africa through in-depth interviews among local African and Chinese participants in Malawi and Tanzania. RESULTS: Our findings reveal shared experiences and views related to challenges in communication; cultural perspectives and historical context; divergence between political and business agendas; organization of aid implementation; management and leadership; and sustainability. Participants were broadly supportive and highly valued Chinese health aid. However, they also shared common insights that relate to challenging coordination between China and recipient countries; impediments to communication between health teams; and limited understanding of priorities and expectations. Further, they share perspectives about the need for shaping the assistance based on needs assessments as well as the importance of rigorous reporting, and monitoring and evaluation systems. Our findings suggest that China faces similar challenges to those experienced by other longstanding development aid and global health donors. As it continues to expand cooperation across Africa and other regions, it will be important for China to consider the issues identified through our study to help inform collaborative and effective global health assistance programs. The insights garnered from this research are not only relevant to China's engagement in Africa but for other global health assistance donors as well.

Tubulin Polymerization Promoting Protein (TPPP) gene methylation and corpus callosum measures in maltreated children.

The goal of the current study was to evaluate the impact of Tubulin Polymerization Promoting Protein (TPPP) methylation on structural and fractional anisotropy (FA) corpus callosum (CC) measures. TPPP is involved in the development of white matter tracts in the brain and was implicated in stress-related psychiatric disorders in an unbiased whole epigenome methylation study. The cohort included 63 participants (11.73 y/o ±1.91) from a larger study investigating risk and resilience in maltreated children. Voxel-based morphometry (VBM) was used to process the structural data, fractional anisotropy (FA) was determined using an atlas-based approach, and DNA specimens were derived from saliva in two batches using the 450 K (N = 39) and 850 K (N = 24) Illumina arrays, with the data from each batch analyzed separately. After controlling for multiple comparisons and relevant covariates (e.g., demographics, brain volume, cell composition, 3 PCs), 850 K derived TPPP methylation values, in interaction with a dimensional measure of children's trauma experiences, predicted left and right CC body volumes and genu, body and splenium FA (p < .007, all comparisons). The findings in the splenium replicated in subjects with the 450 K data. The results extend prior investigations and suggest a role for TPPP in brain changes associated with stress-related psychiatric disorders.

Social supports moderate the effects of child adversity on neural correlates of threat processing.

BACKGROUND: Child abuse and other forms of adversity are associated with alterations in threat processing and emotion regulation brain circuits. OBJECTIVE: The goal of the current investigation is to determine if the availability of positive social support can ameliorate the negative impact of adversity on these brain systems. PARTICIPANTS AND SETTING: Subjects included 55 children ages 7-16 (X = 11.8, SD = 2.0). Approximately one-third of the cohort had no significant history of adversity, one-third had a history of moderate adversity, and one-third had a history of severe adversity. Brain imaging was conducted at the University of Vermont using a 3.0 T Philips scanner. METHODS: The Emotional Go-NoGo task with fearful and calm facial stimuli was used to assess the neural correlates of threat processing and emotion regulation in children during functional magnetic resonance imaging (fMRI). Dimensional measures of anxiety, social supports, and children's adverse experiences were also obtained. RESULTS: A conjunction analysis was used to test if trauma-related brain activation in responding to fearful vs. calm targets was impacted by social support. This approach identified multiple activation foci, including a cluster extending from the left amygdala to several other key brain regions involved in emotion regulation, including the orbitofrontal cortex, anterior cingulate cortex (ACC), anterior insula, nucleus accumbens, and frontal pole (Family Wise Error (FWE) correction, p < 0.05). CONCLUSIONS: Greater social support may reduce the effect that adversity has on neural processing of threat stimuli, consistent with the protective role of positive supports in promoting resilience and recovery demonstrated in the literature.

Computer-Assisted Psychiatric Diagnosis.

Accurate psychiatric diagnosis is critical for both sound clinical interventions and valid research methodology. Over the years, attempts to improve diagnostic reliability and accuracy led to the development of more explicit operationalized diagnostic criteria, starting with DSM-III, and subsequently fully structured and semistructured diagnostic interviews.1 As diagnostic assessment changed and with advances in technology, the use of computers soon developed in parallel to improve the reliability and validity of psychiatric diagnosis. As far back as 1968, computers were used to help clinicians formulate psychiatric diagnoses, by helping them process clinical information according to diagnostic algorithms.2 Since that time, there has been an exponential rise in the use of technology in clinical research and practice. Indeed, computers have been used both to transition diagnostic interviews from paper-and-pencil format to instruments that are clinician-administered via an electronic platform and to create self-report versions of clinician-administered diagnostic interviews. We will discuss each of these in turn.

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.

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.

Child maltreatment and psychosis.

This paper reviews the literature on the association between experiences of child abuse and neglect and the development of psychoses. It then explores the premise that psychotic patients with a history of maltreatment may comprise a clinically and biological distinct subgroup. The review demonstrates that there is a growing consensus in the field that experiences of child maltreatment contribute to the onset of psychotic symptoms and psychotic disorders. There is also strong support for the premise that patients with psychotic disorders and histories of child maltreatment have distinct clinical characteristics and unique treatment needs, and emerging preliminary data to suggest psychotic patients with a history of maltreatment may comprise a distinct neurobiological subgroup. The mechanisms by which experiences of child maltreatment confers risk for psychotic disorders remains unknown, and the review highlights the value of incorporating translational research perspectives to advance knowledge in this area.

Correction to: China's health assistance to Africa: opportunism or altruism?

Please note that following publication of the original article [1], one of the authors has flagged that the abbreviations section lists "BRIC" as "Britain, Russia, India and China".

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.

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.