Editorial: Can Improving Youth Mental Health Reduce Mortality?

It is well established that mental health conditions, including substance use disorders, are associated with premature mortality. A meta-analysis1 has demonstrated that this association holds across a range of diagnoses. Although the effect is stronger for schizophrenia, depression and anxiety contribute to more deaths overall because of their high prevalence rates. Moreover, more than two-thirds of associated deaths were explained by natural causes.1 The next logical questions, then, are as follows: which mechanisms underlie this association, and can they can be mitigated? In the current issue of JAACAP, Clark et al.2 aim to tie mental health symptoms and substance use to the acceleration of biological aging.

Polygenic Variation Underlying Educational Attainment and Attention-Deficit/Hyperactivity Disorder Indexes Behavior Ratings of Executive Functions in Child Psychiatry Outpatients.

OBJECTIVE: We leveraged common genetic variation underlying ADHD, educational attainment (EA) and cognition (COG) to understand the nature of the Behavior Rating Inventory for Executive Functions (BRIEF) and its relationship to academic functioning. METHOD: Participants were 991 youth, ages 7 to 17, consecutively referred for neuropsychiatric evaluation. Polygenic scores (PGS) for ADHD, EA, and COG were related to the BRIEF using regression analyses. Structural equation models were used to examine the associations between the PGS, BRIEF and academic outcomes (math, reading, and special education services [EDPLAN]). RESULTS: After modeling the PGS together, only the EA and ADHD PGS significantly associated with the BRIEF. The BRIEF partially mediated the relationships between EA PGS with math and EDPLAN and fully mediated the relationship between ADHD PGS and EDPLAN. CONCLUSION: Genetic data extend evidence that the BRIEF measures a construct relevant to educational success that differs from what is indexed by cognitive testing.

Editors' Best of 2023.

There is, in the content of the Journal, an embarrassment of riches, and picking a "best" seems to demand a certain qualification: is the "best" the most interesting, most surprising, most educational, most important, most provocative, most enjoyable? How to choose? We are hardly unbiased and can admit to a special affection for the ones that we and the authors worked hardest on, modifying version after version into shape. Acknowledging these biases, here are the 2023 articles that we think deserve your attention or at least a second read.

Editors' Note: Third Annual Report Regarding JAACAP's Antiracist Journey.

In 2020, we wrote to you of our dedication and vision for JAACAP "to be antiracist at every level."1 Over the last 3 years, we have pursued initiatives "to reshape the Journal to pursue this vision."2,3 In this article, we provide an update on these goals and initiatives (Figure 1). With the launching of our new open access journal, JAACAP Open,4 in late 2022, we now extend these initiatives to both scientific journals in the JAACAP family and aspire to be a leader among mental health journals in our intentional pursuit of antiracist policies and practices.

Differences in cognitive and academic performance during the COVID-19 pandemic in child psychiatric outpatients.

This study examined the impact of the COVID-19 pandemic on cognitive and academic functioning in 574 youth presenting for outpatient clinical neuropsychiatric evaluations. We extended the prior literature by (a) determining the extent to which academic difficulties documented in population and community samples also occurred in child psychiatric outpatients; (b) evaluating the impact of the pandemic on neuropsychological functions relevant to academic performance (overall cognition, executive functions, and graphomotor skill); and (c) investigating the moderating impact of attention deficit hyperactivity disorder (ADHD) diagnosis. We compared cross-sectional scores on standardized measures for groups of youth evaluated at three time periods related to the COVID-19 pandemic: (a) prior to onset (PRIOR; N = 198), (b) during Year 1 (Y1; N = 149), and (c) during Year 2 (Y2; N = 227). Relative to overall cognitive ability, math scores were lower in Y1 and Y2 and reading scores were lower in Y2. Additionally, relative to overall cognitive ability, youth showed lower working memory in Y1 and lower processing speed in Y1 and Y2. Graphomotor skill and parent-rated executive functions (EF) did not vary significantly across the three time periods. ADHD status did not moderate psychometric test scores but did moderate parent-rated EF. These data suggest that the COVID-19 pandemic has negatively impacted academic and executive functions in child psychiatry outpatients. More research is needed to understand the long-term implications for development. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Youth Team Sports Participation Associates With Reduced Dimensional Psychopathology Through Interaction With Biological Risk Factors.

Background: Physical activity is associated with mental health benefits in youth. Here, we used causal inference and triangulation with 2 levels of biology to substantiate relationships between sports participation and dimensional psychopathology in youths. Methods: Baseline data from the Adolescent Brain Cognitive Development (ABCD) Study, which recruited children from 9 to 10 years of age across the United States, were included in multilevel regression models to assess relationships between lifetime participation in team sports (TS), individual sports, and nonsports activities and Child Behavior Checklist (CBCL) scores. We calculated polygenic risk scores for 8 psychiatric disorders to assess interactions with sports exposure on CBCL scores among European descendants. Following rigorous quality control, FreeSurfer-extracted brain magnetic resonance imaging structural data were examined for mediation of CBCL-activities relationships. Results: Among those with complete data (N = 10,411), causal estimates using inverse probability weighting associated lifetime TS exposure with a 1.05-point reduction in CBCL total (95% CI, -1.54 to -0.56, p < .0001) a relationship that was specific to TS and strengthened with more years of exposure. Associations of attention-deficit/hyperactivity disorder polygenic loading with CBCL total weakened in European children with TS exposure (n = 4041; beta = -0.93, SE = 0.38, p = .013). Furthermore, TS participation and lower CBCL each associated with increased subcortical volumes (n = 8197). Subcortical volume mediated 5.5% of TS effects on CBCL total. Conclusions: Our findings support prior associations of TS participation with lower psychopathology in youths through additional studies that demonstrate specificity, dose response, and coherence across 2 levels of biology. Longitudinal studies that further clarify causal relationships may justify interventional studies of TS for high-risk youth.

Genetic patterning for child psychopathology is distinct from that for adults and implicates fetal cerebellar development.

Childhood psychiatric symptoms are often diffuse but can coalesce into discrete mental illnesses during late adolescence. We leveraged polygenic scores (PGSs) to parse genomic risk for childhood symptoms and to uncover related neurodevelopmental mechanisms with transcriptomic and neuroimaging data. In independent samples (Adolescent Brain Cognitive Development, Generation R) a narrow cross-disorder neurodevelopmental PGS, reflecting risk for attention deficit hyperactivity disorder, autism, depression and Tourette syndrome, predicted psychiatric symptoms through early adolescence with greater sensitivity than broad cross-disorder PGSs reflecting shared risk across eight psychiatric disorders, the disorder-specific PGS individually or two other narrow cross-disorder (Compulsive, Mood-Psychotic) scores. Neurodevelopmental PGS-associated genes were preferentially expressed in the cerebellum, where their expression peaked prenatally. Further, lower gray matter volumes in cerebellum and functionally coupled cortical regions associated with psychiatric symptoms in mid-childhood. These findings demonstrate that the genetic underpinnings of pediatric psychiatric symptoms differ from those of adult illness, and implicate fetal cerebellar developmental processes that endure through childhood.

Uncovering and mitigating bias in large, automated MRI analyses of brain development.

Large, population-based MRI studies of adolescents promise transformational insights into neurodevelopment and mental illness risk 1,2. However, MRI studies of youth are especially susceptible to motion and other artifacts 3,4. These artifacts may go undetected by automated quality control (QC) methods that are preferred in high-throughput imaging studies, 5 and can potentially introduce non-random noise into clinical association analyses. Here we demonstrate bias in structural MRI analyses of children due to inclusion of lower quality images, as identified through rigorous visual quality control of 11,263 T1 MRI scans obtained at age 9-10 through the Adolescent Brain Cognitive Development (ABCD) Study6. Compared to the best-rated images (44.9% of the sample), lower-quality images generally associated with decreased cortical thickness and increased cortical surface area measures (Cohen's d 0.14-2.84). Variable image quality led to counterintuitive patterns in analyses that associated structural MRI and clinical measures, as inclusion of lower-quality scans altered apparent effect sizes in ways that increased risk for both false positives and negatives. Quality-related biases were partially mitigated by controlling for surface hole number, an automated index of topological complexity that differentiated lower-quality scans with good specificity at Baseline (0.81-0.93) and in 1,000 Year 2 scans (0.88-1.00). However, even among the highest-rated images, subtle topological errors occurred during image preprocessing, and their correction through manual edits significantly and reproducibly changed thickness measurements across much of the cortex (d 0.15-0.92). These findings demonstrate that inadequate QC of youth structural MRI scans can undermine advantages of large sample size to detect meaningful associations.

Behavior ratings of executive functions index multiple domains of psychopathology and school functioning in child psychiatric outpatients.

Behavior rating scales of executive functions (EFs) are convenient and associate with academic and other outcomes; however, prior studies indicate limited correlations with psychometric tests of EFs. To better understand their potential for clinical utility, we examined the extent to which parent ratings on the Behavior Rating Inventory of Executive Function (BRIEF) related to psychopathology constructs and psychometric test scores in a sample of N = 692 psychiatric outpatients aged 8-17. Then, in a subsample of the youth (N = 261), we related the BRIEF, psychopathology constructs, and psychometric test scores to teacher ratings of school functioning. BRIEF scales were significantly associated with multiple types of psychopathology including ADHD, autism spectrum, mood, anxiety, conduct, oppositional defiant, and psychotic disorders. While the BRIEF showed limited associations with psychometric EF tests, its Global Executive Composite score explained additional variance in teacher-reported functioning beyond what was predicted by clinical diagnoses (additional explained variance of 9.9% in study skills) and psychometric tests (additional explained variance of 2.1% in learning problems and 4.5% in study skills). The Global Executive Composite was not significantly related to teacher-rated school functioning after psychiatric symptoms were accounted for. These findings support further investigation of the unique contribution of the BRIEF in clinical practice.

Associations Between Genetic Risk for Adult Suicide Attempt and Suicidal Behaviors in Young Children in the US.

Importance: Suicide rates have been increasing among youth in the US. While the heritability of suicide risk is well established, there is limited understanding of how genetic risk is associated with suicidal thoughts and behaviors in young children. Objective: To examine whether genetic susceptibility to suicide attempts (SAs) is associated with suicidal thoughts and behaviors in children. Design, Setting, and Participants: This case-control study examined data from the Adolescent Brain Cognitive Development (ABCD) study, a population-based longitudinal study of 11 878 US children enrolled at age 9 and 10 years from September 2016 to November 2018. Youth reports of suicidal ideation (SI) and SAs were obtained from the Kiddie Schedule for Affective Disorder and Schizophrenia at baseline and 2 subsequent years. After conservative quality control of genotype data, this analysis focused on 4344 unrelated individuals of European ancestry. Data analysis was conducted from November 2020 to February 2022. Main Outcomes and Measures: Children's lifetime experiences of SI and SAs were assessed each year from ages 9 to 10 years to ages 11 to 12 years. Polygenic risk scores (PRSs) for SAs were calculated for ABCD study participants based on the largest genome-wide association study of SA cases and controls of European ancestry (total sample n = 518 612). Results: Of 4344 children of European ancestry (2045 [47.08%] female; mean [SD] age, 9.93 [0.62] years), significant associations were found between children's SA PRSs and their lifetime SAs with the most robust association in the follow-up year 2 (odds ratio, 1.43 [95% CI, 1.18-1.75]; corrected P = 1.85 × 10-3; Nagelkerke pseudo R2 = 1.51%). These associations remained significant after accounting for children's sociodemographic backgrounds, psychopathology symptoms, parental histories of suicide and mental health, and PRSs for major depression and attention-deficit/hyperactivity disorder (likelihood ratio test P < .05). Children's depressive mood and aggressive behavior were the most significant partial mediators of SA genetic risk on SAs (mediation analysis P < 1 × 10-16). Children's behavioral problems, such as attention problems, rule-breaking behavior, and social problems, also partially mediated the association of SA PRSs with SAs (mediation analysis false discover rate < 0.05). Conclusions and Relevance: This study's findings indicate that there may be genetic factors associated with SA risk across the life span and suggest behaviors and conditions through which the risk could be mediated in childhood. Further research is warranted to examine whether incorporating genetic data could improve the identification of children at risk for suicide.

Identifying Pediatric Mood Disorders From Transdiagnostic Polygenic Risk Scores: A Study of Children and Adolescents.

Objective: Mood disorders often co-occur with attention-deficit/hyperactive disorder (ADHD), disruptive behavior disorders (DBDs), and aggression. We aimed to determine if polygenic risk scores (PRSs) based on external genome-wide association studies (GWASs) of these disorders could improve genetic identification of mood disorders.Methods: We combined 6 independent family studies that had genetic data and diagnoses for mood disorders that were made using different editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM). We identified mood disorders, either concurrently or in the future, in participants between 6 and 17 years of age using PRSs calculated using summary statistics of GWASs for ADHD, ADHD with DBD, major depressive disorder (MDD), bipolar disorder (BPD), and aggression to compute PRSs.Results: In our sample of 485 youths, 356 (73%) developed a subthreshold or full mood disorder and 129 (27%) did not. The cross-validated mean areas under the receiver operating characteristic curve (AUCs) for the 7 models identifying participants with any mood disorder ranged from 0.552 in the base model of age and sex to 0.648 in the base model + all 5 PRSs. When included in the base model individually, the ADHD PRS (OR = 1.65, P < .001), Aggression PRS (OR = 1.27, P = .02), and MDD PRS (OR = 1.23, P = .047) were significantly associated with the development of any mood disorder.Conclusions: Using PRSs for ADHD, MDD, BPD, DBDs, and aggression, we could modestly identify the presence of mood disorders. These findings extend evidence for transdiagnostic genetic components of psychiatric illness and demonstrate that PRSs calculated using traditional diagnostic boundaries can be useful within a transdiagnostic framework.

Distinct patterns of emotional and behavioral change in child psychiatry outpatients during the COVID-19 pandemic.

BACKGROUND: Studies are documenting the impact of the COVID-19 pandemic on youth mental health. We extended this literature by characterizing a child psychiatric outpatient sample in the United States during the middle of the 2020-2021 school year. We also used a computational strategy to identify distinct patterns of psychopathology symptom change and examined correlates and predictors of such change. Among potential predictors were cognition and clinical diagnoses, which have not been studied in this context previously. METHODS: Participants were 171 youth (aged 10.6 ± 3.1) referred for neuropsychiatric evaluation who enrolled in research and whose parents filled out a survey on COVID-19. The questionnaire included eight psychiatric and six psychosocial domains rated retrospectively prior to the pandemic and currently at the time of evaluation. We examined change in severity of individual domains with Wilcoxon signed-rank tests. We used a latent profile analysis (LPA) to identify groups with distinct symptom change profiles. Using multinomial logistic regression, we examined potential predictors and correlates of LPA-derived groups. Models controlled for age, sex, and assessment date and corrected for multiple testing. RESULTS: Although the majority of individual psychopathology domains were worse on average during the 2020-2021 school year, youth showed distincive patterns of symptom change. In addition to a large group (72.2%) with relatively stable symptoms and a small group (6.4%) that improved on most symptoms, there were two groups with different constellations of worsening symptoms. These latter groups both showed increased sadness, anxiety and oppositionality; however, one had increased hyperactivity/impulsivity and no change in hopelessness while the other showed greater hopelessness and no change in hyperactivity. Symptoms related to the distinguishable domains of these groups predicted group membership, and changes in screen time, conflict with parents and social isolation were correlates of worsening. Cognition and lifetime clinical diagnoses failed to predict group membership. CONCLUSIONS: In youth outpatients, psychiatric and psychosocial difficulties were worse on average during the school year following the spring 2020 COVID-19 lockdown; yet, some youth experienced greater and distinctive symptom change. A personalized approach to support may be needed as youth emerge from this period.

Genetic Association of Attention-Deficit/Hyperactivity Disorder and Major Depression With Suicidal Ideation and Attempts in Children: The Adolescent Brain Cognitive Development Study.

BACKGROUND: Suicide is among the leading causes of death in children and adolescents. There are well-known risk factors of suicide, including childhood abuse, family conflicts, social adversity, and psychopathology. While suicide risk is also known to be heritable, few studies have investigated genetic risk in younger individuals. METHODS: Using polygenic risk score analysis, we examined whether genetic susceptibility to major psychiatric disorders is associated with suicidal behaviors among 11,878 children enrolled in the ABCD (Adolescent Brain Cognitive Development) Study. Suicidal ideation and suicide attempt data were assessed using the youth report of the Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5. After performing robust quality control of genotype data, unrelated individuals of European descent were included in analyses (n = 4344). RESULTS: Among 8 psychiatric disorders we examined, depression polygenic risk scores were associated with lifetime suicide attempts both in the baseline (odds ratio = 1.55, 95% CI = 1.10-2.18, p = 1.27 × 10-2) and in the follow-up year (odds ratio = 1.38, 95% CI = 1.08-1.77, p = 1.05 × 10-2), after adjusting for children's age, sex, socioeconomic backgrounds, family history of suicide, and psychopathology. In contrast, attention-deficit/hyperactivity disorder polygenic risk scores were associated with lifetime suicidal ideation (odds ratio = 1.15, 95% CI = 1.05-1.26, p = 3.71 × 10-3), suggesting a distinct contribution of the genetic risk underlying attention-deficit/hyperactivity disorder and depression on suicidal behaviors of children. CONCLUSIONS: The largest genetic sample of suicide risk data in U.S. children suggests a significant genetic basis of suicide risk related to attention-deficit/hyperactivity disorder and depression. Further research is warranted to examine whether incorporation of genomic risk may facilitate more targeted screening and intervention efforts.

Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments.

BACKGROUND: A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE). METHODS: The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8-40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses. RESULTS: When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, ß = 0.088, p = 0.02) but not for CE (R2 = 0.011, ß = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10). CONCLUSIONS: We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.

Neuropsychological Profile of an Adolescent Female With Ectodermal Dysplasia With Hypohidrosis.

The ectodermal dysplasias are a group of rare genetic disorders that are caused by abnormalities in cell and tissue development of the embryonic ectoderm. A paucity of research has systematically examined the cognitive, academic, and psychological phenotype of individuals with ectodermal dysplasia. We describe the neuropsychological profile of a female adolescent with ectodermal dysplasia with hypohidrosis. Using a battery of standardized tests, we assessed the adolescent's intellectual functioning, language processing, visuospatial and visuomotor functioning, perceptual reasoning, sensory-motor functioning, memory, executive functioning, academic functioning, emotional and behavioral functioning, and adaptive functioning. Results from the testing indicated that the adolescent possessed relative verbal strengths, with scores generally falling in the low average to average range. However, she exhibited severe deficits in visuospatial functioning, visuomotor construction/organization, visuomotor integration, visual memory, executive functioning, reading, and math. She also presented with symptoms of anxiety and depression but had relatively strong adaptive skills. Based on the testing results from our evaluation, the adolescent met the criteria for specific learning disorders with impairment in reading and math, generalized anxiety disorder, and major depressive disorder. To our knowledge, this is the first case report to comprehensively characterize the full neuropsychological and academic profile of an adolescent female with ectodermal dysplasia with hypohidrosis. Recommendations from the evaluation are presented to inform clinical practice with, and future research of, this population.

Association of adverse prenatal exposure burden with child psychopathology in the Adolescent Brain Cognitive Development (ABCD) Study.

OBJECTIVE: Numerous adverse prenatal exposures have been individually associated with risk for psychiatric illness in the offspring. However, such exposures frequently co-occur, raising questions about their cumulative impact. We evaluated effects of cumulative adverse prenatal exposure burden on psychopathology risk in school-aged children. METHODS: Using baseline surveys from the U.S.-based Adolescent Brain and Cognitive Development (ABCD) Study (7,898 non-adopted, unrelated children from 21 sites, age 9-10, and their primary caregivers), we examined 8 retrospectively-reported adverse prenatal exposures in relation to caregiver-reported total and subscale Child Behavior Checklist (CBCL) scores. We also assessed cumulative effects of these factors on CBCL total as a continuous measure, as well as on odds of clinically significant psychopathology (CBCL total ≥60), in both the initial set and a separate ABCD sample comprising an additional 696 sibling pairs. Analyses were conducted before and after adjustment for 14 demographic and environmental covariates. RESULTS: In minimally and fully adjusted models, 6 exposures (unplanned pregnancy; maternal alcohol, marijuana, and tobacco use early in pregnancy; pregnancy complications; and birth complications) independently associated with significant but small increases in CBCL total score. Among these 6, none increased the odds of crossing the threshold for clinically significant symptoms by itself. However, odds of exceeding this threshold became significant with 2 exposures (OR = 1.86, 95% CI 1.47-2.36), and increased linearly with each level of exposure (OR = 1.39, 95% CI 1.31-1.47), up to 3.53-fold for ≥4 exposures versus none. Similar effects were observed in confirmatory analysis among siblings. Within sibling pairs, greater discordance for exposure load associated with greater CBCL total differences, suggesting that results were not confounded by unmeasured family-level effects. CONCLUSION: Children exposed to multiple common, adverse prenatal events showed dose-dependent increases in broad, clinically significant psychopathology at age 9-10. Fully prospective studies are needed to confirm and elaborate upon this pattern.

Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets.

OBJECTIVE: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. METHODS: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. RESULTS: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing. CONCLUSION: Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

Shared genetic background between children and adults with attention deficit/hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.

Integrating questionnaire measures for transdiagnostic psychiatric phenotyping using word2vec.

BACKGROUND: Recent initiatives in psychiatry emphasize the utility of characterizing psychiatric symptoms in a multidimensional manner. However, strategies for applying standard self-report scales for multiaxial assessment have not been well-studied, particularly where the aim is to support both categorical and dimensional phenotypes. METHODS: We propose a method for applying natural language processing to derive dimensional measures of psychiatric symptoms from questionnaire data. We utilized nine self-report symptom measures drawn from a large cellular biobanking study that enrolled individuals with mood and psychotic disorders, as well as healthy controls. To summarize questionnaire results we used word embeddings, a technique to represent words as numeric vectors preserving semantic and syntactic meaning. A low-dimensional approximation to the embedding space was used to derive the proposed succinct summary of symptom profiles. To validate our embedding-based disease profiles, these were compared to presence or absence of axis I diagnoses derived from structured clinical interview, and to objective neurocognitive testing. RESULTS: Unsupervised and supervised classification to distinguish presence/absence of axis I disorders using survey-level embeddings remained discriminative, with area under the receiver operating characteristic curve up to 0.85, 95% confidence interval (CI) (0.74,0.91) using Gaussian mixture modeling, and cross-validated area under the receiver operating characteristic curve 0.91, 95% CI (0.88,0.94) using logistic regression. Derived symptom measures and estimated Research Domain Criteria scores also associated significantly with performance on neurocognitive tests. CONCLUSIONS: Our results support the potential utility of deriving dimensional phenotypic measures in psychiatric illness through the use of word embeddings, while illustrating the challenges in identifying truly orthogonal dimensions.

Characteristics of child psychiatric outpatients with slow processing speed and potential mechanisms of academic impact.

While slow processing speed (PS) is well documented in youth with ADHD, growing evidence suggests that this difficulty affects children with other neuropsychiatric conditions. Clarifying the relationship between slow PS and different forms of psychopathology is important clinically, given the potential impact of PS on academic functioning, and conceptually. In 751 youth, ages 6-21, consecutively referred for neuropsychiatric evaluation, we examined the association between slow PS (i.e., Wechsler PS Index < 85) and seven neuropsychiatric diagnostic groups. In 492 of these youth, we also related slow PS to eight psychopathology symptom dimensions. Finally, we modeled the relationship between PS, other cognitive functions and academic achievement. Data are from the Longitudinal Study of Genetic Influences on Cognition. Analyses included one-sample t tests, ANOVA, logistic regression, mixed modeling, and structural equation modeling (SEM), controlling for age, sex, and medication. Compared to normative data, all clinical groups showed PS decrements. Compared to referred youth without full diagnoses and accounting for other psychopathology, risk for slow PS was elevated in youth with autism spectrum disorder (OR = 1.8), psychotic disorders (OR = 3.4) and ADHD-inattentive type (OR = 1.6). Having multiple comorbidities also increased risk for slow PS. Among dimensions, inattention (OR = 1.5) associated with slow PS but did not fully explain the association with autism or psychosis. In SEM, PS had direct effects on academic achievement and indirect effects through working memory. Findings extend evidence that PS relates to multiple aspects of child psychopathology and associates with academic achievement in child psychiatric outpatients.