Biological Psychiatry Global Open Science

BackgroundSuicide is the leading cause of death in youth worldwide.1 Identifying children with high risk for suicide remains challenging.2 Here we test the extents to which genome-wide polygenic scores (GPS) for common traits and psychiatric disorders are linked to the risk for suicide in young children. MethodsWe constructed GPSs of 24 traits and psychiatric disorders broadly related to suicidality from 8,212 US children with ages of 9 to 10 from the Adolescent Brain Cognitive Development stud...

ObjectivePolygenic scores (PGS) are widely used in psychiatric genetic associations studies due to their impressive power to predict focal outcomes. However, they lack in discriminatory power, in part due to the high degree of genetic overlap between psychiatric disorders. The lack of prediction specificity limits the clinical utility of psychiatric PGS, particularly for diagnostic applications. The goal of the study was to enhance the discriminatory power of psychiatric PGS for two highly comor...

Autism spectrum disorder (ASD) and schizophrenia spectrum disorders (SZ) are both characterized by difficulty with social cognition. Likewise, social brain activity is atypical in both disorders and indicates atypical reception of facial communication - a key area in the Research Domain Criteria framework for identifying common biological underpinnings of psychiatric disorders. To identify areas of overlap and dissociation between ASD and SZ, this paper reviews studies of electrophysiological (E...

IMPORTANCEAutism frequently co-occurs with other mental health conditions. In the general population, these co-occurring mental health conditions are highly heritable and genetically correlated; however, the genetic architecture of co-occurring mental health conditions among autistic individuals is unclear. OBJECTIVETo investigate the relationship between common and rare genetic variation and co-occurring mental health conditions and latent factors among autistic individuals. DESIGNCross-secti...

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition influenced by complex genetic and environmental factors, necessitating a population neuroscience approach to understand its etiology. Reclassifying ADHD subtypes through efficient and universally applicable measurements offers the potential to address its heterogeneity, thereby advancing personalized diagnosis and treatment. MethodsThis cross-sectional study leverages normative brain charts...

BackgroundAttention-deficit/hyperactivity disorder (ADHD) and Body Mass Index (BMI) are associated. However, it remains unclear whether this association reflects causal relationships in either direction, or confounding. Here, we implemented genetically informed methods to examine bidirectional causality and potential confounding. MethodsThree genetically informed methods were employed: (1) cross-lagged twin-differences analysis to assess bidirectional effects of ADHD symptoms and BMI at ages 8,...

Although the schizophrenia rate is increased in autism spectrum disorder (ASD), it is difficult to identify which youth with ASD will go on to develop psychosis. We explored the relationship between ASD and emerging psychotic-like experiences in the Adolescent Brain Cognitive Development (ABCD) cohort of school-aged children. We predicted that ASD would robustly predict psychotic-like experience severity, even relative to other established predictors, and that ASD youth with psychotic-like exper...

BackgroundAutistic individuals experience a heightened risk of depression and lower quality of life; however, it remains to be established whether disrupted sleep and circadian factors mediate this increased risk. ObjectivesWe assessed whether disruption of self-reported sleep and circadian factors mediate the associations of autistic traits with depression symptom severity and quality of life. Methods838 participants (mean: 52.8 [SD = 1.3] years, 70% females) from a large-scale observational ...

BackgroundCognitive functioning is a critical dimension of psychopathology that remains under-investigated. Because cognitive deficits often transcend diagnostic boundaries, it has been challenging to delineate specific relationships between psychiatric disorders and cognitive functioning. Genetic research offers novel, powerful tools to disentangle shared (transdiagnostic) from disorder-specific effects, opening new avenues for understanding how psychopathology relates to cognitive functioning....

BackgroundSocial impairments are core features of multiple neurodevelopmental disorders. Previous neuroimaging studies have focused on elucidating associations between brain function and social impairments within disorders but have not predicted these impairments from brain connectivity in a transdiagnostic manner, across several diagnostic categories. This study used a machine learning approach to examine functional connectivity that predicts elevated social impairments in a transdiagnostic sam...

Neurodevelopmental conditions are highly heritable, heterogeneous, and frequently co-occur with one another. Transdiagnostic dimensional approaches have advanced our understanding of psychiatric disorders and informed their classification, but have largely omitted neurodevelopmental conditions. We investigated the structure of a transdiagnostic "neurodevelopmental spectrum", its etiology, and its ability to predict functional outcomes across development, using longitudinal data for >10,000 twins...

Externalising and internalising symptoms span multiple psychiatric diagnoses. Although similar measures assess these traits in autistic and non-autistic populations, it remains unclear whether their polygenic influences and biological mechanisms align. This study compared genetic contributions to these symptoms in autistic individuals (SPARK, N=3,486) and the general population (ABCD, N=4,637; external datasets: Neff=523,150 externalising; Neff=132,260 internalising). Regression models tested as...

ObjectiveDespite the significant and growing burden of childhood psychiatric disorders, treatment is hindered by lack of evidence-based precision approaches. We utilized parent cognitive and behavioral traits in a predictive framework to provide a more individualized estimate of expected child neuropsychiatric and neuroanatomical outcomes relative to traditional case-control studies. We examined children with Noonan Syndrome, a neurogenetic syndrome affecting the Ras/mitogen-activated protein ki...

Although autism has been historically conceptualised as a condition that emerges in early childhood, many autistic people are diagnosed later in life. It is unknown whether earlier and later diagnosed autism have different developmental trajectories and genetic profiles. Using longitudinal data from four independent birth cohorts, we demonstrate that two different socioemotional and behavioural trajectories are associated with age at diagnosis. In independent cohorts of autistic individuals, com...

Polygenic scores (PGSs) have emerged as promising tools for predicting complex traits from genetic data, however, their predictive performance for psychiatric disorders remains limited and the added value of deep learning (DL) over linear models is underexplored. In this study, we compared our DL model, Genome-Local-Net (GLN), with the linear model bigstatsr in predicting five psychiatric disorders--ADHD, ASD, BIP, MDD, and SCZ--using individual-level genotype data. We further assessed whether c...

BackgroundAdverse mental health consequences of COVID-19, including anxiety and depression, have been widely predicted but not yet accurately measured. There are a range of physical health risk factors for COVID-19, but it is not known if there are also psychiatric risk factors. MethodsWe addressed both questions using cohort studies derived from an electronic health records (EHR) network of 69 million patients including over 62,000 cases of COVID-19. Propensity score matching was used to contr...

One of the most complex human behaviours that defies singular explanatory models is suicidal behaviour, especially in the youth. A promising approach to make progress with this conundrum is to parse distinct subtypes of this behaviour. Utilizing 1,624 children with suicidal thoughts and behaviors (STBs) and 3,224 healthy controls from the ABCD Study, we clustered children with STB based on thirty-four cognitive and psychopathological measures which capture suicide-related risk-moderating traits....

IntroductionThe externalizing disorders of ADHD, Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) exhibit a strong uptick in incidence in late childhood to become some of the most common mental health conditions in adolescence and strong predictors of adult psychopathology. While treatable, substantial diagnostic overlap exists among the externalizing disorders, complicating intervention planning. Thus, early adolescence is a period of considerable interest in understanding which fa...

PURPOSE: In children with autism spectrum disorder (ASD), early diagnosis permits early access to therapeutic interventions which may improve outcomes. Factors affecting the age of diagnosis in ASD are not fully understood. METHODS: Here, two large independent datasets were analyzed to investigate age of autism diagnosis and co-occurring psychiatric conditions, including bipolar disorder, depressive disorder, anxiety disorder, obsessive-compulsive disorder, attention deficit hyperactivity disord...

Oral cannabidiol (CBD) treatment has been suggested to alleviate severe symptoms of autism spectrum disorder (ASD). While many CBD preparations have been studied in clinical trials involving ASD, none has used purified CBD preparations or preparations approved by the U.S. Food and Drug Administration, nor have they focused on children with ASD with higher support needs. Previous studies have identified several candidate electrophysiological biomarkers of cognitive and behavioral disabilities in ...