Biological Psychiatry Global Open Science

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...

BackgroundParental genetics matters for childrens behavioural difficulties, but the extent to which this is due to direct genetic transmission versus environmentally mediated indirect genetic effects remains unclear. MethodsWe studied eight European birth cohorts with over 33,000 family-based trio samples. We analysed polygenic scores (PGSs) for 13 mental health and neurodevelopmental conditions and their composite indices (PC1 and mean) representing general neuropsychiatric liabilities, as wel...

Autism Spectrum Disorder (ASD) is a heterogenous condition that has no biologically relevant subtypes yet. Here, we utilized a multidimensional approach considering social deficits in ASD alongside negative valence and empathy dysfunction to distinguish ASD from Neurotypicals (NT) and to generate ASD subtypes using machine learning approaches. 114 subjects were analyzed, with 70 being NT and 44 ASD, all male with an IQ greater than 70, with 5 domains of personality (NEO-PI-r) and Reading the Min...

Attention Deficit Hyperactivity Disorder (ADHD) affects 5-7% of children worldwide, yet diagnosis continues to rely on clinical-behavioral assessments. The theta/beta ratio (TBR) derived from electroencephalography (EEG) has long been proposed as a complementary neurobiological marker of ADHD, based on reports of elevated TBR in affected children. However, accumulating evidence has raised concerns about the robustness and generalisability of these findings, pointing to a strong sensitivity to me...

Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with intellectual disability and increased vulnerability to traits such as anxiety, perseveration, and belief inflexibility. In the general population, these traits are linked to self-reported thought disturbances such as paranoia and delusions. However, little is known about how such disturbances present in WS, largely due to concerns regarding the validity of self-report in this population. To address this gap, we collecte...

BackgroundAdolescence is a period of rapid neurobiological and behavioural change, yet it remains unclear how deviations from normative brain maturation relate to the development of internalising and externalising symptoms. MethodsUsing data from the Adolescent Brain Cognitive Development (ABCD) Study, we combined brain age prediction with bivariate latent growth curve (BLGC) models to test whether deviations in brain maturation - indexed by the brain age gap (BAG) - relate to mental health dev...

ImportanceMotor skill impairments affect up to 87% of children with autism spectrum disorder (ASD) and are associated with greater severity of repetitive behaviors. Yet, most research examining this relationship has treated ASD as a unitary condition. Understanding whether motor-behavior relationships differ by genetic etiology could inform stratified approaches to ASD research and clinical care. ObjectiveTo determine whether the relationship between motor function and restricted and repetitive...

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental condition marked by pronounced heterogeneity in brain structure, which limits the development of targeted interventions. Morphological brain networks (MBNs) enable mapping of coordinated structural features across brain regions at the individual level. However, the specific organization of such networks in ASD and their potential relationships with underlying neurotransmitter systems remain largely unexplored. AimsTo characterize ...

AO_SCPLOWBSTRACTC_SCPLOWAutism Spectrum Disorder standardized behavioral assessments provide quantitative measures of symptoms, yet their reliability and consistency have not been systematically evaluated. We present the first large-scale comparative analysis of four widely used assessments. We analyzed behavioral assessments across three autism cohorts using correlations, clustering, and diagnostic agreement analyses. We related behavioral variation to genetic and imaging data to evaluate bioma...

Rare pathogenic variants in many genes contribute to neurodevelopmental disorders (NDDs), including intellectual disability and/or global developmental delay (ID), autism spectrum disorder (ASD), epilepsy (EP), and cerebral palsy (CP). These conditions frequently co-occur and share genetic etiologies, yet the broader phenotypic eYects and the extent of shared versus distinct genetic influences remain unclear. Here, we adopt a cross-disorder framework to examine NDD genes across four diagnostic c...

BackgroundTransdiagnostic genetic factor models organize shared liability across psychiatric disorders, but they may leave systematic pairwise genetic overlap unexplained. MethodsUsing publicly available PGC cross-disorder LD score regression genetic correlations and published five-factor genomic SEM parameters, we computed model-implied disorder correlations and derived edge-level residual genetic correlations (observed minus model-implied) for all disorder pairs. We summarized residual misfit...

Predictive processing has been proposed as an explanatory framework for symptom development in both autism (ASD) and schizophrenia (SSD) spectrum disorders, with ASD being associated with an overweighting of (low-level) sensory evidence whereas SSD is characterized by an overweighting of (high-level) prior beliefs. The goal of the present study was to investigate these hypotheses in subclinical expressions of ASD and SSD in the domain of language processing. To test this, we used an auditory com...

BackgroundAdverse life events and psychosocial stressors contribute to a range of neuropsychiatric disorders. However, the role of inflammatory dynamics around stress exposure remains unclear. Using TriNetX, a large international electronic health records database, we examined how systemic inflammatory activity and its temporal dynamics relate to subsequent risk of mental illness and somatic symptoms. MethodsWe compared 36,772 individuals with records of adverse life events and leukocytosis in ...

BackgroundEmerging evidence suggests that cognitive impairment cuts across traditional psychiatric diagnoses and may reflect a shared underlying cognitive liability. We examined whether a general cognitive factor (gFc) accounts for transdiagnostic deficits across schizophrenia (SZ), bipolar disorder (BD), obsessive-compulsive disorder (OCD) and substance use disorder (SUD). MethodsA total of 472 affected individuals and 253 population healthy controls (HC) completed a standardized cognitive bat...

BackgroundImpairments in cognitive functioning (CF) contribute to the onset, severity, and persistence of psychiatric symptoms. While specific CF domains may relate differentially to psychopathology, evidence also supports a general factor of cognitive impairment (the C-factor). We aimed to examine how general and domain-specific CF impairments relate to psychopathology using both diagnosis-specific and transdiagnostic symptom frameworks. MethodsData were drawn from five cognitive tasks adminis...

PTSD is defined by a core of inter-connected symptom clusters. It is currently unclear whether this pattern of interconnections remains stable across the lifespan or differs across key developmental periods. Synthesising seven international trauma-exposed samples (N=5,470), we compared network interrelationships among core self-reported and/or caregiver-reported PTSD symptom clusters (re-experiencing, avoidance and arousal) in preschoolers, school-aged children, adolescents, and adults. For self...

Psychotic-like experiences (PLEs) are common in youth and predict later mental health problems. Bullying victimization is a robust environmental risk factor for psychopathology including PLEs, but whether its association with PLEs reflects shared genetic liability, individual-specific putatively causal effects, or reciprocal processes is unclear. We analyzed seven waves of longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study, examining associations across the sample in ...

Mild Behavioural Impairment (MBI) is defined by later-life onset of persistent behavioural changes and is recognized as a risk marker for cognitive decline and dementia. Apathy, a core MBI domain characterized by diminished interest, initiative, and emotional reactivity, can emerge before dementia and is hypothesized to be associated with structural brain changes. While previous studies have explored Alzheimer disease (AD)-related neuroanatomical substrates of apathy in the dementia clinical st...

BackgroundAttention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by attentional deficits, hyperactivity and impulsivity that often persists into adulthood. While dysfunction of dopaminergic neurotransmitter systems has been observed, underlying mechanisms remain incompletely understood. Current treatments with methylphenidate and amphetamines show limited long-term effectiveness and do not address broader clinical needs. The endocannabinoid system represen...

Very preterm infants (<30 weeks gestation) are at elevated risk for neurodevelopmental and social-behavioral challenges. DNA methylation (DNAm) may provide a biological link between preterm birth and later behavioral outcomes. We examined associations between DNAm profiles at neonatal intensive care unit (NICU) discharge and at age 5 with Social Responsiveness Scale (SRS) scores which measure social communication, social interaction, and repetitive behaviors at age 5, including sex-specific effe...