Biological Psychiatry Global Open Science

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...

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...

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...

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...

Evidence-based psychotherapies are first-line treatments for psychiatric disorders, yet response rates remain suboptimal. Noninvasive brain stimulation (NIBS) may augment psychotherapy by modulating treatment-engaged circuits. We conducted a systematic review and meta-analysis of randomized controlled trials comparing active NIBS plus evidence-based psychotherapy versus sham NIBS plus psychotherapy. Following Cochrane methods, we searched six databases through February 2025, screening 1,017 reco...

BackgroundThe present study examines the link between DNA methylation at the nerve growth factor-induced protein A (NGFI-A) binding domain of the NR3C1 1F promoter and later cognitive functions in children from families living in disadvantaged psychosocial conditions. MethodsParticipants were 132 children who took part in a Swiss Parents as Teachers (PAT) randomized controlled trial (72 in the intervention group, 60 in the control group). DNA methylation was quantified from saliva samples colle...

BackgroundWhile growing evidence implicates sleep-wake and circadian rhythm disturbances (SCRDs) in the onset and course of mood and psychotic disorders, longitudinal studies using objective measures are limited. This clinical cohort study examined whether actigraphy-derived SCRDs (sleep duration, timing, and efficiency) predicted transition to (i) any full-threshold mental disorders; and then specifically: (ii) full-threshold bipolar or psychotic disorders or (iii) other full-threshold (i.e. de...

Perinatal depression (PD) is common and disabling, yet its longitudinal comorbidity patterns and predictability remain poorly understood. This study leveraged 8,804 women with delivery records in the All of Us cohort, including 438 with clinically diagnosed postpartum depression (PPD), to characterize multimorbidity trajectories and develop integrated prediction models. Comorbidities were grouped into 38 conditions across psychiatric, autoimmune, metabolic, neurological/pain, and reproductive/gy...

Study ObjectivesNarcolepsy type 1 (NT1) is characterized by excessive daytime sleepiness and cataplexy. Previous studies have implicated the amygdala, thalamus, brainstem and hippocampus in the pathophysiology of NT1. We here aimed to examine more detailed subregional case-control differences in MRI-based segmentations of these brain regions to gain deeper insights. MethodsWe obtained 3T MRI brain scans from 54 NT1 patients (39 females, mean age 21.8 {+/-} 11.0 years, 51 with confirmed hypocret...

Major depression (MD) is a disorder class that exhibits substantial phenotypic and clinical heterogeneity, yet many large-scale molecular genetic investigations treat MD as a unitary outcome. Here, we applied Genomic Structural Equation Modeling (Genomic SEM) to characterize the genetic variation in two clinically relevant MD subtypes, childhood-onset (child-onset) and treatment-resistant MD, that are independent of the field-standard GWAS of MD in all its forms. In addition, we fit a complement...

The COVID-19 pandemic had substantial impact on healthcare systems across the globe, including psychiatric services. Use of electroconvulsive therapy (ECT), a lifesaving intervention for severe mental illness, was reported to have declined during the pandemic in several countries, but nationwide data remain scarce. Using nationwide data from the Danish National Patient Register, we examined all ECT treatments administered in Denmark from September 2019 to May 2025. Weekly treatment numbers were ...

BackgroundSleep disturbance is a core feature of bipolar disorder (BD) and often precedes mood recurrence, particularly in youth. Although actigraphy provides objective sleep measurement, it is limited by cost and monitoring duration. Passive smartphone-based mobile sensing offers a scalable alternative, but its validity in youths with BD is unclear. MethodsAnalyses included adolescents and young adults (ages 14-25) with BD-I/II from the PROMPT-BD study with at least four days of concurrent act...

BackgroundLipidomic alterations have been reported across schizophrenia (SCZ) and bipolar disorder (BD), but findings are heterogeneous and often overlap across diagnoses, limiting diagnostic specificity. Associations between lipid profiles and illness severity have also been inconsistent when assessed using single symptom scales, raising the possibility that unidimensional measures fail to capture biologically relevant variation. Whether plasma lipidomic alterations relate to multidimensional p...

ObjectivesElectroconvulsive Therapy (ECT) is an effective treatment for bipolar disorder, particularly in severe acute cases or for illness resistant to pharmacotherapy. However, the risk of relapse following ECT is high, necessitating intervention to reduce this risk. Based on findings from ECT studies in unipolar depression and its well-known mood-stabilizing properties, it is likely that lithium treatment may reduce the risk of relapse of bipolar disorder following ECT. Therefore, we conduct...

ObjectiveAlthough mental health and healthy lifestyle interventions are associated with functional outcomes in adolescence, the extent to which particular lifestyle factors explain relationships between mental health and outcome are unclear. Here we examined mediating effects of lifestyle factors on relationships between mental health and two functional outcomes measured 2-3 years later as well as the moderating effect of environmental risk factors on mediation strength in early adolescence. Me...

BackgroundMajor depressive disorder (MDD) involves immune-metabolic dysregulation, psychosocial adversity, and multidomain cognitive disturbances, yet single cognitive indices often show small and inconsistent effects. We derived a multivariate Cambridge Neuropsychological Test Automated Battery (CANTAB)-based cognitive phenotype ("cognitype") and tested whether it adds explanatory value beyond adverse childhood experiences (ACEs) and an acute-phase protein (APP) index in acute-phase MDD. Metho...

IntroductionResearch has shown that social and physical stressors of early-life adversity (ELA) can negatively affect long-term health trajectories. Despite differences in types of ELA exposure, previous studies have identified common health-related outcomes in adults who had experienced less favourable conditions during developmentally sensitive periods. This meta-analysis investigates the potential role of DNA methylation in mediating these adverse health trajectories by identifying common bio...

In-scanner head motion is a recognized source of bias in structural magnetic resonance imaging (sMRI), yet it remains under-addressed in psychiatric neuroimaging where structural difference in patient populations are considered foundational. We examined motion-related bias in grey matter volume estimates across eight independent cohorts comprising 9,664 individuals, including 8,979 neurotypical controls (NC), 497 patients with schizophrenia (SCZ), and 188 patients with bipolar disorder (BD). Mot...

ObjectiveTo identify immunomodulatory drug targets with genetic evidence in major depressive disorder (MDD), probe symptom-level heterogeneity in their effects, and identify drug repurposing opportunities. MethodsWe used cis-Mendelian randomisation to evaluate the targets of 204 immunomodulatory compounds, including immunosuppressants, cytokine inhibitors, and anti-infectives. As exposures, we selected genetic instruments from nine genome-wide association studies (GWASs) of protein or gene tran...