Nature Human Behaviour

Twin studies reveal high genetic overlap between anxiety disorders and depression, contributing to the internalising spectrum. Some genetic specificity for fear-based anxiety disorders (fear), distinct from general anxiety and depression (distress), has also emerged. Limited datasets with detailed phenotyping across anxiety disorders have restricted most genome-wide association studies (GWAS) to "any anxiety diagnosis". Additional genome-wide evidence to discern genetic differences between fear ...

BackgroundWhile previous genome-wide association studies (GWAS) identified multiple risk loci for suicide ideation (SI) and suicide attempt (SA), there is still a limited understanding of the genetic predisposition underlying suicidal behaviors in diverse populations. This study aimed to conduct a large-scale investigation of the suicidality spectrum (SP) to generate new insights into its biology and epidemiology. MethodsLeveraging ancestrally diverse participants (SI Ncase/control=179 881/1 01...

Public health monitoring traditionally relies on active reporting from diverse data sources, including clinical and administrative data, disease registries, and population-based surveys. Yet these surveillance methods often face challenges such as incomplete reporting, time lags, and variable population coverage. Meanwhile, diagnostic laboratories routinely generate vast volumes of operational data that are currently untapped for public health monitoring. As these data are not collected for scie...

Large language models (LLMs) are increasingly used by the public to seek health information, yet their reliability in addressing common vaccine myths remains unclear. We conducted an exploratory multi-vendor evaluation of three LLMs (GPT-5, Gemini 2.5 Flash, Claude Sonnet 4) using officially curated vaccination myths from Germanys public health institution and two realistic user framings as prompts: a curious skeptic and a convinced believer. All model responses were independently evaluated by t...

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...

ObjectiveComorbidity between urinary incontinence (UI) and affective disorders, including anxiety and depression, is well established in cross-sectional studies and prospective bidirectional associations have also been reported. It is, however, unclear whether these associations are causal. We applied two-sample Mendelian randomization (MR) analysis to examine if there are causal bidirectional relationships between UI and anxiety, depression, and neuroticism in women. Materials and methodsWe us...

BackgroundThe prevalences of suicidal ideation (SI) and suicide attempt (SA) are influenced by genetic, behavioral, and environmental factors. Alcohol use disorder (AUD) and adverse childhood experiences (ACEs) may mediate or moderate genetic liability for suicidality. MethodsUsing data from 10,275 participants (43.8% female; 47.2% African-like genetic ancestry [AFR], 52.8% European-like genetic ancestry [EUR]), we tested whether polygenic scores (PGS) for SI and SA predicted lifetime SI or SA....

Suicide is one of the worlds leading public health problems, with more than 720,000 deaths annually. Suicide has traditionally been studied from an individual perspective. However, research has increasingly highlighted the influence of community-level factors on suicide risk. This study aimed to (1) analyse the spatial distribution of suicide mortality at the provincial level in Spain (2018-2022); (2) perform stratified analyses by sex and age group; and (3) compare suicide risk across differen...

BackgroundUnderstanding how variation in brain structure and function contributes to psychiatric and behavioral phenotypes remains a key challenge. The absence of neuroimaging data in many study samples limits this effort. MethodsWe used genome-wide association study (GWAS) summary statistics from the UK Biobank to impute 301 brain imaging-derived phenotype (IDP) genetic scores (IGS) in the Yale-Penn cohort, which is enriched for substance use disorders (n = 10,275; 52.8% European-like [EUR] an...

Background and AimsSubstance use disorders (SUDs) are heritable and share genetic variance with externalizing and internalizing psychopathology. Although recent gene identification efforts have demonstrated the value of modeling the shared genetic architecture among SUDs and externalizing, most research has thus far failed to account for overlap with internalizing. In this study, we aim to characterize the genetic relationships of both externalizing and internalizing with SUDs. Design and setti...

Violent victimisation affects 1-4% of populations annually and constitutes a major risk factor for psychiatric morbidity and suicidal behaviours. However, the aetiological mechanisms underlying vulnerability to severe victimisation remain poorly understood. We examined genetic and environmental contributions to victimisation risk across development using nationwide family data from 4,458,368 individuals born in Sweden (1973-2004) and Finland (1970-2003). Violent victimisation was identified thro...

Externalizing spectrum disorders--spanning attention-deficit/hyperactivity disorder, conduct disorder, substance use disorders, and other disorders characterized by disinhibition--frequently co-occur within individuals due, in part, to shared genetic etiology. To advance understanding of this genetic architecture, we conducted a multi-ancestry, multivariate genome-wide association analysis of more than 4 million individuals, identifying 1,294 genomic regions linked to an externalizing factor. Fi...

Daylight Saving Time (DST) remains contentious: some policymakers highlight behavioral benefits, while others emphasize health risks. Existing evidence relies largely on aggregated data and strict modeling assumptions, obscuring individual-level patterns and yielding associational rather than causal insights. We address these limitations using objective, longitudinal Fitbit measures from the NIH All of Us Research Program. Avoiding strict modeling assumptions, we employed a natural difference-in...

Large-scale epidemics are consistently associated with increased psychological distress and substantial changes in human mobility, yet the relationship between mental health responses and effective population mobility remains overlooked. During the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) such as lockdowns and travel restrictions altered daily movement patterns while simultaneously affecting psychological well-being. Importantly, formal policy stringency alone does not fully ca...

PurposeTo create a publicly available, interactive data platform to visualize various data measures reflecting Colorado and its residents to support research and outreach efforts, specifically focusing on cancer burden and disparities throughout the state. This platform, named ECCO (Exploring Cancer in Colorado), aims to integrate diverse public data sources into a unified, user-friendly interface, accessible to researchers, community members, and outreach programs alike. MethodsA multi-discipl...

The plasma metabolome represents a valuable molecular readout of a persons physiological state, yet its relation to health, stress and lifestyle remains underexplored collectively. Here, we conducted an untargeted metabolomics analysis using 3804 paired samples from 1902 participants of the Netherlands Study of Depression and Anxiety at baseline and 6-year follow-up, quantifying 680 plasma metabolites. We characterised five metabolome profiles using principal component analysis, three with disti...

Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular disease (CVD) risk, yet the epigenetic mechanisms underlying this link remain unclear. We investigated whether DNA methylation (DNAm) within Conserved Regions of Systemic Interindividual Variation (CoRSIVs), genomic regions showing stable within-individual, but variable between-individual methylation, mediates the association between PTSD symptom severity (PTSS) and CVD. We analyzed blood-derived DNAm from three c...

Electronic health records (EHRs) have enabled large-scale genetic studies of psychiatric disorders, but their diagnostic imprecision introduces substantial misclassification bias. This challenge is particularly pronounced for psychiatric traits, which lack objective biomarkers, exhibit high comorbidity, and are often underdiagnosed due to stigma and help-seeking barriers. We first used simulations to examine how misclassification bias interacts with the classic "super-normal" control design. The...

Recent findings suggest that sugar rationing during the first 1000 days of life may influence chronic disease risk in adulthood. Given the link between mental health and non-communicable diseases, early-life sugar restriction may be associated with later-life incidence of anxiety and depression. Using UK Biobank data, participants born between October 1, 1951, and March 31, 1956 (n = 46,448) were grouped by duration of exposure to sugar rationing: R270 (rationed from conception to 270 days of li...

We assessed the impact of plasma protein quantitative trait loci (pQTL) on therapeutic hypotheses backed by human genetic evidence. We show that pQTL-supported target-indication pairs were 4.7 times more likely to advance from Phase I to launch, compared to a 2.6-fold increase observed only with human genetic evidence. Moreover, pQTL-based enrichment was prominent in druggable protein families which had limited enrichment from human genetic evidence alone.