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 ...

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...

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...

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...

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.

Hypothalamic-pituitary-adrenal axis (HPA axis) dysregulation is a risk factor for poor mental and physical health. Animal studies indicate that DNA methylation may be one mechanism through which stress can influence the function of the HPA axis, however human studies have not identified consistent individual loci. Machine learning can be used to develop methylation profile scores (MPSs), but this method has not yet been applied to HPA axis function. Using a novel machine learning pipeline, we de...

ObjectivesNon-communicable diseases (NCDs) account for almost 90% of deaths in Europe, yet comparative estimates of the productivity costs associated with premature NCD mortality across diseases and countries remain limited. This study estimates and compares productivity losses attributable to cardiovascular disease (CVD) and cancer mortality among working-age populations across Europe. Population-based data were used to estimate productivity costs for CVD and cancer deaths across 30 European co...

The COVID-19 pandemic led to substantial life expectancy losses globally. Historically, life expectancy reversals have been followed by rapid returns to previous trajectories, but whether this is true for the COVID-19 pandemic is still unknown. We update life expectancy estimates through 2024 for 34 high-income countries and quantify annual and cumulative life expectancy "deficits" by comparing observed life expectancy with counterfactuals based on pre-pandemic trends. Five years after the pande...

ObjectiveThis study explored the recovery experiences of individuals who report having (largely) recovered from long covid and who attributed their improvement to mind-body approaches. Design, setting and participantsWe conducted an explorative qualitative study using purposive recruitment through social media and snowball sampling. Eighteen adult women (aged 37-62 years), who self-identified as having had long covid and having substantially recovered through mind-body approaches participated i...

Loneliness and psychological well-being are increasingly recognized as critical public health concerns, yet their multi factorial determinants remain poorly understood. Traditional research often examines demographic, lifestyle, or social variables in isolation, yielding fragmented insights that overlook complex psychosocial interactions. In this study, we leverage a rich behavioral and psychological dataset from the Human Phenotype Project (HPP) to examine how lifestyle behaviors, social health...

BackgroundThe Antidepressant Medications: Biology, Exposure & Response (AMBER) research programme was established to investigate the biological mechanisms underlying antidepressant action and variability in treatment response. Generation Scotland holds detailed genomic, clinical, and health information with recontacting consent, making this cohort ideal for investigating these aims. MethodsWe deployed a questionnaire, developed with input from a Lived Experience panel, to the Generation Scotlan...

Long-term adherence to prescribed therapies remains a persistent challenge in chronic and ultra-rare conditions where clinical outcomes depend on continuous medication use. Even brief gaps in therapy can compromise disease control, yet patients frequently encounter structural barriers including high out-of-pocket costs, prior-authorization (PA) delays, annual re-verification cycles, and refill logistics that disrupt persistence. This study evaluates a patient-centric Markov-chain framework for a...

Rapid risk stratification is essential in the clinic, yet vital signs, laboratory tests, and triage scores may not fully capture risk at presentation. We investigated whether facial photographs taken after emergency admission provide an additional mortality signal. Using 27,660 smartphone facial photographs, we trained deep neural networks to identify mortality risk with a Cox proportional hazards framework. Face-derived risk scores strongly stratified short- and long-term mortality, outperformi...

Health behaviors such as physical activity and sleep affect mental health, but the effect of each health behavior varies substantially across individuals, limiting the usefulness of generic behavioral recommendations. We collected one year of continuous wearable and ecological momentary assessment data from 3,139 participants in the Intern Health Study (2018-2023), and examined individual-level associations between wearable-derived features and mood across the internship year. The behaviors asso...

BackgroundTraumatic events, such as terror attacks and war, are expected to impact mental health. These potential effects can be explored by assessing the mental health of the general population of Israel, from before the events of October 7, 2023 and over the course of the Swords of Iron war. MethodsGeneral population data were collected from Jewish adults in Israel before October 7 (April 2022), after October 7 (December 2023), and over the course of the ongoing war (March 2024, June 2024, Fe...

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...