Sleep disturbances are linked to psychiatric disorders, and obesity is associated with a higher risk of several psychiatric disorders. However, evidence is lacking on how a composite sleep score relates to psychiatric disorder risk in preclinical obesity and on the proteomic pathways that mediate this relationship. Our study aimed to investigate the association of composite sleep score and the risk of multiple specific psychiatric disorders in participants with preclinical obesity.

The prospective cohort study from the UK Biobank included 91,380 participants with preclinical obesity. Six groups were categorized according to sleep scores. Hazard ratios (HRs) for the incidence risk of psychiatric disorders were estimated using multiple Cox proportional hazards regression analysis. Mediation analysis of plasma proteomics in this association was conducted in a subset of participants (n = 9,486).

After a mean follow-up period of 12.9 years, a total of 8,992 incident cases of psychiatric disorders were observed. Using Group 1 as the reference, the risk of psychiatric disorders decreased significantly across Groups 2–6 with increasing sleep score, reaching the lowest in Group 6 (fully adjusted HR = 0.47, 95% CI: 0.33–0.67). Analyses of specific psychiatric disorders revealed that the inverse associations remained significant after full adjustment, with the most notable effect observed for attention deficit hyperactivity disorder (HR = 0.24, 95% CI: 0.08–0.72). Mediation analysis further identified 16 plasma proteins that exerted significant partial mediating effects in this association.

Our findings underscore that better sleep quality is associated with a lower risk of psychiatric disorders among individuals with preclinical obesity. The identification of proteomic mediators may provide further insight into the underlying biological mechanisms, highlighting the clinical significance of integrating sleep-related assessment and intervention.

Betel quid chewing (BQC) is a common psychoactive habit in Taiwan and other Asian regions. Evidence regarding its association with specific psychiatric disorders remains limited. This study examined associations between BQC assessed at Taiwan Biobank enrolment and major psychiatric disorders recorded in linked health-insurance claims data.

We analysed 51,522 male participants from the Taiwan Biobank successfully linked to the National Health Insurance Research Database, including 7,973 ever-users (BQC) and 43,549 never-users of betel quid (non-BQC). Psychiatric disorders included schizophrenia, bipolar disorder, major depressive disorder (MDD), depressive disorders, obsessive-compulsive disorder (OCD), panic disorder, generalized anxiety disorder, attention-deficit/hyperactivity disorder (ADHD) and dementia. Multivariable logistic regression models were constructed with sequential adjustment for age, claims-record ascertainment period, education, urbanization, cigarette smoking and alcohol drinking. No correction for multiple testing was applied across the nine psychiatric outcomes.

Compared with non-users, BQC users were older, had lower educational attainment and had markedly higher prevalence of cigarette smoking and alcohol drinking. In crude analyses, BQC was associated with higher odds of schizophrenia, bipolar disorder, MDD, depressive disorders, and panic disorder but lower odds of OCD and ADHD. After full adjustment, BQC remained associated with depressive disorders (adjusted OR: 1.19, 95% CI: 1.09–1.31). An exploratory inverse estimate for OCD (adjusted OR: 0.62, 95% CI: 0.39–0.98) was based on only 24 exposed cases. All estimates were nominal because no correction for multiple testing was applied.

In these linked Taiwanese data, BQC was modestly associated with depressive disorders, whereas associations with most other psychiatric conditions were attenuated after adjustment for sociodemographic and lifestyle factors. As BQC was assessed at a single time point and psychiatric diagnoses could predate or follow that assessment, the findings represent associations and do not establish temporality or causality.

To identify and characterise active national illicit drug use sentinel surveillance systems worldwide.

We conducted a scoping review to identify and characterise active sentinel surveillance systems for illicit drug use worldwide. Inclusion criteria: 1) articles describing or analysing data from sentinel networks with an established national scope, 2) supported by public agencies, and 3) data accessible via online repositories. We excluded articles on networks which did not have drug surveillance as their main designated objective.

Ten sentinel surveillance systems targeting recreational drug use at the national level were identified. Even though each has its own structure and functionality, they are often integrated in larger surveillance programmes. Although health professionals in emergency departments are the main informants, some systems also include information directly from people who use drugs or from community stakeholders. Systems also varied in their operational characteristics, including reporting frequency and methods used to disseminate findings.

Having similarities, awareness of these different characteristics makes it possible to improve the design of surveillance systems directed towards illicit drug use monitoring and surveillance.

Adverse childhood experiences are critical contributors to the development of psychiatric disorders. Despite its pervasive impact on mental health, childhood neglect remains underexplored. Here, we performed a first comprehensive synthesis of the association between neglect subtypes and psychiatric disorders.

The primary aim was to quantify the overall association between neglect and psychiatric disorders, by estimating the odds ratios from clinical and control groups. The secondary aim was to examine the association between unspecified, physical and emotional neglect, and specific psychiatric disorders.

Studies were systematically selected from three databases (PubMed, EMBASE and PsycINFO), focusing on adult populations with diagnosed psychiatric disorders and corresponding control groups. Meta-analyses assessed overall associations between neglect and psychiatric disorders, as well as subtypes-specific associations with distinct psychiatric conditions. Multiple meta-regressions were performed to explore moderating factors.

Strong associations were found between neglect and psychiatric disorders across all subtypes (unspecified neglect: odds ratio 3.63, 95% CI 2.19–6.01; physical neglect: odds ratio 3.27, 95% CI 2.51–4.25; emotional neglect: odds ratio 3.36, 95% CI 2.58–4.38). Subgroup analyses showed the strongest associations between unspecified neglect and bipolar disorder, physical neglect and schizophrenia spectrum disorders, and emotional neglect and major depressive disorder. Other associations emerged, although their interpretation was limited by a small number of studies and high heterogeneity levels.

Neglect is significantly associated with psychiatric disorders, with distinct patterns across neglect subtypes and mental health outcomes. These findings highlight the need for early identification and tailored interventions to mitigate neglect’s long-term burden on mental health.

Glucocorticoids are widely prescribed for autoimmune and inflammatory conditions, but their long-term use carries serious risks. Patients with psychiatric disorders have a high burden of medical comorbidities, which may be associated with higher odds of receiving sustained glucocorticoid therapy.

We examined whether psychiatric patients were more likely to receive sustained oral glucocorticoid therapy compared with controls, and assessed variation across psychiatric subgroups.

This retrospective, nationwide cohort study used South Korea’s National Health Insurance Service database. Adults diagnosed with a major psychiatric disorder in 2021 (n = 331 020) were compared with a sample without psychiatric disorders (n = 668 980). Propensity score matching generated 283 942 participants per group. The outcome was sustained oral glucocorticoid use in 2022, defined as ≥90 cumulative days with continuous therapy ≥90 days and prescription gaps ≤30 days.

Before propensity score matching, glucocorticoid use in 2022 was more frequent in psychiatric patients (13.8%) than controls (10.8%; odds ratio 1.32, 95% CI 1.31–1.34; P < 0.001). After matching, the difference persisted (14.7 v. 12.5%; odds ratio 1.18, 95% CI 1.16–1.19; P < 0.001). Multivariable analyses confirmed higher odds of glucocorticoid use (odds ratio 1.05, 95% CI 1.03–1.06; P < 0.001). Increased risk was observed for anxiety disorders (odds ratio 1.06) and obsessive–compulsive disorder (odds ratio 1.07), whereas major depressive disorder showed no significant association.

Psychiatric patients are more likely to receive sustained glucocorticoid therapy, underscoring the need for cautious prescribing and monitoring in this vulnerable population.

Few studies have quantitatively characterised the shared and distinct features of the epigenetic age signature of schizophrenia, bipolar disorder and major depressive disorder.

To construct a multi-platform epigenetic clock tailored to human blood and brain tissues, and to characterise variations in epigenetic age acceleration across these three common psychiatric disorders.

We integrated 31 publicly available DNA methylation data-sets generated on the platforms Illumina 27K, 450K and EPIC (850K) from patients with schizophrenia, bipolar disorder or major depressive disorder, and from matched controls. Using elastic net regression combined with sure independence screening, we developed the blood–brain clock and applied it to assess disorder-specific epigenetic age acceleration in blood and brain.

The blood–brain clock achieved high accuracy across tissues and outperformed established predictors, particularly in brain samples. Epigenetic age acceleration was reduced in schizophrenia, increased in bipolar disorder and major depressive disorder and strongly elevated in Alzheimer’s disease (positive control). Alterations appeared earlier in blood than in brain. Meta-analysis confirmed that both reduced acceleration (schizophrenia) and increased acceleration (bipolar disorder, major depressive disorder, Alzheimer’s disease) were significantly associated with disease prevalence. Differential methylation analyses further revealed that the blood–brain clock probes captured disease-associated signals, with schizophrenia showing the greatest overlap with causal risk loci, and opposite methylation patterns distinguishing schizophrenia from bipolar disorder or major depressive disorder. A subset of blood DNA methylation probes enabled high-precision classification between schizophrenia and bipolar disorder or major depressive disorder.

This blood–brain clock reveals distinct patterns of epigenetic age acceleration across psychiatric disorders, reflecting disorder-specific and shared biological ageing signatures. The manifestation of these alterations in peripheral blood highlights its potential as a non-invasive biomarker for early detection, risk stratification and differential classification of schizophrenia, bipolar disorder and major depressive disorder.

Neuroimaging studies have consistently revealed neuroanatomical abnormalities in individuals with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ). However, it remains unknown whether and to what extent disorder-selective gray matter variations occur in these prominent psychiatric disorders. This study conducted a meta-analysis of 25 years of published voxel-based morphometry (VBM) research to assess the presence of selective and robust neuroanatomical substrates of gray matter variation in BD, MDD, and SZ.

Peer-reviewed experiments encompassing subjects with target disorders were systematically searched in the MEDLINE database. Additionally, peer-reviewed data on 30 other psychiatric disorders and 65 neurological diseases were obtained from the BrainMap database. Experiments reporting whole-brain group comparisons between patients and healthy controls were included if they identified significant reductions in gray matter morphometry.

The data were analyzed using the Bayes fACtor mOdeliNg algorithm. A total of 1,021 VBM experiments were included, comprising 29,540 patients and 28,177 healthy controls. Primary analyses of psychiatric data revealed strong evidence of gray matter reduction in the right middle temporal gyrus for BD and the posterior dorsal anterior cingulate cortex for SZ (P ≥ 95% selectivity). The robustness of these findings was confirmed using the fail-safe method tailored to the neuroimaging meta-analytic environment. No selective findings were observed in additional analyses that included neurological diseases.

Taken together, these findings offer a framework that underscores the significance of diagnosis-selective neural substrates in psychopathology, a new perspective that could inform distinct pathophysiological processes and assist in diagnosis and treatment.

Adults with intellectual disability (ID) experience marked mental health inequities, yet population-wide estimates that capture both primary- and specialist-care diagnoses remain scarce.

Using nationwide Swedish registries, including primary care, specialist, inpatient, prescription drug, criminal, and suspicion registers, we included all individuals born in Sweden between 1958 and 1997 (N = 3,970,600), including 38,818 individuals with ID diagnoses (0.98%; 49.1% mild, 13.3% moderate, and 9.6% severe/profound). Hazard ratios (HR) were calculated using Cox proportional hazards regression to estimate the relative risk of lifetime diagnoses of major depression, anxiety disorders (ANX), obsessive-compulsive disorder (OCD), bipolar disorder (BD), attention-deficit/hyperactivity disorder (ADHD), drug use disorder, alcohol use disorder, schizophrenia, and other nonaffective psychosis. Additionally, cohort effects on psychiatric diagnosis risks in adults with intellectual disabilities versus the general population were evaluated.

People with ID were at higher risk for all psychiatric and substance use disorders, with HRs ranging from 1.7–2.0 for major depression and anxiety, drug and alcohol use disorders, 3.5–5.8 for BD, OCD and ADHD, and 10.9–12.7 for schizophrenia and other nonaffective psychosis. Higher prevalence was consistently seen among those with mild versus moderate or severe/profound intellectual disability. Relative risks narrowed modestly in successive birth cohorts, although absolute differences remained substantial.

Across six decades of follow-up, adults with ID faced markedly higher psychiatric and substance-use morbidity – most pronounced for psychotic disorders – than the general population. Whole-system mental-health screening and tailored interventions are required to address this persistent disparity.

Structural abnormalities in cortical and subcortical brain regions are consistently observed in schizophrenia; however, substantial inter-individual variability complicates identifying clear neurobiological biomarkers. The Person-Based Similarity Index (PBSI) quantifies individual structural variability; however, its applicability across schizophrenia stages remains unclear. This study aimed to compare cortical and subcortical structural variability in recent-onset and chronic schizophrenia and explore associations with clinical measures.

Neuroimaging data from 41 patients with recent-onset schizophrenia, 32 with chronic schizophrenia, and 59 healthy controls were analysed. The PBSI scores were calculated for cortical thickness, surface area, cortical grey matter volume, and subcortical volumes. Group differences in PBSI scores were assessed using linear regression and analysis of variance. Correlations between the PBSI scores and clinical measures were also examined.

Both patients with recent-onset and chronic schizophrenia exhibited significantly lower PBSI scores than healthy controls, indicating greater morphometric heterogeneity. However, significant differences between the recent-onset and chronic patient groups were limited to subcortical and cortical thickness PBSI scores. Correlations between PBSI scores and clinical symptoms are sparse and primarily restricted to surface area variability and symptom severity in patients with recent-onset schizophrenia.

Patients with schizophrenia show marked structural brain heterogeneity compared with healthy controls, which is detectable even in the early stages of the illness. Although there were few differences in PBSI scores between the recent-onset and chronic schizophrenia groups and limited correlations between PBSI scores and clinical measures, the PBSI may still provide valuable insights into individual differences contributing to clinical heterogeneity in schizophrenia.

Impulsivity, a multifaceted construct, is a core feature of borderline personality disorder (BPD), associated with functional impairment and suicide mortality. Findings on motor inhibitory control, a key dimension of impulsivity, in BPD are heterogeneous.

This PRISMA-guided meta-analysis examines motor inhibitory control in adults with BPD compared to healthy controls (HCs), using Stop-Signal Task and Go/No-Go Task data. Thirty-seven datasets from 35 articles were included.

Results from random-effect models suggest that BPD patients exhibit significantly higher motor inhibitory control deficits than HCs, with a small to moderate effect size. Contrary to common assumptions, a mixed-model effect found that emotional factors did not moderate inhibitory control in BPD. Finally, the meta-analysis revealed that self-reported impulsivity measures did not correlate with task performance, suggesting that subjective and objective measures of impulsivity may assess different facets of the construct.

These findings highlight the need for greater standardization of task-based measures of impulsivity, as methodological heterogeneity and quality currently limit replicability across studies.

Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).

Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.

By synthesising findings from both clinical and preclinical research, this review aims to provide an understanding of the interplay between 5-HT2A receptor psychedelics and the immune system and considers how their immunomodulatory effects associate with neuronal and behavioural changes.

A PubMed literature search covering the past 30 years was conducted using keywords such as ‘5-HT2A receptor’, ‘psychedelics’, ‘immune system’, and ‘HPA axis’. Studies were included if they addressed the effects of 5-HT2AR psychedelics on immune function, neuroimmune interactions, or HPA axis involvement. This narrative review synthesises evidence highlighting the bi-directional effects of 5-HT2AR psychedelics between the immune and nervous systems, identified through this search process.

Preclinical and clinical studies report that 5-HT2AR psychedelics have some direct immunomodulatory properties with downregulation of gene regulators like NF-κB, and reduced cytokine expression such as TNF-α, IL-6, and IL-1β at a central and peripheral level, accompanied by modulation of corticotrophin releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), and cortisol. Direct immunomodulatory effects are mediated by pathways involving serotonin receptors, the Sigma-1 receptor, and the TrkB receptor. Immunomodulation is further mediated indirectly via the HPA axis.

Further studies will determine the molecular and cellular mechanisms underlying these immunomodulatory effects. There is growing interest in the potential of 5-HT2AR psychedelics for treating a range of mental health and brain disorders. In keeping with their immunomodulatory actions, the likely modulation of brain glia and glial-neuronal interaction remains to be determined, representing a promising direction of further research on the therapeutic potential of 5-HT2AR psychedelics.

Individuals who die by suicide tend to share more characteristics with those who attempt suicide using violent methods than with those who employ nonviolent means. To date, limited research has been published on the demographic characteristics of individuals who engage in violent suicide attempts.

This study aimed to examine trends in the characteristics of violent suicidal behavior in comparison to nonviolent suicidal behavior.

Patients included in the study were consecutively admitted between 2016 and 2021 to the Dr. Manninger Jenő National Trauma Center and the Psychiatric and Toxicology Wards of Péterfy Sándor Hospital in Budapest, Hungary, for medical treatment following violent or nonviolent suicide attempts. Differences in demographic characteristics, risk factors associated with violent suicidal behavior, and methods of attempt were analyzed using Chi-square tests and logistic regression models.

A total of 298 inpatients (46.1% male, 53.9% female), aged between 18 and 65 – representing the economically active population – were included in the study. The sample comprised 145 individuals who attempted suicide using nonviolent methods (73% female, 27% male) and 153 who used violent methods (64.7% male, 35.3% female). Of the total sample, 22 individuals (12.1%) died during treatment due to severe medical complications. Among male attempters, the highest proportion fell within the economically active age range of 18–55 years, whereas among female attempters, the 18–35 age group represented the highest proportion. The most common violent methods, in descending order of frequency, were stabbing (49.7%), jumping from a height (29.8%), and jumping in front of a train (7.7%). The most frequently diagnosed psychiatric disorders among the sample were major depressive disorder (42.2%), anxiety disorders (44.9%), and bipolar disorder (12%). The leading reported motives for violent suicide attempts, in decreasing order of frequency, were marital conflict (32.4%), divorce/separation/break-up (30.2%), and severe or chronic somatic illnesses (12%). When comparing the two subgroups, the strongest risk factors associated with violent suicide methods included male gender, older age, and residence in the capital city.

Previous studies suggest that risk factors are largely indistinguishable between individuals who engage in violent versus nonviolent suicide attempts. However, individuals who attempted suicide using violent methods exhibited characteristics more closely aligned with those who died by suicide than with the remainder of the sample. The majority of data in this study were collected during the COVID-19 pandemic – a period marked by multiple overlapping crises – which may have played a disproportionately large role in the emergence of suicide risk.

Limited studies have examined the association between the whole range of parental psychopathology and offspring major depression (MD). No previous study has examined this association by age of onset of offspring MD, or restricting to parental psychiatric diagnoses before offspring birth.

This nested case–control study included 37,677 cases of MD and 145,068 controls, identified from Finnish national registers. Conditional logistic regression models examined the association between parental psychopathology and MD, adjusting for potential confounders.

Increased risk of MD, expressed as adjusted odds ratio and 95% confidence interval (aOR [95% CI]) were most strongly observed for maternal diagnoses of schizophrenia and schizoaffective disorders (2.51 [2.24–2.82]) and depression (2.19 [2.11–2.28]), and paternal diagnoses of schizophrenia and schizoaffective disorders (2.0 [1.75–2.29]) and conduct disorders (1.90 [1.40–2.59]). The aORs for any psychiatric diagnosis were (2.66 [2.54–2.78]) for mothers, (1.95 [1.86–2.04]) for fathers, and (4.50 [4.24–4.79]) for both parents. When both parents had any psychiatric diagnosis, the highest risk was for MD diagnosed at the age of 5–12 years (7.66 [6.60–8.89]); versus at 13–18 years (4.13 [3.85–4.44]) or 19–25 years (3.37 [2.78–4.07]). A stronger association with parental psychopathology and offspring MD was seen among boys than girls, especially among 13–19 years and 19–25 years.

Parental psychiatric disorders, including those diagnosed before offspring birth, were associated with offspring MD, indicating potential genetic and environmental factors in the development of the disorder.

Recent years show an exponential increased interest (“renaissance”) in the use of psychedelics for the treatment of mental disorders and broader. Some of these treatments, such as psilocybin for depression, are in the process of formal regulation by regulatory bodies in the US (FDA) and Europe (EMA), and as such on the brink of real-world implementation. In the slipstream of these developments increasing commercial initiatives are taking shape. The European Psychiatric Association (EPA) acknowledges both the therapeutic potential of psychedelic substances and the challenges for both research and clinical implementation. Steps need to be taken toward a well-balanced policy based upon sound scientific evidence and research, aiming at safe, ethical responsible integration of psychedelic therapy available for all patients who can potentially benefit.

In this EPA policy paper, we highlight the potential benefits, and also the challenges of psychedelic treatments, which can be relevant for the future real-world implementation of these treatments.

In addition to an overview of the current evidence and hypotheses of working mechanisms of psychedelic treatment, this policy paper specifically highlights the importance of the psychosocial components of the treatment as well as the ethical and professional aspects playing a role in real-world implementation.

Four recommendations are formulated for further research and clinical implementation.