Depression exhibits significant heterogeneity in its genetic underpinnings. The role of genetic components in the development of depression and its comorbidities remains insufficiently explored.

First, depression risk loci from a large-scale genome-wide meta-analysis were annotated to Gene Ontology (GO) terms by functional enrichment. GO-based polygenic risk scores (GO-PRS) were then calculated for individuals in the UK Biobank. Principal component analysis (PCA) was applied for dimensionality reduction, followed by cluster analysis to identify genetic subtypes of depression. Multistate models were applied to assess the impact of genetic patterns on the trajectory from healthy status to incident depression, and depression to 26 subsequent diseases, as well as the associations between environmental factors and disease trajectories across genetic subtypes.

Participants were categorized into three genetic subtypes: immune-dominant, neuro-dominant, and comprehensive-risk. Significant differences in risk of depression and subsequent diseases, and susceptibility to environmental factors were observed across subtypes. Comprehensive-risk subtype showed higher risks of depression compared to immune-dominant (HR: 1.10, 95% CI: 1.05–1.15) and neuro-dominant subtype (HR: 1.12, 95% CI: 1.08–1.16). Comprehensive-risk subtype exhibited higher risks of transition from depression to subsequent diseases, such as anemia compared to immune-dominant subtype, and diseases of the digestive system compared to neuro-dominant subtype. Environmental factors were more strongly associated with the transition from depression to subsequent diseases in immune-dominant and comprehensive-risk subtypes, including cardiovascular, respiratory, and metabolic diseases.

Our findings highlight the genetic heterogeneity of depression and comorbidities, and shed light on how genetic components modulate responses to environmental factors.

Autistic people are at an elevated risk of premature mortality; however, few studies have identified factors that explain this association. Co-occurring psychiatric conditions are a strong candidate, given that autistic people are at a high risk of such conditions and these conditions are broadly associated with premature mortality.

We aimed to investigate the degree to which co-occurring psychiatric conditions are associated with premature mortality in autistic people. We explored these associations across sex and co-occurring other neurodevelopmental conditions.

We conducted a cohort study based on registry linkage. We identified 2 958 317 individuals born in Sweden from 1974 to 2004, including 70 546 (2.38%) individuals with an autism diagnosis. We identified diagnoses of 13 psychiatric conditions. The cohort was followed up from age 16 to age 46 at the oldest. We compared the risk of mortality (from all-causes, suicide, other external causes and natural causes) across autistic people with psychiatric conditions and (a) non-autistic people without psychiatric diagnoses; (b) autistic people without psychiatric diagnoses; and (c) non-autistic people with psychiatric diagnoses. We conducted separate analyses by sex and co-occurring neurodevelopmental conditions.

The mortality rate in autistic people with psychiatric conditions was 3.2 deaths per 1000 person-years, which was higher than that observed in non-autistic (0.27 deaths per 1000 person-years) and autistic people without psychiatric conditions (0.96 deaths per 1000 person-years). The relative risk of premature mortality was higher in autistic people with psychiatric conditions compared with both non-autistic (hazard ratio 13.85, 12.86–14.91) and autistic people (hazard ratio 3.44, 2.94–4.02) without psychiatric conditions and also exceeded the risk of premature mortality in individuals with psychiatric conditions alone (hazard ratio 1.47, 1.37–1.58). Similar patterns emerged across sex, intellectual disability and attention-deficit hyperactivity disorder.

Co-occurring psychiatric conditions are a risk factor for premature mortality in autistic people. Timely detection and treatment of such conditions in autistic people may facilitate healthier, lengthier lives for autistic people.

People with severe mental illness (SMI) are more likely to develop long-term physical health conditions compared with those without SMI, contributing to an inequality in life expectancy. Chronic kidney disease (CKD) is a growing global health concern set to be the fifth leading cause of life-years lost by 2040. Although people with SMI may have a higher risk of CKD, there is limited research exploring the relationship between CKD and SMI.

This review aimed to examine the prevalence, incidence and risk of CKD among people with SMI.

We searched Medline, Embase, PsycINFO, CINAHL, Scopus and Web of Science for epidemiological research reporting the prevalence of CKD (of any stage according to Kidney Disease Improving Global Outcomes guidelines) among people with SMI. Records were imported into Covidence and screened by two reviewers. Meta-analyses were conducted using random-effects models to examine the prevalence, incidence and risk of CKD among people with SMI.

Forty-eight studies were included in the review. The pooled prevalence of CKD was 8% in studies of people with SMI (95% CI 5%, 18%) and was highest in studies focused only on participants with bipolar disorder (95% CI 0.15 (0.06, 0.26)). The pooled incidence rate of CKD was 26.83 cases (95% CI 18.66, 38.58) per 1000 person-years. People with SMI had significantly higher odds of CKD compared with those without SMI (odds ratio 2.33 [95% CI 1.70, 3.21]).

People with SMI are at a significantly higher risk of having CKD compared with those without SMI. Although psychiatric medication and high rates of diabetes may play a role, the drivers of this inequality are under-researched.

People with intellectual disabilities experience higher rates of mental disorders, contributing to restrictive practices and premature mortality. Prevalence data are essential to understanding the patterns of disease, and for the development of tailored interventions.

To systematically examine the burden and pattern of mental disorders in people with intellectual disabilities across the lifespan.

We searched six databases (inception to 17 October 2024), and conducted a manual search up to 15 December 2024, for systematic reviews on the prevalence of mental disorders in people with intellectual disabilities with or without neurodevelopmental conditions. We conducted a narrative synthesis of prevalence rates, including those stratified by intellectual disability level, sex, age and autism, where available, and compared these with published prevalence rates in people without intellectual disabilities (International Prospective Register of Systematic Reviews, no. CRD42024610611).

We included 26 systematic reviews: 7 meta-analyses and 19 narrative reviews. Compared with the general population, the prevalence of schizophrenia (3.55–4.80%), anxiety (5.4–5.5%) and obsessive–compulsive disorders (2.4%) appeared higher, whereas that of mood (6–7%), personality and post-traumatic stress disorders appeared lower. Study quality was moderate to critically low. For syndromic intellectual disabilities we noted high anxiety rates in fragile-X, Williams and 22q11.2 deletion syndromes, and in those with co-occurring autism. We found gaps on dementia, bipolar, substance use and eating disorders, and limited data stratified by intellectual disability level, sex and age.

This umbrella review confirms the high prevalence of mental disorders among people with intellectual disabilities, and highlights limited evidence for several conditions and population subgroups, including for minoritised ethnic groups. Standardised, high-quality epidemiological research is needed to shape clinical care and public mental health policy.

Individuals with severe mental illness (SMI) have increased risk of physical comorbidities, linked to worse outcomes such as greater psychopathology, frailty, and neurocognitive impairment. Mechanisms underlying this burden remain unclear. This study examined whether frailty and psychopathology predict evening chronotype, especially in SMI with comorbidities.

A longitudinal study assessed 165 participants at two time points over one year: schizophrenia (n = 30), bipolar disorder (n = 42), major depressive disorder (n = 35), and healthy controls (n = 58). The SMI group (n = 107) was divided into SMI with comorbidities (SMI-C; n = 47) and without (SMI; n = 60). Measures included psychopathology, frailty, chronotype, neurocognitive and functional performance, and hematological biomarkers.

Neurocognitive and functional impairments were greater in SMI groups than controls (F = 10.3–31.4; p < 0.0001; η²p = 0.12–0.34). The SMI-C group showed worse frailty than controls at T1 (F = 4.3; p < 0.01; η²p = 0.05) and than SMI at T2 (F = 8.5; p < 0.0001; η²p = 0.12), and elevated MCV/MCH (F = 3.8–9.4; p < 0.05–0.0001; η²p = 0.04–0.11). Chronotype distribution did not differ. Frailty and psychopathology predicted chronotype in SMI (p < 0.05–0.01); in controls, frailty and performance did so (p < 0.05).

Psychopathological and hematological profiles are associated with chronotype and may help identify subgroups for chronobiology-informed interventions. These findings support more personalized treatment approaches.

The dual burden of tuberculosis (TB) and diabetes mellitus (DM) presents a growing challenge for health systems in low- and middle-income countries (LMICs), including Pakistan. Despite global and national policies advocating for integrated care, evidence on health facility readiness to operationalize integration remains scarce. This study assessed the readiness of TB basic management units (BMUs) to deliver integrated TB-DM care and explored implementation barriers using the Consolidated Framework for Implementation Research (CFIR).

We conducted an explanatory sequential mixed-methods study from September 2024 to February 2025 across 13 TB BMUs in five districts of Pakistan. Quantitative readiness data were collected using a structured tool adapted from the WHO Service Availability and Readiness Assessment (SARA), generating a composite score across four domains. Subsequently, qualitative data were gathered through multi-stakeholder focus group discussions with healthcare providers, facility managers, patients, caregivers, and policymakers. Reflexive thematic analysis was conducted and mapped to CFIR Inner Setting constructs to contextualize quantitative findings.

Only one facility demonstrated high readiness, while 12 showed low readiness. Facilities lacked routine comorbidity screening, trained staff, diagnostic capacity, and essential medicines. Key barriers included inadequate infrastructure, workforce shortages, fragmented information systems, and low prioritisation of integrated care. Financial constraints and limited coordination further hindered implementation.

This study highlights critically low readiness among TB facilities in different districts of Pakistan to deliver integrated TB-DM care, reflecting systemic weaknesses across core domains. Strengthening systems, building capacity, and improving integration strategies are essential to bridge gaps between policy and practice.

Dual disorder, comprising of substance use and mental health disorders, requires a comprehensive treatment approach. The most effective is integrated dual disorder treatment, which involves addressing both conditions concurrently by the same specialists and in the same setting. This study examines characteristics of integrated dual disorder care offered by treatment services across European countries.

In 2022, representatives of 14 integrated care for dual disorder providers in 10 European countries were asked to respond to a survey about their treatment process, outcomes, barriers and facilitators when implementing dual disorder treatment in respective countries. Thematic qualitative analysis was used to explore closed- and open-ended responses, focusing on commonalities and differences between surveyed services.

Integrated care services varied in treatment settings and structure, but all offered comprehensive support for dual disorder. Among 14 services, half addressed tobacco addiction or provided suicide prevention, three treated cannabis use, and none accepted patients in opioid agonist therapy. Few services reported evaluating treatment outcomes in standardised way. Services supported patients with social security, employment, housing and education, but also noted difficulties in coordinating post-treatment care due to divergent views on dual disorder among specialists from different services.

Integrated care services provide comprehensive and tailored support for people with dual disorder but remain distinct within the healthcare options available to this patient group across Europe. Existing and future integrated care services would benefit from addressing tobacco and cannabis use, measuring treatment outcomes and improving continuity of care.

Antipsychotics used to treat severe mental illness (SMI) markedly raise the risk of metabolic syndrome. Early weight gain predicts worse outcomes, making timely intervention vital, particularly within the first 6 months, when the most weight loss is achievable. This meta-analysis evaluated non-pharmacological weight/body mass index (BMI) management interventions during the first 6 months of their use in people receiving antipsychotics for SMI, to identify effective components with the aim of preventing long-term metabolic complications. Systematic searches of five databases (to October 2024) yielded 1483 studies; 8 (643 participants) met inclusion criteria. Interventions included exercise, nutrition, education, monitoring and psychological input, delivered individually or in groups.

Meta-analysis showed significant weight (−1.93 kg) and BMI (−1.12 kg/m2) reductions. Group-based, multi-component programmes with psychological input were most effective.

Group-based, multi-component interventions that include a psychological element produced the greatest reductions in weight and BMI. Future research should focus on refining and embedding psychologically informed, multi-component group programmes into routine psychiatric care to optimise long-term physical health outcomes.

A clinic to assess and treat mental health (MH) within a community substance use disorder (SUD) service has been implemented with the aim to facilitate engagement, progress, and completion of substance use treatment.

This study was completed to assess the effectiveness of such an integrated service. The records of individuals seen within the clinic during 2022 and 2023 were assessed for the reason for referral, diagnosis, and treatment offered, and outcome of MH and SUD.

A total of 118 individuals were assessed. The majority (58%) were referred due to a lack of progress in treatment. The most frequent MH diagnosis was bipolar disorder (57%), followed by smaller numbers of diagnoses of psychosis, PTSD, anxiety and depression. Seventy-four (63%) individuals improved in MH, and eighty (68%) in SUD.

Despite the limitations due to the naturalistic methodology, this early work suggests that an integrated type of provision of MH treatment within a SUD service might have a beneficial complementary role within the existed parallel treatment model implemented in England.

Known influences on tic severity include medical, biological and contextual factors.

We aimed to further understanding of contextual factors by exploring if tic severity is influenced by calendar month.

This study used data from the Calgary Child Tic Registry. Children are extensively clinically phenotyped at their first visit and followed prospectively until adulthood. We evaluated the mean Yale Global Tic Severity Scale-Revised (YGTSS-R) total tic severity score based on the calendar month. Multivariable linear regression models were fit to assess the individual months adjusted for age, gender, comorbidity and tic treatment variables.

The study included 370 participants, with 549 assessments of tic severity performed. In the univariable analysis based on calendar month, August had the lowest tic severity, with a mean YGTSS-R total tic severity score of 15.68 (95% CI 13.41–17.95). This was significantly lower than the month with the highest tic severity, February, with a mean score of 20.41 (95% CI 18.19–22.63). In multivariable models adjusted for age, gender, comorbidity and treatment for tics, the omnibus test for whether month contributes to a better fit were not significant (YGTSS-R total tic score P-value: 0.495). The only significant predictors of increased tic severity were treatment for tics (P < 0.0001), diagnosis of depression (P = 0.003) and diagnosis of obsessive–compulsive disorder (P = 0.02).

While our univariate analysis of tic severity by calendar month supported significantly lower tic severity in August compared with February, this association was no longer statistically significant when controlling for other variables known to impact tic severity.

In 2018, the UK government commissioned National Health Service Talking Therapies (NHS TT) services to provide integrated mental and physical health care for individuals with a long-term condition (LTC) and coexisting depression and/or anxiety. Nevertheless, evidence on the effectiveness of NHS TT in physical LTCs remains inconsistent.

This review aims to evaluate the impact of NHS TT on mental health outcomes among adults with physical LTCs.

We conducted a systematic review and meta-analysis of quantitative studies published between 2008 and 2024. We used several databases for the search, including Embase, MEDLINE, Cochrane Library, NHS Evidence, PsycINFO, Bielefeld Academic Search Engine and ProQuest. We combined terms related to NHS TT, LTCs and mental health outcomes to identify eligible studies. The Population, Intervention, Comparison, Outcomes and Study framework guided the development of the inclusion criteria. We employed the random-effects model for meta-analysis and assessed heterogeneity bias using the I2 statistic, and the Newcastle–Ottawa scale to evaluate the overall quality of the evidence.

Twenty-four studies met the inclusion criteria. The meta-analysis revealed a significant pre–post NHS TT intervention effect on reliable improvement (odds ratio 0.77, 95% CI: 0.60–0.98) and reliable recovery (odds ratio 0.80, CI: 0.68–0.95). There were no significant differences in NHS TT accessibility (e.g. treatment engagement) between participants with and without LTCs (odds ratio 0.97, 95% CI: 0.82–1.14). However, heterogeneity between the studies was high (>90%).

The observed evidence provides reassurance for individuals with LTCs engaging with treatment; however, the association with post-treatment distress is still of concern. Furthermore, extensive and rigorous research is needed to strengthen and guide service development for individuals with LTCs, thereby improving effectiveness.

Bipolar disorder and attention-deficit/hyperactivity disorder (ADHD) share overlapping clinical symptoms and cognitive deficits. Up to 20% of individuals with bipolar disorder also meet the criteria for ADHD (bipolar disorder + ADHD), a subgroup that may experience greater cognitive and functional impairments than those with bipolar disorder or ADHD alone.

To (a) characterise cognitive profiles in bipolar disorder, ADHD and bipolar disorder + ADHD compared with healthy controls; (b) examine associations between cognitive and occupational functioning; and (c) investigate associations between cognitive function and polygenic scores (PGS) for bipolar disorder, ADHD and educational attainment.

In this observational study, 477 euthymic individuals with bipolar disorder (including 78 with bipolar disorder + ADHD), 59 adult individuals with ADHD and 171 healthy controls completed standardised neuropsychological testing. Full-scale IQ and final school grades indexed current and premorbid cognitive ability, respectively. Occupational functioning was evaluated both cross-sectionally and through 5 years of registry-based follow-up. PGS were available for 295 bipolar disorder and 132 healthy control participants.

All patient groups performed significantly below healthy controls across most cognitive domains. Bipolar disorder + ADHD exhibited poorer working memory than bipolar disorder (d = −0.35, 95% CI [−0.66, −0.03]). Occupational function was lowest in bipolar disorder + ADHD (versus bipolar disorder, d = −0.44, 95% CI [−0.69, −0.19]). In bipolar disorder, poorer executive function (standardised regression coefficient (standβ) = 0.20, 95% CI [0.09, 0.31]) and older age predicted reduced occupational outcomes. PGS for educational attainment was associated positively with cognition in both bipolar disorder (working memory: standβ = 0.19, 95% CI [0.08, 0.30]) and healthy controls (executive function: standβ = 0.20, 95% CI [0.09, 0.32]), while PGS for bipolar disorder or ADHD were not significantly associated with cognitive performance.

Individuals with bipolar disorder + ADHD showed disproportionate working memory and functional impairment compared with bipolar disorder or ADHD alone. Executive function is a key predictor of occupational outcomes in bipolar disorder and is partly shaped by genetic propensity for educational attainment. These findings highlight the importance of considering ADHD comorbidity and cognitive profiles when evaluating functional prognosis and tailoring interventions.