Mental and physical disorders are leading contributors to global disability. However, estimates of their health-related burden often overlook the pervasive comorbidity among conditions. This study aimed to quantify the independent and combined effects of these disorders on self-rated health in nationally representative Chinese adults, explicitly accounting for comorbidity.

Data were drawn from the China Mental Health Survey (CMHS), a cross-sectional nationally representative survey. Mental disorders were assessed using the Composite International Diagnostic Interview 3.0, and physical disorders were measured through structured self-report. Health-related burden was assessed using a 0–100 visual analogue scale (VAS) of self-rated health over the past 30 days. Nested regression models examined disorder-specific and multimorbidity effects, followed by interaction-based counterfactual simulations to estimate disorder-specific burden net of comorbidity at individual and population levels.

Among 27,505 respondents included in multivariate analyses, comorbidity was highly prevalent. In crude models, all 20 disorders were associated with lower VAS scores, with the largest decrements observed for mental disorders such as generalized anxiety disorder (GAD), bipolar disorder and major depressive disorder (MDD). After accounting for disorder type and comorbidity structure, many associations were attenuated and the independent effect of disorder count became non-significant. Counterfactual simulations showed the largest individual-level burdens for GAD (–14.71), cancer (–9.02), bipolar disorder (–8.59) and MDD (–8.53). At the population level, insomnia symptoms (–1.56), arthritis (–0.81) and cardiovascular disorders (–0.64) contributed the greatest burden.

Accounting for comorbidity substantially alters estimates of disorder-specific health burden. Mental disorders impose the greatest impairment at the individual level, whereas prevalent physical conditions dominate population burden.

Cognitive fusion (CF), a core maladaptive process in obsessive-compulsive disorder (OCD), describes overidentification with intrusive thoughts. While implicated in symptom maintenance, its neuroanatomical basis and treatment prediction utility remain poorly understood.

We enrolled 80 first-episode, drug-naïve OCD patients and 70 matched healthy controls. All participants underwent structural magnetic resonance imaging and clinical assessment. Patients received 8-week selective serotonin reuptake inhibitors treatment with endpoint reevaluation. Using multimodal neuroimaging, we examined group differences in gray matter volume (GMV) and structural covariance network (SCN), tested whether CF levels modulated connectivity, and evaluated baseline features for predicting treatment response. Transcriptomic analysis linked the findings to the Allen Human Brain Atlas data.

OCD patients showed GMV reductions in frontal-limbic regions and increases in parietal/inferior frontal areas. SCN analysis revealed enhanced structural covariance within fronto-parieto-cerebellar circuits. Higher CF scores were associated with stronger structural coupling between the left angular gyrus and the right middle temporal/medial superior frontal gyri. Baseline GMV in the left dorsolateral superior frontal gyrus (SFGdl) positively correlated with CF improvement, remaining significant after controlling for overall symptom reduction. Transcriptomic analysis indicated the left SFGdl GMV patterns spatially associated with glutamatergic synapse and calcium signaling pathways.

CF in OCD links to altered structural integration between large-scale networks, with the left SFGdl emerging as a potential CF-specific treatment predictor. This multiscale study highlights combining neuroimaging with psychological constructs to understand treatment-relevant changes in OCD.

Although adolescent depression has been linked to individual chronic conditions, its broader role in shaping multimorbidity risk remains understudied.

A total of 87,562 UK Biobank participants were included, of whom 18,851 had documented adolescent depression. Cox proportional hazards models were applied to evaluate associations between adolescent depression and 24 chronic diseases, followed by stratified analyses by sex and age. Two-sample Mendelian randomization (MR) was then conducted to infer causality for diseases showing significant associations. Genomic colocalization analyses were performed using relevant GWAS data to identify shared causal variants. Mediation analyses were performed to detect possible mediating factors, including the frailty index, KDM biological age acceleration, allostatic load and 30 circulating biomarkers.

Adolescent depression was associated with elevated risk for 12 chronic diseases, with strongest associations for hypothyroidism (HR = 1.29 [1.18–1.42]), diabetes (HR = 1.25 [1.13–1.38]) and chronic obstructive pulmonary disease (COPD) (HR = 1.74 [1.50–2.01]). Risks were notably higher among females and younger adults. MR confirmed likely causal relationships for hypothyroidism (OR = 1.45 [1.03–2.05]), diabetes (OR = 1.01 [1.01–1.02]) and COPD (OR = 1.04 [1.02–1.06]). Genomic colocalization revealed a shared genetic signal at the CDSN/PSORS1C1 locus between adolescent depression and hypothyroidism. Mediation analyses revealed disease-specific pathways: creatinine for hypothyroidism, testosterone for diabetes, KDM biological ageing for COPD and frailty index across all three conditions.

Adolescent depression confers systemic vulnerability through genetic and metabolic mechanisms, with amplified risks in females and individuals aged ≤55 years. These findings support early, integrated interventions to mitigate long-term multimorbidity.

The role of loneliness and social isolation in the progression from incident type 2 diabetes mellitus (T2DM) to subsequent depression remains underexplored. Further investigation is essential to better understand how these factors influence disease progression.

This study enrolled 427,594 participants without T2DM and depression at baseline. Multistate models were employed to assess the impact of loneliness and social isolation on transitions from a healthy state to incident T2DM, then to subsequent depression, and finally to death. These associations were further examined across individuals with varying glycemic statuses, including normal glucose tolerance and prediabetes.

Over a median follow-up period of 13.66 years, 14,141 incident cases of T2DM, 1,149 subsequent cases of depression, and 33,024 death events were recorded. Loneliness and social isolation were associated with elevated risks of disease progression across most transitions. For the transition from incident T2DM to subsequent depression, the loneliness group exhibited a significantly higher risk (HR = 1.802, 95% CI: 1.521–2.135) compared to the no-loneliness group. Similarly, the most isolated group had an HR of 1.390 (95% CI: 1.185–1.632) compared to the least isolated group. Additionally, participants with prediabetes faced a higher risk of developing depression following T2DM compared to those with normal glucose tolerance. Interaction analyses revealed that employment status and history of cancer modified the association between loneliness and the transition from baseline to death.

These findings underscore the importance of targeted interventions to address loneliness and social isolation, potentially reducing the risk of disease progression and mortality in individuals with T2DM.

Two functional genetic polymorphisms, ADH1B rs1229984 and ALDH2 rs671, play key roles in ethanol metabolism and are especially prevalent in East Asian populations. The rs1229984 variant accelerates the conversion of ethanol to acetaldehyde, whereas rs671 reduces enzymatic activity for converting acetaldehyde into acetic acid. These variants affect alcohol use disorder risk and have been implicated in various systemic conditions.

To investigate the broader associations of ADH1B rs1229984 and ALDH2 rs671 with habitual alcohol use in large, unselected populations.

We analysed data from 146 374 Taiwanese adults (aged 20–90 years) enrolled in the Taiwan Biobank.

Both variants showed clear associations with habitual alcohol use. The ADH1B rs1229984 CC genotype was associated with a higher prevalence of drinking, indicating a substantial contribution to alcohol-related behaviour. The ALDH2 rs671 A allele was linked to markedly reduced drinking, reflecting known intolerance among carriers rather than implying a uniformly larger effect than ADH1B. Beyond alcohol use, rs671 showed a protective association with gout, whereas rs1229984 was not significantly associated with chronic diseases after correction.

In this large population sample, both ADH1B rs1229984 and ALDH2 rs671 demonstrate meaningful, genotype-dependent effects on habitual alcohol use. Their combined effects underscore the importance of evaluating gene–gene interactions rather than attributing disproportionate influence to a single locus.

Blood culture over-ordering is a recognized diagnostic stewardship challenge, contributing to contamination, inappropriate antimicrobial escalation, and laboratory burden. Validated tools to guide culture ordering at initial patient assessment are lacking.

We aim to derive and externally validate a two-step diagnostic stewardship rule for blood culture ordering in the emergency department (ED) patients with suspected infection.

We derived the Stepwise Culture Assessment with NEWS and NLR in ED (SCANNED) rule using consecutive blood cultures from a Singapore ED (April–July 2025) and validated it in Vancouver, Canada (2016–2019). The rule uses age-stratified National Early Warning Score (NEWS) thresholds (Step 1), followed by neutrophil-lymphocyte ratio (NLR) ≥5 for remaining patients (Step 2). Thresholds were selected via exhaustive grid search, optimizing culture reduction while constraining the false-negative rate to <5%.

We included 1,224 derivation and 808 validation encounters. Blood culture positivity was 9.6% (117/1,224) and 13.8% (112/808), respectively. The optimal rule (NEWS ≥5 if age <75 or NEWS ≥3 if age ≥75; NLR ≥5 for remainder) reduced cultures by 18.8% (95% CI 16.6–20.9%) in derivation and 15.1% (95% CI 12.8–17.6%) in validation, missing <5% of bacteremia cases in both cohorts. Performance was consistent across infection sources, including unclear/occult infections (17.5% reduction, 3.7% false-negative rate).

The SCANNED rule represents a practical diagnostic stewardship intervention that can reduce unnecessary blood cultures by 15–19% while maintaining >95% sensitivity for bacteremia. It requires no electronic health record integration and can be applied at triage. Prospective validation is needed before clinical implementation.

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.

Dialectical behavior therapy skills training (DBT-ST) has received empirical evidence for treating non-suicidal self-injury (NSSI). However, its effectiveness in Chinese contexts remains understudied. This study aims to explore the effectiveness of DBT-ST for NSSI in a clinical sample of individuals with NSSI.

We conducted a multicenter, randomized clinical trial in China to evaluate the effectiveness of a 13-week DBT-ST compared with social support group therapy (SSGT). A total of 196 individuals with mental disorders and NSSI were recruited. The primary outcome was the frequency of NSSI thoughts and behaviors, assessed using the Ottawa Self-Injury Inventory.

Participants were randomized to the DBT-ST group (n = 97) or the SSGT group (n = 99). DBT-ST was significantly more effective than SSGT in reducing the frequency of NSSI behaviors. It also showed superior effects on borderline symptoms and multiple domains of psychological functioning, including emotion dysregulation, impulsivity, alexithymia, mindfulness, psychological resilience, and emotional intelligence. Both groups exhibited significant reductions in the frequency of NSSI thoughts, suicidal ideation and attempts, and depression, with no significant between-group differences in these outcomes.

These findings confirm that the 13-week DBT-ST intervention is an effective treatment for Chinese patients with NSSI in clinical settings.

Methylphenidate is sometimes used to address residual symptoms of major depressive disorder (MDD), but concerns about psychiatric destabilization and limited long-term evidence have constrained its use. We examined the psychiatric safety of methylphenidate in adults with MDD in a large, real-world cohort.

Using the TriNetX Global Collaborative Network, we identified adults with MDD who initiated methylphenidate and matched them 1:1 with controls who did not receive methylphenidate. Patients with attention-deficit/hyperactivity disorder, bipolar disorder, mania, or recent psychiatric destabilization were excluded. The primary outcome was a composite of all-cause hospitalization or emergency room visits; secondary outcomes included hospitalization, emergency visits, suicidal behavior, manic episodes, and recurrence of MDD. Hazard ratios (HRs) were estimated with Cox proportional hazards models after propensity score matching.

Of 425,190 eligible patients, 3,211 matched pairs were included (mean age, 55.8 years; 58% female). Over 1 year, the composite outcome occurred less frequently in the methylphenidate group than in controls (574 vs. 694; HR, 0.85; 95% CI, 0.76–0.95). No significant differences were observed for hospitalization, emergency visits, suicidal behavior, manic episodes, or MDD recurrence. Results were consistent across subgroups defined by sex, age, and antidepressant class.

In adults with MDD, methylphenidate use was associated with a lower risk of hospitalization or emergency visits and was not linked to increased risk of suicidality, mania, or recurrence. These findings support the psychiatric safety of methylphenidate as an adjunctive treatment for selected patients, though longer follow-up is needed.