General Psychiatry最新文献

Background: Mental disorders pose a significant global health burden, especially after the coronavirus disease 2019 pandemic.

Aims: This study aimed to characterise trends in the burden of mental disorders among adolescents and young adults by sex, age, sociodemographic index (SDI) quintile, region and country from 1990 to 2021.

Methods: Estimates and 95% uncertainty intervals (UIs) for disability-adjusted life years (DALYs) were extracted from the Global Burden of Diseases Study 2021. The number and rate of DALYs, as well as the percentage change from 1990 to 2021, were estimated by sex, age, SDI quintile, region and country.

Results: The number of DALYs for mental disorders increased from 26.1 (95% UI 19.3 to 34.4) million to 36.3 (26.6 to 48.1) million. The DALY rate increased from 1687.8 (1245.3 to 2225.4) per 100 000 population in 1990 to 1923.7 (1408.7 to 2548.4) per 100 000 population in 2021, representing a 14% (12% to 16%) increase. Females (16% (13% to 18%)) and individuals aged 15-19 years (16% (13% to 18%)) showed the greatest increase in DALY rates. Between 1990 and 2021, DALY rates rose significantly across all SDI quintiles and regions, except East Asia (-5% (-9% to -1%)). The most rapid increases were observed in parts of Latin America, particularly for anxiety and depressive disorders.

Conclusions: The global burden of mental disorders among adolescents increased significantly from 1990 to 2021, necessitating attention to policies targeting high-risk populations and specific regions.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with behavioural symptoms and grey matter volume (GMV) changes. However, previous studies have not fully elucidated the progressive and causal GMV changes associated with behavioural symptoms in ADHD.

Aims: This study aimed to explore the causal relationship between GMV alterations and behavioural symptoms in children and adolescents with ADHD using behaviour-causal structural covariance network (BCaSCN) analysis.

Methods: Structural magnetic resonance imaging (sMRI) data from 135 children and adolescents with ADHD and 182 neurotypical controls (NCs) were analysed. ADHD subtypes were identified based on GMV using a clustering algorithm to address the neuroanatomical heterogeneity. To investigate the causal relationships of GMV changes related to behavioural symptoms, sMRI data were sequentially ordered by ADHD index, inattentive index and hyperactive/impulsive index values to generate pseudo-time series data. These data were then analysed using region-of-interest-based BCaSCN analysis to explore potential progressive patterns of GMV change.

Results: Neuroanatomical subtyping revealed two ADHD subtypes with distinct GMV patterns compared with NCs. BCaSCN analysis showed that ADHD subtype 1 was closely associated with inattentiveness, involving prominent nodes in the frontal regions and cerebellum. In contrast, ADHD subtype 2 was more strongly linked to overall disease severity, with the cerebellum and hippocampus as primary hubs.

Conclusions: ADHD is associated with heterogeneous changes in GMV corresponding to distinct behavioural domains, highlighting the need for subtype-specific diagnostic and therapeutic strategies.

Background: GW117 (N-(2-(6-chloro-7-deuteromethoxy-naphthalen-1-yl) ethyl) acetamide) is a dual-acting agent (MT1/MT2 agonist, 5-HT_2C antagonist) with prior evidence of antidepressant efficacy and favourable safety.

Aims: To preliminarily evaluate the efficacy and safety of GW117 in major depressive disorder (MDD) and to explore the optimal dosing.

Methods: A total of 280 eligible patients aged 18-65 years with MDD were randomly assigned (1:1:1:1) to 8 weeks of double-blind treatment with fixed doses of GW117 tablets (20, 40, 60 mg/day) or placebo. The primary endpoint was the change from baseline to Week 8 in the total score of the Hamilton Rating Scale for Depression-17 item (HAMD-17). Key secondary endpoints included changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score over the same period.

Results: In the full analysis set (n=276), GW117 showed numerically greater reductions versus placebo in the HAMD-17 and MADRS total scores, as well as higher response rates at Week 8. However, these differences did not reach statistical significance, potentially due to a high placebo response and other contributing factors. In a post hoc analysis of an optimal subgroup (baseline HAMD-17 >24 or insomnia factor >4), GW117 showed efficacy in improving multidimensional symptoms, including insomnia. The 20 mg dose demonstrated a significant 3.66-point greater reduction in MADRS (p=0.026) and a 23.16% higher response rate (p=0.013) compared with placebo. GW117 was well-tolerated, with no cases of alanine aminotransferase or aspartate aminotransferase exceeding 3× the upper limit of normal and no concerning safety signals reported.

Conclusions: This exploratory study found that GW117 demonstrated encouraging antidepressant efficacy and a favourable safety profile in patients with MDD. Although differences versus placebo did not reach statistical significance in the overall population, GW117 20 mg monotherapy showed significant improvements in multidimensional depressive symptoms, including insomnia, in the optimal response subgroup. No hepatotoxicity was reported, supporting its promising therapeutic potential for further clinical development.

Trial registration number: NCT06796868.

Date of retrospective registration: 23 April 2025.

Background: Physical frailty and depression may share common pathophysiological pathways associated with dementia and thus interact with each other. However, previous studies have primarily focused on the individual impact of these factors on dementia.

Aims: To examine the joint effect and interaction of physical frailty and depression on the risk of all-cause dementia.

Methods: We conducted prospective analyses among participants aged ≥60 years from three cohorts: the UK Biobank (UKB), the English Longitudinal Study of Ageing (ELSA) and the Health and Retirement Study (HRS). Physical frailty was assessed using modified versions of the Fried frailty phenotype. Depression was evaluated through mental health questionnaires or combined with hospital admission records. The primary outcome was incident all-cause dementia, identified via active follow-up and passive surveillance. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: A total of 220 947 participants (mean age: 64.5 years; 53.3% female) were included. Over 2 832 696 person-years of follow-up, 9088 participants (7605 in UKB, 1207 in HRS and 276 in ELSA) developed incident all-cause dementia. Compared with robust individuals, frail participants faced a 155% increased risk of dementia (pooled HR: 2.55, 95% CI 2.36 to 2.76; I²=72.3%). Depression conferred a 1.59-fold excess risk for dementia (pooled HR: 1.59, 95% CI 1.50 to 1.69; I²=56.8%). Adding physical frailty and depression to a traditional dementia risk model significantly improved prediction accuracy (all p-Δarea under the curve<0.05). Jointly, participants with both physical frailty and depression exhibited the highest dementia risk (pooled HR: 3.23, 95% CI 2.86 to 3.65; I²=41.6%) compared with those without physical frailty and depression. Moreover, a significant additive interaction between physical frailty and depression was observed (pooled relative excess risk due to interaction: 0.38, 95% CI 0.13 to 0.63), with 17.1% (95% CI 6.0% to 28.3%) of dementia risk attributed to their interactive effects.

Conclusions: Individuals with both physical frailty and depression had the highest risk of dementia. More importantly, these two factors interact in an additive manner, further amplifying dementia risk.

Background: Metabolic dysregulation has been implicated in major depressive disorder (MDD).

Aims: We aimed to explore the potential role of plasma metabolites in MDD.

Methods: We conducted Mendelian randomisation (MR) analysis to evaluate the causal effects of 871 circulating metabolites on MDD, using the Genome-Wide Association Studies datasets of MDD (N=1 035 760) and metabolites (N=8299). Bayesian colocalisation and druggability analyses were employed to identify genetic variants contributing to both MDD and levels of metabolites in plasma and to pinpoint metabolites with therapeutic potential, respectively.

Results: MR analysis identified 11 metabolites associated with MDD (false discovery rate<0.05). Eight metabolites, including arachidonate (20:4n6) (odds ratio (OR): 0.97), 1-arachidonoyl-GPC (20:4n6) (OR: 0.98), 1-(1-enyl-palmitoyl)-2-palmitoleoyl-GPC (P-16:0/16:1) (OR: 0.97), succinoyltaurine (OR: 0.98), 3-methoxycatechol sulphate (1) (OR: 0.98) and 11β-hydroxyandrosterone glucuronide (OR: 0.97), showed protective effects against MDD. Three metabolites were associated with increased risk, namely, butyrylglycine (OR: 1.03), 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (OR: 1.02) and 1-(1-enyl-stearoyl)-2-oleoyl-GPE (p-18:0/18:1) (OR: 1.02). Colocalisation analysis supported shared genetic signals between five lipid metabolites and MDD, particularly at loci harbouring FADS and ATP9A. Notably, a majority of metabolites associated with MDD are being explored as therapeutic targets for various psychiatric disorders.

Conclusions: Genetically predicted levels of certain circulating metabolites make a causal contribution to MDD. Further investigation of their roles may provide novel pathophysiological insights and give clues for targeted therapies.

Background: Depression is a common comorbidity in Parkinson's disease (PD) and Lewy body dementia (LBD). However, studies examining the rate of incident depression in the period preceding and following the diagnosis of PD and LBD are lacking in the literature.

Aims: To quantify the incidence of depression in the period preceding and following the diagnosis of PD and LBD.

Methods: We conducted a retrospective case-control study. Specifically, we used Danish registers to identify all patients with a diagnosis of PD or LBD in the period from 2007 to 2019. These patients were matched by age, calendar year of diagnosis and sex with up to three patients diagnosed with rheumatoid arthritis (RA), chronic kidney disease (CKD) or osteoporosis, respectively. The outcome was incident depression. The incidence of depression was assessed for up to 10 years before and up to 10 years after the diagnosis of PD or LBD. Hazard rates of incident depression for patients with PD or LBD, both before and after diagnosis, were compared with those for patients with RA, CKD or osteoporosis using a Cox-proportional hazards model.

Results: We identified 17 711 patients with PD or LBD. Their median age was 74.98 (68.10-80.85) years, and 39.92% were females. These patients were matched to 19 556, 40 842 and 47 809 patients with RA, CKD and osteoporosis, respectively. From 7 to 8 years before diagnosis to 5 years after diagnosis, patients with PD and LBD consistently had higher hazard rates of incident depression than all comparator groups.

Conclusions: These findings are compatible with depression being an early manifestation of the neurodegenerative changes eventually leading to PD and LBD and imply that incident depression at a late age should raise awareness of potential PD and LBD.

Background: Persistent somatic symptoms are a common feature in many psychiatric disorders. Moderate-to-severe cases often necessitate treatment in specialised inpatient psychiatric settings.

Aims: This study evaluated the efficacy, safety and acceptability of resonant breathing (personalised slow breathing to maximise heart rate variability (HRV)) as adjunctive treatment for hospitalised patients with psychiatric disorders presenting with persistent somatic symptoms on admission, when patients typically present with high symptom severity.

Methods: This multicentre, randomised, placebo-controlled cross-over study included 78 patients diagnosed with somatic symptom disorder or affective disorders with persistent somatic symptoms. Participants underwent light-guided resonant breathing and sham light therapy two times per day for 5 weekdays each, starting an average of 11 days after admission. The primary outcomes were changes in self-reported somatic well-being and arousal (efficacy), and adverse effects (safety). Secondary outcomes included somatic, anxiety, depression and insomnia symptoms, HRV measures and patient satisfaction (acceptability). The trial was preregistered in the German Clinical Trial Register (ID: DRKS00027323) and funded by the Austrian Research Promotion Agency (Grant ID. F0999886082).

Results: Resonant breathing rates were six breaths per minute in 60% of patients and higher in the remaining participants. The study found no intervention-specific effect on primary outcomes of self-reported somatic well-being and arousal. Patients reported no adverse effects and expressed high satisfaction with the breathing intervention. Resonant breathing significantly reduced secondary outcomes of self-reported anxiety (η²_p=0.09, 95% CI 0.01 to 0.22) and insomnia symptoms (η²_p=0.10, 95% confidence interval (CI) 0.01 to 0.23) after 10 sessions. It also significantly improved several HRV measures acutely (η²_p range: 0.23 (95% CI 0.09 to 0.38) to 0.51 (95% CI 0.35 to 0.62)).

Conclusions: While resonant breathing did not improve somatic well-being or arousal, it was safe, well-tolerated and effective at reducing anxiety and insomnia symptoms during early hospitalisation. These findings support further investigation into resonant breathing for these specific indications over extended periods.

Trial registration number: DRKS00027323.

Background: Obsessive-compulsive disorder (OCD) is classified by the World Health Organization as 1 of the 10 most disabling conditions. However, nationally representative epidemiological data on OCD are not yet available in China.

Aims: To investigate the prevalence, comorbidity, role impairment and healthcare utilisation of OCD in China.

Methods: The present study used a multistage clustered area probability sample to obtain representative population-based data of adults from 157 nationwide disease surveillance points across 31 provinces in China. Trained interviewers conducted face-to-face interviews with respondents to collect information based on the Composite International Diagnostic Interview 3.0. Data weighting was performed to account for differential selection probabilities and response rates, and to post-stratify the sample to ensure its representativeness of the population in China.

Results: A total of 28 140 respondents (12 537 (44.55%) males and 15 603 (55.45%) females) completed the diagnostic interview. Two-thirds of the respondents with lifetime OCD had comorbid mental disorders, with OCD typically emerging later than the comorbidities. The most common comorbidities were mood disorders (39.67%, odds ratio (OR): 9.60, 95% confidence interval (CI 7.35 to 12.53) and anxiety disorders (32.75%, OR: 13.33, 95% CI 10.14 to 17.52). Overall, 588 (weighted 58.19%) respondents with obsessions or compulsions experienced role impairment, which was most severe in those reporting unspecified symptoms. Only 46 (6.74%) respondents with lifetime OCD and 28 (6.48%) with 12-month OCD received any healthcare services for their conditions.

Conclusions: The weighted lifetime and 12-month prevalence of OCD were 2.43% and 1.63%, respectively. Most patients with OCD reported comorbid mental disorders and role impairment, but very few sought healthcare services. National programmes to expand service coverage and increase awareness of OCD are essential to meet healthcare needs in China.