Journal of affective disorders最新文献

Anhedonia, a core symptom of depression, is often resistant to conventional treatments and significantly impacts quality of life. This secondary analysis aimed to evaluate the effects of psilocybin-assisted psychotherapy (PAP) on anhedonia severity in individuals with treatment-resistant depression (TRD). Participants (n = 30) with TRD and a primary diagnosis of Major Depressive Disorder or Bipolar II Disorder received at least one 25 mg dose of oral psilocybin with psychotherapy as part of a randomized, waitlist-controlled trial (NCT05029466). The primary outcome of the present secondary analysis was changes in anhedonia, measured by the Snaith-Hamilton Pleasure Scale (SHAPS). Exploratory analysis examined whether changes in anhedonia were mediated through changes in overall depression severity, measured by the Montgomery-Asberg Depression Rating Scale (MADRS). A mixed ANOVA, adjusted for sex and age, revealed a statistically significant reduction in SHAPS scores following PAP at the 2-week primary endpoint (F(8, 143.48) = 3.43, p = 0.001, n = 29) with clinically significant improvements observed at 3-month and 6-month secondary endpoints. Our findings from this preliminary analysis suggest that PAP may offer a promising intervention for addressing anhedonia in TRD, but further research with larger, placebo-controlled trials are needed to confirm these effects and elucidate potential mediators. This study adds to a growing body of evidence supporting the therapeutic potential of PAP.

Background and objectives: Spousal bereavement affects health and well-being, but gender differences and temporal patterns remain unclear. We examined associations between spousal loss and various outcomes by gender over time.

Research design and methods: This longitudinal study used three-wave data (2013, 2016, 2019) from the Japan Gerontological Evaluation Study, a nationwide cohort of independent adults aged ≥65 (n = 25,957; 34,252). For those married in 2013, spousal bereavement was assessed in 2016 and categorized into no bereavement, bereavement between 2015 and 2016, and bereavement between 2013 and 2015. We employed an outcome-wide approach to examine 37 outcomes across seven domains: physical and cognitive health, mental health, subjective well-being, social well-being, prosocial and altruistic behaviors, health behaviors, and cognitive social capital. Logistic, modified Poisson, and linear regression were performed with Bonferroni correction.

Results: Spousal loss was associated with higher risks of mortality and dementia among men, with weaker or no associations among women. Widowed men experienced increased depressive symptoms and hopelessness and decreased happiness during the first year, which diminished over time. Conversely, widowed women showed no increase in depressive symptoms and reported increased happiness and life satisfaction later. Both genders reported increased social participation; however, only men experienced reduced social support. Men also showed higher alcohol consumption, whereas women were more likely to attend health screenings but became more sedentary.

Discussion and implications: Men showed greater vulnerability to adverse outcomes, whereas women demonstrated resilience. These results highlight the necessity for gender-specific policy interventions to support recovery and adaptation among widowed older adults.

Background: A growing body of evidence links microRNAs (miRNAs) to major depressive disorder (MDD). However, the causal nature of these associations remains unclear.

Objectives: This study aimed to investigate the potential causal association between miRNAs and MDD by combining Mendelian Randomization (MR) analyses and experimental validation.

Methods: Single-nucleotide polymorphisms (SNPs) significantly associated with the expression levels of miRNAs identified in the Framingham Heart Study (FHS) were used as instrumental variables serving as a proxy for miRNA exposure. The outcome was derived from the genome-wide association study (GWAS) of MDD (cases = 170,756, controls = 329,443). Two-sample MR was conducted to assess the association of miRNAs with MDD. The miRNAs identified from MR analyses were further validated in blood samples from individuals in the Women's Health in Lund Area (WHILA) cohort using qPCR.

Results: MR analysis identified six miRNAs significantly associated with MDD risk, including miR-133a-3p [Odds Ratio (OR) = 1.03, 95% Confidence interval (CI):1.00-1.05], miR-130a-3p (OR = 1.06, 95% CI:1.03-1.09), miR-138-5p (OR = 1.06, 95% CI:1.01-1.11), miR-629-5p (OR = 0.96, 95% CI:0.93-0.99), miR-132-3p (OR = 0.97, 95% CI:0.94-1.00) and miR-635-3p (OR = 0.97, 95% CI:0.95-0.99). Among them, miR-130a-3p (OR = 2.06, 95% CI:1.08-4.28, P = 0.04) and miR-132-3p (OR = 0.51, 95% CI:0.29-0.88, P = 0.02) were further confirmed to be associated with MDD by experimental validation.

Conclusions: Combining genetic and experimental approaches, this study provides evidence supporting a potential causal role for specific circulating miRNAs in MDD. While the MR findings were limited by single-SNP instruments, precluding formal pleiotropy assessment, the experimental validation of miR-130a-3p and miR-132-3p strengthens the evidence. Further research with multi-SNP instruments and larger cohorts are needed to confirm causality and explore clinical relevance.

Background: Bipolar disorder (BD) is associated with significantly reduced life expectancy, yet national trends and demographic disparities in BD-related mortality remain under characterized.

Objective: To evaluate long-term patterns and sociodemographic disparities in BD-related mortality among U.S. adults from 1999 to 2023.

Methods: We conducted a retrospective, population-based analysis using the CDC WONDER Multiple Cause of Death database, including all deaths among adults aged 25 years and older where BD (ICD-10 code F31) was listed as an underlying or contributing cause. Age-adjusted mortality rates (AAMRs) per 100,000 population were estimated annually. Temporal trends were analyzed using Joinpoint regression, and mortality was stratified by sex, race/ethnicity, age group, census region, and urban-rural classification.

Results: A total of 68,086 BD-related deaths occurred between 1999 and 2023. The AAMR increased from 0.26 to 1.13 per 100,000, with periods of accelerated rise from 1999 to 2001 and 2016-2021, followed by a slight decline. Females consistently exhibited higher AAMRs than males. Mortality rates were highest among non-Hispanic White adults, older adults, residents of the Midwest and West, and those in rural areas. Substantial state-level variation was also observed. The mortality gap persisted and widened across sex, racial, geographic, and age groups.

Conclusions: BD-related mortality has risen markedly over the past 25 years in the United States, with persistent disparities by sex, race/ethnicity, region, and rurality. These findings underscore the urgent need for integrated clinical care, targeted prevention strategies, and policies to reduce preventable deaths in this high-risk population.

Background: Prolonged Grief Disorder (PGD) in later life may involve volumetric patterns indicative of accelerated brain aging. This study examined whether structural brain age differs between individuals with PGD and those with integrated grief (IG), and whether it is associated with clinical severity.

Methods: Chronically grieving older adults with PGD (n = 36) and IG (n = 56), equated on demographics and time since loss, underwent structural MRI. Machine learning-derived indices were computed for each participant: Brain Age Gap (SPARE-BAG), Alzheimer's disease-like atrophy (SPARE-AD), and five dominant brain aging patterns. Group differences and associations with symptom severity were assessed, along with moderation by age, cognitive status, medical burden, and current and past depression.

Results: Compared to IG, the PGD group showed significantly higher SPARE-BAG (t = 2.61, p_corrected = 0.021), SPARE-AD (t = 2.04, p_corrected = 0.045), and medial temporal lobe atrophy pattern (t = 3.44, p_corrected = 0.005). However, these findings were attenuated and no longer significant after accounting for comorbid depressive symptoms. In the PGD group, both SPARE scores positively correlated with grief and depressive symptom severity (p_corrected < 0.03). The SPARE-BAG-grief symptom association was moderated by younger age (z = -2.92, p_FDR = 0.018) and higher depressive symptoms (z = 1.88, p = 0.061); SPARE-AD-depressive symptom correlation was moderated by past depression history (z = 2.64, p_corrected = 0.041).

Conclusion: Adults with PGD exhibit structural brain patterns consistent with accelerated and AD-like aging. However, these findings were largely driven by comorbid depressive symptoms. The brain aging indices were associated with both grief and depressive symptom severity, highlighting the cumulative neurobiological burden associated with PGD and co-occurring depression and underscoring the need for integrative clinical approaches addressing both conditions.

Introduction: Suicide is a leading cause of premature death, with risk peaking around psychiatric hospitalization. Emotion dysregulation (ED) is recognized as a key factor contributing to suicidal ideation and behavior across psychiatric diagnoses. The efficacy of interventions that target ED for suicidality reduction remains unclear, so we aimed to assess these interventions in psychiatric inpatients.

Methods: We conducted a PRISMA-compliant, PROSPERO-registered (CRD420251140949) systematic review and meta-analysis of randomized and non-randomized trials evaluating interventions targeting emotion regulation (ER) for psychiatric inpatients with suicidal ideation and/or behavior. Searches covered PubMed, Embase, and PsycINFO to September 18, 2025. Standardized mean differences (Hedges' g) were pooled under random-effects models and heterogeneity was assessed (Q, I², τ²). Exploratory meta-regressions examined age, sex, and study quality; small-study effects were explored with funnel plots.

Results: Twelve studies met inclusion (n = 1708), spanning dialectical behavior therapy (DBT), mindfulness-based interventions, acceptance and commitment therapy (ACT), and other ER-related protocols. Across modalities, feasibility and acceptability were high and interventions consistently improved suicide-related outcomes in transdiagnostic adolescents and adult populations. Suicide attempts and ideation met outcome criteria for exploratory meta-analyses, and, for both, ER-targeted interventions outperformed usual care, despite heterogeneity and small samples. Exploratory meta-regressions were non-significant; funnel plots did not suggest marked publication bias, though power was limited.

Conclusions: ER-targeted interventions delivered during psychiatric hospitalization are feasible and show promising benefits on suicide-related outcomes. Given heterogeneity and limited sample sizes, larger, well-powered randomized trials using standardized suicidality endpoints are needed to establish efficacy, refine inpatient protocols, and inform acute care pathways.

Speech encodes emotional, cognitive, and motor states, offering an objective, non-invasive window into mental health. In major depressive disorder (MDD), vocal alterations are reported, yet their cross-dataset reproducibility, symptom specificity, and longitudinal stability remain uncertain, especially under naturalistic, content-variable speech tasks. We conducted a large, multi-cohort study of 1857 participants spanning a primary discovery dataset, an independent secondary clinical dataset, and an 8-week longitudinal follow-up. From standardized recordings we extracted 6373 acoustic features and examined (i) baseline case-control screening in each dataset, (ii) severity-related feature patterns across depression levels, (iii) symptom-dimension markers using stability-enhanced elastic net, and (iv) longitudinal feature changes over 8 weeks, integrating unsupervised clustering and mediation analyses, with false discovery rate control. Across cohorts, correlation-based redundancy reduction yielded a compact final set of 23 non-redundant representative features for cross-cohort reporting and interpretation. Symptom-factor analysis identified distinct, non-overlapping feature sets for HAMD-24 dimensions, with somatic and depressed mood yielding the most stable markers. Longitudinally, 38 features exhibited heterogeneous recovery trajectories and mediation patterns consistent with symptom improvement, with spectral-shape and modulation markers showing higher temporal sensitivity than energy and voice-quality features. Overall, our findings indicate that a compact set of speech-derived markers can support symptom-informed monitoring in MDD. A small subset of acoustic features is robust, symptom-specific, and temporally informative, refining assumptions of uniform vocal change and enabling targeted, symptom-informed speech biomarkers for personalized monitoring and early intervention. Future work should verify these markers using task-matched speech prompts and alternative feature representations, given potential content-related confounding in free-response speech and reported reliability limitations of some high-dimensional acoustic feature toolkits. TRIAL REGISTRATION: ChiCTR2500095151.