Psychiatry Research最新文献

Background: Alexithymia and social cognitive deficits may be the risk factors of depression. Guided by the cognitive-development theory of emotional awareness, this study aims to construct an integrated framework to elucidate the dynamic relationships among alexithymia, social cognition and depression at the dimensional level.

Methods: A two-wave follow-up survey was conducted among 1651 college students. Participants completed measures assessing depression (CES-D), alexithymia (TAS-20), mentalization (MentS), and empathy (IRI-C). Data were analyzed using a combination of cross-sectional network analysis, cross-lagged panel network (CLPN) analysis, and structural equation modeling (SEM).

Results: (1) Both contemporaneous networks showed that depressed affect, difficulty identifying feelings (DIF) and motivation to mentalize had the highest strength centrality. (2) CLPN analysis showed that DIF at baseline predicted increases in difficulty describing feelings (DDF) and depressed affect, decreases in self-oriented mentalization over time. DIF had the highest out-Expected Influence (out-EI = 1.284); DDF had the highest in-Expected Influence (in-EI = 1.224); personal distress exhibited the highest Bridge Expected Influence (BEI = 0.150). (3) SEM revealed that DIF not only directly affected depression (β = 0.559, p < 0.001), but also through three indirect pathways: through self-oriented mentalization and personal distress (β = 0.128, p < 0.001), through DDF and motivation to mentalize (β = 0.159, p< 0.001), and through single motivation to mentalize (β = -0.125, p < 0.001).

Conclusions: Difficulty identifying feelings is the core driver in the alexithymia-social cognition-depression network. The primary psychological mechanism involves difficulty identifying feelings eroding the capacity for self-oriented mentalization, which in turn fosters empathic personal distress, ultimately leading to depression.

Background: Zonulin, a key regulator of epithelial tight junctions, is implicated in intestinal and blood-brain barrier permeability and neuroinflammation. Although elevated zonulin is reported in schizophrenia, its expression in unaffected siblings and status as an endophenotype remain unclear. We compared serum zonulin levels among patients with schizophrenia, unaffected siblings and healthy controls, investigating association with symptom severity and cognitive function.

Methods: This cross-sectional study included 43 patients with schizophrenia (SZ), 43 unaffected siblings (UAS), and 43 healthy controls (HC). Serum zonulin was measured via sandwich enzyme-linked immunosorbent assay (ELISA). Clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) and cognition with the Cognitive Assessment Interview-Turkish Version (CAI-TR). Group differences were examined using ANOVA/ANCOVA (adjusting for age, sex, BMI and smoking), and associations via Spearman correlations.

Results: Unadjusted serum zonulin levels (ng/mL) were higher in SZ (146.8 ± 11.5) and UAS (145.6 ± 9.7) compared with HC (140.1 ± 6.4). After adjustment for confounders, the SZ-HC difference remained significant, while the UAS-HC difference was no longer statistically significant. Correlations between zonulin and PANSS domains were null after FDR correction. Zonulin was not significantly associated with CAI-TR domains or total scores in patients or siblings (all p > 0.05).

Conclusions: Elevated zonulin in schizophrenia, together with its unadjusted elevation in unaffected siblings and lack of robust association with symptom severity or cognition, suggests that zonulin may represent a candidate trait-related marker of gut-brain barrier dysfunction within an endophenotypic framework. However, the sibling finding was attenuated after adjustment for confounders and should be interpreted cautiously.

This study aimed to explore the age-specific characteristics and research trends of Behavioral Activation (BA) interventions through a Keyword Network Analysis (KNA). A comprehensive review of experimental studies applying BA was conducted, covering literature published between 2003 and 2023. Keywords were extracted by age group children and adolescents, adults, and older adults and analyzed using network metrics and cohesive structure evaluation. BA interventions were consistently associated with reductions in depression and anxiety symptoms and improvements in quality of life across all age groups. However, the focal areas of BA varied by age: in children and adolescents, BA-related keywords were linked to emotional regulation and health disparities; adult-focused studies emphasized distress management, digital healthcare integration, and overall wellbeing; among older adults, BA was associated with increased activity scheduling, greater social participation, and reduced social isolation. Across all groups, depression emerged as the most central keyword. These age-specific patterns were further clarified through cohesive structure analysis, which revealed thematic differences across developmental stages and underscored the need for age-tailored BA strategies. Specifically, BA implementation tended to emphasize emotional and social skills in adolescents, stress regulation and digital self-management in adults, and structured activity planning in older adults. Together, these findings support the potential of BA as a flexible, transdiagnostic mental health intervention that can be integrated across the lifespan.

Background: Although the association between depressive symptoms and cardiovascular disease (CVD) has been extensively studied, evidence for a long-term causal relationship remains sparse. This research employed advanced causal inference techniques to evaluate this longitudinal effect and its potential reversibility.

Method: We analyzed data from 37,668 participants across three prospective cohorts: CHARLS (China), HRS (USA), and KLoSA (South Korea). Applying the Longitudinal Targeted Maximum Likelihood Estimation (LTMLE) method across five time points, we assessed the causal effect of depression (defined by CES-D scale cutoffs) on self-reported physician-diagnosed CVD. Subgroup analyses were conducted by gender and age. Multiple sensitivity analyses were conducted to validate the robustness of the findings.

Results: Across all cohorts, the risk of CVD significantly increased with longer follow-up durations under persistent depressive symptoms. For example, in CHARLS, the adjusted odds ratio (OR) increased from 1.570 (95% CI: 1.398-1.798) at Year 2 to 2.097 (95% CI: 1.659-2.651) by Year 9. Further analysis of different exposure sequences of depressive symptoms revealed that the risk of CVD increased gradually with a greater cumulative number of waves with depressive symptoms, whereas it decreased correspondingly with more waves without depressive symptoms, demonstrating a pattern consistent with reversible association.

Conclusions: This multi-cohort study provides evidence for a longitudinal causal relationship between depressive symptoms and CVD, showing temporal cumulative effect and a risk pattern consistent with reversible association. These results highlight the need to integrate mental health care into CVD prevention.

Background: Major depressive disorder (MDD) is a common and disabling mental health condition, with a substantial proportion of patients failing to achieve symptom relief through standard pharmacological or psychotherapeutic treatments. Treatment-resistant depression (TRD), therefore, remains a significant clinical and public health challenge. To address this, our team developed Avatar Therapy, a virtual reality-based intervention with strong experiential and relational components. This pilot clinical trial aimed to evaluate the short-term efficacy of Avatar Therapy for TRD on 12 participants.

Methods: During therapy sessions, participants engaged in dialogue in virtual reality with an avatar representing a person who played a significant role in their depressive symptoms. The avatar was animated in real-time by the therapist. The primary outcomes were the rates of response and remission, along with depressive symptom severity. Secondary outcomes were severity of anxiety symptoms, self-esteem, quality of life, and functioning. Changes in these outcomes between the pre- and post-therapy assessment periods were analyzed using linear mixed-effects models.

Results: Among completers, the response rate was 80%, and the remission rate was 20%. At post-therapy, results showed a significant large reduction in depressive symptoms as measured both by self-report (d=1.48, p<0.001) and clinician-rated assessments (d=1.36, p<0.001). Moreover, large significant improvements were observed in the severity of anxiety (d=1.27, p<0.001), self-esteem (d=1.11, p=0.003), quality of life (d=1.42, p<0.001), and functioning (d=1.21, p=0.003).

Conclusion: This unique psychotherapy shows promising preliminary results for treating individuals with TRD. Future trials should assess efficacity in larger controlled samples and its long-term out.

Objective: To evaluate the efficacy and safety of brexpiprazole in patients with early-episode schizophrenia.

Methods: Data were pooled from four 6-week, randomized, double-blind, placebo-controlled trials in schizophrenia. Three trials (ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380) enrolled adults aged 18-65 years; one trial (NCT03198078) enrolled adolescents aged 13-17 years. Data from participants meeting early-episode criteria (age 13-35 years, ≤5 years illness duration) were pooled for participants randomized to brexpiprazole 2-4 mg or placebo. Efficacy on schizophrenia symptoms was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS; primary endpoint in all trials). Change in functioning was measured using the Personal and Social Performance (PSP) scale in adults and Children's Global Assessment Scale (CGAS) in adolescents. Safety was also assessed.

Results: Across 476 participants (brexpiprazole 2-4 mg/day, n = 289; placebo, n = 187), change from baseline to Week 6 was greater with brexpiprazole versus placebo on PANSS total score (least squares [LS] mean difference -3.6; 95% confidence interval [CI] -7.0, -0.1; p = 0.04; Cohen's d 0.19), and a combined PSP/CGAS functioning score (LS mean difference 2.3; 95% CI: 0.1, 4.5; p = 0.04; Cohen's d 0.19). The incidence of treatment-emergent adverse events (TEAEs) was 50.7% with brexpiprazole and 46.3% with placebo. The most common TEAEs with brexpiprazole were insomnia (brexpiprazole, 9.2%; placebo, 9.5%) and akathisia (brexpiprazole, 6.5%; placebo, 2.1%).

Conclusion: This analysis expands the evidence base for brexpiprazole in schizophrenia by demonstrating efficacy in patients who are early in their disease course. The safety profile of brexpiprazole was consistent with previous clinical trials.

Background: Telomere length, a biological marker related to cellular aging, has been associated with several psychiatric conditions, including bipolar disorder (BD). However, previous meta-analyses were limited by small sample sizes and substantial heterogeneity in measurement methods, sampling sources, and clinical characteristics.

Methods: We systematically searched Embase, MEDLINE, Cochrane CENTRAL, CINAHL, and Scopus for observational studies comparing telomere length between patients with BD and healthy controls. Random-effects models were used to estimate pooled effect sizes. Subgroup analyses were conducted according to sampling source, mood status, and measurement method. Meta-regression was performed to explore potential clinical moderators. The certainty of evidence was assessed using the GRADE approach.

Results: Thirty studies were included, comprising 5639 patients with BD and 226,358 healthy controls. Overall, BD was associated with shorter telomere length compared with controls (Hedges' g = -0.309, 95% CI -0.437 to -0.181). This association was observed in studies using peripheral blood leukocytes and lymphoblastoid cell lines, but not in studies using post-mortem brain tissue. Shorter telomere length was observed across studies sampling different mood states at the group level and in studies using qPCR or Southern blot methods, but not Q-FISH. Meta-regression revealed that the sex distribution difference between patients and control significantly moderated the magnitude of telomere length differences.

Conclusion: This updated meta-analysis suggests an association between bipolar disorder and shorter telomere length at the group level. However, substantial heterogeneity and the observational nature of the included studies resulted in a very low certainty of evidence, warranting cautious interpretation.

Childhood trauma has been consistently associated with adverse physical and metabolic outcomes in schizophrenia, yet the neurobiological mechanisms translating early-life adversity into long-term metabolic risk remain unclear. Oxytocin, a stress-sensitive neuropeptide involved in metabolic regulation, may modulate stress-related metabolic vulnerability. In this 24-month prospective cohort study, 90 individuals with schizophrenia receiving stable antipsychotic monotherapy and 60 age- and sex-matched healthy controls underwent assessments of anthropometric measures, metabolic parameters, and plasma oxytocin levels at baseline and follow-up. Metabolic outcomes included Continuous Metabolic Syndrome Severity Scores (cMetS-S) and metabolic syndrome (MetS) incidence, while childhood trauma was assessed using the Childhood Trauma Questionnaire-Short Form with cross-validation interviews. Generalized estimating equations were applied to evaluate longitudinal associations, and moderation analyses tested oxytocin × childhood trauma interactions. Greater childhood trauma exposure was associated with lower plasma oxytocin levels (p = .001), higher body mass index (p < .001), and greater metabolic burden over time (p = .009). At 24-month follow-up, individuals with schizophrenia exhibited higher MetS incidence (p = .043) and higher cMetS-S (p = .006) compared with healthy controls.Lower oxytocin levels predicted increased MetS risk (OR = 0.27, p = .009). Importantly, a significant childhood trauma × oxytocin interaction (OR = 0.95, p = .018) indicated that higher oxytocin levels attenuated trauma-related metabolic deterioration. These findings suggest that oxytocinergic dysregulation may be involved in the association between early-life trauma and metabolic risk in schizophrenia and support oxytocin as a candidate biomarker associated with trauma-related metabolic vulnerability.

This meta-analysis investigated the prevalence and moderators of personality disorders (PDs) in adults with Attention-Deficit/Hyperactivity Disorder (ADHD), synthesizing data from 11 studies encompassing 2120 participants across clinical and nonclinical settings. The results indicate a substantial but highly variable burden of personality pathology, with a pooled prevalence for the presence of at least one comorbid PD estimated at 57 % (95 % CI [42-71]). However, this figure was largely driven by specialized outpatient populations, and statistical heterogeneity was exceptionally high (I² > 90 %), suggesting that prevalence is deeply context-dependent. Among specific diagnoses, the highest co-occurrence rates were observed for Passive-Aggressive (25.3 %), Avoidant (23.1 %), and Borderline (21.9 %) personality disorders. Moderator analyses revealed that these estimates were significantly influenced by diagnostic methodology; structured clinical interviews (such as the SCID-II) and self-report inventories (like the MCMI) consistently yielded higher rates than standard clinical assessments. Furthermore, setting played a critical role, with ADHD-specific clinics showing significantly higher coexistence than prison or student samples. While tests for publication bias were non-significant, they were limited by low statistical power. Ultimately, these findings underscore the high frequency of personality-related impairment in adult ADHD while highlighting the challenges of "diagnostic noise" and phenotypic overlap. The extreme fluctuations in reported rates suggest that clinicians must look beyond categorical labels, acknowledging that the identified prevalence is often a byproduct of the specific instruments and clinical frameworks employed.