Annals Of General Psychiatry[JOURNAL]
Sun
200 papers
Efficacy of aerobic exercise as a combination therapy for depression compared to standardized therapy: a systematic review and meta-analysis of randomized controlled trials.
Zhu C, von Deneen KM, Ibrahim HB … +9 more , Chi P, Shao M, Du W, Zhu X, Wei X, Wu Z, Chi A, Peng T, Hou L
Ann Gen Psychiatry · 2026 Mar · PMID 41913186 · Full text
BACKGROUND: Utilizing aerobic exercise prevails as a popular choice for physical activity, serving as the predominant exercise intervention for addressing depression. It is also used as supplementary therapy to standardi...
BACKGROUND: Utilizing aerobic exercise prevails as a popular choice for physical activity, serving as the predominant exercise intervention for addressing depression. It is also used as supplementary therapy to standardized treatments, including pharmacotherapy, psychotherapy, and treatment as usual (TAU). Despite this, the therapeutic mechanism of aerobic exercise as an adjunctive therapy, as well as its interaction with standardized treatments, has not been fully elucidated. The primary goal of the current study was to evaluate the effectiveness of aerobic exercise as an adjunct to these standardized treatments in enhancing the antidepressant effect, compared with standardized treatment alone. METHOD: We systematically searched randomized controlled trials that compared the efficacy of combining aerobic exercise with standardized therapy against standardized therapy alone in treating depression. The final analysis incorporated 20 trials, with a total of 914 participants. Calculation of the pooled standardized mean difference between aerobic exercise combined therapy and standardized therapy was conducted using a random-effects model. RESULTS: Compared with standardized therapy alone, aerobic exercise combined therapy demonstrated a significant moderate effect (SMD = -0.72 [-0.96, -0.47], p < 0.00001, I² = 66%). In subgroup analyses, older patients showed a numerically larger effect, but the age subgroup difference was not statistically significant (p = 0.06). In analyses stratified by standardized treatment modality, aerobic exercise combined with pharmacotherapy showed the largest effect (SMD = -0.97 [-1.41, -0.54], p < 0.0001, I² = 78%), and the between-subgroup difference was significant (p = 0.02). In addition to antidepressant effects, aerobic exercise combined therapy was also associated with improvements in other health-related outcomes. Subgroup findings further suggested that both low- and moderate-intensity aerobic exercise were associated with favorable treatment outcomes, with low-intensity exercise showing potential in patients with lower baseline physical fitness or more severe depressive symptoms. Moreover, a higher total exercise dose was generally associated with greater therapeutic benefit. CONCLUSIONS: Aerobic exercise may be a useful adjunct to standardized treatment for depression and may help improve overall treatment outcomes. However, these findings should be interpreted cautiously given the substantial heterogeneity across studies, the conceptual breadth of “standardized therapy,” and the limited evidence available for several secondary outcomes. Future studies should further clarify the optimal exercise prescription, underlying mechanisms, and long-term effectiveness across different patient subgroups.
Alterations in serum melatonin, IL-6 and BDNF levels and their clinical correlations in first-episode major depressive disorder.
Yan C, Xu Y, Liang J … +2 more , Xia Q, Shan F
Ann Gen Psychiatry · 2026 Mar · PMID 41906159 · Full text
OBJECTIVE: Melatonin, a key regulator of circadian rhythms and sleep-wake cycles, is implicated in the pathophysiology of major depressive disorder (MDD). Emerging evidence supports its anti-inflammatory, cytoprotective,...
OBJECTIVE: Melatonin, a key regulator of circadian rhythms and sleep-wake cycles, is implicated in the pathophysiology of major depressive disorder (MDD). Emerging evidence supports its anti-inflammatory, cytoprotective, and neuroprotective roles, including promotion of neuroplasticity. This study aims to investigate alterations in serum melatonin, interleukin-6 (IL-6), and brain-derived neurotrophic factor (BDNF) levels in first-episode MDD patients, and explores their clinical correlations. METHODS: A total of 74 first-episode patients diagnosed with MDD and 72 healthy controls were enrolled in this study. The severity of depressive symptoms was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24). All blood samples were collected in the morning, and serum levels of melatonin, IL-6, and BDNF were quantified via enzyme-linked immunosorbent assay (ELISA). Baseline serum concentrations of melatonin, IL-6, and BDNF were compared between the MDD group and the control group. Additionally, the discriminative ability of these biomarkers (melatonin, IL-6, and BDNF) in distinguishing MDD patients from healthy controls was evaluated using receiver operating characteristic (ROC) curve analysis. Pearson correlation analysis or Spearman's rank correlation analysis was performed to explore the relationships between serum melatonin levels and clinical disease severity, as well as with IL-6 and BDNF levels, in patients with MDD. RESULTS: Compared with the control group, the MDD group showed significantly higher serum levels of melatonin (Z = -3.861, P < 0.001) and IL-6 (Z = -4.240, P < 0.001), but significantly lower serum BDNF levels (t = 9.537, P < 0.001). Moreover, the combined panel of BDNF, IL-6, and melatonin achieved high accuracy in distinguishing MDD patients from healthy controls, with an area under the curve (AUC) of 0.905. Additionally, no significant correlations were found between serum melatonin levels and clinical disease severity (assessed by HAMD-24 scores), IL-6 levels, or BDNF levels in MDD patients (all P > 0.05). CONCLUSIONS: These findings suggest that dysregulation of melatonin, IL-6, and BDNF may contribute to the pathophysiology of first-episode MDD, with their combined measurement offering strong diagnostic potential.
Association between Apolipoprotein B (ApoB) and suicidal ideation: a cross-sectional study and Mendelian randomization analysis.
Guo M, Zhang H, Fu C … +4 more , Wan H, Cai X, Dong H, Cheng H
Ann Gen Psychiatry · 2026 Mar · PMID 41888837 · Full text
BACKGROUND: Research suggests that lipid levels may be associated with suicide risk. However, the specific relationship between Apolipoprotein B and suicidal ideation remains unclear. The aim of this study was to investi...
BACKGROUND: Research suggests that lipid levels may be associated with suicide risk. However, the specific relationship between Apolipoprotein B and suicidal ideation remains unclear. The aim of this study was to investigate the association between ApoB levels and suicidal ideation and to further explore the causal relationship using Mendelian randomization. METHODS: A cross-sectional study of 6520 U.S. adults was conducted using the 2011-2016 National Health and Nutrition Examination Survey (NHANES) dataset. Multiple logistic regression, smoothed curve fitting, stratified analyses, and interaction tests were used to reveal the relationship between ApoB levels and suicidal ideation. MR analyses were conducted using inverse variance weighting (IVW), GSMR, Maximum likelihood method, and cML-MA-BIC MR method. Sensitivity analyses included MR-Egger intercept test, MR-PRESSO global test, and leave-one-out (LOO) analysis. RESULTS: Multivariate logistic regression analysis showed that serum ApoB levels were positively associated with suicidal ideation, and the association remained significant even after multiple covariates (P = 0.0463). Subgroup analyses showed that the risk of suicidal ideation was significantly increased in the highest tertile (T3) of the population compared to the lowest tertile (T1) of ApoB levels (OR = 1.48, 95% CI: 1.04-2.12, P = 0.0312). In addition, the association between ApoB and suicidal ideation was more significant in the smoking subgroup (P interaction = 0.034). However, MR analysis failed to confirm a significant causal effect of ApoB levels on suicidal ideation (P > 0.05), and these results were robust to sensitivity analyses. CONCLUSION: The present study found a significant positive association between serum ApoB levels and suicidal ideation, especially among smokers. MR analysis failed to provide causal evidence of ApoB on suicidal ideation. More research is needed to clarify the potential role of ApoB in the development of suicidal ideation.
Divergent prefrontal activation between genders in depression during verbal fluency task: evidence from a large-scale fNIRS study.
Zhang Y, Zhang Z, Zheng M … +4 more , Wang Y, Zhu D, Xiao Q, Wei Q
Ann Gen Psychiatry · 2026 Mar · PMID 41882763 · Full text
BACKGROUND: Depression exhibits marked sex differences in prevalence and clinical presentation, yet its neural underpinnings remain poorly understood. This study aimed to identify abnormal brain activation patterns durin...
BACKGROUND: Depression exhibits marked sex differences in prevalence and clinical presentation, yet its neural underpinnings remain poorly understood. This study aimed to identify abnormal brain activation patterns during cognitive tasks in depressed males and females using functional near-infrared spectroscopy (fNIRS), providing neurobiological evidence for sex-specific therapeutic strategies. METHODS: Prefrontal activation was measured with fNIRS during verbal fluency task in a large sample of young adults, including 431 individuals with depression and 422 healthy controls. RESULTS: Compared with male healthy controls, the male depression group showed reduced oxyhemoglobin activation in the right frontal eye field. In contrast, the female depression group exhibited lower oxyhemoglobin activation in left dorsolateral prefrontal cortex than the female healthy controls. Furthermore, a significant difference in oxyhemoglobin activation was observed between male and female depression groups in the left dorsolateral prefrontal cortex. CONCLUSIONS: The findings revealed dissociable neural patterns of depression across sexes, moving beyond a uniform model of prefrontal hypoactivation. The neurological basis of depression in males may involve the right frontal eye field, while in females it may be linked to the left dorsolateral prefrontal cortex. The left dorsolateral prefrontal cortex appeared to be a key region for sex-specific brain alterations in depression.
Psychiatric consultation for suicidal behaviour in emergency departments: a comparison between the university hospital Systems of Alessandria and Novara.
Gambaro E, Gramaglia CM, Ferrante D … +6 more , Franchino V, Mauceri C, Prelati M, Gavelli F, Bellan M, Zeppegno P
Ann Gen Psychiatry · 2026 Mar · PMID 41851719 · Full text
BACKGROUND: Suicide attempts constitute a significant public health emergency, with Emergency Departments (EDs) serving as a primary point of contact for individuals in acute psychiatric crisis. This observational, multi...
BACKGROUND: Suicide attempts constitute a significant public health emergency, with Emergency Departments (EDs) serving as a primary point of contact for individuals in acute psychiatric crisis. This observational, multicentric study aimed to analyse and compare the profiles of psychiatric consultations provided in the EDs of the University Hospital Systems (AOU) of Novara and Alessandria between January and December 2024, focusing on suicidal behaviours, clinical characteristics, and intervention outcomes. We hypothesised that territorial differences in patient demographics and service organisation would lead to distinct management patterns: Novara, expecting younger patients with chronic histories requiring hospitalisation, versus Alessandria, with older, self-referred cases, favouring territorial approaches. METHODS: Sociodemographic and clinical data were collected anonymously and pseudonymized from institutional software (Track Care, PsNet, REDCap). A total of 1,196 accesses requiring psychiatric evaluation were recorded. Multilevel logistic regression was performed to account for centre-level clustering (ICC = 0.12). RESULTS: The Novara cohort was significantly younger (mean age 42.5 vs. 47.1 years, p = 0.001) with more complex psychiatric histories (76.3% previous psychiatric history vs. 57.3%, p = 0.001) and higher rates of suicidal ideation and self-harm. Novara showed higher rates of acute pharmacological therapy (51.13% vs. 39.59%, p = 0.001) and voluntary hospital admissions (40.74% vs. 25.85%, p = 0.001). Conversely, Alessandria's older population (mean age 47.1 years) exhibited greater conscious suicidal intent (39.68% vs. 23.36%, p = 0.024) and used high-lethality methods. Alessandria adopted a more territorial management approach with higher discharge rates (27.23% vs. 18.89%) and community mental health centre (CMHC) referrals (21.23% vs. 17.96%). Substantial methodological differences were observed in substance use screening protocols. Novara reported 67.84% positive screens versus Alessandria's 12.22% (naive OR 14.2, 95% CI 11.0-18.3). Multilevel analysis accounting for centre-level effects reduced this estimate to OR 5.3 (95% CI 3.8-7.4, ICC = 0.12), representing a 63% attenuation. Sensitivity analysis restricted to the 537 patients uniformly screened yielded OR 4.9 (95% CI 3.5-6.8). These findings underscore that the apparent centre difference is substantially attributable to measurement bias rather than true epidemiological prevalence. Multivariate logistic regression confirmed a significant association between female sex and self-harming behaviours (OR 1.57, 95% CI 1.13-2.19, p = 0.008). CONCLUSIONS: This multicentric study revealed significant territorial differences in psychiatric emergency management between Novara and Alessandria. The Novara centre manages a younger population with complex, chronic psychiatric disorders, requiring an intensive, hospital-oriented approach. Alessandria serves an older population with higher conscious suicidal intent, managed primarily through territorial services. Standardisation of diagnostic protocols-particularly substance use screening-is essential for valid epidemiological comparison and uniform, evidence-based care.
A narrative review on trazodone as a multimodal and multifunctional antidepressant: clinical relevance of formulations, dosing, and pharmacokinetic/pharmacodynamic targets.
Cuomo A, Pompili M, Vita A … +3 more , Spina E, Caraci F, Fagiolini A
Ann Gen Psychiatry · 2026 Mar · PMID 41845402 · Full text
BACKGROUND: Trazodone, an antidepressant, has only been approved for use in major depressive disorder (MDD), but has demonstrated potent therapeutic potential in various conditions, such as insomnia and anxiety. It targe...
BACKGROUND: Trazodone, an antidepressant, has only been approved for use in major depressive disorder (MDD), but has demonstrated potent therapeutic potential in various conditions, such as insomnia and anxiety. It targets multiple serotonergic, adrenergic, and histaminergic receptors. Given this multimodal and multifunctional profile, we aimed to provide a comprehensive overview of the pharmacodynamic and pharmacokinetic properties of trazodone and its clinical applications across various conditions. MAIN TEXT: Trazodone demonstrates sedative and anxiolytic effects even at a low dose (25-75 mg) and a full antidepressant effect at higher doses (150-300 mg). The availability of trazodone in immediate-release, extended-release, intravenous, and intramuscular formulations enables flexible and personalized treatment based on the patient's symptoms, medical history, tolerability, and clinical settings. Clinical evidence also demonstrates that trazodone is effective and well-tolerated across various conditions, including MDD, treatment-resistant depression, insomnia (off-label), neurological disorders, dementia, and delirium, highlighting its versatility. Additionally, the low risk of sexual dysfunction, limited withdrawal symptoms, and weight-neutral effects make it suitable for use in patients with comorbid conditions. CONCLUSION: Trazodone is a multimodal and multifunctional antidepressant that exhibits a broad range of therapeutic effects in MDD and other comorbid conditions. Further research on the pharmacokinetic and pharmacodynamic relationship of trazodone, its parenteral use in acute settings, and the development of prescribing algorithms for predicting treatment responses may enhance its therapeutic outcomes in patients with MDD.
A novel sex-specific role for 27-hydroxycholesterol in early-onset schizophrenia.
Sun Z, Liu M, Yan J … +6 more , Wu Y, Wang H, Li Y, Tang Y, Zheng Y, Li R
Ann Gen Psychiatry · 2026 Mar · PMID 41776627 · Full text
BACKGROUND: Although Schizophrenia is a serious mental illness which more common in adults, it can also manifest in childhood with disease onset before age 18 as "early-onset schizophrenia" (EOS). While our previous rese...
BACKGROUND: Although Schizophrenia is a serious mental illness which more common in adults, it can also manifest in childhood with disease onset before age 18 as "early-onset schizophrenia" (EOS). While our previous research identified circulating oxysterols-24(S)-hydroxycholesterol (24 S-OHC) and 27-hydroxycholesterol (27-OHC)-as potential biomarkers in adult schizophrenia, their role in EOS remains unknown. This study aimed to characterize the developmental trajectories of these oxysterols during early life and evaluate their clinical relevance in EOS, with particular emphasis on sex-specific effects. METHODS: We recruited 142 healthy individuals (aged 1 to 41 years) to define age-related oxysterol patterns and 71 EOS patients (aged 4 to 18 years) to identify disease-associated changes. Plasma concentrations of 24 S-OHC and 27-OHC were measured using liquid chromatography-tandem mass spectrometry. RESULTS: Healthy participants exhibited significant age-dependent variations, with younger individuals showing higher 24 S-OHC and lower 27-OHC levels. While EOS patients showed no overall differences in oxysterol levels compared to age-matched healthy controls, a striking sex-based divergence emerged: male patients exhibited significantly elevated levels of 27-OHC compared to females. Additionally, the 24 S-OHC/27-OHC ratio showed a positive correlation with negative symptom severity, which did not survive correction for multiple comparisons but may still indicate a potential relationship. Notably, sex-stratified analysis revealed opposing correlations between 27-OHC levels and PANSS scores, most prominently for positive symptoms. CONCLUSIONS: This study represents the first evidence of sexually dimorphic oxysterol regulation in EOS and highlights 27-OHC as a sex-sensitive factor linked to clinical symptom expression, even in the absence of group-level oxysterol alterations.
Brief pharmacist-led intervention using a structured questionnaire to improve attitudes toward medication adherence in patients on antipsychotics: a single-site before-after study.
Maehara M, Sugiyama M, Kobayashi D … +3 more , Mutoh J, Noguchi K, Wada M
Ann Gen Psychiatry · 2026 Mar · PMID 41772640 · Full text
BACKGROUND: Medication adherence among patients with psychiatric disorders is a significant challenge that often leads to poor clinical outcomes. Although pharmacist-led interventions have demonstrated the potential to i...
BACKGROUND: Medication adherence among patients with psychiatric disorders is a significant challenge that often leads to poor clinical outcomes. Although pharmacist-led interventions have demonstrated the potential to improve medication adherence, evidence remains limited, particularly in patients treated with antipsychotics. This study aimed to evaluate the effectiveness of a brief pharmacist-led intervention in enhancing medication adherence among outpatients receiving antipsychotic therapy. METHODS: This exploratory, prospective, single-arm study was conducted at a community pharmacy in Japan. Fifty outpatients prescribed antipsychotic medications participated in the study. A brief pharmacist-led intervention was delivered focusing on identifying and addressing barriers to adherence. The primary outcomes were changes in Drug Attitude Inventory-10 (DAI-10) scores and the proportion of participants with unused medications. RESULTS: Participants taking preexisting medications exhibited a significant improvement in DAI-10 scores (mean increase, + 2.05 points; from 5.81 ± 4.00 to 7.86 ± 2.90, p = 0.00619). The proportion of participants who reported non-adherence to medication regimens decreased significantly from 42% to 24% (p= 0.0159). CONCLUSIONS: The brief pharmacist-led intervention was effective in improving attitudes toward medication and behavioral adherence among patients receiving antipsychotic treatment in our study group. These findings underscore the importance of active pharmacist engagement for supporting medication adherence.
Psychiatry in transition: an assessment in the context of societal change.
Wedmann FM, Albasini F, Davidson R … +2 more , Mayr A, Conca A
Ann Gen Psychiatry · 2026 Feb · PMID 41749268 · Full text
AIMS: To explore how global challenges such as climate change, artificial intelligence (AI), and migration intersect with generational change among psychiatric trainees and reshape specialist training. METHODS: An integr...
AIMS: To explore how global challenges such as climate change, artificial intelligence (AI), and migration intersect with generational change among psychiatric trainees and reshape specialist training. METHODS: An integrative review drawing on symposium contributions and a comprehensive literature review to assess the evolving priorities and challenges in psychiatric training. RESULTS: Younger psychiatrists increasingly prioritize work-life balance, sustainability, and participatory learning environments. However, gaps remain in integrating climate-related knowledge, transcultural competence, AI literacy and neurodevelopmental disorders within psychiatric curricula. Generational tensions and traditional hierarchical structures further complicate training. CONCLUSIONS: A new training model is needed that fosters mutual understanding between generations, encourages reflective dialogue, and supports collaborative learning. Preparing psychiatrists for the future requires updated content and a commitment to relational transformation and co-created educational practices.
Depression and apathy: examining an overlooked dimension.
Carbone EA, de Filippis R, Scalzo A … +7 more , Calabretta E, Lodari S, Rania M, Menculini G, Tortorella AAV, Segura-Garcia C, De Fazio P
Ann Gen Psychiatry · 2026 Feb · PMID 41736125 · Full text
BACKGROUND: Apathy is a significant yet frequently overlooked aspect of Major Depressive Disorder (MDD), often confused with anhedonia, and with the potential to influence clinical outcomes and quality of life regardless...
BACKGROUND: Apathy is a significant yet frequently overlooked aspect of Major Depressive Disorder (MDD), often confused with anhedonia, and with the potential to influence clinical outcomes and quality of life regardless of the severity of depressive symptoms. Despite its importance, the relationship between apathy and depression remains underrepresented in current research. This study aims to assess the prevalence of apathy in a sample of outpatients affected by MDD and to explore its clinical, cognitive, and functional correlates. METHODS: Outpatients with MDD (n = 154) during a clinical stability phase have been assessed using the Apathy Evaluation Scale-Clinician version (AES-C), Dimensional Apathy Scale (I-DAS), MADRS, BDI-II, MMSE, PANSS, EQ-5D-3 L, and CGI-S. Patients were categorized into two groups according to the presence/absence of apathy (AES-C score ≥ 42). Groups comparison and a stepwise logistic regression were run to identify clinical differences between groups and the predictors of apathy. RESULTS: Apathy was detected in 48% of the sample. Patients with apathy scored higher on depression scales, had lower cognitive performance, more negative and general psychopathology, greater clinical severity, and reduced quality of life. Significant differences emerged in initiation and executive apathy. Logistic regression identified MADRS item 8 “inability to feel” and BDI-II item 12 “loss of interest” as the factors showing the strongest association with apathy. CONCLUSION: Apathy is a prevalent and clinically relevant feature in MDD, associated with greater psychopathology and functional impairment. Findings support the need to routinely assess apathy in clinical setting, even during symptomatic stability phases. Specific symptoms may serve as key markers for its identification.
The bidirectional effects of hemorrhoids, depression, and anxiety: a prospective cohort study in the UK Biobank.
Huang Z, Yi X, Liu X … +4 more , He Y, Huang J, Liang S, Ming WK
Ann Gen Psychiatry · 2026 Feb · PMID 41721337 · Full text
BACKGROUND: This study examines the bidirectional association between hemorrhoidal disease and mental health conditions, specifically depression and anxiety. While a plausible connection exists, research on their interpl...
BACKGROUND: This study examines the bidirectional association between hemorrhoidal disease and mental health conditions, specifically depression and anxiety. While a plausible connection exists, research on their interplay is limited. METHODS: Using data from the UK Biobank (until March 2024), this prospective study analyzed two cohorts: 48,620 participants in the hemorrhoids-to-mental disorder cohort and 87,310 in the mental disorder-to-hemorrhoids cohort. Analyses were adjusted for multiple sociodemographic, lifestyle, and clinical covariates, including age, sex, ethnicity, BMI, smoking status, alcohol consumption, socioeconomic indicators, and comorbidities. We employed time-varying Cox proportional hazards models in conjunction with propensity score matching to estimate associations, assessing risk within 5 years, within 10 years, and over long-term follow-up. RESULTS: Fully adjusted models revealed significant associations between hemorrhoidal disease and mental disorders. A diagnosis of hemorrhoidal disease was associated with a higher risk of subsequent depression (HR, 1.56 [95% CI, 1.46-1.66]) and anxiety (HR, 1.55 [95% CI, 1.46-1.66]). Conversely, a diagnosis of depression was associated with an increased risk of subsequent hemorrhoidal disease (HR, 1.14 [95% CI, 1.09-1.19]), as was a diagnosis of anxiety (HR, 1.46 [95% CI, 1.38-1.54]). CONCLUSION: This study identifies a significant bidirectional association between hemorrhoidal disease and mental health conditions. Notably, the interaction between smoking and anxiety highlights a subgroup at elevated risk that may benefit from closer clinical attention. These findings support an integrated care perspective that considers both gastrointestinal and mental health conditions, while acknowledging that causal inferences cannot be definitively established from observational data.
Associations between immigration background, adverse childhood experiences, and depressive symptoms in adulthood in immigrants and descendants of immigrants in France: a mediation analysis.
Zarei K, Surkan PJ, van der Waerden J … +5 more , Wiernik E, Aradhya S, Hollander AC, Choi K, Melchior M
Ann Gen Psychiatry · 2026 Feb · PMID 41703605 · Full text
INTRODUCTION: In France, 10% of the population are immigrants and another 11% are children of immigrants. Both have worse mental health than the native French. The role of adverse childhood experiences (ACE) in immigrant...
INTRODUCTION: In France, 10% of the population are immigrants and another 11% are children of immigrants. Both have worse mental health than the native French. The role of adverse childhood experiences (ACE) in immigrants’ mental health is not well characterized. We aimed to examine associations between immigration background, ACEs, and depressive symptoms. METHODS: Data came from the baseline and 2020 follow-up questionnaires of the French CONSTANCES study ( = 116,495), a national cohort. The exposure was immigration background categorized by immigration generation (1st : immigrants; 2nd : French-born with ≥ 1 immigrant parent; and native French) and the geographic origin of the participant (1st generation) or ≥ 1 parent (2nd generation). The mediator was experiencing ACEs. The outcome was depressive symptoms ascertained with the Center for Epidemiologic Studies Depression scale at study inclusion. Mediation analysis using multivariable logistic regression and path analysis (PA) was used to assess associations between the exposure, mediator, and outcome, overall and stratified by sex, minimally adjusting for age and sex or adjusting for all covariates. RESULTS: The prevalence of depressive symptoms was 18.5%. In minimally adjusted models, compared to native French, there were higher odds of depressive symptoms in 1st and 2nd generation adults except those with ≥ 1 parent from Asia. Mediation effects of ACEs from PA ranged from 0.03 to 0.10. In the fully adjusted model including after adjusting for experiencing ACEs, only immigrants from North Africa had significantly increased odds of depressive symptoms (AOR = 1.52, 95%CI: 1.29, 1.79). CONCLUSIONS: In France, non-native adults have higher prevalence and odds of depressive symptoms than the native French, with ACEs having a significant mediating effect. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12991-025-00612-7.
Altered subgenual anterior cingulate cortex connectivity in psoriasis patients with depression: a resting-state fMRI case-control study.
Liu N, Wang X, Zhang Y … +4 more , Han X, Yi F, Huo J, Chang T
Ann Gen Psychiatry · 2026 Feb · PMID 41699678 · Full text
BACKGROUND: Psoriasis is a chronic inflammatory skin disease frequently comorbid with depression, yet the underlying neurobiological mechanisms remain unclear. This study investigated functional connectivity (FC) alterat...
BACKGROUND: Psoriasis is a chronic inflammatory skin disease frequently comorbid with depression, yet the underlying neurobiological mechanisms remain unclear. This study investigated functional connectivity (FC) alterations of emotion-regulation circuits and their association with inflammatory markers in psoriasis patients with depression. METHODS: Seventeen psoriasis patients with depression and 17 matched controls underwent resting-state functional magnetic resonance imaging (rs-fMRI) examination. Seed-based FC analysis was performed to examine connectivity abnormalities of the subgenual anterior cingulate cortex (sgACC), a key emotional regulation region, with the following statistical thresholds: voxel-level p < 0.001 (uncorrected) with cluster-level false discovery rate (FDR) correction at p < 0.05 for multiple comparisons. Correlation analyses were conducted to evaluate relationships between sgACC connectivity patterns and depression severity (Self-rating Depression Scale, SDS), pruritus intensity (Visual Analog Scale, VAS), and serum levels of IL-6 and IL-17 in a subgroup of participants (n = 7). RESULTS: Psoriasis patients with depression showed increased sgACC connectivity with DMN nodes (posterior cingulate cortex(PCC), angular gyrus(AG)) and executive network regions (superior frontal gyrus (SFG), middle frontal gyrus (MFG)) versus controls. FC between sgACC-AG correlated with SDS scores (r = 0.598, p = 0.011), while sgACC with right SFG (r = 0.893, p = 0.007) and left MFG (r = 0.929, p = 0.003) connectivity positively associated with IL-17 levels. CONCLUSIONS: The findings reveal a "dual-circuit" dysfunction pattern in psoriatic depression: sgACC-DMN hyperconnectivity linked to depressive symptoms, and sgACC-dlPFC (dorsolateral prefrontal cortex) alterations associated with IL-17 elevation. These results establish the sgACC as a neural hub bridging inflammation and mood dysregulation, supporting the "skin-brain axis" hypothesis. The identified FC patterns may serve as biomarkers for targeted interventions in inflammation-related depression.
Understanding suicide risk in mild cognitive impairment: a systematic review of suicide epidemiology in older adults.
Bungaro N, Quinto RM, Scoma L … +6 more , Dattilo L, Imperatori C, Innamorati M, Genova F, Balsamo M, Carlucci L
Ann Gen Psychiatry · 2026 Feb · PMID 41699654 · Full text
BACKGROUND: Late-life suicide represents a major public health issue, with older adults showing the highest lethality and completion rates. Mild Cognitive Impairment (MCI), a critical stage of increased psychological vul...
BACKGROUND: Late-life suicide represents a major public health issue, with older adults showing the highest lethality and completion rates. Mild Cognitive Impairment (MCI), a critical stage of increased psychological vulnerability, may represent an acute phase of suicide vulnerability. This systematic review aimed to synthesize existing evidence on suicide risk among older adults with MCI, examining the prevalence of suicide ideation and behaviors, as well as associated factors and therapeutic outcomes. METHODS: Following PRISMA guidelines, four databases (PubMed, Scopus, MEDLINE, PsycINFO) were searched. Eligible studies included participants aged ≥ 65 years, presence of MCI, and an assessment of suicide risk. Methodological quality was appraised using JBI Critical Appraisal Checklists. RESULTS: Seventeen records published between 2002 and 2024 met inclusion criteria. Across studies, individuals with MCI consistently reported higher rates of suicide ideation compared both with cognitively intact controls and older adults showing more severe cognitive impairment. Prevalence estimates ranged from 0.5% in a large community sample to as high as 84% in a clinical cohort. Depressive symptoms, particularly late-life depression, emerged as the strongest correlate, along with social isolation, female gender, younger age, being single, and multimorbidity. Across three randomized controlled trials, psychotherapeutic interventions and supportive care conditions were associated with reductions in suicide ideation, likely mediated by improvements in emotional regulation and depression. CONCLUSION: MCI may represent a particularly vulnerable stage of cognitive decline, marked by preserved insight, loss of autonomy, and heightened existential distress. Standardizing diagnostic criteria and suicidality measures, and implementing tailored psychotherapeutic approaches, are essential steps toward prevention and early interventions in this high-risk population.
Lurasidone continuation in real-world clinical cases in Japan: retrospective study of factors associated with six-month persistence.
Fujita K, Sugimoto Y, Aratake R … +6 more , Yoshimoto T, Kawai M, Fukatsu T, Mori Y, Nishihara M, Miyata J
Ann Gen Psychiatry · 2026 Feb · PMID 41692791 · Full text
BACKGROUND: Treatment discontinuation remains a major challenge for patients with schizophrenia, often resulting in relapse and subsequent rehospitalization. While treatment persistence is a practical marker of real-worl...
BACKGROUND: Treatment discontinuation remains a major challenge for patients with schizophrenia, often resulting in relapse and subsequent rehospitalization. While treatment persistence is a practical marker of real-world effectiveness, findings related to lurasidone continuation in clinical settings in Japan are limited. METHODS: For this retrospective observational study, the records of 62 patients with schizophrenia who had lurasidone treatment initiated at Aichi Medical University Hospital between June 2020 and December 2024 were analyzed. Treatment persistence was defined as continuation of lurasidone for ≥ 180 days. Associations of baseline characteristics, including illness duration, prior antipsychotic class (serotonin-dopamine antagonist, SDA; dopamine partial agonist, DPA; multi-acting receptor-targeted antipsychotic, MARTA), and other clinical variables, with six-month persistence were analyzed using Kaplan-Meier survival analysis and log-rank testing. RESULTS: The six-month treatment persistence rate was 54.8%. Patients with illness duration < 5 years showed a significantly greater rate of persistence (71.4%) as compared to those with a longer duration (46.3%) (P = 0.046). Persistence also varied based on prior antipsychotic class, with the rate 76.5% for SDA, 50.0% for DPA, and 35.0% for MARTA (P = 0.045). No statistically significant differences in six-month persistence were observed across sex, treatment setting, or lurasidone dose range. CONCLUSIONS: This is the first known study to evaluate real-world lurasidone persistence in patients in Japan. The findings indicate that both pharmacodynamic compatibility and early-phase treatment can enhance persistence. The insights obtained underscore the importance of individualized treatment planning, though require further validation by use of prospective, multi-center studies.
Mechanisms and clinical potential of combined tDCS and virtual reality in psychiatric disorders: a systematic review.
Guo X, Jiang H, Zheng Z … +3 more , Zhang J, Cao L, Jiang H
Ann Gen Psychiatry · 2026 Feb · PMID 41691330 · Full text
BACKGROUND: Transcranial direct current stimulation (tDCS) and virtual reality (VR) have emerged as promising non-invasive interventions in treating psychiatric disorders. Despite their individual efficacy in improving s...
BACKGROUND: Transcranial direct current stimulation (tDCS) and virtual reality (VR) have emerged as promising non-invasive interventions in treating psychiatric disorders. Despite their individual efficacy in improving symptoms of various psychiatric conditions, the understanding of the combined use of tDCS and VR is limited. This review aims to evaluate the clinical effects and mechanisms of combined tDCS and VR in treating psychiatric disorders. METHODS: We conducted a PRISMA 2020-compliant systematic review, searching major databases (PubMed, Web of Science, Scopus, PsycINFO, ScienceDirect, Cochrane Library, Google Scholar, medRxiv and ClinicalTrials.gov) for studies from January 2000 to July 2025 that evaluated combined tDCS-VR in psychiatric populations. Eligible clinical trials were screened, with tDCS/VR parameters and clinical outcomes extracted, and randomized controlled trials appraised using the Cochrane Risk of Bias 2 tool. RESULTS: Fourteen studies met inclusion criteria: seven reviews and seven empirical trials (five randomized controlled trials, two pilot/feasibility studies) using mainly 1-2 mA prefrontal tDCS paired with disorder-congruent VR. In post-traumatic stress disorder (PTSD) and specific phobias showed short-term symptom reductions, with some PTSD benefits maintained up to 12 months. Evidence for social anxiety and mild cognitive impairment-related depression was limited to single small RCTs with transient or inconsistent improvements. Overall confidence in the evidence is limited by small sample sizes, variable protocols, and risk‑of‑bias concerns. CONCLUSION: Although seven small, heterogeneous studies indicate that combined tDCS-VR is feasible and shows preliminary therapeutic promise-most consistently in PTSD and, to a lesser extent, in specific phobias-the overall evidence base remains limited. Mechanistic findings suggesting modulation of medial and ventromedial prefrontal-amygdala circuits are still exploratory. Given substantial methodological heterogeneity, small sample sizes, and risk of bias, tDCS-VR should be regarded as experimental. The larger, well‑designed, disorder‑tailored randomized controlled trials using standardized stimulation/VR protocols, mechanistic outcome measures, and efforts to identify predictors of response are required before routine clinical implementation.
Reflections from individuals with schizophrenia on a life with delusions and hallucinations: a phenomenological study.
Uzun S, Ediz Ç, Burak Erdaş M
Ann Gen Psychiatry · 2026 Feb · PMID 41689044 · Full text
BACKGROUND: Despite their profound influence on the lives of individuals with schizophrenia, few studies explore delusions and hallucinations from the first-person perspective using a phenomenological approach. This stud...
BACKGROUND: Despite their profound influence on the lives of individuals with schizophrenia, few studies explore delusions and hallucinations from the first-person perspective using a phenomenological approach. This study aimed to examine how individuals diagnosed with schizophrenia experience delusions and hallucinations from their own perspective. METHODS: This descriptive phenomenological study was conducted between August and September 2023. Semi-structured, in-depth interviews were conducted with 14 individuals diagnosed with schizophrenia who regularly attended a state community mental health center in eastern Turkey. Interviews were audio-recorded, transcribed verbatim, and analyzed using Colaizzi's seven-step method. The study was reported in line with the COREQ checklist. RESULTS: Four main themes were identified: (1) effects of schizophrenia, (2) triggers for delusions and hallucinations, (3) the impact of delusions and hallucinations on daily life, and (4) coping with delusions and hallucinations. Ten sub-themes captured psychological, physical, and social effects and triggers, as well as control mechanisms, challenges in life, perceived social support, and emotions. CONCLUSION: The findings highlight the pervasive psychological, physical, and social burden of living with delusions and hallucinations and the variability in coping resources and support. Developing and evaluating tailored psychosocial interventions may help individuals with schizophrenia manage these experiences more effectively. These findings suggest the need for developing psychoeducation programs focused on identifying personal symptom triggers, family-based support interventions that enhance communication and stigma reduction, and community mental health interventions aimed at strengthening coping skills, social participation, and emotional regulation.
Prevalence and associated risk factors of psychotic experiences in the general population during the COVID-19 pandemic: a systematic review and meta-analysis.
Fekih-Romdhane F, Azzi V, Harb F … +2 more , Obeid S, Hallit S
Ann Gen Psychiatry · 2026 Feb · PMID 41680907 · Full text
BACKGROUND: COVID-19 is strongly associated with common mental disorders, but little is known about its association with psychotic experiences (PEs). Subclinical psychotic experiences, such as hallucinations and delusion...
BACKGROUND: COVID-19 is strongly associated with common mental disorders, but little is known about its association with psychotic experiences (PEs). Subclinical psychotic experiences, such as hallucinations and delusions, can precede psychotic disorders. This review sought to consolidate estimates and correlates of PEs in population-based samples during the COVID-19 pandemic. METHODS: This systematic review and meta-analysis was conducted in accordance with PRISMA and was registered in PROSPERO (CRD42024499153). A systematic search in EMBASE, MEDLINE (PubMed), Web of Science, Google Scholar, Scopus, APA PsycINFO, and other databases was conducted for relevant papers published between January 2020 (when COVID-19 was declared a worldwide health emergency) and September 30, 2024. Papers were included if they investigated the prevalence of self-reported PEs among people from the general public during the COVID-19 pandemic. The Newcastle-Ottawa Scale was used to evaluate the risk of bias. Meta-analyses were performed based on the random-effects model, and the effect size was presented as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Twenty-five studies involving 264,504 adults were eligible. The prevalence of non-clinician administered self-reported PEs (12 studies) was 15.2% (pool). Subgroup analyses demonstrated that prevalence was higher in non-students compared to students (defined in the reference studies as individuals enrolled in college or university), those assessed during lockdown or quarantine than those assessed outside of lockdown or quarantine, and participants in Western versus non-Western countries. There was no meaningful difference between adolescents (≤ 24 years) and adults (> 24 years). Substantial heterogeneity (I² = 100%) was found, probably owing to differences in measurement instruments, participants, and settings. CONCLUSION: The results indicated that more than one-in-seven non-help-seeking individuals from the general public were screened as having self-reported PEs and a high-risk profile for psychosis during the pandemic. Elevated prevalence rates observed during lockdowns and among specific subgroups support the need for psychosis risk screening in public health strategies. Further research is needed to directly compare pre- and post-pandemic rates and explore long-term outcomes.
Understanding individual and structural factors behind extensive care needs in personality disorders: an interpretative phenomenological analysis.
Strand J, Di Leone F, Dervisoski E … +2 more , Iranmanesh P, Sand P
Ann Gen Psychiatry · 2026 Feb · PMID 41656219 · Full text
Extensive care needs, including frequent hospitalizations and compulsory care, are common among individuals with personality disorders (PD), yet the outcomes of such interventions remain uncertain. This study aimed to ex...
Extensive care needs, including frequent hospitalizations and compulsory care, are common among individuals with personality disorders (PD), yet the outcomes of such interventions remain uncertain. This study aimed to explore patient perspectives on the individual and structural factors contributing to the high demand for psychiatric interventions. Eleven high-care-consuming patients diagnosed with PD were interviewed, and data were analyzed using interpretative phenomenological analysis. The findings indicate that emergency department visits often stem from emotional turmoil and social isolation, reflecting acts of desperation. Participants described inpatient treatments as impersonal, lacking direction, and primarily focused on repeated pharmacological interventions that exacerbated feelings of hopelessness. Both inpatient and outpatient care were perceived as "a state of waiting for something that never happens," reflecting an ongoing sense of invalidation and unmet needs. These results highlight the urgent need for healthcare systems to prioritize individualized care plans, improved communication, and explore alternative approaches for managing crises or reforming emergency department practices for this group of patients. Addressing these factors could enhance patient well-being, reduce self-destructive tendencies, and alleviate reliance on the mental health system.
Analysis of the correlation between the expression levels of caspase-1/IL-1β in the peripheral blood and clinical efficacy in patients with first-episode MDD.
Gu JY, Di DC, Gu MY … +1 more , Liu HZ
Ann Gen Psychiatry · 2026 Feb · PMID 41654910 · Full text
BACKGROUND: Major depressive disorder (MDD) pathogenesis is associated with immune-inflammatory dysregulation. This study investigated the mechanistic role of caspase-1-mediated inflammatory pathways in MDD, exploring th...
BACKGROUND: Major depressive disorder (MDD) pathogenesis is associated with immune-inflammatory dysregulation. This study investigated the mechanistic role of caspase-1-mediated inflammatory pathways in MDD, exploring their therapeutic targeting potential and clinical predictive utility. METHODS: Peripheral blood levels of caspase-1, IL-1β, and IL-10 were assessed in MDD patients, with longitudinal analysis of dynamic changes pre-/ post-antidepressant treatment. The predictive performance of the biomarker was validated using leave-one-out cross-validation (LOOCV) and receiver operating characteristic (ROC) analysis. A chronic unpredictable stress (CUS) rat model was established to evaluate the combined therapeutic effects of caspase-1 inhibitors with fluoxetine. RESULTS: Clinical data revealed that expression levels of caspase-1 and IL-1β exhibited an negative correlation with clinical treatment response in patients with MDD, with varying levels observed among patients with differing depression severity. In contrast, IL-10 expression demonstrated a positive correlation with therapeutic efficacy. Following treatment, significant reductions in caspase-1 and IL-1β levels were observed, concurrent with an elevation in IL-10. Caspase-1 demonstrated superior predictive accuracy for treatment response (0.8529 ± 0.3542), yielding an area under the ROC curve (AUC) of 0.72. In animal models, co-administration of a caspase-1 inhibitor with fluoxetine accelerated the onset of antidepressant effects, while simultaneously reducing peripheral blood caspase-1 and IL-1β levels. CONCLUSIONS: The caspase-1/IL-1β axis contributes to MDD pathogenesis by disrupting the pro-inflammatory/anti-inflammatory balance. Its mediated immune response pattern represents a potential therapeutic target for novel antidepressant development. Combined caspase-1 modeling provides a reliable tool for predicting clinical efficacy in MDD, while caspase-1-targeted intervention strategies may overcome the limitation of slow onset of action associated with conventional therapies.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe