The objective of this study was to examine the association between generalized anxiety disorder (GAD) and health-related quality of life (HRQOL) in the general Korean population, and whether this relationship differed by multimorbidity profiles and household income. We included 5,542 participants aged 19 years or older from the data of the 2021 Korean National Health and Nutrition Examination Survey. The GAD was assessed using the Generalized Anxiety Disorder 7-item scale (GAD-7). Participants with a GAD-7 score ≥ 10 were classified as having GAD. HRQOL was measured using the Health-related Quality of Life Instrument with 8 Items (HINT-8). Multimorbidity profiles were derived using latent class analysis. Survey-weighted regression models were used to evaluate associations and interaction effects. The weighted prevalence of GAD was 4.23%, with a mean GAD-7 score of 1.99. The mean HINT-8 index was 0.80. Higher GAD-7 scores and the presence of GAD were consistently associated with lower HINT-8 index values. GAD was associated with increased odds of problems across all HINT-8 domains, with particularly strong associations for depression (odds ratio [OR] = 34.43) and moderate associations for memory (OR = 4.88) and sleep (OR = 4.68). Three multimorbidity profiles (Healthy, Geriatric Disease, and Cardiometabolic Disease groups) were identified, and the association between GAD-7 scores and HRQOL differed by multimorbidity profile and household income, with similar patterns observed for GAD status. Higher GAD-7 scores and GAD were associated with substantially poorer HRQOL across both physical and psychological domains. The strength of this relationship varied according to multimorbidity profile and socioeconomic context.
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. Data came from the baseline and 2020 follow-up questionnaires of the French CONSTANCES study (n = 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. 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). In France, non-native adults have higher prevalence and odds of depressive symptoms than the native French, with ACEs having a significant mediating effect. The online version contains supplementary material available at 10.1186/s12991-025-00612-7. Compared to the native French, there were generally higher odds of depressive symptoms and experiencing ACEs in immigrants and descendants of immigrants. Experiencing ACEs may have a mediating effect on depressive symptoms among most groups of immigrants and descendants of immigrants. Our findings from a large, diverse cohort have implications for risk factors to prioritize to advance psychosocial health and research among immigrants and their descendants, in relation to both origin-specific and general factors related to depression and ACEs. The online version contains supplementary material available at 10.1186/s12991-025-00612-7.
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. 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). 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. 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.
Depression is recognized as being linked to atherosclerosis and adverse cardiovascular outcomes; however, robust evidence from nationally representative cohorts regarding its association with myocardial infarction (MI) is still insufficient. This study aimed to investigate the relationship between depressive symptoms, measured by the PHQ-9, and the odds of having a history of MI using data from NHANES 2005-2020, while further exploring possible nonlinear patterns and potential modifiers of this association. We included 37,139 adults aged 20 years or older (1,574 with MI) and performed weighted analyses accounting for the NHANES complex survey design. Exposure was defined as PHQ-9 scores, analyzed both continuously and by severity categories (none, mild, moderate, severe), with self-reported MI as the outcome. We fitted three progressively adjusted weighted logistic regression models and employed restricted cubic spline (RCS) analysis to evaluate nonlinearity. We further performed prespecified subgroup and interaction analyses, along with a series of sensitivity analyses. Higher depressive burden was significantly associated with higher odds of MI, with MI prevalence rising progressively across depression severity groups (2.89% vs. 4.39% vs. 5.80% vs. 7.08%, p < 0.001). In the unadjusted model, every 1-point increase in PHQ-9 score corresponded to a 6.2% increase in the odds of MI (OR = 1.062, 95% CI: 1.047-1.077; p < 0.001), while severe depression was linked to approximately a 2.56-fold higher odds compared with non-depressed participants. The association remained robust after sequential full adjustment for potential confounders. Restricted cubic spline analysis revealed no evidence of nonlinearity (p > 0.05), supporting an approximately linear association. Subgroup analyses demonstrated consistent associations across most strata; however, significant interactions were detected for CHF, CHD, and higher V/MPA groups (P for interaction < 0.05), indicating attenuated associations in these groups. In a nationally representative sample of US adults, depressive burden was strongly associated with prevalent MI, with cardiovascular comorbidities and physical activity acting as potential modifiers of this association. These findings underscore the importance of integrating routine depression screening and holistic mind-body management into both general and high-risk populations, and highlight the necessity of prospective and interventional studies to clarify the temporal sequence and evaluate potential causality.
According to the World Health Organization, approximately one in eight people is diagnosed with mental disorders globally. Patient-reported outcomes and quality of life assessments are essential tools for evaluating patient outcomes. This study aimed to identify, characterize, and summarize the literature focusing on quality of life or patient-reported outcomes among patients with mental disorders in the Kingdom of Saudi Arabia undergoing pharmacological treatment. This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 item checklist applicable for Systematic reviews. Searches were run in the following databases: PubMed, MEDLINE via Ovid, MEDLINE via EBSCO, and ProQuest. Databases were searched from January 1, 2000, to July 31, 2025. Ten articles that explored the quality of life of patients undergoing mental disorders treatment in the Kingdom of Saudi Arabia since 2000 met the inclusion criteria. A total of 3,773 patients included, and fifteen different quality of life questionnaires and patient-reported outcome measures were used. One-third of the reviewed articles used the Morisky Medication Adherence Scale (MMAS) and consistently reported low to moderate levels of adherence. This study highlights the need for further research in the mental health field, with a focus on enhancing patients' quality of life and reporting outcomes.
The aripiprazole once-monthly 400 mg two-injection start (AOM 400-TIS) enables treatment initiation at a single clinic visit, without the need for 14 days of concurrent oral aripiprazole supplementation. Previously, results from a survey outlined the views and experiences of healthcare professionals (HCPs) with the AOM 400-TIS in a real-world setting in Europe. The current work extends these findings to include a broader pool of participants from more European countries. This was a non-interventional, cross-sectional survey of HCPs from Germany, Italy, the United Kingdom, Denmark, and Sweden. Participants were licensed nurses/physicians with experience prescribing and/or administering the AOM 400-TIS to patients diagnosed with schizophrenia. Two waves of survey data were pooled and analysed using descriptive methods. Data from 229 HCPs were evaluated. Poor treatment adherence (88.6%), relapse (51.1%), and patient preference (47.6%) were common reasons for using the AOM 400-TIS, while patients not wanting two injections at the same time (52.4%) and concerns about safety (34.1%) and tolerability (33.6%) were common barriers. Among HCPs, 86.0% agreed/strongly agreed they were satisfied with outcomes of patients treated with the AOM 400-TIS, with most agreeing/strongly agreeing that patients appeared satisfied in general (73.4%) and with sustained quality of life and functioning (66.4%). This survey provides a pan-European account of HCPs' views and experiences with the AOM 400-TIS in adults diagnosed with schizophrenia. Initiatives to overcome barriers to AOM 400-TIS use include providing clearer evidence and education on its efficacy and safety and consideration of how the regimen is presented in patient-provider discussions.
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s12991-026-00632-x.
Social isolation and loneliness represent significant public health issues in society. Irritable bowel syndrome (IBS) severely impacts quality of life and requires early prevention. However, the relationship between social isolation, loneliness, and IBS remains uncertain. We aim to investigate the association between social isolation, loneliness, and the incidence of IBS in a large-scale population cohort. This prospective cohort study involved 369,653 participants without IBS from the UK Biobank. The genetic risk of IBS was evaluated using polygenic risk scores. The Cox proportional hazards model was employed to analyze the relationship between social isolation, loneliness, and the risk of IBS incidence. We examined whether depression and anxiety mediate the association between social isolation, loneliness, and IBS risk. Among the 369,653 participants (mean age: 56.7 ± 8.1 years; 47.7% male), 7,663 individuals were diagnosed with IBS during a median 13.6 years of follow-up. After comprehensive adjustment for socioeconomic status, lifestyle factors, health status, and genetic susceptibility, the HR for IBS incidence was 1.156 (1.073, 1.245) among socially isolated participants compared to non-socially isolated participants. The HR for IBS incidence was 1.361 (1.244, 1.490) among lonely participants compared to non-lonely participants. Subgroup analysis showed that, compared to participants without social isolation, the risk of developing IBS in participants without diabetes and those with diabetes under social isolation was 1.133 times (95% CI: 1.050-1.223) and 1.655 times (95% CI: 1.214-2.257) higher, respectively, with the risk being greater in the diabetic group (P for interaction = 0.022). Social isolation and loneliness were associated with an increased risk of developing IBS, although loneliness may have a more significant effect on risk. Participants with diabetes have a higher risk of developing IBS under conditions of social isolation. Depression and anxiety mediated the association between social isolation, loneliness, and the risk of developing IBS.
The purpose was to study preschool teachers' preferences and experiences of an applied learning intervention to support children with ESSENCE symptoms. Preschool teachers (n = 164) filled out a questionnaire about their experiences, and 20 participated in individual interviews about preferences and experiences of the intervention. We used descriptive statistics for the questionnaire and inductive qualitative content analysis to analyze the interviews and free text answers in the questionnaire. The results showed that 74% experienced that they increased their understanding of the child's difficulties, while 48% gained ideas that could be helpful in managing children. Specifically, the respondents emphasized the value of talking and reflecting together with guardians about a specific child. To share experiences from different contexts provided an understanding of the challenges the child, and the adults around them, faced in daily life. It also provided insight into the child's opportunities, abilities and resources. The qualitative latent analyses revealed that the preschool teachers' expectations corresponded well to their experiences after completing the training. The main categories Collaboration between guardians and preschool teachers and Professional knowledge about children with special needs describes their needs for supporting children with neurodevelopmental symptoms. Together they form the theme of a child-centered approach. In conclusion, the present findings add insights about collaborative learning, application of professional knowledge, and guardians and preschool teachers sharing experiences and reflecting together to support the child. In this way, the study contributes to the improvement and application of Child and Family Centered Care in practice.
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. 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. 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. 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 online version contains supplementary material available at 10.1186/s12991-026-00641-w. Apathy is a prevalent and clinically relevant feature in major depressive disorder (MDD). Patients with apathy reported greater clinical severity and poorer quality of life. “Inability to feel” and “loss of interest” are the strongest predictors of apathy in MDD. Apathy in MDD might be a bridging dimension between anhedonia and cognitive symptoms. The online version contains supplementary material available at 10.1186/s12991-026-00641-w.
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. 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). 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). 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.
Obsessive-compulsive disorder (OCD) is a chronic, early-onset condition often associated with high rates of treatment resistance, and affective disturbances are frequent comorbidities and linked to poorer therapeutic outcomes. Recently, the concept of "demoralization syndrome" has been proposed as not fully overlapping with major depressive episodes. Given the disabling nature of OCD, it is relevant to specifically evaluate the states of demoralization, considering that this condition may have treatment implications partially different from those related to other forms of affective disturbances. The aim of the present exploratory study was to evaluate demoralization in subjects with OCD and its relationship with the severity of OCD-related symptoms. Adults with a primary diagnosis of OCD were consecutively recruited from the OCD outpatient clinic of Azienda Ospedaliero-Universitaria Policlinico Umberto I (Rome, Italy). Participants were assessed with clinical interviews as well as with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for OCD severity, the Demoralization Scale (DS) for demoralization, and the Patient Health Questionnaire (PHQ) and Hamilton Depression Rating Scale (HAM-D) for depressive symptoms. Descriptive and correlational analyses have been performed. A total of 43 adults with OCD were included. Both depressive and demoralization symptoms were highly prevalent, with clinically-significant demoralization observed in 88% of patients. A subset of individuals exhibited clinically-significant demoralization without clinically-relevant depression. Demoralization severity showed significant associations with the severity of obsessions. Demoralization was highly prevalent in our sample, and it was significantly associated with the severity of obsessions. Recognizing demoralization states in OCD may improve diagnostic precision and guide tailored therapeutic interventions, complementing standard treatments for the diseases. Further research, including longitudinal studies, is needed to clarify its impact on the course of the disorder.
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. 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. 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. 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.
Climate change represents a major global health challenge with potential implications for mental health. Exposure to climate-related stressors is associated with an elevated risk of psychiatric disorders, including trauma- and stressor-related disorders (e.g., PTSD), depressive disorders, and anxiety disorders. Vulnerable populations-including children, women, older adults, individuals with pre-existing mental health conditions, and communities in low-income or disaster-prone regions-may be disproportionately affected. This umbrella review synthesizes current evidence on the mental health impacts of climate change, focusing on clinically relevant outcomes and underlying mechanisms. A systematic literature search was conducted across Web of Science, PubMed, Scopus, and Google Scholar for systematic reviews published between January 2014 and October 2024. Data extraction and methodological quality assessment were performed using the Joanna Briggs Institute Critical Appraisal Checklist, which evaluates methodological rigor, clarity of research questions, and appropriateness of data synthesis. Only English-language systematic reviews scoring ≥ 5/11 on the JBI checklist-reflecting moderate to high methodological quality-were included. Non-systematic reviews and studies without accessible full texts were excluded. The review protocol was registered in PROSPERO (CRD420251133963). Climate change may affect mental health through both direct and indirect pathways. Direct impacts include elevated risk or worsening of PTSD, depressive disorders, anxiety disorders, and suicidal behaviors, which may be precipitated or exacerbated by climate-related stressors. Indirect effects operate via socioeconomic disruptions, such as food insecurity, forced migration, poverty, and weakened social networks. Psychological responses described as eco-anxiety and solastalgia further illustrate the range of mental health outcomes associated with environmental changes. Climate change is associated with clinically relevant psychiatric outcomes across established diagnostic categories. The mechanisms underlying these associations involve complex neurobiological, socioeconomic, environmental, and cultural pathways. These findings underscore the importance of targeted psychiatric interventions, including cognitive behavioral therapy, trauma focused therapies, resilience-building, strengthening social support, promoting adaptive coping strategies, and enhancing preparedness of mental health services. Prioritizing vulnerable populations for psychiatric assessment, prevention, and intervention is essential. Integrating these strategies into clinical practice and public health planning is critical to support evidence-based mental health care.
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. 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. 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.
Oxidative stress is associated with the pathophysiology of schizophrenia. Peripheral non-enzymatic antioxidants can reflect the degree of oxidative stress and antioxidant levels, and can be used as markers of oxidative stress. However, the relationships between these markers and the clinical phenotypes of first -episode adolescent-onset schizophrenia (AOS) is unclear. This study aimed to elucidate the impact of peripheral non - enzymatic antioxidants on male AOS patients and their association with clinical symptoms. Serum albumin (ALB), total bilirubin (TBIL), and uric acid (UA) of 59 first-episode AOS patients and 55 healthy controls were measured respectively. Furthermore, schizophrenia-related clinical symptoms were evaluated using the five-factor model of the Positive and Negative Syndrome Scale (PANSS). In Han Chinese first-episode male AOS patients, levels of TBIL and UA were significantly increased (p < 0.05), while ALB decreased (p < 0.01) compared with healthy controls. Furthermore, multivariate logistic regression showed that UA, ALB, and TBIL (all p < 0.01) were independently associated with AOS. Moreover, correlation analysis revealed that ALB was positively correlated with the PANSS total, cognitive and excited factor scores (all p < 0.05); TBIL was positively correlated with the excited factor score (p < 0.01); UA was positively correlated with the PANSS total, negative, cognitive and excited factor scores (all p < 0.05). In addition, Receiver operating characteristics assessment indicated that ALB and TBIL could effectively distinguish AOS patients from healthy controls. This study confirms the association of peripheral non-enzymatic antioxidants (ALB, TBIL, and UA) with clinical manifestations and pathophysiology in schizophrenia. ALB and TBIL may serve as potential biomarkers for oxidative stress and symptom severity in AOS, particularly in males, providing insights for diagnostic and therapeutic strategies.
This diagnostic test accuracy meta-analysis aimed to provide clinically interpretable estimates (sensitivity, specificity, likelihood ratios (LR), predictive value (PV) and post‑test probabilities) for machine‑learning (ML) models predicting suicide‑related outcomes. A systematic search of PubMed, Embase, PsycINFO, and Web of Science identified studies published between January 2010 and December 2024. Eligible studies used a single-gate design (cross-sectional or longitudinal), included at least 100 participants, and reported diagnostic performance metrics (e.g., sensitivity, specificity, area under the receiver operating curve (AUC)) for ML algorithms. Models examined included Support Vector Machines (SVM), Logistic Regression, Random Forest, XGBoost, Artificial Neural Networks (ANN), Gradient Boosting, and Ensemble approaches. Two reviewers independently extracted data. Pooled estimates of sensitivity, specificity, PPV, NPV, and AUC were calculated using a bivariate random-effects model. Risk of bias was assessed using QUADAS-2. Of 500 screened records, 22 studies met inclusion criteria. Ensemble models demonstrated the highest pooled AUC (0.95; 95% CI, 0.92-0.96), with specificity of 0.97 (95% CI, 0.95-0.98) and sensitivity of 0.50 (95% CI, 0.29-0.71). Gradient-boosting and ensemble approaches showed strong discriminative performance overall; model-specific estimates are reported in the Results. At a pre-test probability of 25%, post-test probabilities for a positive result ranged from 64% (Logistic Regression) to 88% (Ensemble Models). Machine-learning approaches demonstrated promising diagnostic accuracy for suicide-related outcomes in heterogeneous clinical populations. However, because primary studies rarely reported diagnosis- or outcome-specific performance, these findings should not be assumed to generalize across specific disorders or to suicide mortality. Future research should incorporate diagnosis-stratified and outcome-resolved validation to clarify clinical applicability.
Antidepressant prescribing practices and Adverse-effect profiles are poorly characterised in Pakistan, highlighting the need for systematic evaluation. This study aimed to assess prescribing patterns, validate the Urdu version of the Antidepressant Side-Effect Checklist (U-ASEC), and document patient-reported adverse effects. A cross-sectional questionnaire-based study was conducted at two psychiatry clinics in Lahore and Rawalpindi. All adult patients diagnosed with MDD according to the DSM-5-TR were invited to participate. Sampling was done through a convenient method. The Urdu-translated Antidepressant Side-Effect Checklist (U-ASEC) was developed through forward-back translation, expert panel review and pilot testing, and its psychometric properties such as internal consistency, construct validity were examined. Descriptive statistics were used to summarize demographic and clinical characteristics. Differences in adverse-effect scores across demographic and clinical groups were assessed with Kruskal-Wallis tests followed by Dunn's test with Bonferroni adjustment. Multivariable logistic regression models were fitted for each adverse-effect item to explore associations with antidepressant classes, adjusting for age, sex, tobacco use, comorbidity and duration of MDD. Multicollinearity was checked using variance inflation factors (VIF) (< 3 for all variables), and false discovery rate (FDR) control was used to account for multiple testing. Among the 457 participants, 54.9% were male and 60% of participants were married. Escitalopram was the most frequently prescribed single agent (12.9%), and Selective serotonin reuptake inhibitors as a class accounted for 32.1% of monotherapy prescriptions. Combination therapy was used by 26.7% of participants; typical pairs included mirtazapine + escitalopram (12.2%) and mirtazapine + fluoxetine (5.5%). The U-ASEC demonstrated good internal consistency (Cronbach's alpha = 0.78). Factor analysis identified three clusters of adverse effects: autonomic dysfunction, Central Nervous System effects, and metabolic effects. Dry mouth and insomnia were the most frequently reported adverse effects of SSRIs. Adverse effects varied by class: TCAs had higher rates of nausea/vomiting (41.3%); SNRIs were associated with a higher prevalence of urinary difficulties (32.4%); atypicals reduced dry mouth (18.8%) but increased dizziness (10.4%); and dual therapy showed more metabolic effects, including weight gain (29.5%) and increased body temperature (20.5%). Significant associations were identified for dry mouth (p = 0.0059), nausea and vomiting (p = 0.0202), problem with urination (p = 0.0248), feeling like the room is spinning (p = 0.041), and Tremor (p = 0.0382). Multivariable analysis showed TCAs increased odds of nausea (OR 3.96, 95% CI 1.72-9.03, p = 0.001), urination problems (OR 2.77, 1.10-6.63, p = 0.025), orthostatic symptoms (OR 2.59, 1.07-6.01, p = 0.030) and tremor (OR 2.66, 1.22-5.94, p = 0.015). SNRIs were associated with increased odds of urinary difficulties (OR 12.92, 1.19-284.32, p = 0.040). Atypicals reduced dry mouth (OR 0.18, 0.02-0.94, p = 0.050) but increased dizziness (OR 8.42, 1.47-48.41, p = 0.012). Escitalopram was the most commonly prescribed antidepressant, with dry mouth and insomnia as the most reported adverse effects. This study provides a culturally relevant tool, U-ASEC, for adverse effect monitoring, addressing critical gaps in Pakistan's clinical practices. Our findings underscore the importance of tailoring antidepressant choice to patient characteristics. Not applicable.
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s12991-026-00650-9.
To investigate the discriminative value of the combination of lymphocyte-to-high-density lipoprotein ratio (LHR), neutrophil-to-lymphocyte ratio (NLR), and platelet count for patients with first-episode schizophrenia (FES). A retrospective analysis was performed on 181 antipsychotic-naïve inpatients with FES admitted to Zhenjiang Mental Health Center between January 2015 and February 2025.189 participants, including staff members who underwent health check-ups at the same center from July 2024 to November 2025, were prospectively recruited as the healthy control group. Both groups underwent fasting blood cell analysis. Univariate analysis, binary Logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were employed to assess the diagnostic performance of the combined use of LHR, NLR, and platelet count for FES. Univariate analysis revealed that white blood cell count, neutrophil count, monocyte count, platelet count, high-density lipoprotein (HDL), neutrophil-to-high-density lipoprotein ratio (NHR), LHR, platelet-to-lymphocyte ratio (PLR), NLR, and systemic immune-inflammation index (SIRI) were statistically significant influencing factors associated with FES (all P < 0.05) when comparing the FES group with the healthy control group. Binary Logistic regression analysis further identified platelet count, LHR, and NLR as independent predictors of FES relative to healthy controls (all P < 0.05). The ROC curve analysis demonstrated that the combination of platelet count, LHR, and NLR yielded an area under the curve (AUC) of 0.863 for distinguishing FES. The combination of LHR, NLR, and platelet count is significantly elevated in antipsychotic-naïve FES patients compared with healthy controls. These findings highlight immune-metabolic dysregulation in acute-phase FES, but do not establish diagnostic specificity. Comparative studies with other acute psychiatric disorders are needed.