European Archives Of Psychiatry And Clinical Neuroscience[JOURNAL]
Sun
200 papers
Uncovering causal associations between plasma proteins and psychiatric disorders and identifying comorbidity biomarkers: a mendelian randomization study.
Zheng S, Zhang Y, Lu W … +3 more , Fan T, Han Y, He J
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41925857 · Publisher ↗
BACKGROUND: Psychiatric disorders such as major depressive disorder (MDD), anxiety disorder (ANX), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder (BD), and schizophrenia...
BACKGROUND: Psychiatric disorders such as major depressive disorder (MDD), anxiety disorder (ANX), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder (BD), and schizophrenia (SCZ) are highly prevalent and often comorbid, contributing significantly to the global disease burden. This study aims to explore the potential causal effects of plasma proteins on these psychiatric conditions and to identify shared proteins that may underlie comorbidities. METHODS: We conducted two-sample Mendelian randomization (MR) analyses to assess the causal relationships between 2,940 human plasma proteins and six major psychiatric disorders. Sensitivity analyses were performed to confirm the robustness of the findings. We also identified proteins that showed causal effects on multiple disorders. RESULTS: A total of eight plasma proteins were identified with causal effects on MDD, twelve on ANX, two on ASD, nine on ADHD, thirty-four on BD, and fifty-two on SCZ. Among these, Mesencephalic astrocyte-derived neurotrophic factor and Otoancorin were associated with both MDD and ANX; von Willebrand factor C domain-containing protein 2-like was linked to both ASD and ADHD; and six proteins—Tumor necrosis factor receptor superfamily member 5, Aspartate aminotransferase, cytoplasmic, Pre-B-cell leukemia transcription factor-interacting protein 1, Hsc70-interacting protein, Serine/threonine-protein kinase 4, and SURP and G-patch domain-containing protein 1—were causally linked to both BD and SCZ. CONCLUSION: This study systematically reveals potential causal associations between plasma proteins and multiple psychiatric disorders and highlights shared proteins potentially involved in the biological mechanisms of comorbidities. These findings offer valuable insights for future research on pathogenesis, biomarker development, and therapeutic strategies in psychiatry.
Progressive modeling of multiscale hippocampal subfield structural representation improves the prediction performance of mild cognitive impairment in type 2 diabetes.
Shen Y, Wang RC, Wang JX … +3 more , Li Y, Xu YH, Li YF
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41917441 · Publisher ↗
OBJECTIVE: To construct and validate an imaging-based predictive model grounded in multiscale progressive structural representation, and to systematically evaluate the incremental diagnostic value from whole-brain macros...
OBJECTIVE: To construct and validate an imaging-based predictive model grounded in multiscale progressive structural representation, and to systematically evaluate the incremental diagnostic value from whole-brain macroscopic gray matter volume to hippocampal subfield microstructural texture features in identifying mild cognitive impairment associated with type 2 diabetes mellitus (T2DM-MCI). METHODS: A total of 280 patients with T2DM who met the diagnostic criteria of the American Diabetes Association were retrospectively enrolled, including 82 patients with T2DM-MCI and 198 cognitively normal individuals. All participants underwent 3.0T structural MRI scanning. Whole-brain gray matter volume (GMV) features were extracted based on the AAL atlas. Bilateral 24 hippocampal subfield volumetric features were segmented using FreeSurfer, and 2,232 hippocampal subfield radiomic features were extracted using PyRadiomics. A nested cross-validation framework was constructed, and stepwise dimensionality reduction was performed using the Mann–Whitney U test, mRMR, and LASSO to develop the GMV model, hippocampal subfield volume model (Hip-Volume), and hippocampal subfield radiomics model (Hip-Radscore), respectively. A combined model integrating clinical variables was further established. Model performance was evaluated using AUC, sensitivity, specificity, PPV, and NPV, with comparisons conducted using the DeLong test. Clinical utility was assessed using NRI, IDI, Brier score, and decision curve analysis (DCA). Model explainability was achieved through SHAP analysis, and Spearman correlation was applied to examine the association between Hip-Radscore and MMSE. RESULTS: The whole-brain GMV model demonstrated limited discriminative performance (AUC = 0.63 ± 0.04). When the analysis scale was focused on hippocampal subfield volumes, model performance improved significantly (AUC = 0.71 ± 0.03, P < 0.05). Under consistent anatomical regions, the hippocampal subfield radiomics model further increased to an AUC of 0.78 ± 0.03 (P = 0.004). The combined model integrating clinical variables and hippocampal subfield radiomic features achieved the best performance (AUC = 0.86 ± 0.02) and showed significantly superior reclassification ability compared with the “clinical + volume” model (NRI = 0.30, IDI = 0.08, both P < 0.001). SHAP analysis identified Hip-Radscore as the most important predictor. Hip-Radscore was significantly negatively correlated with MMSE scores (ρ = −0.58, P < 0.001). CONCLUSION: Multiscale progressive structural representation significantly improves the identification performance of T2DM-MCI, and hippocampal subfield radiomic features demonstrate greater early sensitivity than traditional volumetric indicators.
Demographic and clinical profiles of drug-induced psychosis: age, gender, and social context in a German cohort.
Böss N, Koller G, Adorjan K … +3 more , Haller B, Eyer F, Geith S
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41915074 · Publisher ↗
BACKGROUND: Drug-induced psychosis (DIP) represents a complex clinical challenge, particularly among younger substance-using populations. Recent epidemiological data indicate increasing DIP prevalence and decreasing age...
BACKGROUND: Drug-induced psychosis (DIP) represents a complex clinical challenge, particularly among younger substance-using populations. Recent epidemiological data indicate increasing DIP prevalence and decreasing age at first presentation, underscoring its growing clinical and public health relevance. While DIP arises in the context of substance use, distinguishing transient episodes from emerging primary psychotic disorders remains difficult, and data on demographic and clinical variations are limited. METHODS: We conducted a descriptive cohort study of 340 patients diagnosed with DIP (ICD-10: F1X.5) between 2010 and 2020 at two university hospitals in Germany. We collected data from all eligible cases (n = 170) from a toxicology department (Technical University of Munich, TUM), and from the same number of cases from a psychiatry department (Ludwig-Maximilians-Universität in Munich, LMU). Variables assessed included sociodemographic data, psychiatric symptoms, substance use (self-report and toxicology), comorbidities, and family history. Analyses included descriptive statistics, chi-square or Fisher’s exact tests, and Mann–Whitney U tests to examine group differences, and Cohen’s Kappa coefficients to quantify agreement between self-reported and toxicologically confirmed substance use. RESULTS: The cohort was predominantly male (77.4%) with a median age of 27 years. Migration background was present in 27.6%, with admissions peaking in 2015–2018. Psychotic symptoms were dominated by perceptual disturbances (62.3%) and thought disorder (76.3%). Women exhibited higher rates of tactile hallucinations, suicidal ideation, and depression (all p < 0.05) and tended to have higher serum ethanol levels. Daily substance use was common (69.0%), with polysubstance use exceeding 75%. Cannabis and stimulants predominated in younger patients, while opiates, sedatives, and ethanol were more frequent in older groups. Self-reported substance use showed fair to good agreement with toxicological findings, with the highest concordance for opiates and lower agreement for sedatives and ethanol. CONCLUSION: DIP showed clear gender- and age-related differences in psychotic symptom profiles and clinical presentation, alongside high rates of daily and polysubstance use, young male predominance, and migration-related patterns. These findings underscore the need for early, individualized, and demographically informed interventions.
Reciprocal longitudinal relationship between depressive symptoms and problematic alcohol use: a random intercept cross-lagged panel model including a nationwide sample of Korean adults.
Baek SU, Yoon JH
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41915073 · Publisher ↗
BACKGROUND: Problematic alcohol use and mental health problems co-occur frequently. However, the longitudinal, reciprocal relationship between depressive symptoms and problematic alcohol use is not fully understood. This...
BACKGROUND: Problematic alcohol use and mental health problems co-occur frequently. However, the longitudinal, reciprocal relationship between depressive symptoms and problematic alcohol use is not fully understood. This study examined the bidirectional longitudinal association between depressive symptoms and problematic alcohol use. METHODS: A total of 14,569 adults participated in a panel survey, with data collected annually at three time points (2022, 2023, and 2024). Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression (CES-D) scale (11-item version). Problematic alcohol use was assessed using the Alcohol Use Disorders Identification Test (AUDIT) (10-item version). A random intercept cross-lagged panel model (RI-CLPM) with three time points was used to determine the reciprocal relationship between depressive symptoms and problematic alcohol use. RESULTS: The sample consists of 6,406 men and 8,134 women, with a mean (standard deviation) age of 57.7 (19.5) years. At the between-person level, random intercepts of depressive symptoms and problematic alcohol use showed no significant correlations (B = 0.117, P = .566). At the within-person level, depressive symptoms at a given time point were positively associated with problematic alcohol use in the following year (B = 0.050, P = .005). Similarly, problematic alcohol use at a given time point was positively associated with depressive symptoms in the following year (B = 0.062, P = .012). Significant covariance between depressive symptoms and problematic alcohol use were observed across the survey waves. CONCLUSION: This study found a bidirectional longitudinal relationship between depressive symptoms and problematic alcohol use at the within-individual level. Policy interventions should adopt an integrated approach that addresses mental health issues and problematic alcohol use simultaneously.
Kappa opioid receptor antagonism in neuropsychiatry: from molecular mechanisms to clinical prospects.
Wang H, Ji Y, Huang J … +5 more , Yang S, Zhang Q, Hu S, Xu X, Yang C
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41906056 · Publisher ↗
The κ-opioid receptor (KOR) is a key component of the opioid receptor system and belongs to the G protein-coupled receptor family. It is widely distributed in regions such as the mesolimbic system, amygdala and spinal co...
The κ-opioid receptor (KOR) is a key component of the opioid receptor system and belongs to the G protein-coupled receptor family. It is widely distributed in regions such as the mesolimbic system, amygdala and spinal cord, playing a central role in regulating depression, anxiety, drug addiction, and stress responses. While KOR agonists exhibit analgesic effects, they exacerbate negative emotions; conversely, KOR antagonists demonstrate significant potential in the treatment of neuropsychiatric disorders. This review examines the mechanisms of action and clinical translation progress of KOR antagonists, which improve disease phenotypes through mechanisms such as reversing dopamine inhibition, restoring glutamate/gamma-aminobutyric acid balance, and regulating the hypothalamic–pituitary–adrenal axis; they are categorized into three types based on duration of action. Current research focuses on antidepressant, anti-addiction, and stress regulation applications. The paper analyzes bottlenecks such as insufficient receptor selectivity and gender-dose differences, and outlines development strategies for highly selective ligands. Overall, this review synthesizes the molecular mechanisms of blockers, their applications in neuropsychiatric disorders, and clinical research progress.
Cognitive and balance dual-task training for middle-aged and older individuals with schizophrenia: a three-arm randomized controlled trial.
Chen HY, Wang LT, Chang JJ … +4 more , Hsu MJ, Wang PW, Hsu HY, Chen MD
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41906055 · Publisher ↗
BACKGROUND: Individuals with schizophrenia experience premature aging, leading to balance deficits and higher fall risk. Dual-task training integrating balance and cognitive training has emerged as a novel intervention....
BACKGROUND: Individuals with schizophrenia experience premature aging, leading to balance deficits and higher fall risk. Dual-task training integrating balance and cognitive training has emerged as a novel intervention. PURPOSE: This study examined the effectiveness of CogBals (i.e., Cognitive and Balance training Simultaneously software), a researcher-developed novel software designed for dual-task training, on balance function, walking performance, lower extremities muscle strength and cognitive function in individuals with schizophrenia. METHOD: In a single-blind, parallel-group trial, 84 participants (50.18 ± 7.32 years old; 31 females) were recruited from psychiatric rehabilitation centers in Taiwan and randomly assigned (1:1:1) to a COG&BAL group, balance-only (BAL) group, or treatment as usual control group (TAU). Both training groups received the intervention 2x/week, 60 min/session, 12weeks. The primary outcome was balance functions. Data analysis was conducted using Generalized Estimating Equations. RESULT: The mini-BESTest showed improvement in both training groups compared to TAU. The COG&BAL group demonstrated superior improvements in Timed Up and Go Test motor dual-task performance (p=.009), walking speed (p=.010) and stride length (p=.014) under fast walking condition compared to the BAL group. Notably, the TAU group showed significantly decline in balance function. No harms events were identified. CONCLUSION: The dual-task training with CogBals enhanced balance and walking performance in middle-aged and older adults with schizophrenia. This intervention shows potential as an effective dual-task balance training approach for fall risk reduction. Future research is suggested to investigate its long-term effects and applicability in various populations.
Mapping cognitive-behavioral approach in psychedelic-assisted treatment: a systematic review across phases with classic and non-classic psychedelics.
Varela YM, de O Tavares VD, Delgado LM … +12 more , de Faria HAT, Menezes LQ, Almeida RM, Agrícola P, de Carvalho BS, Bienemann B, Falchi-Carvalho M, Cavalcanti-Ribeiro P, Palhano-Fontes F, Fernandes-Osterhold G, de Araujo DB, Galvão-Coelho N
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41902950 · Publisher ↗
The use of psychedelics in the treatment of psychopathologies has been expanding, highlighting Psychedelic-Assisted Psychotherapy (PAP) as a promising resource in mental health care. This systematic review investigates....
The use of psychedelics in the treatment of psychopathologies has been expanding, highlighting Psychedelic-Assisted Psychotherapy (PAP) as a promising resource in mental health care. This systematic review investigates. This systematic review investigates whether and how cognitive-behavioral therapies are integrated with psychedelic substances—both classical and atypical—for the treatment of mental disorders. A PRISMA-based search was conducted across four databases (Embase, PsycArticles, PubMed, and Web of Science) up to May 2025. The review included 9 clinical trials involving a total of 283 patients; these studies used ketamine (n = 5), psilocybin (n = 3), and 3,4-methylenedioxymethamphetamine (n = 1). Among the Cognitive Behavioral Approaches (CBAs) applied, traditional Cognitive Behavioral Therapy (CBT) was predominant (n = 6), followed by emerging modalities such as Mindfulness-Based Cognitive Therapy (MBCT) (n = 2) and Acceptance and Commitment Therapy (ACT) (n = 1). Considerable variability was observed across study designs, particularly in terms of the timing of psychotherapeutic interventions, which occurred before, during, or after the psychedelic experience, with or without concurrent support. The findings indicate that cognitive-behavioral strategies have been incorporated into psychedelic-assisted interventions in diverse ways, across different phases of treatment and with distinct therapeutic purposes. Nonetheless, the therapeutic approaches applied remain highly heterogeneous between studies, highlighting the need for further research to clarify how these models are implemented and characterized in practice.
Effects of BACE2 polymorphisms on verbal memory in the general population.
Garvert L, Killer S, Kirchner K … +4 more , Völzke H, Völker U, Grabe HJ, Van der Auwera S
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41902949 · Publisher ↗
Emerging evidence highlights the potential role of BACE2 (beta-site APP cleavage enzyme 2) in influencing Alzheimer’s disease (AD) risk and cognitive impairment, particularly due to its ability to cleave amyloid precurso...
Emerging evidence highlights the potential role of BACE2 (beta-site APP cleavage enzyme 2) in influencing Alzheimer’s disease (AD) risk and cognitive impairment, particularly due to its ability to cleave amyloid precursor protein (APP) at the θ-site in a non-amyloidogenic manner without the accumulation of neurotoxic Aβ42. Using data from the German population-based Study of Health in Pomerania (SHIP-TREND), we applied general linear regression models to evaluate the associations between 231 genetic variants within BACE2 and two verbal memory scores in a cross-sectional (N = 3791) and a longitudinal setting (N = 2215). Additionally, we examined the moderating effect of APOE ε4 on the relationship between BACE2 variants and memory performance. Three genetic clumps were significantly associated with verbal memory scores in the cross-sectional setting (pFDR<0.05). The minor T-allele of rs61736857 and the minor C-allele of rs1072869 were inversely associated with verbal memory, while the minor C-allele of rs6517661 showed a positive association. No interaction term with APOE ε4 reached statistical significance in the cross-sectional setting. In longitudinal analyses, rs8133778 demonstrated a significant (pFDR<0.05) interaction effect with APOE ε4 on memory. Genotype GG exhibited a more pronounced decline in verbal memory among ε4 carriers, while genotypes AA and AG represented a risk factor for non-carriers. We replicated some BACE2 variants previously reported as potential risk factors in AD at a nominal significance level. In addition, our results identify novel variants that may contribute to cognitive impairment in the general population, some of which have been previously associated with altered BACE2 expression.
Gender differences in working memory impairment and metabolic characteristics among patients with stable schizophrenia: a cross-sectional study.
Gu J, Lei Q, Liu M … +6 more , Wang L, Wang Z, Feng Z, Zhang Y, Dong J, Ji Z
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41902948 · Publisher ↗
This study aimed to identify factors associated with working memory impairment (WMI) among patients with stable schizophrenia, with particular emphasis on gender differences. A total of 1274 patients were included, and c...
This study aimed to identify factors associated with working memory impairment (WMI) among patients with stable schizophrenia, with particular emphasis on gender differences. A total of 1274 patients were included, and comprehensive demographic, clinical, and metabolic data were collected. WMI was assessed with the CBCT Digit Dimension subscale. Binary logistic regression analyses were conducted in the full sample and in gender-stratified subsamples. Overall, 56% of patients had WMI. Longer illness duration and use of first-generation antipsychotics were significant risk factors for WMI in both genders. In the full sample, diabetes, abnormal triglyceride levels, and obesity were also associated with WMI, whereas hypertension and lower HDL cholesterol were associated with lower odds of WMI. Gender-stratified analyses revealed distinct profiles: among male patients, WMI was additionally associated with being divorced and with metabolic abnormalities, whereas among female patients, WMI was primarily linked to clinical and treatment-related factors. These findings underscore the multifactorial nature of WMI in schizophrenia and highlight the need for gender-tailored cognitive intervention strategies.
Community-based service engagement intervention for young adults with schizophrenia in China: study protocol for a randomized controlled trial.
Wang X, Hu J, Zhao M … +1 more , Ding R
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41893891 · Publisher ↗
BACKGROUND: Schizophrenia is a chronic and disabling mental disorder that leads to poor social functioning, low quality of life, and a heavy burden for families and society. In China, service engagement among community-d...
BACKGROUND: Schizophrenia is a chronic and disabling mental disorder that leads to poor social functioning, low quality of life, and a heavy burden for families and society. In China, service engagement among community-dwelling patients remains insufficient, limiting the effectiveness of treatment and rehabilitation. Existing engagement-focused interventions were developed and evaluated primarily in high-income countries, leaving little evidence for low- and middle-income settings, including China. This study describes the protocol of a randomized controlled trial designed to evaluate the effectiveness and cost-effectiveness of a community-based service engagement intervention for young adults with schizophrenia in China. METHODS: A single-blind, individually randomized controlled trial will be conducted in community health service centers in Yangpu District, Shanghai, recruiting 192 eligible patients with schizophrenia. Participants will be randomized 1:1 to the intervention or control group. The intervention consists of six individual sessions and three group sessions over three months, focusing on medical-social support, peer-social support, and service engagement facilitation. Primary outcomes include service engagement, attitudes, and health behaviors; secondary outcomes include recovery, symptoms, quality of life, and costs. Data will be analyzed under the intention-to-treat principle using difference-in-differences models, with multiple imputation for missing values. Cost-effectiveness analysis will include direct and indirect costs reported by patients and caregivers. DISCUSSION: This trial is among the first in China to evaluate a community intervention for improving service engagement in schizophrenia. If shown to be effective and cost-effective, the program could be scaled up within existing community-based rehabilitation systems, offering practical guidance for policymakers and practitioners to enhance recovery, promote social inclusion, and reduce the burden of care. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500113435). Registered, 2025.
Global burden and socioeconomic correlates of drug use disorders in women of childbearing age: insights from GBD and NHANES.
Xu D, Li J, Yan H … +1 more , Yang Z
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41882389 · Publisher ↗
BACKGROUND: Drug use disorders (DUD) pose a serious threat to the health of women of childbearing age (15-49 years), and their disease burden has not been systematically assessed at the global level. This study aimed to...
BACKGROUND: Drug use disorders (DUD) pose a serious threat to the health of women of childbearing age (15-49 years), and their disease burden has not been systematically assessed at the global level. This study aimed to analyze the trends in the disease burden of DUD among women of childbearing age worldwide from 1990 to 2021, the distribution by specific substance, and its relationship with socio-economic development levels, and the relationship between drug use and health status. METHODS: Using the 2021 Global Burden of Disease (GBD) data, we obtained the incidence and disability-adjusted life years (DALYs) and calculated the age-standardized rates (ASR) of DUD among women of childbearing age in 204 countries and territories worldwide. The estimated annual percentage change (EAPC) was used to assess temporal trends. Socio-economic disparities and health system performance were examined using the Socio-demographic Index (SDI) and efficiency frontier analysis. Furthermore, integrating NHANES 2013-2018 data, the relationship between drug use and self-reported health status was analyzed using multivariable ordered logistic regression. RESULTS: In 2021, the global age-standardized incidence rate (ASIR) and age-standardized DALY rate (ASDR) for DUD among women of childbearing age were 265.9 per 100,000 (95% UI: [265.7-266.1]) and 241.8 per 100,000 (95% UI:[241.5-242.0]), respectively. The burden was highly concentrated in high-SDI countries (such as the United States, Canada, Australia), where ASIR and ASDR were significantly higher than in low- and middle-SDI countries, and most showed an increasing trend (EAPC for ASIR = 0.82, 95% UI: [0.70-0.94]; EAPC for ASDR = 4.35, 95% UI: [3.93-4.77]). Opioid use disorder (OUD) was the leading cause of the disease burden, accounting for 74.14% of DALYs. The age distribution showed a bimodal pattern, with incidence peaks at 20-24 and 35-39 years, while the DALY peak was delayed until 25-29 years. NHANES analysis revealed that after adjusting for socio-economic confounders, drug use was significantly associated with poorer health status (OR = 1.36, 95% CI: 1.15-1.62, P < 0.001). CONCLUSION: The burden of DUD among women of childbearing age shows significant socio-economic and geographical inequalities, with high-income countries facing a persistently growing crisis related to opioids and amphetamines. The true health impact of substance use becomes apparent only after adjusting for socio-economic factors. The results call for strengthened screening and early intervention in high-burden countries, the development of gender-sensitive drug policies, and improved risk communication and treatment accessibility.
Integrated multi-omics analysis of gut microbiome and serum metabolome in unipolar and bipolar depression.
Wang Y, Wang L, Zheng Y … +6 more , Wang R, Zhen F, Cheng ZJ, Sun B, Tsui SK, An C
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41882388 · Publisher ↗
OBJECTIVE: This study aimed to identify objective biomarkers for unipolar and bipolar depressive episodes by analyzing the gut microbiome and serum metabolome of patients with major depressive disorder (MDD) and bipolar...
OBJECTIVE: This study aimed to identify objective biomarkers for unipolar and bipolar depressive episodes by analyzing the gut microbiome and serum metabolome of patients with major depressive disorder (MDD) and bipolar disorder (BD). METHODS: The study included 82 outpatients and inpatients (MDD, n = 38; BD, n = 44) from the First Hospital of Hebei Medical University, and 42 healthy controls. Demographic data were collected, and various psychological tests were administered. Stool and blood samples were collected for gut microbiome and non-targeted serum metabolomics analysis using 16S rRNA and ultra-high-performance liquid chromatography coupled with mass spectrometry. Additionally, multi-omics integration was performed using Joint Non-negative Matrix Factorization (JNMF) to construct a fused diagnostic model. RESULTS: Significant differences were observed in the α-diversity and β-diversity indices among the three groups. Seventeen significantly different bacterial populations were identified between BD and MDD groups. The BD group showed higher abundance of g__Bifidobacterium, g__Prevotella_7, and g__un_f_Muribaculaceae, and lower abundance of g__Parasutterella. Fifty differential metabolites were identified, with eight metabolites showing an area under the curve (AUC) greater than 0.7. g__Bifidobacterium was positively correlated with metabolites such as l-lactate and taurine. Notably, the diagnostic model based on integrated features achieved an AUC of 0.934, demonstrating superior discriminative ability compared to single-omics models. CONCLUSIONS: Gut microbiota and serum metabolites effectively distinguished between unipolar and combination of four bacterial genera and eight serum metabolites showed potential value in differential diagnosis. Some differential gut microbiota and metabolites were related to clinical symptoms of the disease, suggesting a mutual influence between gut microbiota and serum metabolites.
Short-term longitudinal changes in metabolic and cardiac parameters in inpatients with schizophrenia: the role of age and sex.
Liu Z, Guo H, Huang S … +5 more , Zhu H, Yu C, Fan F, Liang J, Xie G
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41882387 · Publisher ↗
BACKGROUND: Antipsychotic therapy in schizophrenia is associated with metabolic and cardiac adverse effects. However, the short-term trajectory of these parameters during controlled inpatient stabilization, and the moder...
BACKGROUND: Antipsychotic therapy in schizophrenia is associated with metabolic and cardiac adverse effects. However, the short-term trajectory of these parameters during controlled inpatient stabilization, and the moderating roles of age and sex, remain less clear. METHODS: This study enrolled 586 inpatients with schizophrenia; all stabilized on an unchanged antipsychotic regimen. Fasting blood glucose (FBG), lipid profiles [triglycerides (TG), Cholesterol (CHOL), high-density lipoprotein (HDL), low density lipoprotein (LDL)], and electrocardiogram (ECG) parameters (heart rate, QRS, PR, QTc) were measured at admission and discharge. Changes were analyzed using paired t-tests and multiple linear regression to assess the influence of age and sex. RESULTS: From admission to discharge, significant improvements were observed in FBG (mean change: - 0.56 ± 0.07 mmol/L, pFDR < 0.01) and heart rate (mean change: - 3.81 ± 0.92 bpm, pFDR < 0.01). A significant reduction in HDL was also found (mean change: - 0.11 ± 0.02 mmol/L, pFDR < 0.01). Age-stratified analysis revealed a significant QTc shortening exclusively in patients > 45 years old (p < 0.05). Regression analysis identified sex as a significant independent predictor of HDL change (β = 0.068, p = 0.016). CONCLUSION: The inpatient stabilization phase is a dynamic period marked by both beneficial (improved glycemia, lower heart rate) and adverse (reduced HDL) physiological changes. The differential effects based on age (QTc shortening) and sex (HDL change) underscore the necessity for personalized cardiometabolic monitoring and risk mitigation strategies in patients with schizophrenia.
Efficacy of sertraline combined with low-dose antipsychotics in first-episode schizophrenia.
Bartoli F, Cavaleri D, Crocamo C … +1 more , Carrà G
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41882386 · Publisher ↗
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Transdiagnostic alterations of intrinsic brain activity in major psychiatric disorders.
Zhu DM, Zhu W, Wu D … +7 more , Guan M, Ouyang A, Zhang T, Li C, Hu Q, Fang P, Xie Y
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41870603 · Publisher ↗
Alternations in intrinsic brain activity are increasingly recognized as transdiagnostic markers in major psychiatric disorders, however, the extent to which spontaneous functional abnormalities are shared or disorder-spe...
Alternations in intrinsic brain activity are increasingly recognized as transdiagnostic markers in major psychiatric disorders, however, the extent to which spontaneous functional abnormalities are shared or disorder-specific remain incompletely understood. In this study, we systematically compared whole-brain intrinsic activity alterations among individuals with schizophrenia (SCZ), bipolar disorder (BD), and attention-deficit/hyperactivity disorder (ADHD) relative to healthy controls (HC), utilizing the resting-state amplitude of low-frequency fluctuation (ALFF) metric. We further explored potential neurochemical and microstructural substrates underlying these alterations by integrating disorder-related ALFF maps with normative neurotransmitter system templates and a cortical myelin water fraction atlas. The results revealed widespread diagnosis effects on ALFF, with prominent changes concentrated in the sensorimotor, visual, and limbic networks. Each disorder exhibited distinct regional patterns of ALFF alterations. Specifically, both SCZ and BD showed increased ALFF in the fusiform gyrus accompanied by decreased ALFF in occipital and postcentral regions, whereas ADHD was mainly characterized by reduced ALFF in the cerebellum. Pairwise comparisons further delineated both overlapping and disorder-specific loci of dysfunction across the three conditions. Spatial correlation analyses demonstrated that ALFF alteration patterns were differentially associated with neurotransmitter distributions, with SCZ and BD were commonly linked to dopaminergic markers (D1, D2, and DAT), while serotonergic 5-HT1a distributions were selectively associated with ALFF changes in SCZ and ADHD. Notably, only in schizophrenia did regional ALFF alterations show a significant negative spatial correspondence with cortical myelin water fraction, suggesting a disorder-specific microstructural substrate. These findings highlight convergent and divergent intrinsic activity alterations across major psychiatric disorders and provide multilevel insights into their potential neurochemical and microstructural underpinnings, advancing our understanding of transdiagnostic brain dysfunction.
Cognitive function differences across subtypes of first-episode antipsychotic-naïve schizophrenia: insights from event-related potentials.
Lu C, Li S, Zhang X … +8 more , Han Y, Wang L, Sun W, Zhang C, Wang S, Li S, Li J, Zhang XY
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41863586 · Publisher ↗
BACKGROUND: Schizophrenia (SZ) involves severe psychiatric symptoms and cognitive impairments, but their relationship remains unclear. This study aims to investigate the cognitive function across subtypes of first-episod...
BACKGROUND: Schizophrenia (SZ) involves severe psychiatric symptoms and cognitive impairments, but their relationship remains unclear. This study aims to investigate the cognitive function across subtypes of first-episode antipsychotic-naïve SZ (FEAN-SZ) using event-related potentials. METHODS: The study included 321 FEAN-SZ patients, with patients classified into positive symptom-dominant (PSD), negative symptom-dominant (NSD), and general symptom-dominant (GSD) groups. Sociodemographic and clinical data were collected, and psychiatric symptoms were assessed with the Positive and Negative Syndrome Scale. P300 and N100 components were measured using a three-stimulus auditory oddball paradigm. RESULTS: shorter latencies and larger amplitudes of both P300 and N100 components compared to the NSD and GSD groups (all ps < 0.05), with no significant differences between NSD and GSD groups. Partial correlation analysis revealed a significant positive association between negative symptoms and the latencies of N100, P3a and P3b (r = 0.365, 0.563, 0.458; all ps < 0.001), as well as significant negative associations with their amplitudes (r = -0.352, -0.296, -0.265; all ps < 0.001). Logistic regression further indicated that the latencies (β = 0.040, 0.014, 0.010, all ps < 0.01) and amplitudes (β = -0.142, -0.181, -0.136, all ps < 0.05) of N100, P3a and P3b significantly distinguished the PSD group from the NSD and GSD groups. CONCLUSIONS: Patients with NSD and GSD subtypes exhibit more pronounced alterations in cognitive function, with negative symptoms closely associated with these differences. P300 and N100 components may serve as sensitive electrophysiological markers for characterizing cognitive function across SZ subtypes.
Gender-specific effects of sodium benzoate on cognitive improvement in individuals with dementia: a meta-analysis of randomized controlled trials.
Yeh PY, Liao RM, Chang HY … +4 more , Lin WT, Chen YZ, Lane HY, Lin CH
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41863585 · Publisher ↗
BACKGROUND: Previous double-blind randomized controlled trials (RCTs) have shown that sodium benzoate, a D-amino acid oxidase inhibitor enhancing D-serine availability and NMDA receptor-mediated function, is able to impr...
BACKGROUND: Previous double-blind randomized controlled trials (RCTs) have shown that sodium benzoate, a D-amino acid oxidase inhibitor enhancing D-serine availability and NMDA receptor-mediated function, is able to improve cognition in patients with cognitive decline. Accordingly, this study aimed to compare cognitive outcomes between patients receiving sodium benzoate and those receiving placebo. METHODS: Following the PRISMA guidelines, this meta-analytic study utilized appropriate keyword strings to systematically search the PubMed, Embase, and Cochrane databases for RCTs published in all languages from inception to June 2024. Included criteria were: (1) patients aged 50 or older; (2) those diagnosed with dementia (probable Alzheimer's disease or vascular dementia) or those with mild cognitive impairment (MCI) having a clinical dementia rating score of 0.5; (3) RCTs comparing the effect of benzoate treatment with that of placebo controls; and (4) the use of cognitive tests as therapeutic effect outcomes. RESULTS: Of 351 articles screened, five RCTs were included (246 sodium benzoate, 178 placebo; mean age 72.6 years; mean education 6.01 years; 62% female). The overall effect size for the therapeutic effect of sodium benzoate on cognitive improvement was significant (p = 0.02), with females outperforming males (p = 0.02). Additionally, regression analysis found the cognitive outcome generated from sodium benzoate was not influenced by the use of anti-dementia medication. CONCLUSION: Our findings highlighted a better understanding of the effect of sodium benzoate on cognitive improvement, particularly in female patients with MCI and dementia.
Permutation entropy analysis of EEG during a Go/No-Go task to differentiate patients with suicide attempt from those with suicidal ideation in major depressive disorder.
Hwang HH, Kim S, Shim SH … +1 more , Kim JS
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41863584 · Publisher ↗
Objective neurophysiological markers are needed to complement clinical assessment in distinguishing patients with suicide attempt (SA) from those with suicidal ideation (SI) within major depressive disorder (MDD). Task-e...
Objective neurophysiological markers are needed to complement clinical assessment in distinguishing patients with suicide attempt (SA) from those with suicidal ideation (SI) within major depressive disorder (MDD). Task-evoked electroencephalography (EEG) complexity was quantified during an auditory Go/No-Go task in 126 right-handed, psychotropic-medication-free participants with MDD (SA: n = 63, 23 males and 40 females, mean age 41.43 ± 14.93 years; SI: n = 63, 25 males and 38 females, mean age 39.13 ± 14.52 years). Permutation entropy (PE) was computed in sliding stimulus-locked windows at midline electrodes (Fz, FCz, and Cz). Normalized PE (H, a 0-1 ordinal-pattern complexity index) was estimated for Go and No-Go trials across embedding delays (τ = 1-60). Primary analyses focused on No-Go H; additionally, a Go/No-Go asymmetry index (A)-calculated as the normalized difference between Go and No-Go H-was evaluated. Group differences were assessed using cluster-based permutation tests, with Bonferroni correction across complexity metrics. Task accuracy and reaction time were comparable between groups. No-Go H was reduced in the SA group at Fz during 100-190 ms post-stimulus across τ = 26-40 (Bonferroni-adjusted cluster p = 0.0497). Based on the Nyquist-derived τ-to-frequency mapping, this range corresponds to frequencies in the low-beta band (12.5-19.2 Hz). However, clusters for A at Fz (100-190 ms, τ = 27-38) and Cz (50-140 ms, τ = 14-25) did not remain significant after correction. The findings indicate that an early frontocentral reduction in EEG complexity during response inhibition may serve as a candidate task-evoked neurophysiological feature that differentiates patients with SA from those with SI within MDD.
Gestalt contributions to relational and interactional neuroscience. Reply to authors: Understanding and explaining differences across minds in social interaction: insights from social neuroscience and clinical psychiatry by Kamp, Bolis, Schilbach.
Narzisi A
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41863583 · Publisher ↗
This commentary responds to Kamp et al. (Eur Arch Psychiatry Clin Neurosci 275:2199-2201, 2025) editorial on understanding differences across minds in social interaction. It fully supports their relational perspective, w...
This commentary responds to Kamp et al. (Eur Arch Psychiatry Clin Neurosci 275:2199-2201, 2025) editorial on understanding differences across minds in social interaction. It fully supports their relational perspective, which reframes social cognition and psychopathology as dynamic and interactional rather than individual phenomena. The reply highlights how autism research has been central in this paradigmatic shift: the double empathy problem and the dialectical misattunement hypothesis illustrate that social difficulties arise from reciprocal mismatches rather than unidirectional deficits. Drawing on Gestalt theory, the paper situates these ideas within a historical framework that conceives perception, cognition, and behavior as field-dependent and relational. From a Gestalt perspective, autism can be understood as a qualitative diversity in forming and maintaining social Gestalten-an alternative, not deficient, mode of constructing meaning. The commentary discusses a possible synthesis between social neuroscience and Gestalt theory in relation to an "interpersonalized psychiatry," emphasizing neural and experiential synchrony as potential mechanisms of therapeutic change. Ultimately, it calls for an integrative science of interaction that views the essence of the mind not within individuals, but between them.
Structural neuroimaging correlates of semantic incoherence in schizophrenia.
Arslan B, Kizilay E, Verim B … +6 more , Demirlek C, Demir M, Turan YE, Gelal F, Zorlu N, Bora E
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41854728 · Publisher ↗
Impairments in thought, language and communication in schizophrenia spectrum disorder (SSD) were conceptualized as formal thought disorder (FTD). In particular, disturbances of the thinking processes may be reflected by...
Impairments in thought, language and communication in schizophrenia spectrum disorder (SSD) were conceptualized as formal thought disorder (FTD). In particular, disturbances of the thinking processes may be reflected by semantic incoherence and semantic perseveration in discourse dynamics in the speech of SSD. Recent advancements in natural language processing offer a way to evaluate these semantic impairments objectively by computing semantic similarity between consecutive language units. In this regard, investigating the neuroanatomical substrates of semantic similarity is an important next step. In this study, we collected speech samples from a total of 98 subjects, 64 patients with SSD and 34 healthy control subjects using a semi-structured free speech task. The semantic similarity analysis comprised the mean, variance, 5th percentile and 95th percentile of similarity values between consecutive words. We investigated the neural correlates of semantic similarity using voxel-based morphometry and surface-based morphometry, including cortical thickness, gyrification, sulcal depth and fractal dimension. The correlation analysis resulted in an association of a decrease in the lowest semantic similarities of neighboring words with a decrease in cortical thickness, not only in traditional language processing regions but also extending to bilateral frontal, temporal and parietal regions. The strongest associations were found with bilateral superior frontal and rostral middle frontal regions. We also found a negative association between the lowest semantic similarities and fractal dimension in the left superior frontal region. Altogether, our findings indicate the more integrative proposals that link semantic similarity and FTD with neurocognitive processes. These outcomes suggest that semantic similarity may not solely be an indicator of impairments in language production, but rather disruptions in higher cognitive processes in schizophrenia.
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