European Archives Of Psychiatry And Clinical Neuroscience[JOURNAL]
Sun
200 papers
Causal relationship between tinnitus and 8 psychiatric phenotypes: a Mendelian randomization study.
Guo T, Xie H
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41432741 · Publisher ↗
BACKGROUND: Previous studies have suggested an association between tinnitus and various psychiatric phenotypes; however, the causal relationship and underlying pathways remain unclear. METHODS: We used univariable Mendel...
BACKGROUND: Previous studies have suggested an association between tinnitus and various psychiatric phenotypes; however, the causal relationship and underlying pathways remain unclear. METHODS: We used univariable Mendelian randomization (MR) to investigate the bidirectional causality between tinnitus and 8 psychiatric phenotypes. Multivariable MR was employed to control for potential confounders. Extensive sensitivity analyses were conducted to validate our results. Additionally, two-step MR and genetic pleiotropy analyses were performed to explore potential pathways. RESULTS: Genetic susceptibility to tinnitus was significantly associated with an increased risk of major depressive disorder (MDD) (OR = 1.07, 95% CI = 1.03-1.11). Multivariable MR demonstrated that the impact of tinnitus on MDD was independent of potential confounders. No causal effects were observed from the eight psychiatric phenotypes on tinnitus; likewise, no causal effects were found from tinnitus on the remaining seven psychiatric phenotypes. Two-step MR analysis revealed that hearing difficulties with background noise and insomnia mediated the effect of tinnitus on MDD, with mediation proportions of 20.0% (0.0%-40.1%) and 31.4% (0.9%-61.9%), respectively. Genetic pleiotropy analysis identified a global genetic correlation between tinnitus and MDD (r = 0.36-0.48). PLACO analysis revealed 66 shared loci, primarily enriched in the cerebellum and cerebellar hemisphere. FUMA identified two independent genomic risk loci (rs58825580 and rs729437) and mapped 91 pleiotropic genes, which were mainly enriched in nucleosome and chromatin-remodeling processes, and immune response dysregulation. CONCLUSIONS: This study provides genetic evidence that genetic susceptibility to tinnitus has a causal effect on the risk of MDD, partially mediated by hearing difficulties and insomnia. Our genetic pleiotropy analysis further highlights the shared genetic architecture between tinnitus and MDD.
Brain morphological changes in autism spectrum disorder related to multiple behavioral spectrums: a behavioral-causal structural covariance network analysis.
Zhong T, Wang F, Qiu J … +1 more , Lu W
Eur Arch Psychiatry Clin Neurosci · 2025 Dec · PMID 41432740 · Publisher ↗
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneities in behavioral symptoms and gray matter (GM) volume changes across the brain. However, progressive and causal GM...
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneities in behavioral symptoms and gray matter (GM) volume changes across the brain. However, progressive and causal GM volume changes and their associations with behavioral symptoms remain unclear. Our study aimed to explore the heterogeneity of causal GM volume changes in individuals with ASD across behavioral spectrums. METHODS: Brain structural imaging and clinical data of 131 autistic individuals and 246 neurotypical individuals (NTs) were included, and were clustered into neuroanatomical subtypes. A novel behavioral-causal structural covariance network (BCaSCN) analysis approach was developed. GM volume maps from each ASD subtype were sequenced according to the social responsiveness scale (SRS) value and values from each behavioral domain of SRS, generating pseudo-time series data with disease progression. We performed BCaSCN analysis on the pseudo-time series data to explore the causal relationship of the GM volume changes across behavior spectrums among ASD subtypes. RESULTS: Two neurosubtypes of ASD with distinct GM volume alterations were observed. CaSCN analysis revealed heterogeneity in causal GM volume alterations between the two ASD neurostypes. Furthermore, BCaSCN analysis across behavior spectrums demonstrated that subtype 1 exhibited higher overall out- and in-degree GC values in the cognition domain, whereas subtype 2 displayed higher overall out- and in-degree GC values in the domain of motivation, mannerism and communication. LIMITATION: CaSCN and BCaSCN applied pseudo time-series data rather than real time-series data, longitudinal data are needed to validate the results of this study in the future. Therefore, the results should be interpreted with caution. CONCLUSIONS: These findings suggest that ASD subtypes are associated with heterogeneous causal GM volume changes, which may be related to distinct behavioral domains.
Trans-ethnic conditional-likelihood Mendelian randomization reveals novel causal links between depression and allergic rhinitis/asthma across five global ancestries.
Zeng B, Zhou C, Li L … +1 more , Zhu Y
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41432739 · Publisher ↗
OBJECTIVE: Major depressive disorder (MDD) frequently co-occurs with asthma and allergic rhinitis (AR); however, the causal directions and ancestral differences remain incompletely understood. This study integrates genom...
OBJECTIVE: Major depressive disorder (MDD) frequently co-occurs with asthma and allergic rhinitis (AR); however, the causal directions and ancestral differences remain incompletely understood. This study integrates genome-wide association study data from European (EUR), East Asian (EAS), South Asian (SAS), Hispanic (HIS), and African (AFR) ancestries, employing the trans-ethnic Mendelian randomization (TEMR) method based on conditional likelihood to address prior limitations. METHODS: In the exploratory phase, inverse-variance weighted was utilized as the primary approach for conventional bidirectional two-sample MR analyses, providing validation and comparison. Sensitivity analyses encompassed MRlap, Bonferroni correction, Steiger filtering, RadialMR, and evaluations for horizontal pleiotropy and heterogeneity. In the confirmatory phase, a genetic correlation matrix was constructed using linkage disequilibrium score regression. The EUR population was selected as the auxiliary cohort, with sentinel variants screened and incorporated into the TEMR model. The Nelder-Mead simplex algorithm served as the primary likelihood optimizer, supplemented by verification with Broyden–Fletcher–Goldfarb–Shanno (BFGS), Conjugate Gradient, Limited-memory BFGS with Bounds, and Simulated Annealing algorithms. RESULTS: Genetically predicted MDD and asthma exhibited bidirectional causal effects in EUR, HIS, and EAS populations, with unidirectional effects of asthma increasing MDD risk in SAS and AFR populations. Furthermore, unidirectional effects were observed for MDD increasing AR risk in EUR and AFR populations, and for AR increasing MDD risk in HIS and SAS populations. Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: This TEMR study confirms ancestry-specific bidirectional causal relationships between MDD and allergic airway diseases, highlighting the need for integrated, ancestry-tailored screening and preventive strategies in psychiatric and allergic-disease management.
Schizophrenia recognition via eye movement features in video paradigm.
Li S, Liu Z, Zhang D … +4 more , Song Y, Xu L, Zhang T, Wang J
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41432738 · Publisher ↗
Schizophrenia is a severe mental disorder characterized by abnormal eye movements. However, existing methods for detecting these abnormalities rely primarily on static stimuli that lack ecological validity. This study ex...
Schizophrenia is a severe mental disorder characterized by abnormal eye movements. However, existing methods for detecting these abnormalities rely primarily on static stimuli that lack ecological validity. This study explores the potential of video paradigms for capturing eye movement patterns specific to schizophrenia. Forty patients with schizophrenia (SZ) and forty healthy controls (HCs) completed eye movement tests and cognitive assessments. The participants watched two types of videos: an animated video with low cognitive load and a documentary with high social cognitive load, from which ten eye movement features were extracted. Group differences were compared using analysis of covariance (ANCOVA). Support vector machine (SVM) and random forest (RF) algorithms constructed the classification models, employing leave-one-out cross-validation to optimize performance. Compared to HCs, the SZ group showed significant differences in eye movement metrics, including longer fixation durations, smaller saccade amplitudes, and a reduced pupil size ratio. Furthermore, the SZ group exhibited greater variability in fixation distribution, particularly during the documentary video. When combining eye movement features from both videos, the SVM algorithm achieved a classification accuracy of 84%, while the RF algorithm reached 80%. The video-based eye movement paradigm effectively detected abnormalities in the SZ group, highlighting its potential for objective schizophrenia detection.
Role of the retinoid X receptor-peroxisome proliferator-activated receptor-γ axis in adolescent attention-deficit hyperactivity disorder.
Hsu JW, Chen LC, Bai YM … +2 more , Tsai SJ, Chen MH
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41413660 · Full text
BACKGROUND: Studies have reported the retinoid X receptor (RXR)-peroxisome proliferator-activated receptor-γ (PPAR-γ) axis, a heterodimeric nuclear receptor complex regulating synaptic plasticity and neuroinflammation, i...
BACKGROUND: Studies have reported the retinoid X receptor (RXR)-peroxisome proliferator-activated receptor-γ (PPAR-γ) axis, a heterodimeric nuclear receptor complex regulating synaptic plasticity and neuroinflammation, in neurodevelopment, with emerging evidence suggesting its disruption contributes to cognitive impairments akin to those in attention deficit hyperactivity disorder (ADHD). METHODS: This study included 104 adolescents with ADHD and 87 age-matched neurotypical adolescents. All participants completed working memory and go/no-go tasks. Clinical symptoms were assessed using the Swanson, Nolan, and Pelham IV scale and the Child Behavior Checklist Dysregulation Profile. Fasting serum levels of RXR-α, PPAR-γ, and PPAR-γ coactivator 1α were quantified via enzyme-linked immunosorbent assay. RESULTS: Generalized linear models adjusted for demographic characteristics, ADHD medications, and clinical symptoms revealed that adolescents with ADHD had reduced RXR-α levels (p = 0.001; Cohen's d = 0.47) compared with neurotypical adolescents. No significant between-group difference was noted in the level of PPAR-γ or PPAR-γ coactivator A. Furthermore, RXR-α levels negatively associated with the mean reaction time in the go/no-go task (β = -0.001; Wald χ2 = 0.475; p = 0.029). CONCLUSION: To the best of our knowledge, this study is the first to demonstrate reduced peripheral RXR-α levels in human adolescents with ADHD, independent of medication status and symptom severity, extending preclinical retinoid signaling evidence. Further investigation is required to elucidate the neuromechanisms linking ADHD to the RXR-PPAR-γ axis.
Interplay between motor stereotypies, emotional dysregulation, and sensory reactivity in adolescents and adults with autism spectrum disorder.
Hurtado Ruíz MG, Arranz Calderón MJ, Pérez Solá V … +1 more , Hervás Zúñiga A
Eur Arch Psychiatry Clin Neurosci · 2025 Dec · PMID 41396194 · Publisher ↗
OBJECTIVE: Motor stereotypies (MS), emotional dysregulation (ED), and altered sensory reactivity (SENS) are highly prevalent in children with autism spectrum disorder (ASD). Various studies suggest a relationship among t...
OBJECTIVE: Motor stereotypies (MS), emotional dysregulation (ED), and altered sensory reactivity (SENS) are highly prevalent in children with autism spectrum disorder (ASD). Various studies suggest a relationship among these variables. This study aimed to examine the relationship between ED and sensory patterns and to analyse their combined influence on MS in adolescents and adults with ASD. METHODS: In total, 97 adolescents and adults with ASD were evaluated using the Stereotyped Behavior Scale, the Emotion Dysregulation Inventory, and the Adolescent/Adult Sensory Profile. Correlation coefficients and multiple linear regression models were used to analyse the data. RESULTS: In the multivariate analysis, age, sensory hyporeactivity, and sensory seeking together with ED, explained MS frequency. Conversely, sensory hypo- and hiperreactivity, and ED explained MS severity. ED was correlated with both sensory hypo-/hyperreactivity, but not with sensory seeking. This relationship influenced the effect of ED on MS frequency and severity in regression models both with and without sensory variables. Intellectual disability did not demonstrate a significant influence on MS. The presence of psychopathological comorbidity had a partial influence-greater than that of ED-on MS severity. CONCLUSION: The relationship between MS, ED, and SENS persists in adolescents and adults with ASD, varying according to the sensory patterns analysed. These findings support the importance of studying each pattern separately. The relationship between ED and sensory hypo-/hyperreactivity modulates the effect of ED on MS. Age and psychopathological comorbidity also influenced the results. The factors influencing the frequency and severity of motor stereotypies diverge. These results could improve our comprehension of MS, thereby facilitating more appropriate MS treatment strategies.
Quality of life, disability and antipsychotics-related side effects in schizophrenia spectrum and bipolar disorder: the role of patient-reported outcome measures.
Aprile SF, Rodolico A, Castellano S … +6 more , Cutrufelli P, Di Francesco A, Leucht S, Caraci F, Fiorillo A, Signorelli MS
Eur Arch Psychiatry Clin Neurosci · 2025 Dec · PMID 41396193 · Publisher ↗
BACKGROUND: Schizophrenia and bipolar disorder significantly impair daily functioning and quality of life. Effective treatment monitoring requires tools assessing both clinical symptoms and everyday impairment. AIM: This...
BACKGROUND: Schizophrenia and bipolar disorder significantly impair daily functioning and quality of life. Effective treatment monitoring requires tools assessing both clinical symptoms and everyday impairment. AIM: This cross-sectional study explored relationships between symptoms, side effects, and functioning using clinician-rated and patient-reported measures. We examined whether the Glasgow Antipsychotic Side-Effect Scale (GASS), a patient-reported outcome measure (PROM), is associated with disability and quality of life comparably to the clinician-administered Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale. METHODS: We recruited 100 individuals with schizophrenia spectrum or bipolar disorders receiving antipsychotic treatment. Linear regressions and network analyses were conducted. Linear regressions assessed the association between side effects, disability (World Health Organization Disability Assessment Schedule, WHODAS) and quality of life (EuroQol 5-Dimension scale, EQ-5D). Network analyses were conducted to explore the interplay between side effects, disability, quality of life and symptoms, the latter assessed using the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), and Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Side effects assessed with GASS and UKU significantly impacted disability (GASS: p < .001, 95% CI [0.274; 0.635]; UKU: p < .001, 95% CI [0.313; 1.021]) and reduced quality of life (GASS: p < .001, 95% CI [-1.391; -0.511]; UKU: p < .001, 95% CI [-3.176; -1.668]). Network analysis identified depressive symptoms as central in the UKU network and autonomic side effects as central in the GASS network. CONCLUSION: GASS total and subgroup scores showed comparable associations with disability and quality of life as UKU. Integrating both perspectives enables comprehensive monitoring and patient-centred care.
Association of triglyceride-glucose index with anxiety in first-episode, drug-naïve major depressive disorder: role of subclinical hypothyroidism.
Tian X, Zhou Y, Qiu Y … +3 more , Li M, Li J, Zhang XY
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41359179 · Publisher ↗
OBJECTIVE: The triglyceride-glucose (TyG) index, linked to insulin resistance (IR), is implicated in depression, but its association with anxiety in major depressive disorder (MDD) is unclear. Subclinical hypothyroidism...
OBJECTIVE: The triglyceride-glucose (TyG) index, linked to insulin resistance (IR), is implicated in depression, but its association with anxiety in major depressive disorder (MDD) is unclear. Subclinical hypothyroidism (SCH) is independently associated with metabolic issues and anxiety in MDD. This study aimed to (1) validate the TyG-anxiety link in first-episode, drug-naïve (FEDN) MDD patients and (2) explore SCH's interactive role. METHODS: This cross-sectional study involved 1,654 FEDN MDD patients. Demographics, clinical data, and biochemical markers (including the TyG index) were collected. Depression and anxiety severity were assessed using HAMD-17 and HAMA-14 scales. Multivariable linear regression evaluated the TyG-anxiety association. Stratified analyses by SCH status and interaction tests were conducted. RESULTS: Of 1,654 MDD patients, 79.6% (1,316) had anxiety distress (HAMA-14 ≥ 18). In a fully adjusted model, each 1-unit TyG index increase was associated with a 0.67-point higher anxiety score (β = 0.67, 95% CI: 0.33-1.01). Patients in the highest TyG quintile (Q5: 9.42-10.27) showed a 0.75-point increase versus the lowest quintile (Q1: 6.64-8.59) (P < 0.05). This association was significant in patients with SCH (β = 1.15, 95% CI: 0.68-1.61), not in those without SCH (β = 0.05, 95% CI: -0.44-0.53) (P for interaction<0.05). CONCLUSIONS: The TyG index is independently associated with anxiety symptoms in FEDN MDD patients, particularly in those with comorbid SCH. This suggests that the interaction between thyroid function and metabolism is associated with anxiety symptoms, highlighting a potential biological interplay that warrants further investigation. Clinicians should pay attention to anxiety levels in patients with MDD who also present with metabolic disturbances and SCH. Future longitudinal and basic studies are needed to confirm causality and mechanisms.
Impact of adverse childhood experiences on youth non-suicidal self-injury: the mediating role of rumination.
Bao C, Zou H, Zhang Q … +5 more , Xia Y, Wang X, Tian S, Lu Q, Yao Z
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41359178 · Publisher ↗
Adverse childhood experiences and rumination are both risk factors for non-suicidal self-injury (NSSI) in depression. However, the interaction among these three factors has not been well researched. This study aimed to i...
Adverse childhood experiences and rumination are both risk factors for non-suicidal self-injury (NSSI) in depression. However, the interaction among these three factors has not been well researched. This study aimed to investigate the potential mediating role of rumination between adverse childhood experiences and NSSI frequency. To this end, 276 young patients aged 15–30 years with major depressive disorder (MDD) were recruited as the research subjects. General demographic scales and clinical scales were used to assess adverse childhood experiences, rumination, levels of anxiety and depression, as well as the frequency of NSSI. Based on DSM-5 diagnostic criteria for NSSI, MDD patients were divided into two groups: the NSSI + group (n = 134) and the NSSI- group (n = 142). Mediation analysis was employed to examine the mediating role of rumination in the relationship between adverse childhood experiences and NSSI frequency. The NSSI + group exhibited higher adverse childhood experiences, rumination scores and anxiety/depression levels than the NSSI − group (all p < 0.05). After adjusting for demographic covariates, adverse childhood experiences and different types of rumination (depression related, brooding and reflection) were positively linked to NSSI frequency over three time periods (past month/past 6 months/past year). Additionally, the depression related and brooding subtypes of rumination mediate the relationship between adverse childhood experiences and NSSI frequency. Thus, this study indicates an association between adverse childhood experiences, rumination, and NSSI. These findings suggest that heightened awareness of childhood experiences, combined with interventions targeting rumination, may help reduce the risk of NSSI.
Cognitive impairment and associated white matter organization abnormalities across the illness course of schizophrenia.
Shen CL, Tsai SJ, Lin CP … +1 more , Yang AC
Eur Arch Psychiatry Clin Neurosci · 2025 Dec · PMID 41359177 · Publisher ↗
AIM: Schizophrenia is a chronic brain disorder with cognitive impairment as one of the cardinal manifestations. White matter organization abnormalities shown on brain imaging were also documented in patients with schizop...
AIM: Schizophrenia is a chronic brain disorder with cognitive impairment as one of the cardinal manifestations. White matter organization abnormalities shown on brain imaging were also documented in patients with schizophrenia. However, when and how the cognitive impairment, the white matter organization abnormalities and their correlation occur and evolve throughout the illness course of schizophrenia remain undetermined. We aimed to show cognitive impairment and white matter organization abnormalities across different stages of schizophrenia and the association between them. METHODS: We collected 4 groups of participants: 40 individuals with illness duration of schizophrenia below 5 years, 36 individuals with illness duration of schizophrenia around 15 years, 39 individuals with illness duration of schizophrenia above 25 years, and 78 healthy controls. All participants underwent 3 cognitive tests (Wisconsin Card Sorting Test, Digit Span, Mini-Mental Status Examination) and 2 diffusion tensor imaging analyses of white matter (fractional anisotropy and graph theoretical analysis). RESULTS: We found cognitive impairment aggravated from early stage to the third decade of illness in schizophrenia. The associated white matter structural abnormalities had two steps of change: alteration in network organization occurred at early stage of schizophrenia, and then reduction in white matter tract integrity ensued from the second decade of the illness. The white matter integrity reduction was associated with cognitive impairment. CONCLUSION: By using groups of participants with different illness duration, we found cognitive impairment and white matter organization abnormalities and their association across a three-decade illness course in schizophrenia. Our findings suggested active cognitive rehabilitation to patients with schizophrenia throughout the course of illness may be warranted.
Positive and Negative Symptom Disorder (PND) still the best solution?
Leucht S, Yurtseven DS, van Os J
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41359176 · Full text
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Gender differences and risk factors for suicide attempts in first-episode drug-naïve psychotic versus non-psychotic major depression: a large cross-sectional study.
Cui P, Yang S, Zhou J … +4 more , Xuekelaiti Z, Liu Y, Luo G, Zhang X
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41329182 · Publisher ↗
BACKGROUND: This study aimed to investigate the differential clinical characteristics and distinct risk factors for suicide attempts between patients with psychotic major depression (PMD) and non-psychotic major depressi...
BACKGROUND: This study aimed to investigate the differential clinical characteristics and distinct risk factors for suicide attempts between patients with psychotic major depression (PMD) and non-psychotic major depression (NPMD). METHODS: A cross-sectional analysis was conducted on a cohort of major depressive disorder patients. Comprehensive demographic and clinical data were collected. Assessments included the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale (PANSS) positive subscale, and Clinical Global Impression-Severity scale (CGI-S). Fasting blood samples were analyzed for thyroid function (TSH, TgAb, TPOAb, FT3, FT4), metabolic parameters (fasting blood glucose, lipid profiles), and other biomarkers. RESULTS: Patients with PMD demonstrated a more severe clinical profile, including significantly higher HAMD, HAMA, and CGI-S scores, alongside elevated thyroid antibodies (TgAb, TPOAb) compared to the NPMD group. A critical finding was the divergent set of predictors for suicide attempts between the diagnostic subgroups. For the overall MDD cohort and the NPMD subgroup specifically, the severity of anxiety (HAMA) and depression (HAMD) were the primary risk factors. In stark contrast, for patients with PMD, positive psychotic symptoms (PANSS) and elevated TSH levels emerged as the dominant and unique predictors of suicide attempts. ROC analysis confirmed the high discriminatory power of TSH for suicide in PMD (AUC = 0.863). CONCLUSIONS: The path to suicidal behavior differs significantly between PMD and NPMD. Suicide risk in NPMD is primarily driven by the severity of core mood and anxiety symptoms, whereas in PMD, it is predominantly associated with the presence of psychosis and significant HPT axis dysregulation.
MDMA's resilience mechanisms: serotonin, oxytocin, and a vagus nerve-dependent gut-brain axis.
Zhao MM, Yang JJ, Hashimoto K
Eur Arch Psychiatry Clin Neurosci · 2025 Nov · PMID 41317178 · Publisher ↗
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Association of educational attainment with mental disorders and the mediation role of lifestyle factors: a Mendelian randomization study.
Shi X, Wang S, Fan J … +3 more , Yang Y, Wen L, Jia X
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41317177 · Publisher ↗
BACKGROUND: Educational attainment (EA) was associated with lifestyle behaviors and underlying mental disorders. However, the causality remained poorly understood. This study aimed to elucidate the causal association bet...
BACKGROUND: Educational attainment (EA) was associated with lifestyle behaviors and underlying mental disorders. However, the causality remained poorly understood. This study aimed to elucidate the causal association between EA and mental disorders while exploring the mediation role of lifestyle factors. METHODS: A two-step Mendelian randomization (MR) analysis was performed to evaluate the mediation role of lifestyle factors in the relationship between EA and mental disorders. The total effects of years of education (EduYears) and college completion (College) on 31 lifestyle factors and 7 mental disorders were estimated using univariable MR. Multivariable MR was utilized to assess the independent effects of lifestyle factors on mental disorders. Mediation effects were calculated for factors significantly associated with both EA and mental disorders. RESULTS: EduYears was significantly associated with anorexia nervosa (AN), major depression disorder (MDD), post-traumatic stress disorder (PTSD), and attention deficit hyperactivity disorder (ADHD), with OR (95% CIs) of 0.96 (0.92, 0.99), 0.97 (0.94, 1.00), 0.94 (0.91, 0.97), and 0.84 (0.82, 0.87), respectively. Similarly, genetically determined College was inversely associated with AN, MDD, PTSD, and ADHD. Smoking initiation, processed meat intake, beef intake, and cereal intake mediated the effect of EA on mental disorders from 9% to 31%. CONCLUSION: This study indicated the causal effect of EA on AN, MDD, PTSD, and ADHD. The mediation analysis indicated that smoking and diet partially explained the effect. The results underscored the significance of EA and lifestyle factors in mental health policies.
Mendelian randomization analyses support causal relationships between COVID-19 and changes in brain structure and function.
Wang Q, Liu F, Wang X … +1 more , Chen T
Eur Arch Psychiatry Clin Neurosci · 2026 Feb · PMID 41307719 · Publisher ↗
A range of neuropsychiatric symptoms (including "brain fog") following COVID-19 are clinically prevalent, yet their biological mechanisms remain unclear. Observational studies indicate that this association may be linked...
A range of neuropsychiatric symptoms (including "brain fog") following COVID-19 are clinically prevalent, yet their biological mechanisms remain unclear. Observational studies indicate that this association may be linked to alterations in brain structure and function post-COVID-19; however, it is uncertain whether this relationship is causal. The study data is derived from the summary statistics of a genome-wide association study (GWAS), where COVID-19 encompasses three phenotypes: critical illness (respiratory support or death; n = 1,086,211), hospitalization (n = 2,095,324), and SARS-CoV-2 infection (n = 2,597,856); Brain imaging-derived phenotypes (IDPs) include cortical structures (n = 51,665), subcortical brain structures (n = 30,717), and brain functional networks (n = 47,276); Neuropsychological symptoms comprise ten phenotypes, including cognitive performance (n = 51,710 to 480,359). We conducted a two-sample Mendelian randomization (MR) analysis to explore potential causal relationships between COVID-19 and IDPs, as well as neuropsychological symptoms. Sensitivity analyses were subsequently performed to evaluate the robustness of the results. We identified causal relationships between COVID-19 and 22 cortical structure phenotypes, one subcortical brain structure phenotype, five brain functional network phenotypes, and one neuropsychological symptom phenotype, with some overlap across different COVID-19 phenotypes. Notably, COVID-19 was predominantly negatively correlated with these phenotypes. Our findings suggest a weak causal relationship between COVID-19 and IDPs, as well as neuropsychological symptoms. Although further research is necessary to validate these relationships, these findings may contribute to a better understanding of the associations between COVID-19, IDPs, and neuropsychological symptoms.
Delineating white matter phenotypes of sensori-/psychomotor functioning in large-scale cohorts of healthy individuals and patients with mental disorders across the lifespan (whiteSPAN): rationale and methods of an interdisciplinary bicentric project.
Hirjak D, Volkmer S, Peretzke R … +3 more , Meyer-Lindenberg A, Maier-Hein KH, Neher P
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41288695 · Publisher ↗
Aberrant sensori-/psychomotor functioning-including muscular hand weakness, sedentary behavior, psychomotor agitation, slowing, agitation, apathy, and anxiety-is increasingly recognized as a transdiagnostic feature acros...
Aberrant sensori-/psychomotor functioning-including muscular hand weakness, sedentary behavior, psychomotor agitation, slowing, agitation, apathy, and anxiety-is increasingly recognized as a transdiagnostic feature across mental and neurodegenerative disorders. Objectively measured sensori-/psychomotor abnormalities serve as rapid, noninvasive indicators of cognitive and affective dysfunction, yet large-scale neuroimaging studies examining their white matter (WM) correlates remain limited. This bi-centric research project aims to investigate associations between sensori-/psychomotor functioning and WM microstructure across anxiety disorders (AD), major depressive disorder (MDD), schizophrenia spectrum disorders (SSD), mild cognitive impairment (MCI), and Alzheimer's disease (AD). We will analyze diffusion MRI data from over 2,400 healthy individuals and 1,600 patients, combining publicly available datasets (e.g., Human Connectome Project, Alzheimer's Disease Neuroimaging Initiative) with in-house cohorts comprising >400 deeply-phenotyped SSD and MDD patients. A major strength of the project lies in the harmonization of psychopathological rating scales and sensori-/psychomotor assessments across these populations. Using advanced computational tools-including tractometry, tractomics, normative modeling, and deep learning-we aim to map a WM phenotype of sensori-/psychomotor dysfunction across the lifespan. Multivariate taxometric approaches will help identify biologically informed sensori-/psychomotor biotypes that cut across traditional diagnostic boundaries. By distinguishing disorder-specific WM changes from normative developmental and aging processes, this project seeks to inform precision medicine approaches and guide biomarker-driven interventions for mental and neurodegenerative disorders.
Investigating the causal associations between neuroticism, schizophrenia, and cardiovascular diseases using Mendelian randomization.
Pu L, Zhang R, Pan L … +3 more , Li Y, Hu S, Huang Y
Eur Arch Psychiatry Clin Neurosci · 2025 Nov · PMID 41288694 · Publisher ↗
BACKGROUND: This study employed two-sample Mendelian randomization (MR) to investigate the potential causal associations between neuroticism, schizophrenia, and various cardiovascular diseases (CVDs), including coronary...
BACKGROUND: This study employed two-sample Mendelian randomization (MR) to investigate the potential causal associations between neuroticism, schizophrenia, and various cardiovascular diseases (CVDs), including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), stroke, hemorrhagic stroke, and ischemic stroke, along with its subtypes. METHODS: We identified independent genetic variants associated with neuroticism and schizophrenia, along with summary statistics for the instrument-outcome relationship, from the largest available genome-wide association study (GWAS) of European ancestry. The inverse variance-weighted (IVW) method was utilized as the primary analytical approach. RESULTS: The IVW analysis indicated that genetically determined neuroticism was associated with an increased risk of small-vessel stroke (SVS: odds ratio [95% confidence interval] = 1.42 [1.19-1.68], P < 0.001) and MI (1.13 [1.03-1.25], P = 0.013). Furthermore, a significant association was observed between schizophrenia and HF (1.13 [1.00-1.06], P = 0.026). These associations remained significant after performing multivariable MR to adjust for sleep duration and body mass index. Specifically, the associations between genetic liability to neuroticism and both SVS and MI were statistically significant, with odds ratios of 1.26 (95% CI 1.02-1.58, P = 0.036) and 1.17 (95% CI 1.05-1.32, P = 0.006), respectively. Furthermore, the associations between schizophrenia and HF remained significant, with an odds ratio of 1.05 (95% CI 1.01-1.09, P = 0.007). These results were consistent across extensive sensitivity analyses. CONCLUSION: Our preliminary genetic evidence suggests that neuroticism may increase the risk of SVS and MI, while schizophrenia may elevate the risk of HF. These findings could inform the identification of patient populations that would benefit from CVD prevention strategies that emphasize mental health improvement.
Correction: The role of tight junction proteins in the pathogenesis of schizophrenia.
Yulia S, Zorkina Y, Alisa A … +1 more , Georgy K
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41283995 · Publisher ↗
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Smoking and its associations with metabolic indices, clinical symptoms, and cognitive functioning in schizophrenia.
Liu J, Qin Q, Zhang H … +6 more , Wang L, Han Y, Wang L, Sun W, Zhang Y, Li S
Eur Arch Psychiatry Clin Neurosci · 2025 Nov · PMID 41283994 · Publisher ↗
BACKGROUND: Schizophrenia (SCZ) is characterized by high smoking prevalence, metabolic disturbances, and cognitive impairments. The specific impact of smoking on metabolic and cognitive profiles in SCZ remains poorly und...
BACKGROUND: Schizophrenia (SCZ) is characterized by high smoking prevalence, metabolic disturbances, and cognitive impairments. The specific impact of smoking on metabolic and cognitive profiles in SCZ remains poorly understood. This study aimed to investigate the relationships among smoking behavior, metabolic status, and cognitive functioning in SCZ. METHODS: A total of 773 chronic SCZ patients were assessed for metabolic parameters, including blood pressure, waist circumference, BMI, lipid, and glucose metabolism. Psychiatric symptoms and cognitive functioning were evaluated using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. RESULTS: Of the SCZ patients, 32.99% were smokers. Smoking patients were older, had fewer years of education. Smoking was associated with lower negative symptom scores on the PANSS. Notably, in non-smoking patients, hip circumference was negatively correlated with clinical symptom severity but positively correlated with cognitive function. However, these correlations were not observed among smokers. Instead, the smoking group exhibited a distinct negative association between systolic blood pressure and negative symptoms. CONCLUSION: In non-smoking patients, larger hip circumference was associated with milder negative symptoms and better cognitive function. In smokers, this association disappears. In addition, smokers have less severe negative symptoms than non-smokers.
Bed nucleus of the stria terminalis deep brain stimulation in treatment-refractory obsessive-compulsive disorder: a systematic review.
Goulas A, Mavridis I
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41283993 · Publisher ↗
BACKGROUND: Obsessive-compulsive disorder (OCD) is one of the most disabling psychiatric disorders. Despite the available pharmacological and psychotherapeutic treatments, symptoms persist to a severe degree in a large n...
BACKGROUND: Obsessive-compulsive disorder (OCD) is one of the most disabling psychiatric disorders. Despite the available pharmacological and psychotherapeutic treatments, symptoms persist to a severe degree in a large number of patients who are considered refractory to treatment. For some of them, deep brain stimulation (DBS) offers an appropriate therapeutic method. The purpose of this systematic review is to summarize the existing knowledge about the effectiveness of the stimulation of the bed nucleus of stria terminalis (BNST). MATERIALS AND METHODS: A thorough literature review regarding BNST DBS for the treatment of OCD was conducted. The following sequence ‘’ (Obsessive-Compulsive Disorder) OR (OCD)) AND ((Deep Brain Stimulation) OR (DBS)) AND ((Bed Nucleus of Stria Terminalis) OR (BNST)) ‘’ was used when searching in the two databases, MEDLINE and Scopus. RESULTS: In total, 8 studies were found after the application of the inclusion and exclusion criteria. Overall, 68 patients were included, with a mean age of surgery 41.2 years old. At the last follow-up, the mean reduction of the Yale-Brown Obsessive-Compulsive Scale (YBOCS) compared to baseline was 45.6% with a range across the studies of 38% to 53%. In total, 46 participants were considered responders. The median stimulation parameters were an amplitude of 4.7 V, a frequency of 130 Hz, and a pulse width of 129.2 µs. Finally, there was improvement of depressive and anxiety symptoms, as well as quality of life, without any significant cognitive impairment. CONCLUSION: DBS of the BNST in treatment-refractory OCD appears as a safe and effective treatment option.
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