European Archives Of Psychiatry And Clinical Neuroscience[JOURNAL]
Sun
200 papers
Therapeutic effects of tDCS on behavioral and cognitive functions in adults diagnosed with attention-deficit/hyperactivity disorder: a systematic review and meta-analysis on randomized controlled trials.
Wen YH, Pan WF, Sun CK … +2 more , Cheng YS, Hung KC
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41283992 · Publisher ↗
The current study aimed to investigate the effectiveness of transcranial direct current stimulation (tDCS) in improving the clinical symptoms and cognitive functions in adults diagnosed with attention deficit/hyperactivi...
The current study aimed to investigate the effectiveness of transcranial direct current stimulation (tDCS) in improving the clinical symptoms and cognitive functions in adults diagnosed with attention deficit/hyperactivity disorder (ADHD) as well as its treatment acceptability. Randomized placebo-controlled trials (RCTs) identified from major databases using the main keywords “tDCS” and “ADHD” were reviewed for improvement in clinical symptoms and cognitive functions in adults diagnosed with ADHD. The outcomes of interest were quantified using effect size expressed as standardized mean difference (SMD) and odds ratios (ORs) for continuous and categorical variables, respectively, with 95% confidence interval (CI). Meta-analysis of seven RCTs including 263 participants (mean age = 31.37) revealed significantly a greater improvement in the symptoms of inattention (SMD=-1.24, 95% CI:-0.84 to -1.63, p < 0.01) and cognitive tasks involving attentional performance (SMD= -0.54, 95% CI: -1.07 to -0.01, p = 0.04) in the tDCS group compared with the control group, but no significant difference in the symptoms of hyperactivity/impulsivity (p = 0.19) and inhibitory control (p = 0.17) between the two groups. There was also no significant difference in dropout rate between adults receiving tDCS and their controls (p = 0.07). Our study supported the use of tDCS for improving the self-reported symptoms of inattention and objective attentional performance in adults diagnosed with ADHD. However, the limited number of available trials hindered a robust investigation into the parameters required for establishing a standard protocol such as the optimal location of electrode placement and treatment frequency in this setting. Further large-scale studies are warranted to address these issues.
Low-dose paliperidone combined with sertraline for first-episode and medication-naïve patients with schizophrenia: an open-label, randomized trial.
Lin Z, Guan X, Lang X … +2 more , Xiu M, Wu F
Eur Arch Psychiatry Clin Neurosci · 2025 Nov · PMID 41273452 · Publisher ↗
OBJECTIVE: Many individuals suffering from schizophrenia discontinued antipsychotic drugs, frequently due to dose-related multiple and severe adverse effects, especially in first-episode patients. We hypothesized that a...
OBJECTIVE: Many individuals suffering from schizophrenia discontinued antipsychotic drugs, frequently due to dose-related multiple and severe adverse effects, especially in first-episode patients. We hypothesized that a low-dose paliperidone in combination with sertraline, an SSRI that increases cortical dopamine and serotonin, would reduce serious side effects without affecting treatment efficacy. Therefore, this study was designed to investigate whether low-dose paliperidone plus sertraline would improve negative symptoms and psychosocial functioning without affecting the antipsychotic efficacy of positive symptoms in medication-naive and first-episode (MNFE) patients with schizophrenia to minimize the influence of potential confounding factors, including prior antipsychotic drugs and disease duration. METHODS: This is a 24-week, open-label, randomized controlled trial. In this study, we randomly assigned 188 MNFE schizophrenia patients to receive either a half dose of paliperidone in combination with sertraline (PS group, n = 94) or a usual dose of paliperidone monotherapy (Control group, n = 94). Primary outcome measures included negative symptoms and psychosocial functioning as assessed by the Personal and Social Performance Scale (PSP). Secondary outcome measures included psychotic symptoms as assessed by the Positive and Negative Syndrome Scale (PANSS) and depressive symptoms as evaluated by the Hamilton Depression Rating Scale (HAMD). RESULTS: We found that treatment with paliperidone plus sertraline was correlated with greater improvements from baseline to week 24 in negative symptoms and psychosocial functioning compared to paliperidone monotherapy [mean reductions in negative symptoms: 11.7 [95% confidence interval (CI):11.2 to 12.2] vs. 14.6 (95% CI:14.1 to 15.0), F = 69.8, p < 0.001; mean increases in psychosocial functioning: 43.7 (95% CI:42.8 to 44.6) vs. 53.9 (95% CI:52.9 to 54.8), F = 237.2, p < 0.001]. In addition, improvements in psychosocial functioning were associated with a reduction in negative symptoms in patients (β = − 0.48, t = − 2.8, p = 0.007). The combination treatment was also relatively superior to monotherapy in terms of depressive symptoms (F = 37.0, p < 0.001) and comparable in terms of psychotic symptoms (p > 0.05). CONCLUSIONS: This open-label study demonstrates that half of the usual dose of paliperidone plus sertraline is efficacious in the treatment of MNFE patients with schizophrenia with respect to their negative symptoms and psychosocial functioning. However, the limitations included the open-label design, absence of a placebo arm, and short 12-week follow-up. Further, longer-term, double-blind trials are warranted to confirm our findings. If confirmed, this combination could offer a practical, low-risk strategy to close the persistent efficacy gap for negative and cognitive symptoms in schizophrenia.
Role of emotional intelligence in schizophrenia: ability-based vs. self-reported assessment.
Lin CH, Ma WF, Huang YJ … +3 more , Tsai SH, Chang HY, Lane HY
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41269290 · Publisher ↗
BACKGROUND: Both ability-based tests (such as Mayer-Salovey-Caruso Emotional Intelligence Test-the managing emotions branch [MSCEIT-ME]) and self-reported scales (such as Wong and Law Emotional Intelligence Scale [WLEIS]...
BACKGROUND: Both ability-based tests (such as Mayer-Salovey-Caruso Emotional Intelligence Test-the managing emotions branch [MSCEIT-ME]) and self-reported scales (such as Wong and Law Emotional Intelligence Scale [WLEIS]) have been employed to measure emotional intelligence (EI). While the clinical relevance of MSCEIT-ME performance among schizophrenia patients appeared inconsistent across studies, the role of WLEIS in schizophrenia has not yet been investigated. METHODS: We examined the effect of WLEIS scores on MSCEIT-ME performance in 492 Taiwanese schizophrenia patients (including 92 drug-free and 400 chronic medicated patients), and then the influence of symptomatology and neurocognition (with nine cognitive tests) on EI (MSCEIT-ME or WLEIS). Finally, we explored the differential roles of the two EI instruments in functional outcome (Global Assessment of Functioning [GAF] Scale and the Quality of Life [QoL] Scale). RESULTS: With multiple regression analyses, participants' WLEIS performance showed a positive correlation with MSCEIT-ME scores after controlling sex and age. While male and younger patients with better nonverbal working memory and less severe negative symptoms were more likely to have better MSCEIT-ME performance, older patients with more positive symptoms and fewer depressive symptoms showed greater WLEIS performance. Moreover, female and younger individuals with better MSCEIT-ME and WLEIS scores had more favorable QoL, while higher MSCEIT-ME scores linked to patients' better GAF. In addition, patients' medication status didn't affect the aforementioned findings. CONCLUSION: The results suggest that that MSCEIT-ME and WLEIS may differ in their associations with clinical and neurocognitive profiles, and their impacts on functional outcome. Longitudinal studies in other populations are warranted.
Cognitive impairment, depression, and fatigue in post-COVID and post-vaccination syndrome: a large-scale cross-sectional study.
Hanc E, Koller K, Herold R … +2 more , Erim Y, Morawa E
Eur Arch Psychiatry Clin Neurosci · 2026 Feb · PMID 41258118 · Full text
BACKGROUND: Persistent cognitive difficulties are among the most prevalent symptoms observed after COVID-19. This study examined the neuropsychological characteristics, mental health and risk factors associated with cogn...
BACKGROUND: Persistent cognitive difficulties are among the most prevalent symptoms observed after COVID-19. This study examined the neuropsychological characteristics, mental health and risk factors associated with cognitive impairment in patients with Post-Acute Sequelae of COVID-19 (PASC). In addition, differences regarding the cognitive dysfunctions between individuals with PASC and Post-Vaccination Syndrome (PVS) were explored. METHODS: Participants were consecutively recruited at the Post-COVID Center of the University Hospital Erlangen in Germany (12/2022-02/2025). Assessments included a broad neuropsychological assessment: d2 Test of Attention, digit span backwards from the Wechsler Memory Scale-Revised (WMS-R) and module 1 (formal lexical fluency) of the Regensburger Verbal Fluency Test (RWT), along with assessments of depression, fatigue, and inflammatory markers (C-reactive protein). RESULTS: The sample (N = 793, mean age: 46.1 ± 12.4 years; 66.8% women) included n = 723 PASC patients and n = 70 PVS patients. In the total sample, deficits were most frequent in working speed (61.7%), attention (54.7%) and verbal fluency (48.8%); 30.3% showed multidomain impairment. Clinically significant depressive symptoms (64.5%) and fatigue (92.4%) were common. Cognitive patterns, depressive symptoms and fatigue in the PVS group closely resembled those observed in PASC. In PASC, lower education, older age, depressive symptoms, and elevated CRP were associated with cognitive impairment. CONCLUSION: Cognitive impairment is highly prevalent in PASC and PVS and appears to be influenced by both psychological and biological factors. Similar patterns identified in PVS suggest possible shared mechanisms. Further research is needed to clarify trajectories and optimize treatment strategies.
Nightmare frequency mediates the association between childhood trauma and suicidal ideation among youth: is it sex-specific?
Que J, Lu Y, Liu J … +7 more , Shi L, Wu S, You C, Chen X, Lin D, Liu F, Liu JJ
Eur Arch Psychiatry Clin Neurosci · 2026 Feb · PMID 41247495 · Full text
Childhood trauma has been found to be associated with suicidal ideation among youth. However, the underlying processes that link childhood trauma and suicidal ideation are unclear. This study investigates the role of nig...
Childhood trauma has been found to be associated with suicidal ideation among youth. However, the underlying processes that link childhood trauma and suicidal ideation are unclear. This study investigates the role of nightmare frequency in the association between childhood trauma and suicidal ideation, and the potential moderating effect of sex. Youths were recruited from Fujian Province, China. Childhood trauma was assessed using the Childhood Trauma Questionnaire, and the frequency of nightmares and suicidal ideation were also evaluated. Moderated mediation analyses were conducted with childhood trauma as the independent variable, suicidal ideation as the dependent variable, nightmare frequency as the mediator variable, and sex as the moderator. All statistical analyses were performed in R (version 4.2.3). A total of 3431 individuals completed all the questions assessing childhood trauma, nightmare frequency, and suicidal ideation. Among them, 28.6% reported having experienced suicidal ideation in the past 12 months. Additionally, 25.9% of participants reported frequent nightmares. The association between childhood trauma and suicidal ideation was significantly mediated by nightmare frequency, with an effect size of 0.003 (bootstrap 95%CI: 0.001, 0.005). The indirect effects accounted for approximately 4.11% of the overall effect. However, there was no statistically significant moderating effect of sex on the association between childhood trauma and nightmare frequency. The findings of this study suggest that treating nightmares may serve as a promising intervention target for addressing suicidal ideation in youth with a history of childhood trauma, irrespective of sex.
Immunophenotype-mediated effects of plasma proteins on major depressive disorder: A two-step Mendelian randomization study.
Jia R, Nie M, Wang X … +1 more , Yang Y
Eur Arch Psychiatry Clin Neurosci · 2026 Feb · PMID 41231246 · Publisher ↗
The aim of this study was to investigate the mediating role of immune cells in the relationship between plasma proteins and the risk of major depressive disorder (MDD). Using a two-step, two-sample Mendelian randomizatio...
The aim of this study was to investigate the mediating role of immune cells in the relationship between plasma proteins and the risk of major depressive disorder (MDD). Using a two-step, two-sample Mendelian randomization (MR) approach, we systematically assessed whether immune cells mediate the causal effects of plasma proteins on MDD. We found that eleven plasma proteins (TRABD, CACNB4, EDA, SAR1A, GLRX, COTL1, STOM, CRP, FGF22, and EDA2R) were positively associated with MDD risk, while one protein (SPTLC1) exhibited a negative association. Additionally, seven immune cell phenotypes-including CD14 on CD33dim HLA DR + CD11b + , memory B cells (% of B cells), IgD⁻ CD24⁻ % B cells, CD20 on B cells, CD27 on IgD⁺ CD24⁺, CD27 on IgD⁻ CD38dim, and CD62L on CD62L⁺ DCs-showed potential causal effects on MDD. Further mediation analysis revealed that three immune cell types mediated the effects of four plasma proteins on MDD: CD27 on IgD⁺ CD24⁺ cells mediated the effects of both COTL1 and RNF122 (mediation proportions: 5.13% and 4.50%, respectively); IgD⁻ CD24⁻ % B cells mediated the effect of EDA (12.1%); and CD62L on CD62L⁺ DCs mediated the effect of GLRX (-9.46%). The negative mediation proportion suggests a protective pathway. Sensitivity analyses supported the robustness of these findings.These results provide novel insights into immune-mediated mechanisms linking plasma proteins to MDD and may inform future research into targeted immunotherapeutic strategies.
Personality domains in early stages of psychosis: a systematic review and meta-analysis.
Scala M, Gori D, Roca P … +5 more , Fabbri C, Arroyo Iturra R, Calvo García SF, Fanelli G, Serretti A
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41222667 · Full text
BACKGROUND: Personality traits influence symptoms, functioning, and illness trajectory in chronic psychosis. However, their role in early-stage psychosis remains poorly defined, particularly regarding potential differenc...
BACKGROUND: Personality traits influence symptoms, functioning, and illness trajectory in chronic psychosis. However, their role in early-stage psychosis remains poorly defined, particularly regarding potential differences from healthy controls and their association with clinical outcomes. METHODS: We conducted a systematic review and meta-analysis of studies assessing personality domains in early-stage psychosis using validated dimensional instruments. Searches were performed in PubMed/MEDLINE, CINAHL, and Web of Science until March 2025. The meta-analysis included studies using the NEO Five-Factor Inventory (NEO-FFI), with patient scores compared to published normative data. Studies reporting T-scores and those reporting raw scores were analyzed separately. Associations between personality domains and clinical features were narratively synthesized. RESULTS: Eighteen studies met the inclusion criteria; eight were included in the meta-analysis (n = 1109). Considering studies reporting T-scores, individuals with early-stage psychosis showed higher neuroticism (MD = 27.4, 95% CI [25.0 to 29.9]) and lower extraversion (MD = -6.0, 95% CI [-8.6 to -3.5]) and conscientiousness (MD = -5.5, 95% CI [-7.9 to -3.2]), relative to normative data. Analyses of studies reporting raw scores showed similar effects, though not statistically significant. The same personality domains were consistently associated with symptom severity, treatment adherence, functioning, and service use. CONCLUSIONS: Early-stage psychosis may be characterized by a specific personality profile that modulates clinical presentation. Early personality assessment may guide tailored treatment strategies. Longitudinal studies are needed to clarify their prognostic relevance and potential role in the personalization of treatment.
Correction: Memory deficits in children and adolescents with a psychotic disorder: a systematic review and meta-analysis.
de-la-Higuera-Gonzalez P, Rodriguez-Toscano E, Diaz-Carracedo P … +4 more , Gonzalez-Urrea MJ, Padilla-Quiles G, Diaz-Marsa M, de la Torre-Luque A
Eur Arch Psychiatry Clin Neurosci · 2026 Apr · PMID 41217506 · Full text
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Not only the main streams, but also the tributaries supply the landscape: antidepressants for the prevention of severe COVID-19.
Bonnet U
Eur Arch Psychiatry Clin Neurosci · 2026 Feb · PMID 41212306 · Full text
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Bidirectional causal association between cathepsins and neuropsychiatric disorders: univariate and multivariate Mendelian randomization study.
Li Z, Jia L, Huai S
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41212305 · Publisher ↗
BACKGROUND: Neuropsychiatric disorders are among the most common diseases worldwide and are characterized by complex pathogenic mechanisms. Cathepsins (CTS) are crucially involved in the pathogenesis and treatment of num...
BACKGROUND: Neuropsychiatric disorders are among the most common diseases worldwide and are characterized by complex pathogenic mechanisms. Cathepsins (CTS) are crucially involved in the pathogenesis and treatment of numerous diseases. Increasing evidence suggests a relationship between cathepsins and neuropsychiatric disorders. However, the causal associations remain unclear. METHODS: We performed a bidirectional two-sample Mendelian randomization (MR) analysis, applying univariable (UVMR) and multivariable MR (MVMR) to evaluate the causal association between nine cathepsins and five neuropsychiatric disorders. Data for this study were derived from genome-wide association studies (GWAS). The MR analysis primarily used five methods: Inverse Variance Weighted (IVW), Weighted Median Estimator (WME), MR-Egger regression, Simple mode, and Weighted mode. Additionally, sensitivity tests were employed to assess the robustness of the MR results. RESULTS: MR analyses indicated that CTSH is associated with an increased risk of Alzheimer’s disease (AD) (UVMR: OR, 1.041; 95% CI, 1.013–1.069; p = 0.004; MVMR: OR, 1.040; 95% CI, 1.014–1.066; p = 0.003; replication UVMR: OR, 1.046; 95% CI, 1.014–1.082; p = 0.011). Findings that were significant in only one MR approach, such as the putative causal effects of CTSF on AD and bipolar disorder (BIP), of CTSL2 on major depressive disorder (MDD), and of CTSH and CTSE on Parkinson’s disease (PD) should be interpreted with caution. CONCLUSION: CTSH can be considered a plasma biomarker for AD, offering new insights and potential directions for the prevention and treatment of AD. Additionally, during the treatment of BIP and PD, attention should be paid to CTSF and CTSE expression levels to maintain physiological homeostasis.
Elevated defeatist performance beliefs predict state increases in negative symptoms in daily life in clinical high-risk for psychosis youth: implications for mobile health treatments.
Luther L, Raugh IM, Webber LBG … +5 more , Grant PM, Beck AT, Mittal VA, Walker E, Strauss GP
Eur Arch Psychiatry Clin Neurosci · 2025 Nov · PMID 41212304 · Publisher ↗
BACKGROUND: Negative symptoms are a strong predictor of conversion to a formal psychotic disorder in youth at clinical high-risk for developing psychosis (CHR). Identification of temporally precise mechanisms underlying...
BACKGROUND: Negative symptoms are a strong predictor of conversion to a formal psychotic disorder in youth at clinical high-risk for developing psychosis (CHR). Identification of temporally precise mechanisms underlying increases in negative symptoms could enhance early intervention and specifically support the utility of mobile health treatments. Guided by Cognitive Behavioral models of psychopathology, we examine whether a core type of biased thinking-defeatist performance beliefs (DPB)-is a real-world mechanism of negative symptoms as well as a secondary symptom that is common in CHR youth: depressed mood. METHODS: CHR youth (n = 119) and healthy control (CN; 59) subjects completed ecological momentary assessment surveys assessing DPB, negative symptoms, and depressed mood for six days. RESULTS: CHR youth reported elevated DPB in daily life compared to CN. Greater DPB were associated with greater concurrent negative symptoms and depressed mood in daily life. Time-lagged analyses demonstrated that increased DPB at time t led to elevations in negative symptoms and depressed mood at t + 1 above and beyond the effects of the respective symptom at time t; DPB also varied across time of day, study day, day of the week, activity context, and social partners. CONCLUSIONS: DPB may be a promising shared mechanism contributing to negative symptoms and depressed mood in CHR youth in their daily life. Findings also provide proof-of-concept support for the utility of mobile health treatments targeting DPB by identifying key moments where DPB fluctuate in CHR youths' everyday environments.
The diagnostic validity of central symptoms for major depressive disorder in adults with attention-deficit/hyperactivity disorder: a network analysis.
Gao Y, Pan M, Zhu Z … +8 more , Yue X, Si F, Zhao M, Dong M, Li H, Wang Y, Qian Q, Liu L
Eur Arch Psychiatry Clin Neurosci · 2026 Jun · PMID 41205076 · Publisher ↗
BACKGROUND: An efficient and accurate diagnosis of MDD in adult ADHD is highly significant. Central symptoms identified through network analysis are considered to play a key role in diagnosis, potentially contributing to...
BACKGROUND: An efficient and accurate diagnosis of MDD in adult ADHD is highly significant. Central symptoms identified through network analysis are considered to play a key role in diagnosis, potentially contributing to the achievement of this goal. METHODS: ADHD and MDD symptoms were assessed using the ADHD Rating Scale and Zung Self-Rating Depression Scale (SDS) in a clinical cohort of 418 adults with ADHD, followed by network estimations. Symptoms with high expected influence (EI) in the network were identified as central symptoms and tested for diagnostic validity via ROC curve analysis. Imaging analyses were further adopted to verify the effectiveness of the identified central symptoms from the perspective of construct validity. RESULTS: A five-symptom model was identified, including: "Depressed affect," "Personal devaluation," "Emptiness," "Agitation," and "Interest loss." The model exhibited strong diagnostic validity for MDD in adult ADHD, showing no significant difference compared to using all 20 SDS items. Moreover, significant functional alterations were detected in the left anterior cingulate cortex between groups classified by this model. CONCLUSION: A five-symptom model comprising "Depressed affect," "Personal devaluation," "Emptiness," "Agitation," and "Interest loss" showed strong diagnostic validity for MDD in adult ADHD, and proven effective in exploring its underlying neural mechanisms. These symptoms should be considered a priority in diagnosing MDD in adults with ADHD.
Impairment of the GABAergic system in the prefrontal cortex of male heroin addicts.
von Gilsa A, Steiner J, Gos A … +5 more , Trübner K, Mawrin C, Kaliszan M, Nickl-Jockschat T, Gos T
Eur Arch Psychiatry Clin Neurosci · 2026 Feb · PMID 41205075 · Full text
Opioid addiction is a global concern and the largest health burden among drug use disorders. Prefrontal cortex (PFC) regions play a key multifaceted role in behavioural regulation, and GABAergic interneurons regulate the...
Opioid addiction is a global concern and the largest health burden among drug use disorders. Prefrontal cortex (PFC) regions play a key multifaceted role in behavioural regulation, and GABAergic interneurons regulate the output of the PFC, whose dysfunction has been linked to the behavioural abnormalities observed in opioid-addicted individuals. In these neurons, glutamate decarboxylase (GAD), with its isoforms GAD 65 and 67, is a key enzyme in the synthesis of GABA. Our study, which was performed on paraffin-embedded brains from the Magdeburg Brain Bank, aimed to investigate abnormalities in the GABAergic function of the PFC regions, i.e. the anterior cingulate cortex (ACC), the orbitofrontal cortex (OFC) and the dorsolateral prefrontal cortex (DLPFC), in opioid addiction by densitometric evaluation of GAD 65/67-immunostained neuropil bilaterally. The neuropil was assessed in parallel with the density of immunostained somata. The study showed a significantly decreased neuropil density in layer III of the left ventral part of the ACC (ACCv) in 13 heroin-addicted males, compared to 12 healthy controls (U-test P value 0.04). There were no significant differences in somata density in any of the investigated PFC regions. Analysis of the confounding variables that differed significantly between the compared groups (i.e. age, brain volume, and duration of formalin fixation) showed that these variables did not affect the results. Our findings are the first in human postmortem research to suggest a dysregulation of the GABAergic system in the PFC region in opioid-addicted individuals, which supports human neuroimaging research and contributes to the understanding of opioid addiction.
Identification of genetic associations and key influences contributing to the pathway from social isolation or loneliness to depression.
Sun W, Sun C, Zhang H … +6 more , Sun P, Song H, Wu X, Chen J, Fang Y, Zhang X
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41205074 · Publisher ↗
BACKGROUND: Observational studies have found isolation or loneliness to be associated with depression. However, the causal relationship between isolation or loneliness and depression, as well as the mediating factors inv...
BACKGROUND: Observational studies have found isolation or loneliness to be associated with depression. However, the causal relationship between isolation or loneliness and depression, as well as the mediating factors involved, remains unclear. METHODS: This study aims to establish the causal effects of social isolation and loneliness on depression and to identify key mediators using a two-sample Mendelian randomization (MR) approach. Using genetic variants from the UK Biobank (N = 455,364 for social isolation/loneliness; N = 462,933 for depression), we applied univariate and multivariate MR (UVMR and MVMR) to assess causal relationships and mediation effects. RESULTS: Genetically predicted social isolation and loneliness (β = 0.188, 95% CI 0.109, 0.268, P = 3.594e-06) were significantly associated with increased depression levels. Of the 25 potential risk factors for depression, two were identified as mediators of the relationship between isolation, loneliness, and depression: neuroticism (mediation ratio: 54.3% [95% CI: 43.1%, 65.5%]) and insomnia (15.5% [95% CI: 7.7%, 23.3%]). Multiple sensitivity analyses confirmed the robustness of the findings. CONCLUSION: This study provides genetic evidence that social isolation and loneliness causally contribute to increased depression risk, with neuroticism and insomnia as key mediators, though generalizability to non-European populations requires further investigation.
Causal relationships between four types of sedentary behavior and insomnia: a two-sample Mendelian randomization study.
Qin Z, Niu H, He Y … +2 more , Lan J, Yin J
Eur Arch Psychiatry Clin Neurosci · 2026 Feb · PMID 41205073 · Publisher ↗
OBJECTIVE: This study utilized a two-sample Mendelian randomization (MR) approach to investigate the causal relationships between specific sedentary behaviors-namely, driving, watching television, using a mobile phone, a...
OBJECTIVE: This study utilized a two-sample Mendelian randomization (MR) approach to investigate the causal relationships between specific sedentary behaviors-namely, driving, watching television, using a mobile phone, and using a computer-and insomnia. METHODS: We selected independent genome-wide significant SNPs for each exposure and harmonized them with the insomnia GWAS. GWAS summary statistics were obtained from IEU OpenGWAS (UK Biobank). Instrument selection used P < 5 × 10⁻⁸ and LD clumping at r² < 0.001, 10,000 kb. Primary MR estimates were obtained using inverse variance weighting (IVW), with weighted median and MR-Egger as complementary methods. Sensitivity analyses included Cochran's Q, MR-Egger intercept, MR-PRESSO, and leave-one-out. RESULTS: After harmonization, the numbers of independent SNPs were: driving (n = 6), television (n = 104), mobile phone (n = 31), and computer (n = 80). IVW MR showed a positive association between television watching and insomnia (OR = 1.20, 95% CI: 1.15-1.26, P < 0.001). Driving showed an inverse association with insomnia (OR = 0.821, 95% CI: 0.72-0.94, P = 0.005). Computer and mobile phone use did not show statistically significant IVW associations with insomnia. Sensitivity analyses did not indicate consistent directional pleiotropy; leave-one-out did not identify any influential SNP. CONCLUSION: Our MR results indicated that genetic liability to longer television-watching time is associated with an increased risk of insomnia, whereas genetic liability to longer driving time is associated with a decreased risk of insomnia. It is important to approach these results carefully, as the genetic tools employed in this research mainly reflect a behavior's general duration or tendency, lacking specific contextual information or timing nuances.
Genetic evidence for a causal relationship between 179 lipid species and cognitive function and alzheimer's disease: a bidirectional Mendelian randomization study.
Sun Y, Meng D, Yu H … +6 more , Yin G, Zhang X, Yu W, Liu H, Jiang W, Zhang F
Eur Arch Psychiatry Clin Neurosci · 2025 Nov · PMID 41205072 · Publisher ↗
The public health burden of cognitive decline escalates with population aging. While lipid species alterations are associated with cognitive function and Alzheimer's disease (AD), causal evidence remains limited. We appl...
The public health burden of cognitive decline escalates with population aging. While lipid species alterations are associated with cognitive function and Alzheimer's disease (AD), causal evidence remains limited. We applied two-sample Mendelian randomization (TSMR) and Bayesian-weighted MR (BWMR) to investigate the causal effects of lipid species on cognitive function and to assess the bidirectional causal relationships between lipid species and AD. We analyzed genome-wide association study (GWAS) data from large-scale cohorts: AD (East African Development Bank [EADB], N = 487,511); cognitive function (UK Biobank, N = 20,346); and lipid species (THL Biobank, N = 7,174). Analyses were conducted using multiple MR methods, including inverse variance weighting (IVW), BWMR, MR-Egger regression, and false discovery rate (FDR) correction. Sensitivity analyses-MR-Egger intercept test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), Cochran's Q test, and leave-one-out analysis-were conducted to evaluate horizontal pleiotropy and heterogeneity. TSMR results identified 51 lipid species with causal associations for cognitive function and AD, among which 27 showed protective effects. Conversely, AD was found to influence 17 lipid species, with 14 exhibiting negative effects. These genetically supported findings highlight potential lipid-related targets for preventive and therapeutic interventions aimed at combating cognitive decline.
The role of immune cell phenotypes and metabolites in bipolar disorder risk: a Mendelian randomization-based mediation analysis.
Zhou X, Hu J
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41191089 · Publisher ↗
BACKGROUND: Bipolar disorder (BD) is a multifactorial psychiatric disorder with contributions from genetic susceptibility and environmental exposures. Recent evidence suggests immune dysfunction and metabolic disturbance...
BACKGROUND: Bipolar disorder (BD) is a multifactorial psychiatric disorder with contributions from genetic susceptibility and environmental exposures. Recent evidence suggests immune dysfunction and metabolic disturbances may contribute to BD, but the causal roles and mediation mechanisms remain ambiguous. METHODS: Two-sample MR analyses were conducted leveraging publicly accessible GWAS summary data to investigate causal associations among immune cell phenotypes, circulating metabolites, and BD risk.Immune trait data included 731 phenotypes; metabolite data comprised 486 blood metabolites. BD outcome data (n = 413,466) were sourced from the IEU OpenGWAS database (ID: ieu-b-5110). We applied inverse-variance weighted (IVW), MR-Egger, weighted median, and mode-based methods. Bidirectional MR, two-step MR (TSMR), and multivariable MR (MVMR) were used to assess direct and mediated effects. RESULTS: A significant association was observed between BD and distinct B cell phenotypic profiles. The proportion of naive-mature B cells was inversely associated with risk (β = -0.091, SE = 0.035, P = 0.008), while CD24 + CD27 + B cells showed a positive association (β = 0.093, SE = 0.033, P = 0.005). Carnitine and its derivatives (e.g., acetylcarnitine) were linked to reduced BD risk, whereas maleate, alpha-hydroxyisovalerate, and phospholipid derivatives were positively associated with risk. Naive-mature B cells were positively linked to alpha-hydroxyisovalerate levels. The mediation analysis demonstrated a statistically significant indirect pathway. (β = 0.00269, P = 0.046) with a mediated proportion of -2.95%. CONCLUSION: Our results demonstrate genetic underpinnings of the causal relationships between specific immune cell phenotypes, blood metabolites, and BD pathogenesis. A potential immune-metabolic pathway was identified, where naive-mature B cells affect BD risk via alpha-hydroxyisovalerate. These findings offer mechanistic insight and suggest novel targets for biomarker development and therapeutic intervention.
Baseline cortical thinning in the visual cortex as a predictor of early mild cognitive impairment progression: a population-based follow-up study.
Moon CM, Shin SS, Baek BH … +4 more , Yoon W, Park JS, Heo SH, Lee YY
Eur Arch Psychiatry Clin Neurosci · 2025 Nov · PMID 41186729 · Publisher ↗
Numerous neuroimaging studies have explored brain structural biomarkers to distinguish mild cognitive impairment (MCI) from cognitively normal (CN) individuals using cross-sectional data. We further examined alterations...
Numerous neuroimaging studies have explored brain structural biomarkers to distinguish mild cognitive impairment (MCI) from cognitively normal (CN) individuals using cross-sectional data. We further examined alterations in brain cortical thickness within the visual cortices over time, alongside neuropsychological tests, to predict the progression to MCI in a cohort of older adults. Our dataset included 216 CN controls (non-converters) and 32 CNc subjects (converters) at baseline. After the follow-up period, 216 CN subjects remained stable (CNs), while 32 CNc subjects progressed to MCI. We utilized T1-weighted brain images for neuroimaging analysis, employing a three-dimensional convolutional neural networks-based deep learning algorithm to assess cortical thickness in the visual cortices at baseline and follow-up. Demographic characteristics and cortical thickness were compared using a two-sample t-test, and subsequent classification models were developed. At baseline, no significant differences in neuropsychological scores were observed between the CN and CNc groups. However, during follow-up, a significant difference emerged between the CNs and MCI groups. Notably, the CNc group, compared with the CN group at baseline, and the MCI group, compared with the CNs group at follow-up, exhibited significant cortical thinning in the visual cortices at their respective time points. Additionally, the classification models, incorporating cortical thickness and neuropsychological scores, demonstrated acceptable and robust performance. Specifically, the area under the curve values were 0.62 − 0.67 for CN vs. CNc at baseline and 0.93 for CNs vs. MCI at follow-up. Our findings indicate that cortical thinning in the visual cortices and the performance of classification models hold significant potential for identifying an increased risk of MCI among older adults.
Complete blood count-based inflammation indexes and symptom severity in people with bipolar disorder: an analysis based on structural equation modelling.
Cavaleri D, Crocamo C, Riboldi I … +3 more , Guzzi P, Bartoli F, Carrà G
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41186728 · Full text
AIMS: Bipolar disorder (BD) may be linked to immune-inflammatory dysregulation. Recently, complete blood count (CBC)-based inflammation indexes—neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), an...
AIMS: Bipolar disorder (BD) may be linked to immune-inflammatory dysregulation. Recently, complete blood count (CBC)-based inflammation indexes—neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR)—have emerged as potential, reproducible, and cost-effective markers for mental disorders. This study thus aimed to investigate the relationship of NLR, MLR, and PLR with manic and depressive symptom severity in people with BD, jointly testing the interactions with relevant clinical variables. METHODS: We included inpatients with BD aged ≥ 18 consecutively hospitalized from May 2020 to March 2025. CBC-based ratios were calculated from fasting blood samples. Structural equation modelling (SEM) was performed to test the relationships of CBC-based ratios with manic and depressive symptom severity—assessed by the Young Mania Rating Scale (YMRS) and the Montgomery–Åsberg Depression Rating Scale (MADRS), respectively—accounting for age, sex, body mass index, alcohol/substance use disorders, and psychotropic medication doses. RESULTS: We included 175 participants (mean age 46.8 ± 16.1 years; 48.6% males), 126 with a manic episode and 49 with a depressive episode. The MLR was higher in mania than in depression (p = 0.019), while no significant differences emerged for NLR and PLR. The SEM showed that greater YMRS scores were associated with higher NLR (coeff. = 0.077, p < 0.001) and MLR (coeff. = 0.096, p < 0.001), and lower PLR (coeff. = –0.088, p < 0.001). Moreover, higher MADRS scores were associated with lower MLR (coeff. = –0.189, p < 0.001) and higher PLR (coeff. = 0.123, p < 0.001). CONCLUSION: This study provides novel insights into the differential associations of NLR, MLR, and PLR with symptom severity across manic and depressive episodes, underscoring a complex immune-inflammatory dysregulation in BD. Notwithstanding generally small coefficients, our findings suggest that CBC-based ratios may represent accessible indexes to monitor mood state severity. Further investigation into their clinical utility is needed.
Positive effect of physical activity for depression and major depression: a Mendelian randomization study.
Du Z, Shi L, Zhou Q … +3 more , Lu R, Zhou Z, Zhu H
Eur Arch Psychiatry Clin Neurosci · 2026 Mar · PMID 41165769 · Publisher ↗
OBJECTIVE: To explore the causal relationship between types of physical activity in the last 4 weeks and Depression, Major depression. METHODS: We used summary data from Genome-Wide Association Studies (GWAS) to conduct...
OBJECTIVE: To explore the causal relationship between types of physical activity in the last 4 weeks and Depression, Major depression. METHODS: We used summary data from Genome-Wide Association Studies (GWAS) to conduct a Two-Sample Mendelian Randomization (TSMR) analysis. The main method was the Inverse Variance Weighted (IVW) approach, with weighted median, weighted mode, and MR Egger methods as supplements. The evaluation metrics were P-value, OR value, and 95% Confidence Interval (95% CI). Sensitivity analysis was also performed. RESULTS: Genetically predicted NOPA was significantly associated with an increased risk of Depression. WFP and HDIY were significantly associated with a reduced risk of Depression. LDIY, OE, and SS showed no causal relationship with Depression (P > 0.05). Genetically predicted NOPA was significantly associated with an increased risk of Major depression (NOPA: OR = 15.959, 95% CI: 3.517-72.409, P = 3.98E-03). WFP, HDIY, LDIY, and OE were significantly associated with a reduced risk of Major depression (WFP: OR = 0.235, 95% CI: 0.113-0.487, P = 9.80E-05), (HDIY: OR = 0.419, 95% CI: 0.235-0.748, P = 0.003), (LDIY: OR = 0.467, 95% CI: 0.318-0.685, P = 9.65E-05), (OE: OR = 0.312, 95% CI: 0.145-0.670, P = 0.003). SS showed no causal relationship with Major depression (P > 0.05). CONCLUSION: Our TSMR analysis revealed that types of physical activity in the last 4 weeks, such as WFP and HDIY, may reduce the risk of Depression and Major depression, while NOPA may increase the risk of both. SS had no effect on Depression and Major depression.
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