Eur Arch Psychiatry Clin Neurosci
· 2026 Mar · PMID 41165767
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BACKGROUND: Appetite hormones and proinflammatory cytokines play a role in differentiating between bipolar I disorder (BD1) and bipolar II disorder (BD2). In this study, we developed a composite predictor of appetite hor...BACKGROUND: Appetite hormones and proinflammatory cytokines play a role in differentiating between bipolar I disorder (BD1) and bipolar II disorder (BD2). In this study, we developed a composite predictor of appetite hormones and proinflammatory cytokines to differentiate between BD1 and BD2. METHODS: Adult patients aged 20–59 with either BD1 or BD2 and experiencing a major depressive episode were included in the study. Cytokines such as C-reactive protein, interleukin-2, interleukin-6, and tumor necrosis factor-α and appetite hormones such as leptin, adiponectin, ghrelin, and insulin were evaluated as potential predictors through a classification and regression tree (CRT) to differentiate between BD1 and BD2. RESULTS: A composite predictor of adiponectin, leptin, and ghrelin was significantly more accurate (for BD1: area under the curve = 0.897; for BD2: area under the curve = 0.905, P > 0.05) in differentiating between BD2 and BD1 than any single predictor (four appetite hormones and six cytokines). High levels of adiponectin and ghrelin and high and low levels of leptin (≤ 4430.8 and > 10,957.2 ng/L) were associated with BD2, whereas low levels of adiponectin and ghrelin and intermediate levels of leptin were associated with BD1. CONCLUSIONS: The composite predictor of appetite hormones showed potential for distinguishing between BD1 and BD2 during depressive episodes. However, given the exploratory nature of the analysis and the limited sample size, further studies are needed to validate the model’s utility in clinical settings and to better understand the pathomechanisms underlying BD subtypes
OBJECTIVE: Existing evidence suggests a close association between antidepressants (ATDs) and the increased incidence of psychiatric disorders. However, causality has yet to be confirmed. We aim to evaluate the causal rel...OBJECTIVE: Existing evidence suggests a close association between antidepressants (ATDs) and the increased incidence of psychiatric disorders. However, causality has yet to be confirmed. We aim to evaluate the causal relationship between ATDs and five psychiatric disorders using the Two-sample Mendelian Randomization (TSMR) method. METHODS: This study utilized TSMR analysis to explore the causal impact of ATDs on convulsion (CONV), schizophrenia (SCZ), obsessive-compulsive disorder (OCD), substance abuse (SA), and suicide or self-harm (SOSH). The primary evaluation of causality was conducted using the Inverse Variance Weighted (IVW) method; supplementary validations were performed using the Weighted median, Weighted mode, and MR Egger methods. Sensitivity analyses, including MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis, were conducted to assess potential heterogeneity and pleiotropy. RESULTS: The IVW method results revealed a significant positive causal relationship between genetically predicted ATDs and CONV (OR = 1.174; 95% CI 1.038, 1.328; P = 0.011), SCZ (OR = 1.177; 95% CI 1.038, 1.335; P = 0.011), OCD (OR = 1.755; 95% CI 1.355, 2.273; P = 2.06E-05), SA (OR = 1.326; 95% CI 1.222, 1.440; P = 1.61E-11), and SOSH (OR = 1.461; 95% CI 1.394, 1.532; P = 1.71E-50). The supplementary and sensitivity analyses indicated robust and reliable findings. CONCLUSION: Our study suggests that ATDs are potential risk factors for CONV, SCZ, OCD, SA, and SOSH. It is necessary to comprehensively evaluate both the therapeutic effects and potential risks of ATDs in clinical practice. Individualized treatment plans should be formulated for patients with CONV, SCZ, OCD, SA, and SOSH, with increased attention during the clinical use of ATDs.
Eur Arch Psychiatry Clin Neurosci
· 2026 Apr · PMID 41143990
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BACKGROUND: Differences in symptom presentation of schizophrenia in male and female patients may be related to differences in physiological and hormonal levels between genders. The aim of this study was to investigate th...BACKGROUND: Differences in symptom presentation of schizophrenia in male and female patients may be related to differences in physiological and hormonal levels between genders. The aim of this study was to investigate the potential association of thyroid hormones with positive and negative symptoms in schizophrenic patients of different sex. METHODS: In this study, a total of 158 male and 160 female schizophrenia patients were retrospectively selected from our hospital between January 2023 and July 2025. Their clinical data were analyzed retrospectively. Venous blood samples were collected to measure levels of T3, T4, FT3, FT4, and TSH. The relationship between thyroid hormone levels and the positive symptom scores (SAPS), including its subscales (delusional ideas, hallucinations, bizarre behavior, and formal thought disorders), as well as the negative symptom scores (SANS), encompassing its subscales (expression and motivation and pleasure ), was subsequently analyzed. RESULTS: Male and female patients with schizophrenia showed significant differences in the severity of both positive and negative symptoms. There was a significant interaction between sex and TSH with negative symptoms (p < 0.001). In sex-stratified regression analyses, TSH was positively associated with negative symptoms in male patients (p < 0.001), while both T3 and T4 exhibited negative associations with negative symptoms in both male and female patients (all p < 0.05). CONCLUSIONS: Our research indicates that thyroid hormone levels are associated with the severity of schizophrenia symptoms and vary by sex, highlighting the importance of considering sex differences in clinical practice.
Halil MG, Abi-Dargham A, Krystal JH
… +8 more, Clark DM, Mundt AP, Herrman H, Rataemane S, Weitzenegger F, Dziobek I, Heinz A, Baskow I
Eur Arch Psychiatry Clin Neurosci
· 2026 Feb · PMID 41128856
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INTRODUCTION: Mental illnesses are not only associated with the highest level of subjective suffering compared to other chronic diseases but at the same time with a significantly increased morbidity. Especially in indust...INTRODUCTION: Mental illnesses are not only associated with the highest level of subjective suffering compared to other chronic diseases but at the same time with a significantly increased morbidity. Especially in industrialized countries, a dramatically increasing proportion of sick leave and early retirement due to mental illness diagnoses is observed, pointing to increased social stress factors and a close association with societal changes and emphasizing challenges to the health care system. The following qualitative study was conducted as part of the establishment of the German Center for Mental Health, which unites excellence in psychiatric, psychological and neuroscientific research in Germany to facilitate translation of basic into clinical research and general health care. METHODS: A 120-minute, guided, virtual focus group discussion was conducted with international experts in the field of mental health research from Chile, the USA, the UK, South Africa, and Australia to represent views from different continents. The participants discussed international trends, unrecognized needs and gaps in clinical practice and recognized many opportunities and challenges in the research of the different topics of the German Center for Mental Health. Furthermore, the focus areas of the German Center were presented, and participants were asked about the opportunities and challenges in researching these topics. The evaluation method was based on qualitative content analysis according to Mayring. The focus group discussion was transcribed and coded with MAXQDA 2022 software. The reliability of the coding was checked by using the intercoder reliability and Cohens Kappa. RESULTS: The experts emphasized the high mortality due to comorbidity of somatic and mental disorders including addiction and called for a mechanism-based approach to promote individualized treatment. Furthermore, the impact of poverty, social exclusion, stigma and discrimination was addressed as a key modifiable environmental risk factor. The experts highlighted digital tools, computational models and AI based approaches for precision psychiatry. To systematically evaluate real-world outcomes, the experts emphasized the need for interdisciplinary research including behavioral, computational, social, and neurobiological scientists and experts by experience. DISCUSSION: This study highlights the need for interdisciplinary and participatory approaches in mental health research. Key challenges include the high comorbidity of mental and physical disorders, the impact of social determinants, and gaps in translating research into practice. Experts emphasized the importance of digital tools, computational psychiatry, and community-based interventions to enhance prevention and treatment. The German Center for Mental Health (DZPG) is well-positioned to address these challenges by integrating diverse expertise and fostering innovation in mental health care.
Dysfunction of the dopaminergic reward system has been implicated in the pathophysiology of several neuropsychiatric disorders. The endosomal network encompasses important processes related to neurotransmission in dopami...Dysfunction of the dopaminergic reward system has been implicated in the pathophysiology of several neuropsychiatric disorders. The endosomal network encompasses important processes related to neurotransmission in dopamine neurons, e.g., endocytosis, sorting, recycling and degradation of receptors. We investigated whether genetic variation influencing the endosomal sorting machinery, in particular cargo selection and membrane tubulation, may impact on the activation strength in key regions of the mesolimbic reward system, i.e. the ventral tegmental area (VTA) and the nucleus accumbens (NAcc). To test our hypothesis, VTA and NAcc responses to conditioned reward stimuli were investigated using the 'desire-reason-dilemma' paradigm during functional magnetic resonance imaging in humans. Association of these neural responses with a set of genetic variants related to endosomal sorting processes (SNX1, SNX6, WASHC2C, WASHC3, WASHC4, DNAJC13) were tested in two independent cohorts (N = 182; N = 214). In the first cohort, the gene set was associated with both VTA and NAcc responses to conditioned reward stimuli [empirical P-values: R-VTA: 0.0036; R-NAcc: 0.0016; L-NAcc: 0.0094]. At the level of the gene set, the effect in the R-VTA could be replicated in the second cohort [empirical P-value: R-VTA: 0.0443]. For the NAcc, an additional exploratory analysis of a patient-only subcohort of the first cohort (N = 64) suggested that the gene set may express its effect in this brain region predominantly in patients. These findings provide first evidence that the endosomal sorting processes cargo selection and membrane tubulation may influence neural responses of the reward system to conditioned stimuli.
Kuchler T, Hausinger R, Braunisch MC
… +12 more, Günthner R, Wicklein R, Knier B, Bleidißel N, Maier M, Ribero A, Lech M, Adorjan K, Stubbe H, Kotliar K, Heemann U, Schmaderer C
Eur Arch Psychiatry Clin Neurosci
· 2026 Feb · PMID 41060459
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Monteith S, Glenn T, Geddes JR
… +3 more, Whybrow PC, Achtyes E, Bauer M
Eur Arch Psychiatry Clin Neurosci
· 2026 Feb · PMID 41060458
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Chatbots are widely used by business in everyday life to interact with consumers in e-commerce, social networking, education, and government settings. Anthropomorphism is a fundamental aspect of chatbot design and implem...Chatbots are widely used by business in everyday life to interact with consumers in e-commerce, social networking, education, and government settings. Anthropomorphism is a fundamental aspect of chatbot design and implementation, and increases the interaction of chatbots with humans. As part of the recent expansion of artificial intelligence (AI) technologies, chatbots incorporated AI to engage more personally with consumers. The anthropomorphic characteristics of chatbots, including both visual appearance and language, influence the interaction of chatbots with humans in diverse ways that may have both positive and negative consequences. The purpose of this review is to increase physician awareness of the use of chatbots which use AI to enhance anthropomorphism. Consumers routinely anthropomorphize products including chatbots. Physicians need to be aware of the wide-ranging and routine use of chatbots, and the importance of anthropomorphism in chatbot design and implementation. Physicians also need to recognize potential negative consequences of anthropomorphism of chatbots on mental health.
Sanchez-Alonso S, Canal-Rivero M, Garrido-Torres N
… +4 more, Baca-Garcia E, Crespo-Facorro B, Barrigon ML, Ruiz-Veguilla M
Eur Arch Psychiatry Clin Neurosci
· 2025 Dec · PMID 41051428
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OBJECTIVE: Catatonia and obsessive–compulsive symptoms (OCS) are frequently observed in patients with psychosis, even at early stages, yet their relationship remains unclear. This study aimed to examine the prevalence an...OBJECTIVE: Catatonia and obsessive–compulsive symptoms (OCS) are frequently observed in patients with psychosis, even at early stages, yet their relationship remains unclear. This study aimed to examine the prevalence and association of catatonic symptoms and OCS in early-stage psychosis. METHODS: Seventy patients aged 18–55 years with early-stage psychosis (illness duration < 5 years) were assessed within 72 h of admission. Catatonic symptoms were evaluated using the Bush Francis Catatonia Rating Scale (BFCRS), OCS with the Obsessive–Compulsive Inventory-Revised (OCI-R), and psychotic symptoms with the Positive and Negative Syndrome Scale (PANSS). Correlations between catatonic, obsessive–compulsive, and psychotic symptom dimensions were analyzed. Logistic regression assessed associations between symptom dimensions and catatonia. RESULTS: Catatonic symptoms (BFCRS ≥ 3) were present in 64.3% of patients, and 40% scored above the OCI-R cut-off for clinically significant OCS. Patients with catatonia had significantly higher total OCI-R scores and higher scores across all OCI-R subscales. Strong correlations were observed between mental neutralization and washing OCI-R subscales and BFCRS scores. Logistic regression showed that higher disorganized (OR = 1.699, 95% CI: 1.141–2.529, p = 0.009) and obsessive–compulsive symptoms (OR = 1.253, 95% CI: 1.058–1.483, p = 0.009) were independently associated with increased odds of catatonia, while positive symptoms showed a significant negative association (OR = 0.796, 95% CI: 0.644–0.983, p = 0.034). CONCLUSIONS: There is a high prevalence of both catatonic and obsessive–compulsive symptoms in early-stage psychosis. Disorganized and obsessive–compulsive symptoms are independent risk factors for catatonia, while positive symptoms may be protective. These findings highlight the importance of comprehensive symptom assessment in this population.
The blood-brain barrier (BBB) integrity is important for central nervous system homeostasis, and dysfunction of its components may contribute to the pathogenesis of various neuropsychiatric disorders, including schizophr...The blood-brain barrier (BBB) integrity is important for central nervous system homeostasis, and dysfunction of its components may contribute to the pathogenesis of various neuropsychiatric disorders, including schizophrenia. An additional factor supporting this hypothesis is the association of schizophrenia with DiGeorge syndrome, in which a deletion of a part of one copy of chromosome 22 (22q11DS) leads to haplonephrenia in the Claudin-5 gene (a tight junction protein that forms the BBB). Individuals with 22q11DS have a 25-fold greater risk of schizophrenia than the population average. The aim of our review was to establish the role of tight junction proteins in the pathogenesis of schizophrenia. For this purpose, a systematic literature search was performed. The first part describes genetic polymorphisms of tight junction proteins and studies of patients with DiGeorge syndrome. The second and third parts of the review focus on the expression of tight junction proteins in postmortem samples and serum. The fourth part of the review describes in vitro studies. The fifth part includes animal studies. Mice models with incomplete absence of the Claudin-5 gene have shown specific behavioral and memory impairments. The final part describes the effects of antipsychotics on tight junction proteins and BBB function. The discussed studies support the role of tight junction proteins in the pathogenesis of schizophrenia and the increased permeability of the BBB. However, the number of studies on this topic is extremely small. This review shows the prospects of studying tight junction proteins in psychiatric diseases.
BACKGROUND: Plasma phosphorylated Tau217 (pTau217) represents a sensitive blood-based biomarker for Alzheimer’s disease (AD). This study investigated the performance of plasma pTau217 alone and as a composite score (Aβ1-...BACKGROUND: Plasma phosphorylated Tau217 (pTau217) represents a sensitive blood-based biomarker for Alzheimer’s disease (AD). This study investigated the performance of plasma pTau217 alone and as a composite score (Aβ1-40/Aβ1-42*pTau217) for detecting low Aβ1-42/1-40 in cerebrospinal fluid (CSF) as a surrogate marker of brain β-amyloid pathological changes. METHODS: We analysed plasma samples from 82 pre-selected participants who were dichotomized according to their CSF Aβ42/40 ratio after data-driven cutoff determination by Gaussian mixture modelling. The study cohort included patients in very early disease stages with mild cognitive impairment (MCI) due to AD and mild dementia due to AD in the Aβ-positive group and MCI due to other causes and mild dementia due to other causes in the Aβ-negative group. Concentrations of plasma pTau181 and pTau217 were determined on the fully automated LUMIPULSE platform. Additionally, plasma Aβ1-42/1-40 and pTau217 were assessed after consecutive Aβ- and Tau-immunoprecipitations (IPs). Corrections for age and sex effects in primary variables were done using a multivariate linear model on a logarithmic scale. Results are reported using both adjusted and unadjusted values. RESULTS: After adjustment for age and sex, median plasma pTau217 was increased by 203% in participants with low CSF Aβ1-42/1-40 (i.e. Aβ-positive), while pTau181 was increased by only 61%. PTau217 showed a larger area under the receiver operating characteristics curve (AUC) of 0.88 in identifying Aβ-positive individuals compared to plasma pTau181 (AUC: 0.78). Plasma Aβ1-42/1-40 ratio in Aβ-IP eluates (adjusted for age and sex) was decreased by only 10%, and the standardized effect size (Cohen´s d) was smaller than that of pTau217. Tau-IP did not improve the performance of the pTau217 assay (p = 0.568, DeLong test). However, the Aβ1-40/Aβ1-42*pTau217 ratio following immunoprecipitations appeared to outperform the single blood biomarkers. CONCLUSION: PTau217 as measured with the fully automated Lumipulse G pTau217 Plasma < RUO > assay demonstrated high accuracy for detecting low CSF Aβ1-42/1-40 and appears to represent a particularly attractive biomarker for future implementation in clinical practice. Furthermore, the composite score Aβ1-40/Aβ1-42*pTau217 showed promise for enhancing the blood-based early and differential diagnosis of AD.
BACKGROUND: Childhood trauma exhibits complex associations with adolescent mental health, however the interplay between specific trauma subtypes and psychological symptoms remains underexplored. This study employs networ...BACKGROUND: Childhood trauma exhibits complex associations with adolescent mental health, however the interplay between specific trauma subtypes and psychological symptoms remains underexplored. This study employs network analysis to map symptom-trauma interactions, identify potential intervention targets, and explore gender differences in these interactions among adolescents with major depressive disorder (MDD). METHODS: A total of 723 adolescents diagnosed with MDD were recruited from a psychiatric clinic in China. Psychological symptoms (SCL-90) and childhood trauma exposure (CTQ) were assessed. Regularized partial correlation networks (EBICglasso) were utilized to model interactions among 15 nodes (10 symptoms and 5 trauma types), compute centrality metrics, and test gender differences. RESULTS: The results revealed that Interpersonal sensitivity (IPS) emerged as the most central node, demonstrating the highest expected influence (EI) (1.67), and formed the strongest edge with emotional abuse (weight = 0.41). A tightly coupled community linked emotional abuse/neglect, IPS, and depression. Moreover, IPS functioned as a bridge symptom, connecting trauma clusters to psychological symptoms (bridge strength = 0.98). Node invariance testing revealed significant gender differences in IPS, however, within their respective gender-specific networks, IPS demonstrated the highest strength and EI values in both males and females. Essentially, no obvious significant gender differences were observed in the network. CONCLUSIONS: This pioneering network study of trauma-symptom associations in Chinese adolescents with MDD identifies IPS as a transdiagnostic factor through which childhood trauma is associated with mental health risks. The structural equivalence across genders suggests universal intervention targets during adolescence. Clinically, enhancing interpersonal skills in emotionally traumatized youth may disrupt pathogenic pathways to depression and other psychology symptoms.
Fischer-Vieler T, Rokicki J, Kim M
… +11 more, Leonardsen E, Wolfers T, Bell C, Hjell G, Tesli N, Bang N, Melle I, Andreassen OA, Friestad C, Ringen PA, Haukvik UK
Eur Arch Psychiatry Clin Neurosci
· 2026 Apr · PMID 40991031
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Cerebellar abnormalities have been linked to schizophrenia and aggressive behaviour. Subregional cerebellar morphology reflects structural organization and function and show great heterogeneity, which may be linked to sh...Cerebellar abnormalities have been linked to schizophrenia and aggressive behaviour. Subregional cerebellar morphology reflects structural organization and function and show great heterogeneity, which may be linked to shared or distinct underlying mechanisms of violence and psychosis but remain unexplored in these marginalized groups. Total and subregional cerebellar volumes were estimated from 3 T MRI scans from persons with schizophrenia spectrum disorders without (SSD-NV; n = 107) or with (SSD-V; n = 36) a history of severe violence, violent offenders without schizophrenia (NPV; n = 20), and 411 healthy controls. Group difference analyses by GLMs were complemented by novel heterogeneity analyses using pre-trained models and norm-charts of lifespan cerebellar volumes to assess individual deviation patterns. We found decreased grey matter volumes in the posterior cerebellar hemispheres and the vermal regions in both SSD-V and SSD-NV, but with a different subregional distribution. Specifically, SSD-V showed differences in the right Crus I (p = .045, Cohen’s d = .62) and Vermis IX (p < .001, Cohen’s d = .81) in the groupwise comparisons. In addition, individual-level extreme negative deviations were detected in the Vermis IX region in 11% of SSD-V and in some subregions of the posterior cerebellum and the vermis in > 10% of NPV. By applying novel analytical tools, we report different patterns of cerebellar subregion volume reductions associated with violence in individuals with or without schizophrenia spectrum disorders. The partly converging results from the group comparisons and the normative modelling analyses demonstrate the usefulness of complemental methodological approaches to disentangle the complex biological associations between violence and psychosis.
OBJECTIVE: Increasing evidence suggests an association between Helicobacter pylori(HP) infection and brain health and its clinical manifestations. A growing body of evidence underscored the profound influence of immune c...OBJECTIVE: Increasing evidence suggests an association between Helicobacter pylori(HP) infection and brain health and its clinical manifestations. A growing body of evidence underscored the profound influence of immune cells on brain health. However, the existing evidence is equivocal, and the causal link remains uncertain. This study aims to determine if there is a causal connection between Hp infections and 42 brain-related diseases, as well as 1,325 distinct brain structures, and to explore the potential role of immune cells in mediating these associations. METHODS: Both univariable and multivariable mendelian randomization (UVMR and MVMR) was applied to evaluate the causal relationships between Hp protein antibodies and 1325 brain structure, as well as various brain-related diseases. Finally, we assessed the relationship between immune cells and HP protein antibodies and brain health, and then calculated the mediating effect of immune cells on the significant causal associations. RESULTS: Hp antibodies exhibited disease-specific effects: CagA conferred protection against anorexia nervosa(OR = 0.94, p = 0.015) and schizophrenia(OR = 0.91, p = 0.038).Conversely, catalase antibodies increased risks for frontotemporal dementia(OR = 1.47, p = 0.002) and juvenile absence epilepsy(OR = 1.01, p = 0.007). MVMR confirmed persistent associations with 61 brain structural alterations, such as IgG's impact on anterior cingulate morphology(OR = 1.06, p = 6.09E-05).Immune cells mediated 8.6-47.4% of Hp-brain effects: CD27⁺IgD⁺CD24⁺ B cells linked IgG to depression(18.2% mediation), while HLA-DR⁺ dendritic cells mediated UreA-associated white matter changes (10.9%). CONCLUSION: Hp infection may exert dual neuroprotective and pathogenic effects via antibody-specific mechanisms, modulated by immune cell phenotypes.This study underscores the gut-brain-immune axis as a pivotal frontier in neuropsychiatric research, with implications for precision interventions targeting Hp-related immune dysregulation.
Social behaviors are essential for both reproduction and survival. Human and animals exhibit distinct patterns of social interaction following trauma experienced during puberty, which are shaped by the complex interplay...Social behaviors are essential for both reproduction and survival. Human and animals exhibit distinct patterns of social interaction following trauma experienced during puberty, which are shaped by the complex interplay between environmental and biological factors. Although neuropeptides and early life stress (ELS) influence social behavior, it remains unclear whether the regulation of neuropeptides in response to ELS further modulates social behavior. Two sex neuropeptides, oxytocin (OT) and arginine vasopressin (AVP), exert profound effects on social behaviors. Therefore, we investigate the involvement of OT and AVP in modulating the alterations in social behavior resulting from ELS. The 89 adult men participants were divided into heterosexual (n=32) and gay/bisexual (n=57) groups. Mental health and the serum levels of OT and AVP were evaluated. Our clinical samples reveal significant variations in ELS exposure across sexual orientation groups, which correlate with neuroendocrine alterations, including altered OT and AVP levels. Animal study further substantiates the critical role of OT and AVP in mediating these changes, highlighting their involvement in shaping social behavior. These findings uncover potential underlying mechanisms through which the OT and AVP systems contribute to stress-induced alterations in social behavior.
BACKGROUND: This study employs bidirectional Mendelian randomization (MR) analysis to explore the causal relationship between frailty and common psychiatric disorders. METHODS: Depression, anxiety disorder, bipolar disor...BACKGROUND: This study employs bidirectional Mendelian randomization (MR) analysis to explore the causal relationship between frailty and common psychiatric disorders. METHODS: Depression, anxiety disorder, bipolar disorder, schizophrenia, sleep disorders, and eating disorders were considered as outcomes, with frailty index as the exposure variable. The main method employed was inverse variance weighting. Two-step MR was used to evaluate the mediation proportions of body mass index (BMI) between frailty and psychiatric disorders. Additionally, reverse MR analysis was conducted using the same testing methods. RESULTS: Frailty index was positively associated with depression, anxiety disorder, bipolar disorder, sleep disorders, and eating disorders. Schizophrenia indicated no significant causal association. The effect of frailty index on the risk of sleep disorders, eating disorders, depression were all partially mediated by BMI, with mediation proportion of 24.40%, 14.23% and 5.22%. Reverse MR analysis revealed that depression increased the risk of frailty. CONCLUSION: This study has supported the causal association of frailty with depression, anxiety disorder, bipolar disorder, sleep disorders, and eating disorders. Additionally, individuals diagnosed with depression exhibit a heightened susceptibility to frailty. This sheds new light on the causal relationship between frailty and psychiatric disorders.