Translational Psychiatry最新文献

{"title":"Association of choroid plexus volume with white matter microstructure, glymphatic function, and peripheral systemic inflammation in Alzheimer's disease.","authors":"Huwei Xia, Yijia Feng, Han Zhu, Danlu Yang, Chaoqun Wang, Zhipeng Wang, Hanyuan Zhang, Wenhao Pan, Yifan Zhao, Weihong Song, Yili Wu","doi":"10.1038/s41398-025-03432-1","DOIUrl":"10.1038/s41398-025-03432-1","url":null,"abstract":"<p><p>There has been growing attention to the role of choroid plexus (CP) in neurodegenerative diseases. However, its relationship with various pathophysiological changes in Alzheimer's Disease (AD) remains unclear. The purpose of this study is to investigate the relationship between CP volume (CPV) and white matter microstructure, cognitive function, glymphatic function, and peripheral systemic inflammation in AD. A total of 1351 participants with cognitive impairment who had available 3 T MRI scans were included from ADNI. CPV was automatically segmented using Gaussian Mixture Model (GMM). The Mini-Mental State Examination (MMSE) was employed to assess cognitive function. PSMD and DTI-ALPS based on DTI sequence were used to reflect white matter microstructure and glymphatic system. Peripheral systemic inflammation was represented by the neutrophil-lymphocyte ratio (NLR). Group comparisons and correlations were adjusted for age, sex, education and APOE4 carrier status. Participants with AD exhibited larger CPV (p < 0.001), higher PSMD (p < 0.001) and NLR (p = 0.035), and lower DTI-ALPS (p < 0.001) compared to those with subjective cognitive decline (SCD). CP enlargement was independently associated with higher PSMD (β = 0.223, p < 0.001) and worse cognitive function both cross-sectionally (β = -0.212, p < 0.001) and longitudinally (β = -0.214, p < 0.001). Furthermore, PSMD partially mediates the impact of CP enlargement on the severity and progression of cognitive function. Partial correlation analysis revealed that CP enlargement was associated with higher NLR (r = 0.101, p = 0.001) and lower DTI-ALPS (r = -0.241, p < 0.001). These findings suggest that CPV may reflect underlying pathophysiological processes in AD and serve as a biomarker for white matter damage and cognitive impairment progression.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"238"},"PeriodicalIF":5.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimaging insights into the psychosocial impact of the COVID-19 pandemic: a systematic review.","authors":"Yiling Guo, Nanfang Pan, Yuhan Zou, Yajing Long, Xun Zhang, Qingyuan Li, Xueling Suo, Manpreet K Singh, Song Wang, Qiyong Gong","doi":"10.1038/s41398-025-03423-2","DOIUrl":"10.1038/s41398-025-03423-2","url":null,"abstract":"<p><p>The COVID-19 pandemic has posed an unprecedented threat to global health. However, neural substrates underlying mental health vulnerabilities brought by the pandemic remain elusive. We conducted a systematic review relating structural and functional brain abnormalities to mental health issues associated with COVID-19 at brain regional and network levels. A literature search on neuroimaging studies of mental health problems derived by COVID-19 was conducted in the PubMed, Web of Science and MEDLINE databases. We identified 46 studies across various imaging techniques and found that COVID-19-related mental health problems were principally associated with brain structural and functional alterations in the prefrontal cortex, insula, cingulate, hippocampus, and amygdala, as well as the affective cortical network. This review may facilitate the targeted development of therapies tailored to the pandemic context and provide insights for proactive prevention against future collective stressors and traumas.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"236"},"PeriodicalIF":5.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the genetic and molecular basis of low-frequency rTMS induced changes in functional connectivity density in schizophrenia patients with auditory verbal hallucinations.","authors":"Yuanjun Xie, Muzhen Guan, Tian Zhang, Chaozong Ma, Chenxi Li, Lingling Wang, Xinxin Lin, Yijun Li, Zhongheng Wang, Ma Zhujing, Huaning Wang, Peng Fang","doi":"10.1038/s41398-025-03459-4","DOIUrl":"10.1038/s41398-025-03459-4","url":null,"abstract":"<p><p>Auditory verbal hallucinations (AVH) represent a substantial therapeutic challenge in schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in reducing AVH, yet the underlying neurobiological mechanisms remain incompletely understood. This study investigated the genetic and molecular processes associated with functional connectivity density (FCD) changes induced by 1 Hz rTMS in schizophrenia patients with AVH. The results revealed that the active stimulation group exhibited significant improvement in positive symptoms and AVH severity compared to the sham control group. Specifically, rTMS increased FCD within the frontoparietal network while decreasing FCD in the language network. Notably, baseline FCD values in these networks were predictive of the extent of symptom amelioration. Gene enrichment analysis indicated that rTMS-induced FCD changes were linked to molecular pathways critical for cellular homeostasis and neuronal function. Among the identified hub genes, GAL emerged as a key regulator of these alternations. Furthermore, neurotransmitter systems were implicated, with alterations in mu-opioid (MU) receptor density mediating the effects of GAL on FCD modifications. These findings highlight a multifaceted interplay among genetic, molecular, and connectivity-based mechanisms underlying the therapeutic efficacy of rTMS in treating AVH.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"237"},"PeriodicalIF":5.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using the excitation/inhibition ratio to optimize the classification of autism and schizophrenia.","authors":"Lavinia Carmen Uscătescu, Christopher J Hyatt, Jack Dunn, Martin Kronbichler, Vince Calhoun, Silvia Corbera, Kevin Pelphrey, Brian Pittman, Godfrey Pearlson, Michal Assaf","doi":"10.1038/s41398-025-03455-8","DOIUrl":"10.1038/s41398-025-03455-8","url":null,"abstract":"<p><p>The excitation/inhibition (E/I) ratio has been shown to be imbalanced in individuals diagnosed with autism (AT) or schizophrenia (SZ), relative to neurotypically developed controls (TD). However, the degree of E/I imbalance overlap between SZ and AT has not been extensively compared. In this project, we used resting state fMRI data to estimate the E/I ratio via the Hurst (H) exponent. Our main objectives were (1) to quantify group differences in the E/I ratio between TD, AT, and SZ, (2) to assess the potential of the E/I ratio for differential diagnosis, and (3) to verify the replicability of our findings in an independently acquired dataset. For each participant, we computed the Hurst exponent (H), an indicator of the E/I ratio, from the time courses of 53 independent components. Using a random forest classifier (RF), we ran a classification analysis using the larger of the two datasets (exploratory dataset; 519 TD, 200 AT, 355 SZ) to determine which of the 53 H would yield the highest performance in classifying SZ and AT. Next, taking the ten most important H based on the exploratory dataset, in combination with phenotypic information collected in the replication dataset (55 TD, 30 AT, 39 SZ), we used RF to compare the classification performance using five feature sets: (a) H only; (b) Positive and Negative Syndrome Scale (PANSS) and the Autism Diagnostic Observation Schedule (ADOS) only; (c) PANSS, ADOS, Bermond-Vorst Alexithymia Questionnaire (BVAQ), Empathy Quotient (EQ), and IQ; (d) H, PANSS and ADOS; (e) H, PANSS, ADOS, BVAQ, EQ and IQ. Classification performance using H only was higher in the exploratory dataset (AUC = 84%) compared to the replication dataset (AUC = 72%). In the replication dataset, the highest classification performance was obtained when combining H with PANSS, ADOS, BVAQ, EQ and IQ (i.e., model e; AUC = 83%). These results illustrate the added value of E/I to typical phenotypic data in differentiating AT and SZ.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"234"},"PeriodicalIF":5.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal oral sodium propionate supplementation restores gut integrity and mitigates stress-induced metabolic and behavioral outcomes in offspring.","authors":"Anastasia Bagaev, Debpali Sur, Oryan Agranyoni, Naamah Pe'er, Brajesh Kumar Savita, Beatriz Gonçalves Silva Rocha, Panayotis K Thanos, Shiri Navon-Venezia, Albert Pinhasov","doi":"10.1038/s41398-025-03436-x","DOIUrl":"10.1038/s41398-025-03436-x","url":null,"abstract":"<p><p>Maternal attachment is a critical determinant of offspring's postnatal development, significantly influencing their later-life metabolic and behavioral patterns. We previously showed that stress-vulnerable, socially submissive (Sub) mice exhibit significant disruptions in gut physiology including distorted microbiome composition, lower colonic propionate levels, and increased gut permeability. These alterations exacerbated chronic inflammation, caused metabolic imbalances and reduced maternal care. In this study, we revealed a significant reduction in bacterial diversity and fecal propionate levels in Sub dams. To investigate whether maternal gut integrity could mitigate adverse offspring outcomes, we provided oral sodium propionate (SP) supplementation to Sub dams via drinking water from postpartum day (PD) 0, until weaning (PD21). SP supplementation notably improved maternal care, reflected by faster pup retrieval times and better nesting. Beneficial effects were particularly pronounced in two-month-old male offspring, demonstrating decreased anxiety-like behavior, improved sociability and enhanced short-term memory accompanied by increased abundance of specific gut bacteria (Roseburia, and Shuttleworthia genus). Additionally, male offspring exhibited significant metabolic improvements, including reduced epididymal white adipose tissue (eWAT) mass, decreased adipocyte diameter accompanied by increased eWAT mRNA expression of GPR43 and PPAR-γ. Moreover, SP supplementation increased colon length linked with increased colonic mRNA expression of GPR43, PPAR-γ and Claudin-7, highlighting the importance of propionate in tight junction regulation and inflammation. Importantly, these positive outcomes exhibited notable sex-dependent differences, with male offspring responding robustly, whereas females showed minimal behavioral or metabolic improvements following maternal SP supplementation. Overall, our findings emphasize that innate stress vulnerability-related metabolic and behavioral alterations in offspring can be mitigated by restoring the dams' gut epithelial barrier integrity, highlighting the critical role of the maternal gut environment and demonstrating clear sex-specific responses to gut microbiota-targeted interventions.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"235"},"PeriodicalIF":5.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationships of PGRN with sTREM2 in AD continuum and non-AD pathophysiology and their reciprocal roles in modulating amyloid pathology: two population-based study.","authors":"Liang-Yu Huang, Chen-Chen Tan, Wei Xu, Lan Tan","doi":"10.1038/s41398-025-03457-6","DOIUrl":"10.1038/s41398-025-03457-6","url":null,"abstract":"<p><p>Progranulin (PGRN) and soluble triggering receptor expressed on myeloid cells-2 (sTREM2) are emerging biomarkers of Alzheimer's disease (AD). This study explores the roles of their interplay in modulating amyloid pathology. We analyzed data from 905 participants (mean age = 62.0) in the CABLE cohort and 973 participants (mean age = 73.1) in the ADNI, classified using the A/T/N biomarker framework. One-way ANOVA was used to assess whether cerebrospinal fluid (CSF) PGRN and sTREM2 differed across biomarker profiles and clinical stages. Multiple linear regression models and linear mixed-effects models were used to test the relationships among PGRN, sTREM2, and CSF Aβ_1-42 levels. Mediation analysis was used to explore the reciprocal relationships between sTREM2 and PGRN in influencing amyloid pathology. CSF proteomic and bioinformatic analyses were finally used to investigate the underlying biological mechanisms. In both cohorts, PGRN and sTREM2 were higher in individuals within the TN+ profile irrespective of the A status, and followed similar trajectory across different clinical and biomarker stage. CSF PGRN was associated with higher sTREM2 across AD continuum and non-AD pathophysiology. Bidirectional mediation was observed between PGRN (14.6% in CABLE, 15.6% in ADNI) and sTREM2 (29.7% in CABLE, 33.5% in ADNI) in modulating Aβ pathology (p < 0.0001). Proteomic analysis identified 1539 CSF proteins (Bonferroni-corrected p < 7.13 × 10^-6) simultaneously associated with PGRN, sTREM2, and Aβ_1-42. These proteins are mainly enriched in immune processes and neural plasticity. These findings suggest that the interplay between lysosome function and microglia-related neuroinflammation plays key roles in amyloid metabolism.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"233"},"PeriodicalIF":5.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic liability to major psychiatric disorders contributes to multi-faceted quality of life outcomes in children and adults.","authors":"Yingjie Shi, Nina Roth Mota, Barbara Franke, Emma Sprooten","doi":"10.1038/s41398-025-03443-y","DOIUrl":"10.1038/s41398-025-03443-y","url":null,"abstract":"<p><p>Psychiatric conditions, known for their hereditary nature, exert significant impacts on various life domains. Leveraging this heritability, we examine the relations between genetic susceptibility to major psychiatric disorders and the multifaceted aspects of quality of life in two population-based cohorts, the Adolescent Brain Cognitive Development (ABCD) study (N = 3909 preadolescent children) and the UK Biobank (N = 269,293 adults). Genetic susceptibility to seven major psychiatric disorders was quantified by polygenic scores derived from extensive genome-wide association studies (N = 21,000-413,000). Pervasive associations were found between genetic risk for all seven major psychiatric disorders investigated and age-relevant real-life quality of life indices, with varied patterns of associations for different life domains. We especially highlight the role of genetic risks for ADHD and major depressive disorders. Our findings emphasize the continuous nature of psychiatric traits, extending their influence on daily life experiences and societal functioning beyond symptomatology and diagnostic classifications.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"232"},"PeriodicalIF":5.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"7-Tesla ultra-high field MRI of the parahippocampal cortex reveals evidence of common neurobiological mechanisms of major depressive disorder and neurotic personality traits.","authors":"Dominik Nießen, Ravichandran Rajkumar, Dilsa Cemre Akkoc Altinok, Gereon Johannes Schnellbächer, Shukti Ramkiran, Jana Hagen, Nadim Jon Shah, Tanja Veselinović, Irene Neuner","doi":"10.1038/s41398-025-03435-y","DOIUrl":"10.1038/s41398-025-03435-y","url":null,"abstract":"<p><p>The parahippocampal cortex (PHC) is a highly interconnected region within the medial temporal lobe (MTL) and is essential in memory, emotion and cognition. According to the cognitive model of depression, dysfunctions in these processes constitute the pathophysiological foundation of major depressive disorder (MDD). Research suggests that human personality, and neuroticism in particular, plays an important role in the development and disease progression of MDD. Furthermore, extensive neuroimaging evidence indicates that neuroticism and depression share overlapping structural and functional correlates, potentially including the PHC. In a matched sample of 86 adults (43 MDD patients, 43 control participants, mean age 31.4 years, range 18-61 years, 40 female), PHC thickness was measured using structural MRI at an ultra-high field strength of 7 T and compared to the level of neuroticism as measured by the NEO-FFI scale. MDD patients exhibited significantly lower left hemispheric PHC thickness compared to healthy controls (p_fdr = 0.002, η² = 0.119). Additionally, linear regression analysis revealed a significant association between neuroticism and PHC thickness within both hemispheres (L: p_fdr = 0.012, β = -0.414; R: p_fdr = 0.008, β = -0.512), with highly neurotic individuals displaying reduced cortical thickness. These findings suggest that, in combination with neuroticism, PHC thickness could serve as a potential biomarker of depression. Our results underscore the importance of multimodal assessments in MDD, potentially contributing to the foundation of individualised clinical decision-making and paving the way towards precision psychiatry.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"227"},"PeriodicalIF":5.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurobiological correlates of schizophrenia-specific and highly pleiotropic genetic risk scores for neuropsychiatric disorders.","authors":"Lydia M Federmann, Lisa Sindermann, Sabrina Primus, Federico Raimondo, Konrad Oexle, Janik Goltermann, Juliane Winkelmann, Markus M Nöthen, Katrin Amunts, Thomas W Mühleisen, Sven Cichon, Simon B Eickhoff, Felix Hoffstaedter, Udo Dannlowski, Kaustubh R Patil, Andreas J Forstner","doi":"10.1038/s41398-025-03440-1","DOIUrl":"10.1038/s41398-025-03440-1","url":null,"abstract":"<p><p>Neuropsychiatric disorders show shared and distinct neurobiological correlates. A cross-disorder genome-wide association study (GWAS) identified 23 highly pleiotropic single-nucleotide polymorphisms (SNPs) that were associated with at least four neuropsychiatric disorders, and 22 SNPs that were associated predominantly with schizophrenia. Exploring their link to brain-related traits might advance understanding their distinct neurobiological processes. Using the UK Biobank data (n = 28,952), this study examined the association of both a genetic risk score (GRS) for highly pleiotropic SNPs (PleioPsych-GRS), and a GRS for predominantly schizophrenia-associated SNPs (SCZ-GRS) with 154 measures of subcortical volume, cortical thickness, and surface area as well as 12 outcomes related to mental health. To generate further insights at the individual SNP level, the association between SNPs and brain structure was examined using GWAS summary statistics. The PleioPsych-GRS showed no significant association with brain structure after correction for multiple testing. The SCZ-GRS showed a significant association with an increased surface area of the lateral orbitofrontal region, and an increased volume of the putamen, among others. The PleioPsych-GRS and the SCZ-GRS were associated with eight and four outcomes related to mental health, respectively. Two highly pleiotropic and 10 SCZ-associated SNPs were associated with several structural brain phenotypes. Taken together, these findings indicated that GRSs of highly pleiotropic SNPs and predominantly schizophrenia-associated SNPs have partly distinct associations with brain structure and outcomes related to mental health. Thus, investigating schizophrenia-specific and pleiotropic variants may improve our understanding of the neurobiology of neuropsychiatric disorders.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"230"},"PeriodicalIF":5.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-kingdom microbial changes and their associations with the clinical characteristics in schizophrenia patients.","authors":"Baoyuan Zhu, Liqin Liang, Shuhao Chen, Hehua Li, Yuanyuan Huang, Wei Wang, Heng Zhang, Jing Zhou, Dongsheng Xiong, Xiaobo Li, Junhao Li, Yuping Ning, Xuetao Shi, Fengchun Wu, Kai Wu","doi":"10.1038/s41398-025-03449-6","DOIUrl":"10.1038/s41398-025-03449-6","url":null,"abstract":"<p><p>Accumulating evidence has highlighted alterations in the gut microbiome in schizophrenia (SZ); however, the role of multi-kingdom microbiota in SZ remains inadequately understood. In this study, we performed metagenomic sequencing of fecal samples from 36 SZ patients and 55 healthy controls (HC) to profile bacterial, fungal, archaeal, and viral communities, along with functional pathways. We also conducted co-occurrence network analysis to explore the relationships among differential microbial species and metabolic pathways separately. Additionally, we assessed the associations of these differential species and functional pathways with clinical characteristics. Our findings revealed significant differences in species between SZ patients and HC, identifying not only 17 bacterial species, but also 8 fungal, 26 archaeal, and 19 viral species. Functional pathway analysis revealed 21 metabolic pathways significantly altered in SZ patients, including an increase in tryptophan metabolism, while biosynthesis of amino acids was decreased. Network analysis further uncovered more complex inter-kingdom interactions in SZ patients, with specific fungal species appearing exclusively in the SZ network. Importantly, significant associations were observed between microbial species and functional pathways with clinical characteristics, including symptom severity, cognitive function, and clinical biochemical marker. For instance, the abundance of Streptococcus vestibularis was positively correlated with homocysteine levels; the ubiquinone and other terpenoid-quinone biosynthesis was positively correlated with both symptom severity and C-reactive protein. Our findings reveal the intricate microbial dysbiosis present in SZ patients, suggesting multi-kingdom microbial interactions play a crucial role in SZ patients, highlighting promising avenues for potential diagnostic and therapeutic applications.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"228"},"PeriodicalIF":5.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}