Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Disease-specific alterations of effective connectivity across anti-correlated networks in major depressive disorder and bipolar disorder","authors":"Yun-Shuang Fan ,&nbsp;Saike Zhang ,&nbsp;Wei Sheng ,&nbsp;Jing Guo ,&nbsp;Hezong Ling ,&nbsp;Qian Cui ,&nbsp;Wei Huang ,&nbsp;Huafu Chen","doi":"10.1016/j.pnpbp.2025.111283","DOIUrl":"10.1016/j.pnpbp.2025.111283","url":null,"abstract":"<div><div>Major depressive disorder (MDD) and bipolar disorder (BD) share various clinical behaviors and have confounded clinical diagnoses. Converging studies have suggested MDD and BD as disorders with abnormal communication among functional brain networks involved in mental activity and redirection. However, whether MDD and BD show disease-specific alterations in network information interaction remains unclear. This study collected resting-state functional MRI data of 98 patients with MDD, 55 patients with BD, and sex-, age-, and education-matched 95 healthy controls. Spectral dynamic causal model (spDCM) was used to investigate effective connectivities among three large-scale intrinsic functional networks including the default mode network (DMN), salience network (SN), and dorsal attention network (DAN). Effective connectivities showing disease-specific changes were then used as input features of support vector models to predict clinical symptoms and classify individuals with MDD and BD. Compared with healthy controls, both the MDD and BD groups showed increased DAN → SN connectivity. However, within-network connectivities of DMN and DAN showed opposite effects on the diseases. Notably, MDD and BD also showed different alterations on a connectivity loop of SN → DAN → DMN → SN, which could be used to predict the clinical symptom severity of either MDD or BD. Individuals with MDD and BD could be further classified by using connectivities showing opposite disease effects. Our findings reveal common and unique alterations of network interactions in MDD and BD, and further suggest disease-specific neuroimaging markers for clinical diagnosis.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111283"},"PeriodicalIF":5.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extensive perivascular spaces burden causally affects neurodegenerative diseases and brain structure: A two-sample bidirectional Mendelian randomization study","authors":"Pin Wang ,&nbsp;Heya Luan ,&nbsp;Shaoqi Li ,&nbsp;Xiaodong Han ,&nbsp;Wenxian Sun ,&nbsp;Jin Gong ,&nbsp;Chang Xu ,&nbsp;Runqi Chen ,&nbsp;Cuibai Wei","doi":"10.1016/j.pnpbp.2025.111284","DOIUrl":"10.1016/j.pnpbp.2025.111284","url":null,"abstract":"<div><h3>Background</h3><div>Extensive perivascular spaces (PVS) burden has been reported to be associated with neurodegenerative diseases and brain structure; however, the causal effects has not been determined yet. Therefore, this study aimed to investigate the causal effect of extensive PVS burden on neurodegenerative diseases and brain structure through Mendelian randomization (MR) analysis.</div></div><div><h3>Methods</h3><div>Two-sample bidirectional MR was conducted based on publicly available genome-wide association studies (GWAS) summary statistics. Causal estimates of extensive PVS burden on neurodegenerative diseases and brain structure were primarily assessed using the inverse-variance weighted (IVW) method, supplemented by additional methods, including MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. In addition, we explored whether brain structure act as a mediating factor in the pathway from extensive PVS burden to neurodegenerative diseases.</div></div><div><h3>Results</h3><div>Our MR study found that extensive PVS burden in white matter (WM-PVS) burden was associated with lower Alzheimer's disease (AD) risk (IVW OR (95 % CI) = 0.963(0.929 to 0.999), <em>P</em> = 0.0428), with no heterogeneity and pleiotropy detected. In addition, following FDR correction, we found bidirectional causal relationships between extensive PVS burden and brain structure. Moreover, our results of the mediated analysis showed that the surface area of parahippocampal, as a mediating variable, plays an important role in the causal relationship between WM-PVS and AD. The mediation effect is 18 %.</div></div><div><h3>Conclusions</h3><div>Our study provides evidence for the causal associations of different extensive PVS burden phenotypes with neurodegenerative diseases and brain structures, improving our understanding of the complex relationships between different brain injuries.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111284"},"PeriodicalIF":5.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review","authors":"Zhen Xuen Brandon Low ,&nbsp;Shin Jie Yong ,&nbsp;Hayam A. Alrasheed ,&nbsp;Maha F. Al-Subaie ,&nbsp;Nawal A. Al Kaabi ,&nbsp;Mubarak Alfaresi ,&nbsp;Hawra Albayat ,&nbsp;Jawaher Alotaibi ,&nbsp;Ali Al Bshabshe ,&nbsp;Ameen S.S. Alwashmi ,&nbsp;Amal A. Sabour ,&nbsp;Maha A. Alshiekheid ,&nbsp;Zainab H. Almansour ,&nbsp;Huda Alharthi ,&nbsp;Hani A. Al Ali ,&nbsp;Adel A. Almoumen ,&nbsp;Nabil A. Alqasimi ,&nbsp;Hajir AlSaihati ,&nbsp;Alfonso J. Rodriguez-Morales ,&nbsp;Ali A. Rabaan","doi":"10.1016/j.pnpbp.2025.111279","DOIUrl":"10.1016/j.pnpbp.2025.111279","url":null,"abstract":"<div><h3>Rationale</h3><div>In our ongoing battle against the coronavirus 2019 (COVID-19) pandemic, a major challenge is the enduring symptoms that continue after acute infection. Also known as Long COVID, post-COVID-19 syndrome (PCS) often comes with debilitating symptoms like fatigue, disordered sleep, olfactory dysfunction, and cognitive issues (“brain fog”). Currently, there are no approved treatments for PCS. Recent research has uncovered that the severity of PCS is inversely linked to circulating serotonin levels, highlighting the potential of serotonin-modulating therapeutics for PCS. Therefore, we propose that serotonergic psychedelics, acting mainly via the 5-HT2A serotonin receptor, hold promise for treating PCS.</div></div><div><h3>Objectives</h3><div>Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS.</div></div><div><h3>Results</h3><div>Potential mechanisms through which serotonergic psychedelics may alleviate PCS symptoms are discussed, with emphasis on their effects on inflammation, neuroplasticity, and gastrointestinal function. Additionally, this review explores the potential of serotonergic psychedelics in mitigating endothelial dysfunction, a pivotal aspect of PCS pathophysiology implicated in organ dysfunction. This review also examines the potential role of serotonergic psychedelics in alleviating specific PCS symptoms, which include olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges.</div></div><div><h3>Conclusions</h3><div>Emerging evidence suggests that serotonergic psychedelics may alleviate PCS symptoms. However, further high-quality research is needed to thoroughly assess their safety and efficacy in treating patients with PCS.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111279"},"PeriodicalIF":5.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural circuits mediating chronic stress: Implications for major depressive disorder","authors":"Hongling Guo ,&nbsp;Tahir Ali ,&nbsp;Shupeng Li","doi":"10.1016/j.pnpbp.2025.111280","DOIUrl":"10.1016/j.pnpbp.2025.111280","url":null,"abstract":"<div><div>Major depressive disorder (MDD), also known as depression, is a prevalent mental disorder that leads to severe disease burden worldwide. Over the past two decades, significant progress has been made in understanding the pathogenesis and developing novel treatments for MDD. Among the complicated etiologies of MDD, chronic stress is a major risk factor. Exploring the underlying brain circuit mechanisms of chronic stress regulation has been an area of active research for recent years. A growing body of preclinical and clinical research has revealed that abnormalities in the brain circuits are closely associated with failures in coping with stress in depressed individuals. Nevertheless, neural circuit mechanisms underlying chronic stress processing and the onset of depression remain a major puzzle. Here, we review recent literature focusing on circuit- and cell-type-specific dissection of depression-like behaviors in chronic stress-related animal models of MDD and outline the key questions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111280"},"PeriodicalIF":5.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143200846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol outcomes on anxiety, impulsivity and spatial memory: Possible Omega-3 amelioration effects","authors":"Valentín Cabrera ,&nbsp;Paula Abate ,&nbsp;Verónica Balaszczuk ,&nbsp;Ana Fabiola Macchione","doi":"10.1016/j.pnpbp.2025.111281","DOIUrl":"10.1016/j.pnpbp.2025.111281","url":null,"abstract":"<div><div>Alcohol consumption is a worldwide concern that causes 5 % of the global disease burden and contributes to 3 million deaths per year. Several studies suggest an increase in alcohol drinking and alcohol related problems. Alcohol Use Disorder (formerly referred as alcoholism or alcohol addiction) is one of many possible outcomes of an early and prolonged alcohol consumption and it is highly comorbid with anxiety disorders, impulsivity and memory deficits among others. In this review we approach recent data about global and American prevalence of alcohol use and discuss different factors that contribute to alcohol consumption. Furthermore, we revise evidence of ethanol effects on anxiety-like behaviors, impulsivity and spatial memory. Lastly, we look at the Omega-3 fatty acid as a possible course of action in mitigating the aforementioned deleterious effects of alcohol consumption.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111281"},"PeriodicalIF":5.3,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychedelics in neuroinflammation: Mechanisms and therapeutic potential","authors":"Junia Lara de Deus ,&nbsp;Juliana Marino Maia ,&nbsp;Renato Nery Soriano ,&nbsp;Mateus R. Amorim ,&nbsp;Luiz G.S. Branco","doi":"10.1016/j.pnpbp.2025.111278","DOIUrl":"10.1016/j.pnpbp.2025.111278","url":null,"abstract":"<div><div>Neuroinflammation is a critical factor in the pathogenesis of various neurodegenerative and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder. Psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT), have demonstrated promising therapeutic effects on neuroinflammation, primarily through interactions with serotonin (5-HT) receptors, particularly the 5-HT2A receptor. Activation of these receptors by psychedelics modulates the production of pro-inflammatory cytokines, regulates microglial activity, and shifts the balance between neurotoxic and neuroprotective metabolites. Additionally, psychedelics affect critical signaling pathways, including the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), and mechanistic target of rapamycin (mTOR) pathways, promoting neuroplasticity and exerting anti-inflammatory effects. Beyond the serotonergic system, other neurotransmitter systems—including the glutamatergic, dopaminergic, noradrenergic, gamma-aminobutyric acid (GABAergic), and cholinergic systems—also play significant roles in mediating the effects of psychedelics. This review examines the intricate mechanisms by which psychedelics modulate neuroinflammation and underscores their potential as innovative therapeutic agents for treating neuroinflammatory and neuropsychiatric disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111278"},"PeriodicalIF":5.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal relationship between mental disorders and abdominal aortic aneurysm: Insights from the genetic perspective","authors":"Ming-Gang Deng ,&nbsp;Chen Chai ,&nbsp;Kai Wang ,&nbsp;Zhi-Hui Zhao ,&nbsp;Jia-Qi Nie ,&nbsp;Fang Liu ,&nbsp;Yuehui Liang ,&nbsp;Jiewei Liu","doi":"10.1016/j.pnpbp.2025.111277","DOIUrl":"10.1016/j.pnpbp.2025.111277","url":null,"abstract":"<div><h3>Background</h3><div>This study aims to investigate the genetic link between mental disorders—depression, schizophrenia (SCZ), and bipolar disorder (BIP)—and abdominal aortic aneurysm (AAA).</div></div><div><h3>Methods</h3><div>We first examined the genetic associations between AAA and mental disorders by analyzing global and local genetic correlations as well as shared genomic loci. Global genetic correlation was assessed using linkage disequilibrium score regression (LDSC) and the GeNetic cOVariance Analyzer (GNOVA), while local genetic correlation was analyzed using the SUPERGNOVA approach. To identify shared genetic variants, the pleiotropy-informed conditional and conjunctional false discovery rate (pleioFDR) method was applied. Subsequently, the univariate Mendelian Randomization (UMR) was employed to evaluate the causal relationship, complemented by multivariate MR (MVMR) to account for potential confounding biases. Additionally, mediation analysis was performed to determine whether known risk factors mediate the identified causal relationships.</div></div><div><h3>Results</h3><div>Global correlations showed positive links between depression, SCZ, and AAA, but not BIP. Local analyses identified specific genomic regions of correlation. We found 26, 141, and 10 shared loci for AAA with depression, SCZ, and BIP, respectively. UMR indicated significant associations between genetically predicted depression (OR 1.270; 95 % CI 1.071–1.504; <em>p</em> = 0.006) and SCZ (OR 1.047; 95 % CI 1.010–1.084; <em>p</em> = 0.011) with AAA, but not BIP. These results were confirmed by MVMR analyses. Mediation analyses showed that smoking, hypertension, hyperlipidemia, and coronary atherosclerosis mediated the impact of depression on AAA while smoking mediated SCZ's impact.</div></div><div><h3>Conclusion</h3><div>This study provides evidence that genetically predicted depression and SCZ are linked to an increased risk of AAA, mediated by traditional AAA risk factors.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111277"},"PeriodicalIF":5.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective non-invasive brain stimulation over dorsolateral prefrontal cortex for modulation of food craving and consumption: A systematic and meta-analytic review","authors":"Lei Zheng ,&nbsp;Yinqiang Yu ,&nbsp;Xuebing Wu ,&nbsp;Jun Hu ,&nbsp;Yiqun Gan","doi":"10.1016/j.pnpbp.2025.111271","DOIUrl":"10.1016/j.pnpbp.2025.111271","url":null,"abstract":"<div><div>In recent decades, non-invasive brain stimulation (NIBS) has gained attention as a potential tool for promoting dietary regulation by modulating activity in the dorsolateral prefrontal cortex (dlPFC). However, the findings from individual experimental studies and meta-analyses have been inconsistent. To address this, we conducted a meta-analytic and systematic review of past studies focusing on neuromodulation of the dlPFC. Our research included 13 studies using repetitive transcranial magnetic stimulation (rTMS; 16 samples, 506 participants) and 29 transcranial direct current stimulation (tDCS; 31 samples, 1004 participants). By adjusting the pre-post correlation, we detected small-to-moderate effect sizes of NIBS on food craving (rTMS: Hedge's g = −0.57; tDCS: Hedge's g = −0.26) and food consumption (rTMS: Hedge's g = −0.51; tDCS: Hedge's g = −0.17). Additionally, we observed that the efficacy of NIBS was influenced by various moderators, including stimulation parameters, research protocols, and participant characteristics. Notably, both rTMS and tDCS appeared to enhance dlPFC function in dietary regulation for people with eating disorders or obesity. Furthermore, these effects were more pronounced with multi-session stimulation compared to single-session stimulation. Finally, based on the existing literature, we discuss the role of the dlPFC in the appetitive reward processing pathway and provide suggestions for future research directions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111271"},"PeriodicalIF":5.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Executive dysfunction in Parkinson's disease: From neurochemistry to circuits, genetics and neuroimaging","authors":"Shuyan Tong ,&nbsp;Ruiwen Wang ,&nbsp;Huihua Li ,&nbsp;Zhu Tong ,&nbsp;Deqin Geng ,&nbsp;Xiangrong Zhang ,&nbsp;Chao Ren","doi":"10.1016/j.pnpbp.2025.111272","DOIUrl":"10.1016/j.pnpbp.2025.111272","url":null,"abstract":"<div><div>Cognitive decline is one of the most significant non-motor symptoms of Parkinson's disease (PD), with executive dysfunction (EDF) being the most prominent characteristic of PD-associated cognitive deficits. Currently, lack of uniformity in the conceptualization and assessment scales for executive functions impedes the early and accurate diagnosis of EDF in PD. The neurobiological mechanisms of EDF in PD remain poorly understood. Moreover, the treatment of cognitive impairment in PD has progressed slowly and with limited efficacy. Thus, this review explores the characteristics and potential mechanisms of EDF in PD from multiple perspectives, including the concept of executive function, commonly used neuropsychological tests, neurobiochemistry, genetics, electroencephalographic activity and neuroimaging. The available evidence indicates that degeneration of the frontal-striatal circuit, along with mutations in the Catechol-<em>O</em>-methyltransferase (COMT) gene and Leucine-rich repeat kinase 2 (LRRK2) gene, may contribute to EDF in patients with PD. The increase in theta and delta waves, along with the decrease in alpha waves, offers potential biomarkers for the early identification and monitoring of EDF, as well as the development of dementia in patients with PD. The PD cognition-related pattern (PDCP) pattern may serve as a tool for monitoring and assessing cognitive function progression in these patients and is anticipated to become a biomarker for cognitive disorders associated with PD. The aim is to provide new insights for the early and precise diagnosis and treatment of EDF in PD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111272"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysbiosis is associated with the behavioral phenotype observed in the triple-hit Wisket rat model of schizophrenia","authors":"Szonja B. Plesz ,&nbsp;Leatitia G. Adlan ,&nbsp;Alexandra Büki ,&nbsp;Nóra Makra ,&nbsp;Balázs Ligeti ,&nbsp;Bence Ágg ,&nbsp;Dóra Szabó ,&nbsp;Zoltán S. Zádori ,&nbsp;Péter Ferdinandy ,&nbsp;Gyongyi Horvath ,&nbsp;Gabriella Kekesi","doi":"10.1016/j.pnpbp.2025.111276","DOIUrl":"10.1016/j.pnpbp.2025.111276","url":null,"abstract":"<div><div>Comorbidities between gastrointestinal diseases and psychiatric disorders have been widely reported, with the gut–brain axis implicated as a potential biological basis. Thus, dysbiosis may play an important role in the etiology of schizophrenia, which is barely detected. Triple-hit Wisket model rats exhibit various schizophrenia-like behavioral phenotypes. The present study aimed to compare the diversity and abundance of gut microbiota in Wisket model and control rats; furthermore, to correlate the microbial taxonomic profiles to indices of behavioral change.</div><div>Tail-flick and Ambitus tests were used to assess acute heat pain sensitivity, and record exploration and locomotor activity along with motivation in young adult, control and Wisket model rats. Fecal microbiota composition was profiled by deep sequencing of bacterial 16S rRNA, and it was correlated to behavioral phenotype.</div><div>Wisket rats exhibited significantly decreased pain sensitivity, lower locomotor activity and exploration, and impaired motivation compared with controls. No significant differences were observed in bacterial alpha diversity between the groups; however, clear differences in community structure were observed. Wisket rats showed decreases in several genera of <em>Firmicutes</em> and <em>Saccharimonas</em>, and increases in <em>Bacteriodetes</em> and <em>Helicobacter</em> phyla compared with controls. Correlation analysis revealed significant associations between the microbiota profile and the behavioral phenotype.</div><div>This is the first demonstration that fecal microbiota composition is markedly altered in a triple-hit schizophrenia rat model, suggesting the contribution of the microbiota–gut–brain axis in the development of the schizophrenia-like behavioral phenotype. Thus targeting the gut microbiota may be a novel approach to treat such impairments.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"137 ","pages":"Article 111276"},"PeriodicalIF":5.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}