Translational Psychiatry最新文献

{"title":"Exercise-induced PV network plasticity in the prelimbic cortex regulates the expression of fear memory in male mice.","authors":"Neng-Yuan Hu, Xin Heng, Hao Li, Lang Huang, Yuan-Yue Dou, Yi-Hua Chen","doi":"10.1038/s41398-025-03472-7","DOIUrl":"https://doi.org/10.1038/s41398-025-03472-7","url":null,"abstract":"<p><p>Many psychiatric disorders, such as anxiety disorders, are characterized by abnormal processing of fear-related information. Parvalbumin (PV) neurons in the prelimbic cortex (PL) are critically involved in fear expression. However, the role of plasticity of the local PV neuron network in the regulation of remote fear memory remains unknown. In this study, we showed that the retrieval of both recent and remote fear memory induced the high-PV plasticity in the PL. Acute chemogenetic inhibition of PV neurons in the PL decreased recent fear memory retrieval and suppressed the fear-induced shift toward high-PV neurons, while these effects were not observed three weeks after chemogenetic inhibition. On the other hand, chronic inhibition of these neurons led to a sustained reduction in fear memory retrieval and persistent suppression of fear-induced high-PV plasticity. Notably, voluntary running mimicked the effects of chronic inhibition of PV neurons and decreased the expression of fear memory, which could be blocked by chemogenetic activation of PV neurons. Together, these findings indicate an essential role for PV network plasticity in the PL in regulating fear memory expression and provide alternative methods for the treatment of certain anxiety disorders.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"243"},"PeriodicalIF":5.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional changes across tissue and time provide molecular insights into a therapeutic window of opportunity following traumatic stress exposure.","authors":"Lauren A McKibben, Meghna Iyer, Ying Zhao, Roxana Florea, Sophia Kuhl-Chimera, Ishani Deliwala, Yue Pan, Erica M Branham, Sandrine M Géranton, Samuel A McLean, Sarah D Linnstaedt","doi":"10.1038/s41398-025-03451-y","DOIUrl":"https://doi.org/10.1038/s41398-025-03451-y","url":null,"abstract":"<p><p>Unfortunately, survivors of traumatic stress exposure (TSE) frequently develop adverse posttraumatic neuropsychiatric sequelae (APNS) such as chronic pain and stress/depressive symptoms. Increasing evidence indicates that there is a 'window of opportunity' following TSE in which therapeutic interventions are most effective against APNS, yet mechanisms accounting for this observation are poorly understood. Here, we aimed to better understand such mechanisms by generating snapshots of the transcriptional landscape in the early aftermath of TSE across tissues and time. Adult rats were exposed to a TSE model, single prolonged stress (SPS). Then, eight tissues (hypothalamus, left and right hippocampus, amygdala, dorsal root ganglia, spinal cord, heart, and muscle) were isolated from these animals at 2, 24, and 72 h after SPS and in unexposed controls (n = 6 per group). mRNA expression from deep sequencing was used to identify differentially expressed genes (DEGs), biological pathways enriched over time, and predicted upstream regulators. In all tissues except the amygdala, the highest number of DEGs was observed 2-h post-SPS, but DEGs were detected at all timepoints and in all tissues. Some transcripts were differentially expressed in a consistent manner across multiple tissues at a time point (e.g. Fkbp5, 2 h post-SPS), while others had tissue- or region-specific expression patterns. Stress system pathways were most represented at 2 h post-SPS, then stress/circadian/inflammatory pathways at 24 h, and inflammatory pathways at 72 h. Together these findings provide insights into post-TSE transcriptional landscape dynamics and suggest specific intervention windows of opportunity. Future validation is needed across sex, age, stressor, and cell type.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"244"},"PeriodicalIF":5.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of viral RNAs in the choroid plexus with bipolar disorder and schizophrenia and evidence for the hepatitis C virus involvement in neuropathology.","authors":"Maree J Webster, Ashwin Balagopal, Jeffrey Quinn, Ou Chen, Sarven Sabunciyan","doi":"10.1038/s41398-025-03387-3","DOIUrl":"10.1038/s41398-025-03387-3","url":null,"abstract":"<p><p>Many epidemiological studies have shown an association between infectious agents, particularly viruses, and psychiatric disorders including schizophrenia. However, evidence of a viral infection in the brain that associates with schizophrenia (SCZ), bipolar disorder (BPD), and major depression (MDD) has not been found. A potential reason for this discrepancy may be that viruses are more likely to infect the neuroepithelium than neural tissue. To test this hypothesis, we used viral sequence enrichment technology and performed RNA sequencing in postmortem choroid plexus (CP) isolated from 84 SCZ, 73 BPD, 23 MDD cases and 76 unaffected controls (CNT) from the Stanley Medical Research Institute brain collection. This approach enabled us to identify the presence of 13 viral species in the CP of 46 subjects. We discovered that CP samples collected from subjects with SCZ and BPD are more likely to contain viral sequences. In terms of individual viruses, the Hepatitis C Virus (HCV) was the only viral species that reached the threshold of statistical significance for an association with SCZ and BPD. Therefore, we focused on HCV to characterize the association between psychiatric disorders and viruses. Analysis of the TriNetX electronic health record database with data on 285 million patients revealed that the prevalence of chronic HCV was 3.6 and 3.9 percent in the SCZ and BPD populations respectively. The prevalence of chronic HCV in these populations was almost double that observed for MDD (1.8%) and approximately 7-fold higher than the control population (0.5%). These findings confirm previous studies that report higher HCV prevalence in SCZ and BPD and suggest that HCV infection may be associated with disease pathology rather than behaviors such as intravenous drug injection, since these behaviors are present in all three disorders. We analyzed hippocampus RNA sequencing data from the subjects identified to be HCV positive via sequence capture. We found that although the virus was absent in this tissue, HCV RNA in the CP was associated with consistent host transcriptional changes in the hippocampus that were potentially related to the innate immune response. Our results are consistent with previous studies and provide clues regarding the contribution of viruses to the pathology of psychiatric disorders.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"216"},"PeriodicalIF":5.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627163","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":"Posterior cingulate cortex downregulation training using fMRI neurofeedback in adolescents with early life adversity exposure: a randomized, single-blind trial.","authors":"Xiaoqian Yu, Aki Tsuchiyagaito, Masaya Misaki, Gabe Cochran, Zsofia P Cohen, Manpreet K Singh, Martin P Paulus, Robin L Aupperle, Namik Kirlic","doi":"10.1038/s41398-025-03445-w","DOIUrl":"10.1038/s41398-025-03445-w","url":null,"abstract":"<p><p>Early life adversity (ELA) disrupts default mode network (DMN) integrity subserving self-referential processes involved in emotional awareness and regulation. Mindfulness training (MT) reduces self-referential processing and down-regulates the DMN. We employed neurofeedback-augmented mindfulness training (NAMT), combining a core mindfulness strategy (focusing on breath) with real-time fMRI neurofeedback (rtfMRI-nf) to modulate DMN by targeting the posterior cingulate cortex (PCC). ELA-exposed (ELA; n = 43) and healthy control (HC; n = 40) adolescents completed a scan with three conditions: (a) Focus-on-breath (MT): rtfMRI-nf was presented as a variable-height bar, and adolescents attempted to lower the bar; (b) Describe: engaging self-referential processing; and (c) Rest. ELA were single-blind randomized to active PCC rtfMR-nf (NF; n = 22) or artificial feedback (SHAM; n = 21). Adolescents reported perceived stress, state mindfulness, and affect at baseline, post-training, and one-week follow-up. General linear models (GLMs) examined group differences (ELA vs. HC; NF vs. SHAM) on neural (MT vs. Describe) and self-report measures. ELA showed greater difficulty in PCC down-regulation relative to HC. For ELA, SHAM evidenced similar PCC down-regulation as active NF. All adolescents reported increased state mindfulness post-training. Relative to HC, ELA reported greater improvements in positive affect, negative affect and stress at follow-up. There was no difference in self-reported measures between active and SHAM. PCC responses in ELA confirm the region's utility as a potential treatment target. NAMT was feasible and acceptable for ELA-exposed adolescents, but may not enhance mindfulness training more than SHAM. Optimal strategies for enhancing PCC regulation in ELA may be elucidated with future research.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"242"},"PeriodicalIF":5.8,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620741","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":"Detecting schizophrenia, bipolar disorder, psychosis vulnerability and major depressive disorder from 5 minutes of online-collected speech.","authors":"Julianna Olah, Win Lee Edwin Wong, Atta-Ul Raheem Rana Chaudhry, Omar Mena, Sunny X Tang","doi":"10.1038/s41398-025-03433-0","DOIUrl":"10.1038/s41398-025-03433-0","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Psychosis poses substantial social and healthcare burdens. The analysis of speech is a promising approach for the diagnosis and monitoring of psychosis, capturing symptoms like thought disorder and flattened affect. Recent advancements in Natural Language Processing (NLP) methodologies enable the automated extraction of informative speech features, which has been leveraged for early psychosis detection and assessment of symptomology. However, critical gaps persist, including the absence of standardized sample collection protocols, small sample sizes, and a lack of multi-illness classification, limiting clinical applicability. Our study aimed to (1) identify an optimal assessment approach for the online and remote collection of speech, in the context of assessing the psychosis spectrum and evaluate whether a fully automated, speech-based machine learning (ML) pipeline can discriminate among different conditions on the schizophrenia-bipolar spectrum (SSD-BD-SPE), help-seeking comparison subjects (MDD), and healthy controls (HC) at varying layers of analysis and diagnostic complexity. We adopted online data collection methods to collect 20 min of speech and demographic information from individuals. Participants were categorized as \"healthy\" help-seekers (HC), having a schizophrenia-spectrum disorder (SSD), bipolar disorder (BD), major depressive disorder (MDD), or being on the psychosis spectrum with sub-clinical psychotic experiences (SPE). SPE status was determined based on self-reported clinical diagnosis and responses to the PHQ-8 and PQ-16 screening questionnaires, while other diagnoses were determined based on self-report from participants. Linguistic and paralinguistic features were extracted and ensemble learning algorithms (e.g., XGBoost) were used to train models. A 70-30% train-test split and 30-fold cross-validation was used to validate the model performance. The final analysis sample included 1140 individuals and 22,650 min of speech. Using 5 min of speech, our model could discriminate between HC and those with a serious mental illness (SSD or BD) with 86% accuracy (AUC = 0.91, Recall = 0.7, Precision = 0.98). Furthermore, our model could discern among HC, SPE, BD and SSD groups with 86% accuracy (F1 macro = 0.855, Recall Macro = 0.86, Precision Macro = 0.86). Finally, in a 5-class discrimination task including individuals with MDD, our model had 76% accuracy (F1 macro = 0.757, Recall Macro = 0.758, Precision Macro = 0.766). Our ML pipeline demonstrated disorder-specific learning, achieving excellent or good accuracy across several classification tasks. We demonstrated that the screening of mental disorders is possible via a fully automated, remote speech assessment pipeline. We tested our model on relatively high number conditions (5 classes) in the literature and in a stratified sample of psychosis spectrum, including HC, SPE, SSD and BD (4 classes). We tested our model on a large sample (N = 1150) and demonstrated best-in-class","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"241"},"PeriodicalIF":5.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620738","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 and environmental contributions to the link between synaesthesia and neurodevelopmental and psychiatric features: a twin study.","authors":"Janina Neufeld, Tessa M van Leeuwen, Ralf Kuja-Halkola, Sebastian Lundström, Henrik Larsson, Paul Lichtenstein, Sven Bölte, David Mataix-Cols, Mark J Taylor","doi":"10.1038/s41398-025-03444-x","DOIUrl":"10.1038/s41398-025-03444-x","url":null,"abstract":"<p><p>Synaesthesia is a sensory phenomenon where specific inputs such as written letters or tastes automatically trigger additional sensations (for instance colours). The phenomenon is more common in people on the autism spectrum compared to the general population and seems also to be associated with other neurodevelopmental and psychiatric conditions and features. We assessed the associations between self-reported synaesthesia and eight psychiatric / neurodevelopment features in 18-year-old twins and estimated the genetic and environmental contributions to these associations using classical twin modelling. All of the neurodevelopmental / psychiatric features (related to autism, ADHD, obsessive-compulsive disorder, anxiety, depression, psychotic-like experiences, eating disorders, and (hypo-)mania) correlated positively with self-reported synaesthesia. The strongest association was found with obsessive-compulsive features (r = 0.28). Genetic factors explained more than 50% of most these associations. Environmental factors that are not shared by twins (non-shared environment) influenced the associations to different degrees, while the influence of environmental factors that are shared by twins was estimated to be negligible. Rather than being specifically linked to autism, synaesthesia seems to be associated with a wider range of neurodevelopmental / psychiatric features, and especially obsessive-compulsive features. Genetic factors play a predominant role in most of these associations, suggesting that synaesthesia might share part of its genetic causes with several neurodevelopmental / psychiatric conditions.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"240"},"PeriodicalIF":5.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620739","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":"Integrative analysis identifies IL-6/JUN/MMP-9 pathway destroyed blood-brain-barrier in autism mice via machine learning and bioinformatic analysis.","authors":"Cong Hu, Heli Li, Jinru Cui, Yunjie Li, Feiyan Zhang, Hao Li, Xiaoping Luo, Yan Hao","doi":"10.1038/s41398-025-03452-x","DOIUrl":"10.1038/s41398-025-03452-x","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by social communication deficits and restricted, repetitive behaviors. Growing evidence implicates neuroinflammation-induced blood-brain barrier (BBB) dysfunction as a key pathogenic mechanism in ASD, although the underlying molecular pathways remain poorly understood. This study aimed to identify critical genes linking BBB function and neuroinflammatory activation, with the ultimate goal of evaluating potential therapeutic targets. Through integrative analysis combining differential gene expression profiling with three machine learning algorithms - Least Absolute Shrinkage and Selection Operator (LASSO) regression, Support Vector Machine Recursive Feature Elimination (SVM-RFE), and RandomForest combined with eXtreme Gradient Boosting (XGBoost) - we identified four hub genes, with JUN emerging as a core regulator. JUN demonstrated strong associations with both BBB integrity and microglial activation in ASD pathogenesis. Using a maternal immune activation (MIA) mouse model of ASD, we observed significant downregulation of cortical tight junction proteins ZO-1 and occludin, confirmed through immunofluorescence and qPCR analysis. Bioinformatics analysis revealed a close correlation between JUN and IL-6/MMP-9 signaling in ASD-associated microglial activation. These findings were validated in vivo, with immunofluorescence and qPCR demonstrating elevated IL-6 and MMP-9 expression in ASD mice. Pharmacological intervention using ventricular JNK inhibitor administration effectively downregulated JUN and MMP-9 expression. In vitro studies using IL-6-stimulated BV-2 microglial cells replicated these findings, showing JNK inhibitor-mediated suppression of JUN and MMP-9 upregulation. These results collectively identify the IL-6/JUN/MMP-9 pathway as a specific mediator of barrier dysfunction in ASD, representing a promising target for personalized therapeutic interventions.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"239"},"PeriodicalIF":5.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620740","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":"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}