Schizophrenia (Heidelberg, Germany)最新文献

{"title":"Potential of extracellular vesicle cargo as molecular signals in Schizophrenia: a scoping review.","authors":"Shivaprakash Gangachannaiah, Smita Shenoy, Dinesh Upadhya, Elstin Anbu Raj Stanly, Nachiket Gudi, Pallavi Lakshmi Chandrashekar, Samir Kumar Praharaj","doi":"10.1038/s41537-025-00566-5","DOIUrl":"10.1038/s41537-025-00566-5","url":null,"abstract":"<p><p>The diagnosis of schizophrenia (SCZ) primarily relies on clinical history and mental status assessments by trained professionals. There has been a search for biomarkers to facilitate laboratory diagnosis. Since extracellular vesicles (EVs) communicate with brain cells and can easily cross blood-brain barrier, there is increased interest among experts to explore them as potential molecular signals for disease detection. A scoping review was conducted to provide a comprehensive summary of the existing literature to identify the differentially expressed molecular signals in EVs isolated from SCZ patients. The methodological framework outline provided by Arksey and O'Malley was employed to conduct this scoping review. A systematic search was conducted using a search string across four databases, ultimately leading to selection of 24 relevant studies. Over 1122 differentially expressed biomolecules were identified in EVs extracted from biological fluids and tissues that can be primarily categorized as RNAs, proteins, and metabolites. Among them, 83 biomolecules were identified as validated differentially expressed molecular signals, which included metabolites, circRNAs, lncRNAs, miRNAs, and proteins. These biomolecules were found to affect cellular receptors and intracellular pathways, neurotransmitters, mitochondrial functions, immune-related functions, and metabolic pathways, which could serve as potential biomarkers for SCZ diagnosis.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"17"},"PeriodicalIF":3.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensori- and psychomotor abnormalities, psychopathological symptoms and functionality in schizophrenia-spectrum disorders: a network analytic approach.","authors":"Stefan Fritze, Geva A Brandt, Sebastian Volkmer, Jonas Daub, Dilsa Cemre Akkoc Altinok, Katharina M Kubera, Christoph U Correll, Georg Northoff, Andreas Meyer-Lindenberg, Dusan Hirjak","doi":"10.1038/s41537-024-00547-0","DOIUrl":"https://doi.org/10.1038/s41537-024-00547-0","url":null,"abstract":"<p><p>Sensori- and psychomotor abnormalities are an inherent part of schizophrenia-spectrum disorders (SSD) pathophysiology and linked to psychopathological symptoms as well as cognitive and global functioning. However, how these different symptom clusters simultaneously interact with each other is still unclear. Here, we examined 192 SSD patients (37.75 ± 12.15 years, 73 females). First, we investigated the cross-sectional prevalence and overlap of individual sensori- and psychomotor abnormalities. Second, we applied network analysis methods to simultaneously model the associations between Neurological Soft Signs (NSS), level of akathisia, parkinsonism symptoms, tardive dyskinesia (TD) and catatonia signs as well as cognition, psychopathology, global functioning and daily antipsychotic dose. The largest centralities were exhibited by NSS (0.90), catatonia signs (0.82) and global functioning (0.79). NSS showed strong partial correlations with cognition and parkinsonism symptoms (edge weight, ew = 0.409 and ew = 0.318, respectively). Catatonia signs showed strong connections with global functioning (ew = 0.333). In contrast, TD, akathisia and daily antipsychotic dose were weakly connected with other variables (e.g., largest ew=0.176 between TD and akathisia). In conclusion, NSS and cognition, parkinsonism symptoms and NSS as well as catatonia signs and global functioning seem to be preferentially connected in SSD. The daily medication had little influence on sensori- and psychomotor abnormalities, indicating that they are features of core SSD pathophysiology. Future studies should incorporate these relationships to enhance the understanding of SSD.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"16"},"PeriodicalIF":3.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of identifying Treatment-Resistant and non-Treatment-Resistant Schizophrenia using niacin skin flushing response combined with clinical feature.","authors":"Jizhi Wang, Jinfeng Wang, Siyuan Wang, Yu Gu, Kai Liang, Yingxu Li, Zheng Zhang, Yan Li, Xiaoping Wang, Huijuan Guo, Jiansong Zhou","doi":"10.1038/s41537-025-00567-4","DOIUrl":"10.1038/s41537-025-00567-4","url":null,"abstract":"<p><p>Treatment-resistant schizophrenia (TRS) is a serious mental disease and early identification of this disease is necessary for timely initiation of treatment strategies and management measures. This study aimed to investigate the potential of niacin skin flushing response (NSFR) combined with clinical features in recognizing TRS and non-TRS (NTRS). A total of 269 patients with schizophrenia (99 TRS and 170 NTRS) were included in this study. We conducted NSFR test on 269 participants. Positive and negative syndrome scale (PANSS), repeatable battery for the assessment of neuropsychological status (RBANS) and insight and treatment attitudes questionnaires (ITAQ) were used to assess the patients' psychiatric symptoms, cognitive function, and attitude towards illness and treatment, respectively. Differences in NSFR and clinical features between TRS and NTRS were assessed and the relation was evaluated using Spearman correlation. The efficacy of NSFR and clinical features in identifying TRS was assessed using the receiver operating characteristic (ROC) curve. Patients with TRS have enhanced NSFR compared to patients with NTRS, and NSFR was positively correlated with the course of the disease. PANSS total score was negatively correlated with the age of first onset, RBANS total score, and ITAQ score and positively correlated with the course of disease. Age of first onset, course of disease, RBANS total score, and NSFR were poor indicators for identifying TRS and NTRS. The ITAQ score has better diagnostic validity for TRS compared to the above indicators. Among the clinical features, the ITAQ has an important role in recognizing TRS. The NSFR has poor efficacy in recognizing TRS.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"15"},"PeriodicalIF":3.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classification of schizophrenia, bipolar disorder and major depressive disorder with comorbid traits and deep learning algorithms.","authors":"Xiangning Chen, Yimei Lu, Joan Manuel Cue, Mira V Han, Vishwajit L Nimgaonkar, Daniel R Weinberger, Shizhong Han, Zhongming Zhao, Jingchun Chen","doi":"10.1038/s41537-025-00564-7","DOIUrl":"10.1038/s41537-025-00564-7","url":null,"abstract":"<p><p>Many psychiatric disorders share genetic liabilities, but whether these shared liabilities can be utilized to classify and differentiate psychiatric disorders remains unclear. In this study, we use polygenic risk scores (PRSs) of 42 traits comorbid with schizophrenia (SCZ), bipolar disorder (BIP), and major depressive disorder (MDD) to evaluate their utilities. We found that combining target specific PRS with PRSs of comorbid traits can improve the classification of the target disorders. Importantly, without inclusion of PRSs from targeted disorders, we can still classify SCZ (accuracy 0.710 ± 0.008, AUC 0.789 ± 0.011), BIP (accuracy 0.782 ± 0.006, AUC 0.852 ± 0.004), and MDD (accuracy 0.753 ± 0.019, AUC 0.822 ± 0.010). Furthermore, PRSs from comorbid traits alone can effectively differentiate unaffected controls and patients with SCZ, BIP, and MDD (accuracy 0.861 ± 0.003, AUC 0.961 ± 0.041). Our results demonstrate that shared liabilities can be used effectively to improve the classification and differentiation of these disorders. The finding that PRSs from comorbid traits alone can classify and differentiate SCZ, BIP and MDD reasonably well implies that a majority of the risk variants composing target PRSs are shared with comorbid traits. Overall, our results suggest that a data-driven approach may be feasible to classify and differentiate these disorders.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"14"},"PeriodicalIF":3.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immediate alteration of cerebellar Glx/GABA and cerebello-thalamo-cortical connectivity in patients with schizophrenia after cerebellar TMS.","authors":"Chenyang Yao, Youjin Zhao, Qian Zhang, Ziyuan Zhao, Kai Ai, Bo Zhang, Su Lui","doi":"10.1038/s41537-025-00563-8","DOIUrl":"10.1038/s41537-025-00563-8","url":null,"abstract":"<p><p>Cerebellar dysfunction is a key aspect of schizophrenia, with the cerebello-thalamo-cortical (CTC) hyperconnectivity serving as a neural signature. Abnormalities in gamma-aminobutyric acid (GABA) and glutamate + glutamine (Glx) levels also contribute to this pathology. Transcranial magnetic stimulation (TMS) applied to the cerebellum shows potential in alleviating schizophrenia symptoms, possibly by modulating functional connectivity or neurotransmitter levels. This study aims to explore the immediate effects of cerebellar TMS on CTC circuitry and neurotransmitter levels to elucidate its therapeutic mechanisms in schizophrenia.The study involved 19 stable schizophrenia patients and 26 healthy controls, diagnosed according to DSM-V criteria and assessed for symptom severity using the Positive and Negative Syndrome Scale (PANSS). MRI scans were conducted pre- and post-TMS to detect changes in CTC functional connectivity, GABA, Glx, and Glx/GABA. Linear Mixed-Effects Model (LMEM) and two-sample tests were employed to analyze changes in these variables from baseline to post-TMS. Pearson's correlation analysis was conducted to examine the relationships among these variables and their association with PANSS scores. Mediation analyses were employed to investigate whether GABA and/or Glx serve as potential mediators of CTC hyperconnectivity in patients with schizophrenia. Schizophrenia patients exhibit CTC hyperconnectivity, which remains at a relatively stable level after cerebellar TMS. Compared to healthy controls, schizophrenia patients have significantly higher cerebellar GABA levels, and cerebellar GABA has a significant mediation effect on CTC hyperconnectivity in patients. The Glx/GABA ratio was associated with the severity of clinical symptoms in patients, and cerebellar TMS partially normalized this ratio. Our findings demonstrate that aberrant cerebellar GABA levels contribute to CTC hyperconnectivity in schizophrenia. Additionally, our study shows that cerebellar TMS can increase Glx levels in schizophrenia patients, leading to the normalization of the Glx/GABA ratio, which may contribute to the therapeutic effects of TMS in schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"12"},"PeriodicalIF":3.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying neurobiological heterogeneity in clinical high-risk psychosis: a data-driven biotyping approach using resting-state functional connectivity.","authors":"Xiaochen Tang, Yanyan Wei, Jiaoyan Pang, Lihua Xu, Huiru Cui, Xu Liu, Yegang Hu, Mingliang Ju, Yingying Tang, Bin Long, Wei Liu, Min Su, Tianhong Zhang, Jijun Wang","doi":"10.1038/s41537-025-00565-6","DOIUrl":"10.1038/s41537-025-00565-6","url":null,"abstract":"<p><p>To explore the neurobiological heterogeneity within the Clinical High-Risk (CHR) for psychosis population, this study aimed to identify and characterize distinct neurobiological biotypes within CHR using features from resting-state functional networks. A total of 239 participants from the Shanghai At Risk for Psychosis (SHARP) program were enrolled, consisting of 151 CHR individuals and 88 matched healthy controls (HCs). Functional connectivity (FC) features that were correlated with symptom severity were subjected to the single-cell interpretation through multikernel learning (SIMLR) algorithm in order to identify latent homogeneous subgroups. The cognitive function, clinical symptoms, FC patterns, and correlation with neurotransmitter systems of biotype profiles were compared. Three distinct CHR biotypes were identified based on 646 significant ROI-ROI connectivity features, comprising 29.8%, 19.2%, and 51.0% of the CHR sample, respectively. Despite the absence of overall FC differences between CHR and HC groups, each CHR biotype demonstrated unique FC abnormalities. Biotype 1 displayed augmented somatomotor connection, Biotype 2 shown compromised working memory with heightened subcortical and network-specific connectivity, and Biotype 3, characterized by significant negative symptoms, revealed extensive connectivity reductions along with increased limbic-subcortical connectivity. The neurotransmitter correlates differed across biotypes. Biotype 2 revealed an inverse trend to Biotype 3, as increased neurotransmitter concentrations improved functional connectivity in Biotype 2 but reduced it in Biotype 3. The identification of CHR biotypes provides compelling evidence for the early manifestation of heterogeneity within the psychosis spectrum, suggesting that distinct pathophysiological mechanisms may underlie these subgroups.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"13"},"PeriodicalIF":3.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-based prediction of antipsychotic efficacy from brain gray matter structure in drug-naive first-episode schizophrenia.","authors":"Xiaodong Guo, Enpeng Zhou, Xianghe Wang, Bingjie Huang, Tianqi Gao, Chengcheng Pu, Xin Yu","doi":"10.1038/s41537-025-00557-6","DOIUrl":"10.1038/s41537-025-00557-6","url":null,"abstract":"<p><p>Predicting patient response to antipsychotic medication is a major challenge in schizophrenia treatment. This study investigates the predictive role of gray matter (GM) in short- and long-term treatment outcomes in drug-naive patients with first-episode schizophrenia (FES). A cohort of 104 drug-naive FES was recruited. Before initiating treatment, T1-weighted anatomical images were captured. The Positive and Negative Syndrome Scale and the Personal and Social Performance Scale were adopted to assess clinical symptoms and social function. At the 3-month follow-up, patients were categorized into remission and non-remission groups. At 1-year follow-up, patients were categorized into the rehabilitation and non-rehabilitation groups. Machine learning algorithms were applied to predict treatment outcomes based on GM volume, cortical thickness, and gyrification index, and the model performance was evaluated. Widespread regions, such as the superior temporal gyrus, middle frontal gyrus, supramarginal gyrus, the posterior central gyrus, anterior cingulate gyrus, and parahippocampal gyrus showed substantial predictive value for 3-month treatment efficacy (74.32% accuracy). The inferior frontal gyrus, anterior cingulate gyrus, and inferior occipital gyrus demonstrated significant predictive power for treatment outcome at 1-year follow-up (70.31% accuracy). We developed a machine learning model to predict individual responses to antipsychotic treatments, which could positively impact clinical treatment protocols for schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"11"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of avatar identity on spontaneous perspective-taking in patients with schizophrenia.","authors":"Pei Xie, ChaoZheng Huang, XiaoQuan Wang, HanBin Sang, AiBao Zhou","doi":"10.1038/s41537-024-00551-4","DOIUrl":"10.1038/s41537-024-00551-4","url":null,"abstract":"<p><p>Controversy exists regarding whether the spontaneity of altercentric intrusion is impaired in patients with schizophrenia during implicit visual perspective-taking tasks. This study explored the characteristics of spontaneous visual perspective-taking in patients with schizophrenia and the effect of an avatar identity on their perspective-taking. We recruited 65 patients with schizophrenia and 65 healthy participants to complete 4 visual perspective-taking experiments for uncued other-avatar and self-avatar tasks and cued other-avatar and self-avatar tasks. In uncued other-avatar experiments, healthy controls showed a significant reduction in accuracy and an increase in response latency when the number of visible discs differed from that seen by the other-avatar (inconsistent condition), indicating altercentric intrusion. However, patients with schizophrenia did not exhibit this effect. In uncued self-avatar experiments, when the avatar was defined as the participant themselves, patients with schizophrenia did not show spontaneous perspective-taking. However, in cued other-avatar experiments, they showed altercentric intrusion in response latency, and in cued self-avatar experiments, they showed altercentric intrusion in accuracy and response latency. These results suggest that patients with schizophrenia have the tendency to spontaneously adopt the perspective of others, which is predicated on their awareness of the existence of perspectives. In addition, the avatar's identity as a stranger hinders the spontaneous perspective-taking processes in patients with schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"9"},"PeriodicalIF":3.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring genetic associations and drug targets for mitochondrial proteins and schizophrenia risk.","authors":"Wenxi Sun, Ping Sun, Jin Li, Qun Yang, Qing Tian, Shiting Yuan, Xueying Zhang, Peng Chen, Chuanwei Li, Xiaobin Zhang","doi":"10.1038/s41537-025-00559-4","DOIUrl":"10.1038/s41537-025-00559-4","url":null,"abstract":"<p><p>Numerous observational studies have highlighted associations between mitochondrial dysfunction and schizophrenia (SCZ), yet the causal relationship remains elusive. This study aims to elucidate the causal link between mitochondria-associated proteins and SCZ. We used summary data from a genome-wide association study (GWAS) of 66 mitochondria-associated proteins in 3,301 individuals from Europe, as well as a GWAS on the large, multi-ethnic ancestry of SCZ, involving 76,755 cases and 243,649 controls. We conducted bidirectional two-sample Mendelian randomization (MR) analyses, with inverse variance weighting (IVW) as the primary method. To account for multi-directionality and ensure robustness, we included MR-Egger, weighted median (WM), weighted mode, and simple mode methods as supplementary sensitivity analyses. Moreover, we explored the GWAS catalog and the Drug-Gene Interaction Database (DGIdb) to identify and evaluate potential therapeutic targets. MR analysis revealed significant genetically determined causal associations between ETHE1 (OR: 1.06), SOD (OR: 0.97), CALU3 (OR: 1.03), and C1QBP (OR: 1.05) and SCZ. According to the reverse MR analysis, a causal relationship was shown between SCZ and CA5A (OR: 1.09), DLD (OR: 1. 08), AIF1 (OR: 0.93), SerRS (OR: 0.93) and MULA of NFKB1 (OR: 0.77). After conducting the gene-drug analysis, HRG, F12, GPLD1, C1R, BCHE, CFH, PON1, and CA5A were identified as promising therapeutic targets. This present study reveals a significant causal relationship between mitochondria-associated proteins and SCZ, offering valuable insights into the disease's pathogenicity and identifying potential therapeutic targets for drug development.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"10"},"PeriodicalIF":3.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key regions aberrantly connected within cerebello-thalamo-cortical circuit and their genetic mechanism in schizophrenia: an fMRI meta-analysis and transcriptome study.","authors":"Yarui Wei, Ziyu Wang, Kangkang Xue, Xiaoyu Niu, Longyao Ma, Shaoqiang Han, Baohong Wen, Yong Zhang, Huafu Chen, Jingliang Cheng","doi":"10.1038/s41537-025-00558-5","DOIUrl":"10.1038/s41537-025-00558-5","url":null,"abstract":"<p><p>Recent studies have showed aberrant connectivity of cerebello-thalamo-cortical circuit (CTCC) in schizophrenia (SCZ), which might be a heritable trait. However, these individual studies vary greatly in their methods and findings, and important areas within CTCC and related genetic mechanism are unclear. We searched for consistent regions of circuit dysfunction using a functional magnetic resonance imaging (fMRI) meta-analysis, followed by meta-regression and functional annotation analysis. Gene annotation analysis was performed to identify genes over-expressed in these regions by using the Allen Human Brain Atlas, followed by a set of gene functional feature analyses. 19 studies (1333 patients and 1174 healthy controls) were included in this meta-analysis. SCZ was characterized by hyperconnectivity of the auditory network, visual system, and sensorimotor areas, and hypoconnectivity of the frontal gyrus, cerebellum, thalamus, and caudate nucleus, which were significantly linked to age, sex, duration of illness, and the severity of symptoms and functionally enriched in domains involving self, sensory, action, and social. 2922 genes were significantly over-expressed in these regions, which were enriched for important molecular functions, biological processes, and cellular components of the neurons/cells in the brain as well as SCZ and other mental diseases. These genes were specially expressed in the brain tissue, in the neurons of the cerebellum, subcortex and cortex and during nearly all developmental stages, and constructed a protein-protein interaction network supported by 85 hub genes with functional significance. These findings suggest key regions aberrantly connected within CTCC in SCZ, which may indicate the neural substrate of \"cognitive dysmetria\" and be a consequence of complex interactions from a wide range of genes with diverse functional features.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"8"},"PeriodicalIF":3.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}