Schizophrenia (Heidelberg, Germany)最新文献

{"title":"Body fluid biomarkers and psychosis risk in The Accelerating Medicines Partnership® Schizophrenia Program: design considerations.","authors":"Diana O Perkins, Clark D Jeffries, Scott R Clark, Rachel Upthegrove, Cassandra M J Wannan, Naomi R Wray, Qingqin S Li, Kim Q Do, Elaine Walker, G Paul Amminger, Alan Anticevic, David Cotter, Lauren M Ellman, David Mongan, Christina Phassouliotis, Jenna Barbee, Sharin Roth, Tashrif Billah, Cheryl Corcoran, Monica E Calkins, Felecia Cerrato, Ines Khadimallah, Paul Klauser, Inge Winter-van Rossum, Angela R Nunez, Rachel S Bleggi, Alicia R Martin, Sylvain Bouix, Ofer Pasternak, Jai L Shah, Catherine Toben, Daniel H Wolf, Rene S Kahn, John M Kane, Patrick D McGorry, Carrie E Bearden, Barnaby Nelson, Martha E Shenton, Scott W Woods","doi":"10.1038/s41537-025-00610-4","DOIUrl":"10.1038/s41537-025-00610-4","url":null,"abstract":"<p><p>Advances in proteomic assay methodologies and genomics have significantly improved our understanding of the blood proteome. Schizophrenia and psychosis risk are linked to polygenic scores for schizophrenia and other mental disorders, as well as to altered blood and saliva levels of biomarkers involved in hormonal signaling, redox balance, and chronic systemic inflammation. The Accelerating Medicines Partnership® Schizophrenia (AMP®SCZ) aims to ascertain biomarkers that both predict clinical outcomes and provide insights into the biological processes driving clinical outcomes in persons meeting CHR criteria. AMP®SCZ will follow almost 2000 CHR and 640 community study participants for two years, assessing biomarkers at baseline and two-month follow-up including the collection of blood and saliva samples. The following provides the rationale and methods for plans to utilize polygenic risk scores for schizophrenia and other disorders, salivary cortisol levels, and a discovery-based proteomic platform for plasma analyses. We also provide details about the standardized methods used to collect and store these biological samples, as well as the study participant metadata and quality control measures related to preanalytical factors that could influence the values of the biomarkers. Finally, we discuss our plans for analyzing the results of blood- and saliva-based biomarkers. Watch Dr. Perkins discuss their work and this article: https://vimeo.com/1062879582?share=copy#t=0 .</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"78"},"PeriodicalIF":3.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121641","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":"I fear you're getting too close: neural correlates of personal space violation in paranoia.","authors":"Mélodie Derome, Frauke Conring, Nicole Gangl, Adamantini Hatzipanayioti, Florian Wüthrich, Maximilian Rüter, Stephanie Lefebvre, Sebastian Walther, Katharina Stegmayer","doi":"10.1038/s41537-025-00625-x","DOIUrl":"10.1038/s41537-025-00625-x","url":null,"abstract":"<p><p>Increased personal space (PS) is a clinically relevant marker for paranoia. Neuroimaging evidence suggested limbic and prefrontal circuit alterations related to threat processing and emotion regulation (i.e., amygdala, fronto-parietal cortex). We hypothesize that patients with paranoia will respond with altered activation in PS-relevant brain areas (i.e., limbic regions, fronto-parietal cortex) toward personal space intrusion. We included 79 participants with various degrees of paranoia severity; 49 patients diagnosed with schizophrenia and 30 controls. In this fMRI study, participants passively viewed pictures of facial expressions in approaching, static, or retracting motions. Violation of PS was modelled with the approaching faces condition. We used firstly a cut off to separate patients in high and low paranoia, and secondly the continuous variations of paranoia severity to understand the full picture. While participants were passively watching faces approaching them in contrast to static faces, group comparison revealed that patients with high paranoia showed hypoactivity mainly in the OFC when compared to patients with low paranoia, and hypoactivity in dlPFC and dPCC when compared to controls. Further, paranoia severity was positively associated with activation of the right hippocampus. Altered neural activity in the OFC, dlPFC, and hippocampus may well reflect the neural responses to the paranoid experience of threat and provide evidence for the hypothesized association between limbic dysfunction and paranoid threat. Modelling of paranoia severity captures variance in neural response to approaching threat, which may be previously undetected due to heterogeneity when examined at the group level.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"77"},"PeriodicalIF":3.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113023","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":"Delusion-like thinking is associated with lower individual alpha peak frequency.","authors":"Luca Tarasi, Domenico Romanazzi, Anna Pasini, Vincenzo Romei","doi":"10.1038/s41537-025-00626-w","DOIUrl":"10.1038/s41537-025-00626-w","url":null,"abstract":"<p><p>Schizophrenia and schizotypy are understood to lie along a continuum of neurophysiological and cognitive features, yet the specific neural markers bridging clinical and subclinical manifestations have remained underexplored. In our study (N = 318), we found that reduced Individual Alpha Frequency (IAF)-previously established as a neural marker in schizophrenia-features magical thinking trait in schizotypy. This finding broadens the relevance of IAF to subclinical populations linking it to delusion-like thinking in schizotypy and suggests its potential as a transdiagnostic indicator across the schizophrenia spectrum.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"76"},"PeriodicalIF":3.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102382","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":"Pathways between childhood trauma, clinical symptoms, and functioning in new-onset psychosis: novel insights from a network analysis approach.","authors":"Dimitrios Kiakos, Luis Alameda, Ines Lepreux, Caroline Conchon, Livia Alerci, Marianna Gorgellino, Nadir Mebdouhi, Teya Petrova, Philippe Golay, Lilith Abrahamyan Empson, Philippe Conus, Sandra Vieira","doi":"10.1038/s41537-025-00620-2","DOIUrl":"10.1038/s41537-025-00620-2","url":null,"abstract":"<p><p>Childhood trauma (CT) has been linked to various domains of outcomes in individuals with new-onset psychosis, but the intricate relationships between different types of trauma, clinical symptoms, and functioning remain poorly understood. The aim of this study was to identify patterns of relationships between these three domains in first-episode psychosis (FEP). The study sample consisted of 277 patients from the Treatment and Early Intervention in Psychosis Program (TIPP) at Lausanne University Hospital. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS), functioning was evaluated with an adapted version of the general subscale of the Premorbid Adjustment Scale (PAS), and the five most common CT experiences (sexual, physical and emotional abuse; physical and emotional neglect) was measured using a tailored questionnaire. Data from early assessments (2 and 6 months after admission) were used for analysis. A network model was fitted to estimate the shortest pathways linking different types of CT to various domains of functioning. Our findings revealed two distinct pathways connecting CT to functioning. One pathway influenced occupational functioning through sexual abuse and depression, while another pathway affected socio-personal functioning through physical neglect and stereotyped thinking. Our results suggest that distinct disease phenotypes could be differentially associated with CT and functioning in individuals with new-onset psychosis. This study contributes to the growing evidence supporting the existence of multiple distinct pathways to psychosis, each linked to a different clinical phenotype.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"75"},"PeriodicalIF":3.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082734","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":"Increased face perception in individuals at clinical high-risk for psychosis: mechanisms, sex differences, and clinical correlates.","authors":"Tanya Tran, Brian P Keane, Judy L Thompson, Ben Robinson, Joshua Kenney, Trevor F Williams, James A Waltz, Jason A Levin, Eren Kafadar, James M Gold, Jason Schiffman, Lauren M Ellman, Elaine F Walker, Gregory P Strauss, Vijay A Mittal, Richard E Zinbarg, Philip R Corlett, Albert R Powers, Scott W Woods, Steven M Silverstein","doi":"10.1038/s41537-025-00624-y","DOIUrl":"10.1038/s41537-025-00624-y","url":null,"abstract":"<p><p>Altered visual perception has been observed across all phases of psychotic illness, suggesting that perceptual measures might be useful in identifying people at clinical high risk for psychosis (CHR). In a preliminary study, we found that CHR participants reported perceiving more faces in binarized human portraits on the Mooney Faces Test (MFT). Here, we aimed to replicate these findings and extend understanding of underlying processes and clinical correlates of MFT performance in the Computerized Assessment of Psychosis Risk (CAPR) cohort: CHR (n = 159), help-seeking psychiatric controls (n = 130), and healthy controls (n = 86). The MFT was adapted to include three image conditions (upright, inverted, and scrambled), and included follow-up questions regarding the physical characteristics of the faces that participants reported perceiving, to verify accuracy of perception and assess response bias. The CHR group reported more faces than both control groups in the inverted and scrambled conditions. In addition, the CHR group was as accurate at judging the age and gender of faces as the other groups. Among CHR participants, increased reporting of faces in the inverted condition was significantly correlated with more severe positive symptoms and poorer role functioning. We discuss the findings in terms of multiple perspectives, including changes in perceptual sensitivity, predictive coding, and perceptual organization.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"74"},"PeriodicalIF":3.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12069608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031507","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":"Symptomatic and cognitive effects of D-amino acid oxidase inhibitors in patients with schizophrenia: a meta-analysis of double-blind randomized controlled trials.","authors":"Chun-Hung Chang, Yu-Der Hsia, Wen-Chun Liu, Jia-Hau Lee, Chieh-Hsin Lin, Hsien-Yuan Lane","doi":"10.1038/s41537-025-00604-2","DOIUrl":"https://doi.org/10.1038/s41537-025-00604-2","url":null,"abstract":"<p><p>D-amino acid oxidase inhibitors (DAOI) have demonstrated potential therapeutic benefits for schizophrenia and cognitive impairment; however, existing studies present conflicting results. This meta-analysis aimed to assess the symptomatic and cognitive effects of DAOI on the treatment of schizophrenia. An electronic search was conducted using PubMed, Cochrane Systematic Reviews, and the Cochrane Central Register of Controlled Clinical Trials for double-blinded, randomized controlled trials evaluating DAOI for the treatment of schizophrenia. Published trials up to November 2024 were included in the analysis. A random-effects model was employed to pool data for comparing the treatment effects of DAOI. Participants diagnosed with schizophrenia were recruited. Clinical and cognitive improvements were compared between baseline and post-DAOI treatment using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity across the trials was assessed through funnel plots and the I² statistic. A total of five trials with 530 participants met the inclusion criteria. Four trials utilized sodium benzoate, while one trial employed luvadaxistat. The Positive and Negative Syndrome Scale (PANSS) was used in all studies to evaluate clinical symptoms, with four studies also assessed cognitive function. This analysis highlighted that DAOI surpassed the comparator in reducing the scores of PANSS total (SMD = -0.270, P = 0.035), PANSS positive (SMD = -0.399, P = 0.022), PANSS negative (SMD = -0.171, P = 0.026), and PANSS general psychopathology (SMD = -0.180, P = 0.019). Subgroup analyses identified significant effects in trials using sodium benzoate (SMD = 0.368, P = 0.021). Moreover, DAOI showed greater improvements in cognitive functions (SMD = 0.359, P = 0.017), with a better effect correlated with more female participants. The findings of this meta-analysis suggest that DAOI may be effective in improving clinical symptoms and cognitive function in patients with schizophrenia. Further studies with larger sample sizes are needed to confirm these results.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"73"},"PeriodicalIF":3.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058575","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":"Alterations and potential associations of repetitive transcranial magnetic stimulation on body weight in stable schizophrenic patients.","authors":"Wenxi Sun, Jing Chen, Xiaoyun Dai, Lihong Chao, Chuanwei Li, Longjun Zhu, Xiuxia Wang, Xiaobin Zhang, Xiangdong Du, Guangya Zhang","doi":"10.1038/s41537-025-00621-1","DOIUrl":"https://doi.org/10.1038/s41537-025-00621-1","url":null,"abstract":"<p><p>Although antipsychotic medications are effective in managing schizophrenia (SCZ), there are still no effective strategies or preventive measures to address the weight gain associated with the long-term use of these medications. We performed a single-blind, randomized, sham-controlled clinical trial to explore the efficacy of noninvasive high-frequency repetitive transcranial magnetic stimulation (rTMS) technology in reducing body weight in patients with SCZ. Fifty-three obese patients with chronic stable SCZ (BMI ≥30 kg/m²) completed a 4-week intervention study. The primary outcomes were the changes in body weight and body mass index (BMI) before and after the rTMS intervention. Secondary outcomes included changes in psychiatric symptoms, cognitive function, and routine blood indicators before and after the rTMS intervention. Significant changes in weight and BMI were found before and after the rTMS intervention in the active stimulation group (mean change = -2.25 kg, P < 0.01; mean change = -0.08, P < 0.001). Weight and BMI decreased significantly more in the active stimulation group compared to the sham stimulation group 4 weeks after the intervention (all P < 0.05). In the active stimulation group, immediate memory, attention, and delayed memory were significantly elevated before and after the rTMS intervention (P < 0.001). Delayed memory was more significantly elevated in the active stimulation group relative to the sham stimulation group 4 weeks after the intervention (P < 0.05). In the active stimulation group, weight change was significantly correlated with attention change and cognitive total score change (all P < 0.05). In the active stimulation group, BMI change was significantly associated with attention change and cognitive total score change (all P < 0.05). Our findings indicate that high-frequency rTMS could serve as a potential method for reducing body weight in obese patients with chronic stable SCZ.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"72"},"PeriodicalIF":3.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058686","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":"Assessing the inter-rater reliability of the Schizophrenia Cognition Rating Scale: a non-interventional quantitative study.","authors":"Sebastien Tulliez, Stella Karantzoulis, James C Marcus, Montserrat Casamayor, Cassie Blanchard, Haig Goenjian, Joshua T Kantrowitz, Lara Shirikjian, John Sonnenberg, Corey Reuteman-Fowler, Philip D Harvey, Richard S E Keefe","doi":"10.1038/s41537-025-00619-9","DOIUrl":"https://doi.org/10.1038/s41537-025-00619-9","url":null,"abstract":"<p><strong>Background: </strong>Cognitive impairment is a core feature of schizophrenia, profoundly impacting patients' functional abilities. As such, evaluating cognition-related functional activity/impairment is essential for identifying effective treatments. This study presents findings from a non-interventional quantitative study to assess the inter-rater reliability (IRR) of the Schizophrenia Cognition Rating Scale (SCoRS) with a sample representative of clinical trial populations.</p><p><strong>Methods: </strong>Structured, one-to-one, 10-15-minute live interviews with patients with schizophrenia were conducted by trained SCoRS interviewers (raters), and a separate interview was then conducted with the patient's study partner (informant). Both interviews were recorded so that each interview was assessed by three different SCoRS raters in total (one live, two via recording). IRR was assessed using interclass correlation (ICC) and categorized as low (<0.70), good (0.70-0.90), or excellent (>0.90).</p><p><strong>Results: </strong>A total of 44 patients with schizophrenia were evaluated by 12 raters (overall). The SCoRS Total Score (mean [SD]: 41.4 [10.2]) indicated moderate-to-moderately-severe impairment of cognition-related functioning, with high inter-patient variability. The SCoRS Total Score demonstrated excellent IRR, with an ICC of 0.91 (95% CI 0.88-0.95).</p><p><strong>Conclusion: </strong>The 20-item SCoRS Total Score demonstrated excellent IRR in assessing cognition-related functional capacity in patients with schizophrenia, supporting its use as an endpoint in clinical studies.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"71"},"PeriodicalIF":3.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051838","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":"Heterogeneity of morphometric similarity networks in health and schizophrenia.","authors":"Joost Janssen, Ana Guil Gallego, Covadonga Martínez Díaz-Caneja, Noemi Gonzalez Lois, Niels Janssen, Javier González-Peñas, Pedro Macias Gordaliza, Elizabeth Buimer, Neeltje van Haren, Celso Arango, René Kahn, Hilleke E Hulshoff Pol, Hugo G Schnack","doi":"10.1038/s41537-025-00612-2","DOIUrl":"https://doi.org/10.1038/s41537-025-00612-2","url":null,"abstract":"<p><p>Reduced structural network connectivity is proposed as a biomarker for chronic schizophrenia. This study assessed regional morphometric similarity as an indicator of cortical inter-regional connectivity, employing longitudinal normative modeling to evaluate whether decreases are consistent across individuals with schizophrenia. Normative models were trained and validated using data from healthy controls (n = 4310). Individual deviations from these norms were measured at baseline and follow-up, and categorized as infra-normal, normal, or supra-normal. Additionally, we assessed the change over time in the total number of infra- or supra-normal regions for each individual. At baseline, patients exhibited reduced morphometric similarity within the default mode network compared to healthy controls. The proportion of patients with infra- or supra-normal values in any region at both baseline and follow-up was low (<6%) and similar to that of healthy controls. Mean intra-group changes in the number of infra- or supra-normal regions over time were minimal (<1) for both the schizophrenia and control groups, with no significant differences observed between them. Normative modeling with multiple timepoints enables the identification of patients with significant static decreases and dynamic changes of morphometric similarity over time and provides further insight into the pervasiveness of morphometric similarity abnormalities across individuals with chronic schizophrenia.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"70"},"PeriodicalIF":3.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002045","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":"Unique and overlapping mechanisms of valbenazine, deutetrabenazine, and vitamin E for tardive dyskinesia.","authors":"Chao Li, Chuanjun Zhuo, Xiaoyan Ma, Ranli Li, Ximing Chen, Yachen Li, Qiuyu Zhang, Lei Yang, Hongjun Tian, Lina Wang","doi":"10.1038/s41537-025-00618-w","DOIUrl":"https://doi.org/10.1038/s41537-025-00618-w","url":null,"abstract":"<p><p>In 2017, the Food and Drug Administration (FDA) approved valbenazine and deutetrabenazine, two vesicular monoamine transporter 2 (VMAT2) inhibitors, as treatments for tardive dyskinesia (TD). Additionally, some trials have suggested that vitamin E may benefit TD patients. However, the mechanistic basis for these treatments remains unclear. The objective of this study was to analyze and compare the mechanisms of valbenazine, deutetrabenazine, and vitamin E in TD treatment utilizing network pharmacology and molecular docking approaches. Putative target genes associated with valbenazine, deutetrabenazine, and vitamin E were retrieved from the PharmMapper, CTD, GeneCards, SwissTargetPrediction, and DrugBank databases. TD-related targets were identified using the GeneCards, DisGeNET, OMIM, and TTD databases. A protein-protein interaction (PPI) network was created to identify core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via DAVID, and Cytoscape was used to build a drug-pathway-target-disease network. Molecular docking evaluated drug-target interactions. A total of 32, 36, and 62 targets relevant to the treatment of TD were identified for valbenazine, deutetrabenazine, and vitamin E, respectively. PPI and KEGG pathway analyses suggested that valbenazine and deutetrabenazine may influence TD through the dopaminergic synapse signaling pathway via common core targets (e.g., Dopamine Receptor D1 (DRD1), DRD2, Monoamine Oxidase B (MAOB), Solute Carrier Family 6 Member 3 (SLC6A3), SLC18A2) and specific targets (DRD3 for valbenazine, MAOA for deutetrabenazine). Vitamin E may affect TD by targeting the PI3K-Akt pathway through AKT Serine/Threonine Kinase 1 (AKT1), Brain-Derived Neurotrophic Factor (BDNF), Insulin (INS), Nitric Oxide Synthase 3 (NOS3), and Toll-Like Receptor 4 (TLR4). This study provides insights into the common and unique molecular mechanisms by which valbenazine, deutetrabenazine, and vitamin E may treat TD. Pharmacological experiments should be conducted to verify and further explore these results. The findings offer a theoretical basis for further pharmacological investigation and a resource for TD drug screening.</p>","PeriodicalId":74758,"journal":{"name":"Schizophrenia (Heidelberg, Germany)","volume":"11 1","pages":"69"},"PeriodicalIF":3.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12019491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047825","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}