Alpha psychiatry最新文献

{"title":"Effects of Deep Transcranial Magnetic Stimulation on Cognitive Function in Bipolar Depression: A Randomized Controlled Trial Using the MATRICS Consensus Cognitive Battery.","authors":"Lijun Chu, Xiaoju Jia, Ping Gao, Xia Sun, Jian Zhang, Yu Ding, Shiwang Chen, Fuyou Bi, Chuhao Zhang, Dazhi Li, Yong Zhang","doi":"10.31083/AP47409","DOIUrl":"https://doi.org/10.31083/AP47409","url":null,"abstract":"<p><strong>Background: </strong>Bipolar disorder (BD) is characterized by persistent cognitive deficits. These deficits contribute to functional impairment and often respond poorly to pharmacotherapy. Although deep transcranial magnetic stimulation (dTMS) has demonstrated antidepressant efficacy, there is limited knowledge about its cognitive effects and comprehensive clinical performance in BD. In this study, we assessed the cognitive outcomes, clinical efficacy, and safety of H1-coil dTMS in BD patients.</p><p><strong>Methods: </strong>In this randomized, double-blind, sham-controlled trial, 100 inpatients with BD received 4 weeks of active or sham H1-coil dTMS. The MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB) was used to investigate the cognitive function, and the 17-item Hamilton Depression Rating Scale (HDRS-17) was used to assess depressive symptoms from baseline to week 4.</p><p><strong>Results: </strong>Both groups, active and sham dTMS, showed significant cognitive improvements across most domains (<i>p</i> < 0.05), with no statistically significant between-group differences (all <i>p</i> > 0.05). At the endpoint, the active dTMS group showed statistically significantly lower HDRS-17 scores and a higher response rate than the sham group (mean difference = 2.94, 95% CI [0.10, 5.78], <i>p</i> = 0.04); 50% vs. 24%; OR = 3.17, 95% CI [1.35, 7.44], <i>p</i> = 0.007). All treatments demonstrated a favorable safety profile, with only mild and transient adverse effects.</p><p><strong>Conclusions: </strong>In patients with BD, active dTMS was well-tolerated and was associated with a higher response rate and statistically significant (albeit modest) lower depressive symptom scores compared to sham stimulation, without inducing cognitive adverse effects. However, no specific cognitive benefit beyond its antidepressant effect was established. Overall, these results indicate that dTMS has potential as an adjunctive treatment option for bipolar depression, particularly when medications are limited or poorly tolerated.</p><p><strong>Clinical trial registration: </strong>NCT06524505. Registered 23 July, 2024, https://clinicaltrials.gov/study/NCT06524505.</p>","PeriodicalId":72151,"journal":{"name":"Alpha psychiatry","volume":"27 1","pages":"47409"},"PeriodicalIF":3.5,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367436","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":"UPLC-MS/MS Analytical Method for the Simultaneous Quantification of Diazepam, Nordazepam, and Oxazepam in Patients With Alcohol Dependence.","authors":"Xiao-Lin Li, Wan-Ting Huang, Xiao-Jia Ni, Hao-Yang Lu, Shan-Qing Huang, Yu-Qing Li, Huan-Shan Xie, Yu-Guan Wen, Zhan-Zhang Wang, De-Wei Shang","doi":"10.31083/AP38973","DOIUrl":"https://doi.org/10.31083/AP38973","url":null,"abstract":"<p><strong>Background: </strong>To establish a method for the simultaneous quantification of diazepam (DIA) and its active metabolites, nordazepam (NorD) and oxazepam (OXAZ), and provide a reference range for therapeutic concentrations in patients with alcohol dependence.</p><p><strong>Methods: </strong>Simple and direct protein precipitation was used to extract the biological samples. Subsequent separation was performed on an Agilent XDB-C18 column (50 mm × 4.6 mm, 1.8 μm) with a column temperature maintained at 35 °C and a flow rate of 0.5 mL/min via ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The mobile phase consisted of methanol-water containing 5 mM ammonium formate (75:25, v/v). Detection was conducted using electrospray ionization in multiple reaction monitoring modes: <i>m/z</i> 284.6→193.2 for DIA, <i>m/z</i> 270.5→140.1 for NorD, <i>m/z</i> 286.9→241.1 for OXAZ, <i>m/z</i> 289.6→198.2 for DIA-D5, <i>m/z</i> 275.5→140.0 for NorD-D5, and <i>m/z</i> 291.9→246.1 for OXAZ-D5. The linear response range for DIA, NorD, and OXAZ was 1-1500 ng/mL.</p><p><strong>Results: </strong>The key parameters of the bioanalytical method were validated: the average extraction recovery was 95%-101% (CV <6%); calibration curves exhibited good linearity over the concentration range (R² ≥0.99 for all analytes); accuracy was within 85%-115%; and intra-day and inter-day precision were satisfactory (CVs <15%). The concentrations of analytes in 26 routine therapeutic drug monitoring (TDM) samples from patients with alcohol dependence were determined.</p><p><strong>Conclusions: </strong>We developed and validated a rapid, simple, and economic UPLC-MS/MS method for the quantification of DIA, NorD, and OXAZ in human serum. The method is well-suited for the determination of serum levels of DIA and its active metabolites in patients with alcohol dependence, and could be further applied to TDM and subsequent studies.</p>","PeriodicalId":72151,"journal":{"name":"Alpha psychiatry","volume":"27 1","pages":"38973"},"PeriodicalIF":3.5,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367379","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":"Prediction of Smartphone Addiction Among Korean Adolescents Based on Physical Activity and Mental Health: A Machine Learning Analysis Using LASSO and SHAP From the Korea Youth Risk Behavior Survey.","authors":"Kihyuk Lee, Wooin Seo, Se Young Jung","doi":"10.31083/AP46201","DOIUrl":"https://doi.org/10.31083/AP46201","url":null,"abstract":"<p><strong>Background: </strong>Adolescent smartphone overuse is associated with physical inactivity and mental health problems, such as anxiety. However, few studies have analyzed these factors jointly using both linear and non-linear methods. This study aimed to predict smartphone addiction using physical activity and mental health indicators from the 2020 and 2023 Korea Youth Risk Behavior Survey, applying Least Absolute Shrinkage and Selection Operator (LASSO), multiple machine learning models, and SHapley Additive exPlanations (SHAP) analysis.</p><p><strong>Methods: </strong>A total of 86,744 adolescents were classified into general (n = 63,963), potential risk (n = 20,383), and high-risk (n = 2398) smartphone user groups. For the binary classification, general users were compared with combined-risk users. Twelve key predictors were selected using LASSO. Logistic Regression, Random Forest, Extreme Gradient Boosting (XGBoost), and Light Gradient Boosting Machine (LightGBM) models were implemented with Synthetic Minority Over-sampling Technique balancing; SHAP was used to compare variable importance across models.</p><p><strong>Results: </strong>LASSO identified moderate physical activity (β = -0.156), strength physical activity (-0.149), loneliness (0.144), smartphone usage time (0.085), and anxiety (0.078) as major predictors. Random Forest and Logistic Regression showed the best recall (0.63 and 0.60); LightGBM had the highest accuracy (0.726). It also achieved the highest Area Under the Receiver Operating Characteristic Curve (AUROC) (0.7108); XGBoost showed the lowest AUROC (0.5621). SHAP consistently ranked anxiety and smartphone usage time as the top predictors, with sleep and physical activity showing variable importance.</p><p><strong>Conclusions: </strong>Anxiety and smartphone usage time were consistently dominant predictors. Physical activity variables contributed in some models but showed inconsistent importance. These findings highlight the central role of mental health, with behavioral factors playing a secondary, model-specific role.</p>","PeriodicalId":72151,"journal":{"name":"Alpha psychiatry","volume":"27 1","pages":"46201"},"PeriodicalIF":3.5,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367395","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":"Integrated Interventions for Executive Function Deficits in Children with Autism Spectrum Disorder: From Cognitive Training to Neuroregulation.","authors":"Liuyan Zhu, Dan Yao","doi":"10.31083/AP40062","DOIUrl":"https://doi.org/10.31083/AP40062","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) is classified as a neurodevelopmental disorder primarily characterized by difficulties in social interaction, restricted interests, and repetitive behaviors. Advances in neuropsychological research have highlighted the crucial role of executive function (EF) deficits in children with ASD and their impact on the core symptoms of the disorder. EF encompasses higher-order cognitive processes, including working memory, cognitive flexibility, and inhibitory control. Given that EF deficits represent a significant cognitive impairment in this population, the variability in clinical intervention outcomes underscores the need for targeted strategies informed by underlying neural mechanisms. This narrative review explores the current research landscape on EF deficits in children with ASD. It synthesizes empirical findings related to cognitive and motor training, neuromodulation techniques, and collaborative interventions involving families and schools. The aim is to provide theoretical and practical guidance for enhancing EF and improving the quality of life of children with ASD.</p>","PeriodicalId":72151,"journal":{"name":"Alpha psychiatry","volume":"27 1","pages":"40062"},"PeriodicalIF":3.5,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367420","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":"Alexithymia, Resilience, and Depression in Functional Impairment Among Adolescents With Eating Disorders: A Case-Control Study.","authors":"Yavuz Meral, Saliha Açıkgöz, Alperen Bıkmazer, Büşra Arslan, Oğuzhan Koyuncu, Melike Ayşegül Kara Karaman, Vahdet Görmez","doi":"10.31083/AP45458","DOIUrl":"https://doi.org/10.31083/AP45458","url":null,"abstract":"<p><strong>Background: </strong>Eating disorders (EDs) in adolescence are associated with marked emotional difficulties and broad functional impairment. The objective of this study was to examine the relationships among alexithymia, resilience, internalizing symptoms (anxiety and depression), and functional impairment in adolescents with EDs.</p><p><strong>Method: </strong>A cross-sectional, case-control study included 51 adolescents diagnosed with EDs according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria (primarily anorexia nervosa, bulimia nervosa, and binge eating disorder) and 57 matched controls. Adolescents completed self-report measures assessing alexithymia, resilience, and internalizing symptoms, and parents reported on functional impairment.</p><p><strong>Results: </strong>Adolescents with EDs showed significantly greater functional impairment at both global and subdomain levels, along with higher levels of depressive and anxiety symptoms, higher alexithymia scores, and lower resilience than did controls. Difficulty describing feelings (DDF) was the only variable significantly associated with ED group membership. Within the ED group, functional impairment was positively correlated with depressive symptoms, anxiety symptoms, DDF, and difficulty identifying feelings (DIF), and was negatively correlated with resilience. Depressive symptoms were significantly associated with functional impairment, and mediation analyses indicated that the association between DIF and global functional impairment was statistically mediated by depressive symptoms.</p><p><strong>Conclusion: </strong>These findings suggested that adolescents with EDs experience widespread functional difficulties, with depressive mood, exacerbated by challenges in emotion identification, potentially contributing to these impairments.</p>","PeriodicalId":72151,"journal":{"name":"Alpha psychiatry","volume":"27 1","pages":"45458"},"PeriodicalIF":3.5,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367344","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":"Neurocognitive Processing of Facial Emotion Recognition in Individuals With Depression and Suicidal Ideation: An Eye-Tracking and EEG Study.","authors":"Qianlan Yin, Huijing Xu, Ying Zhu, Meng Liang, Qian Jiang, Bin Zhao, Taosheng Liu","doi":"10.31083/AP44992","DOIUrl":"https://doi.org/10.31083/AP44992","url":null,"abstract":"<p><strong>Background: </strong>Suicide ideation (SI) is a critical concern, and understanding its neurocognitive underpinnings is essential for improved risk assessment. This study investigates altered neurocognitive processing during face recognition in individuals with depression and SI, utilizing a multimodal approach combining eye-tracking, electroencephalography (EEG), and deconvolution modeling.</p><p><strong>Methods: </strong>Eye-tracking and EEG data were recorded during face recognition tasks in individuals with depression, with and without SI. We analyzed visual attention patterns (fixation durations, saccadic velocities) and event-related potentials to emotional stimuli. Deconvolution analysis separated microsaccade-related activities (like regression-based event-related potential (rERP) and regression-based fixation-related potential (rFRP)).</p><p><strong>Results: </strong>Individuals with SI exhibited attentional biases toward emotional faces, characterized by shorter first fixation durations and faster saccadic velocities. Reduced rERP amplitudes in response to surprise and decreased rFRP amplitudes during sad conditions were also observed, suggesting altered neural responses. Integrating eye-tracking and EEG data (the area under the curve (AUC) = 0.771) improved the accuracy of detecting SI compared to eye-tracking alone (AUC = 0.643).</p><p><strong>Conclusions: </strong>These findings provide novel evidence for altered neurocognitive processing of emotional faces in individuals with depression and SI. The multimodal approach highlights the potential of combining eye-tracking and EEG measures as biomarkers for identifying individuals at risk. Future research should focus on larger, more diverse samples and longitudinal designs to validate these findings and translate them into clinical applications.</p>","PeriodicalId":72151,"journal":{"name":"Alpha psychiatry","volume":"27 1","pages":"44992"},"PeriodicalIF":3.5,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367447","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":"ERP Decoding Analysis of Visual Working Memory Processes in Schizophrenia.","authors":"Zhongsi Wang, Chunlei Liu, Yuyan Jing, Zhenzhen Yao, Min Chen","doi":"10.31083/AP42597","DOIUrl":"https://doi.org/10.31083/AP42597","url":null,"abstract":"<p><strong>Background: </strong>Deficits in visual working memory (vWM) represent a core cognitive impairment in schizophrenia; however, the dynamic spatiotemporal characterization of their underlying neural mechanisms remains unclear. The present study employed multivariate pattern classification (MVPC) and searchlight analysis to investigate neural signaling differences between patients with schizophrenia (PSZ) and healthy control subjects (HCS) during a vWM task.</p><p><strong>Methods: </strong>A total of 46 participants (22 PSZ, 24 HCS) completed a change detection task comprising three conditions: two targets, zero distractors (2T0D); two targets, two distractors (2T2D); and four targets, zero distractors (4T0D). Contralateral delay activity (CDA) was extracted through event-related potential (ERP) analysis. MVPC was applied in the temporal dimension, while a searchlight approach was employed in the spatial dimension to decode memory load (2T0D/2T2D/4T0D) and memory side (left/right) information.</p><p><strong>Results: </strong>CDA amplitude was significantly reduced in the PSZ group, particularly in the 2T2D condition (<i>p</i> = 0.01), indicating that the scope and control of attention elicited comparable CDA amplitudes. MVPC analysis revealed that decoding accuracy in the PSZ group was significantly lower than in the HCS group during the time window of 93-652 ms (<i>p</i> _corrected < 0.05), suggesting diminished efficiency of neural information encoding during the delay period. The searchlight analysis identified the most pronounced decrease in decoding accuracy within the left parietal region in the PSZ group, consistent with the hypothesis of abnormal functional connectivity in the inferior parietal gyrus (IPG).</p><p><strong>Conclusions: </strong>This study reveals the spatiotemporal dynamics of vWM deficits in schizophrenia, characterized by ERP decoding technology. It offers a novel target for the development of neuromarker-based cognitive interventions.</p>","PeriodicalId":72151,"journal":{"name":"Alpha psychiatry","volume":"27 1","pages":"42597"},"PeriodicalIF":3.5,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367469","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":"Reducing Disparities and Improving Mental Health for Transgender Persons.","authors":"Osborne F X Almeida, Pedro Morgado","doi":"10.31083/AP45278","DOIUrl":"https://doi.org/10.31083/AP45278","url":null,"abstract":"<p><p>This opinion piece primarily targets health and ancillary professionals, but it is also intended to serve as an unbiased guide for policymakers and legislators worldwide. It calls for the protection of human rights and advocates for evidence-based, inclusive health and socio-legal policies for all, regardless of gender identity. The article clarifies the distinctions between biological sex, sexual orientation, and gender, and critically examines and refutes the growing misconception that recognizing diverse gender identities is a political matter rather than a medical and human rights issue. In fact, gender diversity has existed across cultures for millennia. A major concern addressed in this piece is how societal norms expose transgender and gender non-conforming (TGNC) persons to stigma, discrimination, and social exclusion. The focus, however, is on the heightened vulnerability of TGNC individuals, particularly those from marginalized groups (for example, immigrants, individuals with low socio-economic status, non-White populations), to mental health conditions such as depression, anxiety, eating disorders, substance misuse, and suicidal ideation. Young TGNC persons and those with intersecting marginalized identities (for example, migratory background, socio-economic disadvantage, skin color) are especially susceptible to victimization. Many of these difficulties are exacerbated by discrimination, lack of legal protections, and societal prejudice. The article also addresses disparities in TGNC rights and protections across different regions, with the highest levels in Western Europe and North America and the lowest in the Middle East and Africa, and highlights how the scarcity of robust TGNC research in the Global South may adversely affect the health and well-being of TGNC individuals in those regions. The authors propose eight actionable recommendations to improve mental health outcomes for gender minorities: (i) collecting more nuanced data that distinguishesdifferentiates TGNC people from other sexsexual and gender minorities (under the Lesbian, Gay, Bisexual, Transgender, Queer + umbrella); (ii) fostering dialogue and research to counter misinformation about TGNC persons; (iii) incorporating gender diversity into early education; (iv) promoting human connectedness and social support; (v) developing inclusive mental healthcare services; (vi) improving professional training on gender diversity; (vii) establishing centres specializing in gender medicine; and (viii) banning harmful practices such as gender identity conversion efforts. The importance of cultural sensitivity when implementing these recommendations is emphasized.</p>","PeriodicalId":72151,"journal":{"name":"Alpha psychiatry","volume":"27 1","pages":"45278"},"PeriodicalIF":3.5,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367476","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":"Group Sparse Representation Enhances Brain Network Classification of Major Depressive Disorder in Two Chinese Cohorts.","authors":"Defu Zhang, Cancan Lin, Aoxue Zhang, Xubo Wang, Wenjie Xia, Yue Wang, Yuxin Du, Hao Yu, Shanling Ji","doi":"10.31083/AP40685","DOIUrl":"https://doi.org/10.31083/AP40685","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is associated with altered organization of functional brain networks. This study aims to evaluate the classification efficacy of three brain networks constructed by Pearson correlation (PC), sparse representation (SR), and group sparse representation (GSR) in distinguishing patients with MDD from healthy controls (HCs).</p><p><strong>Methods: </strong>The present study involved the recruitment of 117 Chinese participants, comprising 61 individuals diagnosed with MDD and 56 HCs, all of whom underwent functional magnetic resonance imaging (fMRI). Brain time-series signals were extracted from 116 regions to construct whole-brain networks utilizing PC, SR, and GSR. A linear support vector machine (SVM) classifier with least absolute shrinkage and selection operator (LASSO) feature selection was trained using leave-one-out cross-validation (LOOCV) to optimize generalizability. An independent dataset of Chinese (124 first-episode drug-naïve MDD and 105 HCs) was utilized for additional validation.</p><p><strong>Results: </strong>Compared to the PC and SR, the GSR network yielded superior classification results, with an area under the receiver operating characteristic curve of 0.85, an accuracy of 0.81, and a sensitivity of 0.95. Similar results were observed in the independent MDD dataset. We identified 17 brain connections and 27 brain regions within the GSR network.</p><p><strong>Conclusions: </strong>Our findings support the adoption of GSR-based brain networks as a robust tool for MDD diagnosis, challenging the conventional reliance on PC in neuroimaging research.</p>","PeriodicalId":72151,"journal":{"name":"Alpha psychiatry","volume":"27 1","pages":"40685"},"PeriodicalIF":3.5,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367482","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":"Altered Expression of GABA-Related Genes in Schizophrenia: Insights from Meta-Analyses of Brain and Blood Samples and iPSC-Derived Organoids.","authors":"Yuval Singer, Assif Yitzhaky, Libi Hertzberg","doi":"10.31083/AP43531","DOIUrl":"https://doi.org/10.31083/AP43531","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia, one of the most disabling mental disorders, affects approximately seven per 1000 individuals worldwide and has an estimated heritability of around 80%; however, its pathophysiology remains incompletely understood. The disorder has been linked to dysregulation of multiple neurotransmitter systems, including dopamine, serotonin, γ-aminobutyric acid (GABA), and glutamate. GABA, the primary inhibitory neurotransmitter in the central nervous system, is synthesized by the enzymes glutamic acid decarboxylase 67 (GAD67) and glutamic acid decarboxylase 65 (GAD65), encoded by the <i>GAD1</i> and <i>GAD2</i> genes, respectively. The genes (<i>SST</i>) and parvalbumin (<i>PVALB</i>) encode somatostatin and parvalbumin, which are characteristic markers of specialized GABAergic interneuron subpopulations involved in maintaining excitatory-inhibitory balance and supporting cortical circuit function. While reduced <i>GAD1</i> expression has been consistently reported in schizophrenia, findings regarding <i>GAD2</i> expression have been inconsistent.</p><p><strong>Methods: </strong>In this study, we examined the expression of <i>GAD1</i>, <i>GAD2</i>, <i>SST</i>, and <i>PVALB</i> across three biological levels: postmortem brain tissue, peripheral blood samples, and patient-derived induced pluripotent stem cell (iPSC)-derived brain organoids, compared with healthy controls. The meta-analysis of brain tissue included seven independent datasets (295 samples: 151 individuals with schizophrenia and 144 healthy controls) and was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Patient-derived iPSC organoids were used to investigate early neurodevelopmental alterations, while a separate meta-analysis of peripheral blood gene expression included 293 samples (160 schizophrenia, 133 controls) to explore biomarker potential.</p><p><strong>Results: </strong>Both <i>GAD1</i> and <i>GAD2</i> were significantly downregulated in postmortem brain samples (meta-analytic effect sizes <-0.5) and in iPSC-derived organoids, supporting the hypothesis that reduced expression of these genes emerges prior to clinical onset and may contribute to disease development. In contrast, decreased expression of <i>SST</i> and <i>PVALB</i> was observed in brain tissue but not in organoids, suggesting that alterations in these interneuron markers may occur at later stages of the disease. Notably, reduced <i>PVALB</i> expression was also detected in peripheral blood samples, indicating its potential utility as a peripheral biomarker for schizophrenia.</p><p><strong>Conclusions: </strong>Further studies are required to clarify the causal role of reduced GABAergic activity in schizophrenia pathogenesis and to evaluate the clinical relevance of <i>PVALB</i> expression for diagnosis and treatment monitoring.</p>","PeriodicalId":72151,"journal":{"name":"Alpha psychiatry","volume":"27 1","pages":"43531"},"PeriodicalIF":3.5,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367311","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}