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Potential protective role of ACE-inhibitors and AT1 receptor blockers against levodopa-induced dyskinesias:a retrospective case-control study

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Neural Regeneration Research 2021年第12期16卷 2475-2478页

作者： Elena Contaldi Luca Magistrelli Anna VMilner Marco Cosentino Franca Marino Cristoforo Comi Movement Disorders Centre Neurology UnitDepartment of Translational MedicineUniversity of Piemonte OrientaleNovaraItaly PhD Program in Medical Sciences and Biotechnology University of Piemonte OrientaleNovaraItaly PhD Program in Clinical and Experimental Medicine and Medical Humanities University of InsubriaVareseItaly Center of Research in Medical Pharmacology University of InsubriaVareseItaly Center for Research in Neuroscience University of InsubriaVareseItaly

Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrostriatal pathway,thus affecting the development of levodopa-induced dyskinesia in Parkinson’s disease(PD).In the present study,we analyzed whether the use of this class of medication was associated with a reduced occurrence of levodopa-induced dyskinesia,using electronically-stored information of idiopathic PD patients enrolled at Novara University Hospital“Maggiore della Carità”.We conducted a retrospective case-control study identifying PD patients with dyskinesias(PwD;n=47)as *** each PwD we selected a non-dyskinetic control(NoD),nearly perfectly matched according to sex,Unified Parkinson’s Disease Rating Scale(UPDRS)part III score,and duration of antiparkinsonian *** logistic regression was used to evaluate whether dyskinesias were associated with ACEi/ARBs ***-four PD patients were included,aged 72.18±9 years,with an average disease duration of 10.20±4.8 years and 9.04±4.9 years of antiparkinsonian *** mean UPDRS part III score was 18.87±7.6 and the median HY stage was *** the NoD group,25(53.2%)were users and 22(46.8%)non-users of ACEi/***,in the PwD group,11(23.4%)were users and 36 non-users(76.6%)of this drug class(Pearson chi-square=8.824,P=0.003).Concerning general medication,there were no other statistically significant differences between *** controlling for tremor dominant phenotype,levodopa equivalent daily dose,HY 3-4,and disease duration,ACEi/ARBs use was a significant predictor of a lower occurrence of dyskinesia(OR=0.226,95%CI:0.080-0.636,P=0.005).Therefore,our study suggests that ACEi/ARBs may reduce levodopa-induced dyskinesia occurrence and,thanks to good tolerability and easy management,represent a feasible choice when dealing with the treatment of hypertension in PD patients.

关键词： angiotensin-converting enzyme inhibitors AT1 receptor blockers dyskinesias hypertension levodopa motor complications neuroinflammation Parkinson’s disease renin-angiotensin system

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srp54 promotes motor neuron development and is required for motility in zebrafish

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neuroscience 2025年 579卷 24-34页

作者： Nikaela Losievski Pooja Kamath Ashley Fox Natalie M Aloi Megan C Baird Amy Everest Thomas L Gallagher Sharon L Amacher Stephen J Kolb Department of Neurology The Ohio State University Wexner Medical Center Columbus OH USA Neuroscience Graduate Program The Ohio State University Columbus OH USA. Department of Neurology The Ohio State University Wexner Medical Center Columbus OH USA. Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus OH USA. English Department PhD Program in Writing Rhetoric and Literacy The Ohio State University Columbus OH USA. Department of Molecular Genetics The Ohio State University Columbus OH USA. Department of Molecular Genetics The Ohio State University Columbus OH USA Center for RNA Biology The Ohio State University Columbus OH USA. Department of Biological Chemistry & Pharmacology The Ohio State University Wexner Medical Center Columbus OH USA Center for RNA Biology The Ohio State University Columbus OH USA Center for Muscle Health and Neuromuscular Disorders The Ohio State University and Nationwide Children's Hospital Columbus OH USA. Center for Muscle Health and Neuromuscular Disorders The Ohio State University and Nationwide Children's Hospital Columbus OH USA. Electronic address: Stephen.Kolb@osumc.edu.

The signal recognition particle (SRP) is a highly conserved ribonucleoprotein (RNP) that translocates a subset of secreted and integral membrane proteins to the endoplasmic reticulum for proper localization. The most conserved SRP protein component, SRP54, has been implicated in the molecular etiology of spinal muscular atrophy (SMA). A key feature of SMA is the selective loss of motor neurons; however, the mechanism underlying this selectivity is unknown. SMA arises from deficient levels of the ubiquitously expressed Survival of Motor Neuron (SMN) protein. SMN is proposed to assemble the SRP, and SMN deficiency in SMA may attenuate SRP function and contribute to motor neuron death in patients. Using zebrafish embryos homozygous for a srp54 nonsense mutation (srp54), we investigated the requirement of Srp54 protein in motor axon development. The first grossly distinguishable phenotype observed in srp54 embryos was reduced motility at 30 h postfertilization (hpf). Additionally, we detected reduced length and branching of caudal primary motor axons in srp54 embryos compared to srp54 and srp54 siblings at 30 hpf, suggesting that defective motor neurons may contribute to the observed immotility. We also examined additional neural, secretory, and migratory cell types at 30 hpf to assess whether motor neurons are especially vulnerable to Srp54 deficiency. Of the cell types evaluated, only the hatching gland had distinct expression pattern alterations in srp54 embryos at this developmental stage. Our findings suggest that Srp54 deficiency results in motor neuron developmental defects and support the hypothesis that SRP54 may influence motor neuron selectivity in SMA.

关键词： Central nervous system Hatching gland Neurodevelopment Signal recognition particle Spinal muscular atrophy

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Differences in bipolar disorder type I and type II exposed to childhood trauma: A retrospective cohort study

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Journal of Affective Disorders Reports 2025年 19卷 100869-100869页

作者： Guillen-Burgos, Hernán F Gálvez-Flórez, Juan F Moreno-Lopez, Sergio Kwan, Angela T.H. Gomez, Oscar González-Haddad, Gerardo McIntyre, Roger S. Universidad Simon Bolivar Centro de Investigaciones en Ciencias de la Vida Center for Clinical and Translational Research Barranquilla Colombia Faculty of Medicine Center for Clinical and Translational Research Universidad El Bosque Bogotá D.C. Colombia Department of Psychiatry and Mental Health PhD Program of Neuroscience Hospital Universitario San Ignacio Pontificia Universidad Javeriana Bogotá D.C. Colombia School of Medicine Universidad de Los Andes Bogotá D.C. Colombia Faculty of Medicine University of Ottawa Ottawa K1H 8L1 ON Canada Division of Alcohol Drugs and Addiction McLean Hospital Harvard Medical School Boston MA United States Department of Psychiatry University of Toronto Toronto M5T 1R8 ON Canada

Background: Childhood trauma (CT) exposure is associated with a more pernicious course in bipolar disorder (BD). However, few studies have reported differences between BD I and BD II regarding CT exposure. We explore the differences in the CT trajectories in bipolar disorders. Methods: A retrospective cohort study of individuals with BD (BD I = 73 vs BD II = 73) was carried out. Early age at onset (EAO) and suicide ideation/behavior were used as severity outcomes. Timespan between EAO and treatment was documented and the associations between CT and comorbid alcohol used disorder (AUD), anxiety disorders (AD), and post-traumatic stress disorder (PTSD) were also described. Univariate, bivariate analyses, and a Poisson regression model with bootstrap resampling were used. Results: Higher scores of CT, physical abuse (PA), and sexual abuse (SA) were statistically significant for BD II than BD I (p < 0.001, p = 0.048, p < 0.001, respectively). Early age at onset, suicide ideation/behavior and treatment delay were associated with CT in both BD I and BD II. However, AUD and PTSD showed association with CT only for BD I. Limitations: Sample size, non-comparison control group, and recall bias. Conclusions: There are differences in CT subtype exposure between BD I and BD II with regards to early age onset, suicide ideation/behavior, delayed time to treatment, and comorbid mental disorders. These results claim for early access to strategies such as CT exposure screening in individuals with BD to detect possible pernicious course and improve the quality of life and clinical outcomes. © 2024

关键词： Bipolar disorder Childhood trauma Early age onset Mental comorbidities Suicide ideation/behavior Treatment delay

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Emerging roles of microglia cells in the regulation of adult neural stem cells

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Neuroimmunology and Neuroinflammation 2016年第1期3卷 204-206页

作者： Eduardo Lira-Diaz Oscar Gonzalez-Perez Laboratory of Neuroscience School of PsychologyUniversity of ColimaColima 28040Mexico Medical Sciences PhD Program School of MedicineUniversity of ColimaColima 28040Mexico

MICROGLIA CELLS Microglia cells are antigen presenting cells with myeloid origin that constituted approximately 10%of all glial cells of the adult mouse brain.^([1])In the early embryo,the microglial precursors are located in the yolk sac and progressively migrate throughout the primitive brain.^([2])In the adult brain,some of microglial cells derive from the bone marrow,but this process only takes place when the brain is lesioned.^([1])Microglial cells can display 4 morphological and functional stages:(1)resting microglia;(2)active microglia;(3)phagocytic microglia;and(4)senescent microglia.

关键词： neural migrate adult

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Tactile information from the vibrissal system modulates hippocampal functioning

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Current Research in Neurobiology 2022年第0期3卷 000-000页

作者： Ibarra-Castaneda, Nereida Moy-Lopez, Norma A. Gonzalez-Perez, Oscar Laboratory of Neuroscience School of Psychology University of Colima Colima Mexico Medical Science PhD Program School of Medicine University of Colima Colima Mexico

Most mammals have sensory tactile hairs, also known as whiskers or vibrissae. Traditionally, whiskers are associated with diverse survival skills, including tactile discrimination, distance assessment, food acquisition, gap crossing, and social interaction. Vibrissae functions are processed in the somatosensorial cortex, commonly referred to as the barrel cortex. Hence, most of the whisker-related research has been focused on this cortical region. However, increasing evidence indicates that the vibrissal system modulates several aspects of hippocampal physiology. This graphical review aims to summarize cumulative evidence indicating that whiskers regulate the neural function and cellularity in several hippocampal subfields. Interestingly, lack of whiskers notably affects neuronal firing in CA1 and CA3 hippocampal subfields, alters spatial mapping, impairs navigational skills, modifies cytoarchitecture, and reduces the adult neurogenesis in the dentate gyrus. This evidence extends our understanding of how whiskers are related to hippocampal function and offers insights to explore novel associations between whisker functions and neural plasticity in the hippocampus. © 2022 The Authors

关键词： Adult neurogenesis Barrel cortex Hippocampus Subgranular zone Vibrissae

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Tract Integrity Predicts Neurological Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy

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Pediatrics & Neonatology 2025年

作者： Pei-Ling Tsai Yu-Chun Lo Yi-Shan Tsai Yea-Shwu Hwang Ting-Chun Lin Yao-Wen Liang Chen-En Huang Fu-Chun Hsu Yi-Fang Tu You-Yin Chen Institute of Allied Health Sciences College of Medicine National Cheng Kung University Tainan Taiwan PhD Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei Taiwan Department of Medical Imaging National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan Department of Occupational Therapy College of Medicine National Cheng Kung University Tainan Taiwan Department of Biomedical Engineering National Yang Ming Chiao Tung University Taipei Taiwan College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Department of Pediatrics National Cheng Kung University Hospital College of Medicine National Cheng Kung University Tainan Taiwan Institute of Clinical Medicine College of Medicine National Cheng Kung University Tainan Taiwan Medical Device Innovation and Translation Center National Yang Ming Chiao Tung University Taipei Taiwan

Objective Early prognostication in infants with neonatal hypoxic-ischemic encephalopathy (HIE) is crucial for follow-up management. Alternations of microstructural integrity of neural fiber tracts in large-scale neural networks might predict neurological outcomes. Methods All consecutively-admitted patients with neonatal HIE from 2016 to 2020 were enrolled. Diffusion tensor imaging (DTI) tractography was performed at 4–7 days of age. Neurodevelopmental outcomes at 24 months of age were assessed with Bayley Scales of Infant Development, 3rd edition. Results A total of 62 HIE infants were enrolled, and 53 of these underwent DTI. Fractional anisotropy (FA) and mean diffusivity (MD) were measured to indicate the microstructural integrity of tracts, including the arcuate fasciculus, uncinate fasciculus, inferior fronto-occipital fasciculus, corticospinal tract (CST), and optic radiations (OR). Lower FA values of target tracts were associated with lower developmental scores at 24 months of age, particularly in the CST and OR (all P ≤ 0.003). The prognostic accuracy of FA values in CST surpassed that in the region of thalamus/basal ganglia (area under curves 0.839, 95% CI: 0.728–0.950 vs. 0.755, 95% CI: 0.583–0.928). Furthermore, the correlation between FA values in target tracts and developmental scores was most significant in infants with HIE stage III and this was not affected by therapeutic hypothermia. Conclusion Tract integrity in the CST and OR detected by DTI provides valuable insights for early prognostication in infants with HIE, regardless of therapeutic hypothermia.

关键词： neonatal hypoxic-ischemic encephalopathy diffusion tensor imaging tractography corticospinal tract optic radiations neurodevelopmental outcome

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Application of generalized linear models to investigate functional synaptic coupling and synchrony in an animal model of schizophrenia

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BMC neuroscience 2015年第1期16卷 1-2页

作者： Jennifer L Zick Rachael K Blackman Matthew V Chafee Theoden I Netoff Graduate Program in Neuroscience University of Minnesota Minneapolis MN 55455 USA Medical Scientist Training Program (MD/PhD) University of Minnesota Minneapolis MN 55455 USA Brain Sciences Center VA Medical Center Minneapolis MN 55417 USA Department of Biomedical Engineering University of Minnesota Minneapolis MN 55455 USA

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The mystery of phospho-Drp1 with four adaptors in cell cycle: when mitochondrial fission couples to cell fate decisions

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Cell Cycle 2023年第21-22期22卷 2485-2503页

作者： Wu, Nian-Siou Ma, I-Chu Lin, Yi-Fan Ko, Huey-Jiun Loh, Joon-Khim Hong, Yi-Ren Department of Education Hsin-Chu Branch National Taiwan University Hospital Hsinchu Taiwan PhD Program in Molecular Medicine National Tsing Hua University Hsinchu Taiwan Division of Neurology China Medical University Hospital Taichung Taiwan Department of Education National Taiwan University Hospital Taipei Taiwan Department of Biochemistry College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Neurosurgery Kaohsiung Medical University Hospital Kaohsiung Taiwan Graduate Institutes of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Biological Sciences National Sun Yat-Sen University Kaohsiung Taiwan Department of Medical Research Kaohsiung Medical University Hospital Kaohsiung Taiwan Center for Cancer Research Kaohsiung Medical University Kaohsiung Taiwan Neuroscience Research Center Kaohsiung Medical University Kaohsiung Taiwan

Recent study had deepened our knowledge of the mitochondrial dynamics to classify mitochondrial fission into two types. To further clarify the relationship between the two distinct fission machinery and the four major adaptors of Drp1, we propose a model of mechanism elucidating the multiple functions of phospho-Drp1 with its adaptors during cell cycle and providing in-depth insights into the molecular basis and evolutionary implications in depth. The model highlights not only the clustering characteristics of different phospho-Drp1 with respective subsets of mitochondrial pro-fission adaptors but also the correlation, crosstalk and shifting between different clustering of phosphorylated Drp1-adaptors during different key fission situations. Particularly, phospho-Drp1 (Ser616) couples with Mff/MiD51 to exert mitochondrial division and phospho-Drp1 (Ser637) couples with MiD49/Fis1 to execute mitophagy in M-phase. We then apply the model to address the relationship of mitochondrial dynamics to Parkinson’s disease (PD) and carcinogenesis. Our proposed model is indeed compatible with current research results and pathological observations, providing promising directions for future treatment design. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

关键词： cell cycle Drp1 Mitochondrial Adaptors mitophagy phosphorylation

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Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration Research 2024年第11期19卷 2365-2376页

作者： Victoria Cunha Alves Eva Carro Joana Figueiro-Silva Neurodegenerative Diseases Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical Research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical Genetics University of ZurichZurichSwitzerland Department of Molecular Life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA *** review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease *** examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease *** entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the ***,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal ***,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory *** complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation *** the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease *** research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2L RHBDF2

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Atlas of Gray Matter Volume Differences Across Psychiatric Conditions: A Systematic Review With a Novel Meta-Analysis That Considers Co-Occurring Disorders

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Biological Psychiatry 2025年

作者： Fortea, Lydia Ortuño, Maria De Prisco, Michele Oliva, Vincenzo Albajes-Eizagirre, Anton Fortea, Adriana Madero, Santiago Solanes, Aleix Vilajosana, Enric Yao, Yuanwei Del Fabro, Lorenzo Solé, Eduard Verdolini, Norma Farré-Colomés, Alvar Serra-Blasco, Maria Picó-Pérez, Maria Lukito, Steve Wise, Toby Carlisi, Christina Arnone, Danilo Kempton, Matthew J. Hauson, Alexander Omar Wollman, Scott Soriano-Mas, Carles Rubia, Katya Norman, Luke Fusar-Poli, Paolo Mataix-Cols, David Valentí, Marc Via, Esther Cardoner, Narcis Solmi, Marco Zhang, Jintao Pan, Pinglei Shin, Jae Il Fullana, Miquel A. Vieta, Eduard Radua, Joaquim Institut d'Investigacions Biomèdiques August Pi I Sunyer Barcelona Spain Department of Medicine University of Barcelona Institute of Neuroscience Barcelona Spain Centro de Investigación Biomédica en Red de Salud Mental Instituto de Salud Carlos III Madrid Spain Bipolar and Depressive Disorders Unit Hospital Clínic Barcelona Spain Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy Psychiatric and Psychology Service Hospital Clínic Barcelona Spain Schizophrenia Unit Hospital Clínic Barcelona Spain Department of Psychology The University of Hong Kong Hong Kong Department of Systems Neuroscience University Medical Center Hamburg-Eppendorf Hamburg Germany Department of Pathophysiology and Transplantation University of Milan Milan Italy Local Health Unit Umbria 1 Department of Mental Health Mental Health Center of Perugia Perugia Italy Department of Addictive Behaviour and Addiction Medicine Central Institute of Mental Health Medical Faculty of Mannheim Heidelberg University Mannheim Germany eHealth ICOnnecta't Program and Psycho-Oncology Service Institut Català d'Oncologia L'Hospitalet de Llobregat Spain Psycho-oncology and Digital Health Group Health Services Research in Cancer Institut d'Investigació Biomèdica de Bellvitge L'Hospitalet del Llobregat Spain Live and Health Sciences Research Institute University of Minho Braga Portugal ICVS/3B's PT Government Associate Laboratory Guimarães Braga Portugal Departamento de Psicología Básica Universitat Jaume I Castelló de la Plana Spain Department of Child and Adolescent Psychiatry Institute of Psychology Psychiatry and Neuroscience King's College London London United Kingdom Department of Neuroimaging Institute of Psychiatry Psychology & Neurosciences King's College London London United Kingdom Division of Psychology and Language Sciences University College London London United Kingdom Centre for Affective Disorders Psychological Medicine King's College London Londo

Background: Regional gray matter volume (GMV) differences between individuals with mental disorders and comparison participants may be confounded by co-occurring disorders. To disentangle disorder-specific GMV correlates, we conducted a large-scale multidisorder meta-analysis using a novel approach that explicitly models co-occurring disorders. Methods: We systematically reviewed voxel-based morphometry studies indexed in PubMed and Scopus up to January 2023 that compared adults with major mental disorders (anorexia nervosa, schizophrenia spectrum, anxiety, bipolar, major depressive, obsessive-compulsive, and posttraumatic stress disorders plus attention-deficit/hyperactivity, autism spectrum, and borderline personality disorders) with comparison participants. Two authors independently extracted data and assessed quality using the Newcastle-Ottawa Scale. We derived GMV correlates for each disorder using: 1) a multidisorder meta-analysis that accounted for all co-occurring mental disorders simultaneously and 2) separate standard meta-analyses for each disorder in which co-occurring disorders were ignored. We assessed the alterations’ extent, intensity (effect size), and specificity (interdisorder correlations and transdiagnostic alterations) for both approaches. Results: We included 433 studies (499 datasets) involving 19,718 patients and 16,441 comparison participants (51% female, ages 20–67 years). We provide GMV correlate maps for each disorder using both approaches. The novel approach, which accounted for co-occurring disorders, produced GMV correlates that were more focal and disorder specific (less correlated across disorders and fewer transdiagnostic abnormalities). Conclusions: This work offers the most comprehensive atlas of GMV correlates across major mental disorders. Modeling co-occurring disorders yielded more specific correlates, supporting this approach's validity. The atlas NIfTI maps are available online. © 2024 Society of Biological Psychiatry

关键词： Anxiety disorders Comorbidity Gray matter volume Major depressive disorder Meta-analysis Psychiatric conditions

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