American Journal of Medical Genetics Part B: Neuropsychiatric Genetics最新文献

{"title":"Schizophrenia Genetics Modulates Clinical Depressive Features","authors":"Alessandro Serretti,&nbsp;Daniel Souery,&nbsp;Siegfried Kasper,&nbsp;Joseph Zohar,&nbsp;Stuart Montgomery,&nbsp;Panagiotis Ferentinos,&nbsp;Dan Rujescu,&nbsp;Raffaele Ferri,&nbsp;Giuseppe Fanelli,&nbsp;Chiara Fabbri,&nbsp;Raffaella Zanardi,&nbsp;Francesco Benedetti,&nbsp;Bernhard T. Baune,&nbsp;Julien Mendlewicz","doi":"10.1002/ajmg.b.33066","DOIUrl":"10.1002/ajmg.b.33066","url":null,"abstract":"<p>Schizophrenia (SCZ) genetic liability, quantified by polygenic scores (PGS), may influence clinical phenotypes in major depressive disorder (MDD). We investigated the effect of the SCZ-PGS derived from the latest SCZ genome-wide association study (GWAS) on MDD symptom severity, comorbidities, and treatment outcomes. The study included 1060 adults diagnosed with MDD from the GSRD sample, with replication in the STAR*D sample (<i>n</i> = 1503 MDD). Baseline and current depressive symptoms were assessed along with functional impairment and comorbid conditions. SCZ-PGS was calculated based on the latest SCZ GWAS summary statistics. Higher SCZ-PGS was associated with more severe baseline depressive symptoms, including apparent sadness, inner tension, lassitude, pessimistic thoughts, and suicidality. Functional impairment in social, familial, and work domains also increased with higher SCZ-PGS. Multivariable models suggested a small but significant independent association between elevated SCZ-PGS and poorer outcomes, confirmed in the STAR*D sample. Elevated SCZ-PGS correlated with a series of features suggesting more severe depression in both samples. Our findings confirm that the latest SCZ genetic liability scores contribute to MDD clinical heterogeneity, increasing depressive severity, functional impairment, and anxiety comorbidity. Although its influence on treatment response appears modest, SCZ-PGS may serve as a marker for more severe depressive presentations.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 3","pages":"180-193"},"PeriodicalIF":1.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.33066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 4","pages":"257-269"},"PeriodicalIF":1.5,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148066002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 4","pages":"300-310"},"PeriodicalIF":1.5,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148079071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 4","pages":"246-256"},"PeriodicalIF":1.5,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148085074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 4","pages":"291-299"},"PeriodicalIF":1.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148069774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 4","pages":"270-290"},"PeriodicalIF":1.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148067106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 4","pages":"227-245"},"PeriodicalIF":1.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148094857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Genetic Landscape of Kynurenine Predicts Neurovascular Pathology and Disrupted White Matter Integrity in Patients With Mood Disorders","authors":"Beatrice Bravi,&nbsp;Lidia Fortaner-Uyà,&nbsp;Marco Paolini,&nbsp;Stefano Comai,&nbsp;Sara Poletti,&nbsp;Cristina Lorenzi,&nbsp;Sara Spadini,&nbsp;Alessandro Serretti,&nbsp;Cristina Colombo,&nbsp;Raffaella Zanardi,&nbsp;Francesco Benedetti","doi":"10.1002/ajmg.b.33060","DOIUrl":"10.1002/ajmg.b.33060","url":null,"abstract":"<div>\u0000 \u0000 <p>Low-grade systemic inflammation is linked to cardiometabolic diseases and increased cardiovascular risk. Patients with mood disorders, such as Major Depressive Disorder (MDD) and Bipolar Disorder (BD), also show elevated cardiovascular risk and inflammatory markers, suggesting shared biological pathways between mood and cardiometabolic conditions. The kynurenine (KYN) pathway, activated by inflammatory cytokines and involved in neurotransmitter systems linked to mood, provides a promising area to explore inflammatory-related genetic overlaps in these disorders, with increasing interest in the SH2B3 rs3184504 SNP. Imaging markers like white matter hyperintensities (WMHs) and white matter (WM) microstructure alterations are associated with mood and cardiovascular disorders. This study aimed to investigate the genetic load linked to KYN levels, such as KYN polygenic risk score (PRS) and its effect on white matter hyperintensities (WMHs), outcomes of presumed vascular suffering, and WM microstructure in a sample of 95 MDD and 80 BD patients. Higher PRS for KYN was associated with increased circulating KYN levels and KYN/TRP ratio. KYN PRS predicted the presence of WMHs. The SH2B3 rs3184504 T variant was associated with increased PRS for KYN and a higher number of WMHs. KYN levels and KYN/TRP ratio were not associated with WMHs, while KYN PRS positively correlated with higher axial (AD) and mean diffusivity (MD), with a nominal significance for radial diffusivity (RD). The findings support a genetic contribution to elevated KYN and WM integrity alterations in mood disorders. PRS for KYN indicates a potential predisposition to inflammatory and vascular dysregulation, and SH2B3 rs3184504 may modulate this risk.</p>\u0000 </div>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 2","pages":"144-155"},"PeriodicalIF":1.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treg Cells Modulate Neuroinflammation and Behavioral Deficits in Autism: Evidence From MR-Based Genetic Analyses and Experimental Models","authors":"Zuqing Nie,&nbsp;Xinyi Xu,&nbsp;Junhao Chen,&nbsp;Huiling Chen,&nbsp;Meng Li,&nbsp;Yang Zhang,&nbsp;Zhiwei Li,&nbsp;Chen Shen,&nbsp;Jie Wen,&nbsp;Xia Cao","doi":"10.1002/ajmg.b.33061","DOIUrl":"10.1002/ajmg.b.33061","url":null,"abstract":"<p>Autism spectrum disorder (ASD) is a neurodevelopmental condition that is increasingly linked to immune dysfunction and neuroinflammation. Regulatory T cells (Tregs), which are crucial in maintaining immune homeostasis, have been implicated in the pathogenesis of ASD. However, their role in neuroimmune interactions and behavioral outcomes remains poorly understood. We employed Mendelian Randomization (MR) to assess the causal relationship between Tregs and ASD risk, using genetic data to infer causality. To further confirm the reliability of the MR results, we incorporated data from an independent genome-wide association study (GWAS) and conducted a meta-analysis to strengthen causal inference. Additionally, we validated our findings in an ASD-like mouse model (BTBR mice) treated with the IL-2/JES6.1 complex to enhance Tregs' function. Neuroinflammation and behavioral outcomes were assessed in treated and control mice. MR analysis revealed significant associations between several Tregs subsets and ASD risk. The proportion of CD127^‒ CD8⁺ T cells among total T cells showed a consistent protective effect (OR = 0.84, <i>p</i> = 0.01166), which was validated across multiple analytical methods. The absolute count of resting CD4⁺ regulatory T cells was also inversely associated with ASD risk and demonstrated an independent protective effect in multivariable MR analysis. Sensitivity analyses revealed no evidence of horizontal pleiotropy or heterogeneity. Experimental treatment with IL-2/JES6.1 in BTBR mice significantly increased CD4⁺ Tregs populations, enhanced CD4⁺ Tregs activation, and improved social interactions and repetitive behavior. Furthermore, IL-2/JES6.1 treatment reduced neuroinflammatory markers, including microglial activation. Transcriptomic analysis revealed that IL-2/JES6.1 treatment induced neuroendocrine and synaptic plasticity pathways in the hippocampus and cortex while suppressing inflammatory signaling. This study demonstrates that Tregs modulation can influence ASD pathogenesis through immune regulation and behavioral improvement. Our findings highlight the potential of Treg-targeted therapies for ASD. Future studies should focus on the mechanistic pathways involved and explore the clinical applicability of these therapies.</p>","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 2","pages":"127-143"},"PeriodicalIF":1.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajmg.b.33061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pseudo-Schizophrenia Should Always Be Considered in Genetic Studies Regarding Psychosis","authors":"João Gama-Marques,&nbsp;Josef Finsterer","doi":"10.1002/ajmg.b.33062","DOIUrl":"10.1002/ajmg.b.33062","url":null,"abstract":"","PeriodicalId":7673,"journal":{"name":"American Journal of Medical Genetics Part B: Neuropsychiatric Genetics","volume":"201 2","pages":"91-92"},"PeriodicalIF":1.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}