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Transdiagnostic and disorder\u2010specific brain changes associated with familial risk for developing these disorders remain poorly understood. We carried out a meta\u2010analysis of diffusion tensor imaging (DTI) studies to investigate white matter microstructure abnormalities in relatives that might correspond to shared and discrete biomarkers of familial risk for psychotic or mood disorders. A systematic search of PubMed and Embase was performed to identify DTI studies in relatives of SCZ, BD, and MDD patients. Seed\u2010based <jats:italic>d<\/jats:italic> Mapping software was used to investigate global differences in fractional anisotropy (FA) between overall and disorder\u2010specific relatives and healthy controls (HC). Our search identified 25 studies that met full inclusion criteria. A total of 1,144 relatives and 1,238 HC were included in the meta\u2010analysis. The overall relatives exhibited decreased FA in the genu and splenium of corpus callosum (CC) compared with HC. This finding was found highly replicable in jack\u2010knife analysis and subgroup analyses. In disorder\u2010specific analysis, compared to HC, relatives of SCZ patients exhibited the same changes while those of BD showed reduced FA in the left inferior longitudinal fasciculus (ILF). The present study showed decreased FA in the genu and splenium of CC in relatives of SCZ, BD, and MDD patients, which might represent a shared familial vulnerability marker of severe mental illness. The white matter abnormalities in the left ILF might represent a specific familial risk for bipolar disorder.<\/jats:p>","DOI":"10.1002\/hbm.25827","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T09:04:56Z","timestamp":1647248696000},"page":"2936-2950","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Structural connectivity associated with familial risk for mental illness: A meta\u2010analysis of diffusion tensor imaging studies in relatives of patients with severe mental disorders"],"prefix":"10.1002","volume":"43","author":[{"given":"Mengyuan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Radiology West China Hospital of Sichuan University  Chengdu China"},{"name":"Research Unit of Psychoradiology Chinese Academy of Medical Sciences  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology West China Hospital of Sichuan University  Chengdu China"},{"name":"Research Unit of Psychoradiology Chinese Academy of Medical Sciences  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Hochwalt","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengmin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiology West China Hospital of Sichuan University  Chengdu China"},{"name":"Research Unit of Psychoradiology Chinese Academy of Medical Sciences  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naici","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology West China Hospital of Sichuan University  Chengdu China"},{"name":"Research Unit of Psychoradiology Chinese Academy of Medical Sciences  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Radiology West China Hospital of Sichuan University  Chengdu China"},{"name":"Research Unit of Psychoradiology Chinese Academy of Medical Sciences  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Radiology West China Hospital of Sichuan University  Chengdu China"},{"name":"Research Unit of Psychoradiology Chinese Academy of Medical Sciences  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa P.","family":"DelBello","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3541-1769","authenticated-orcid":false,"given":"Su","family":"Lui","sequence":"additional","affiliation":[{"name":"Department of Radiology West China Hospital of Sichuan University  Chengdu China"},{"name":"Research Unit of Psychoradiology Chinese Academy of Medical Sciences  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiano G.","family":"Nery","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"107","article-title":"The anterior cingulate cortex \u2010 the evolution of an interface between emotion and cognition","volume":"935","author":"Allman J. 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