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Individuals vary on the degree to which they exhibit neurobiological and clinical differences following maltreatment. Individuals with bipolar disorder exhibit greater magnitude of maltreatment-related prefrontal-paralimbic gray matter volume (GMV) deficits compared to typically developing individuals. It is unclear if greater structural differences stem from greater neural vulnerability to maltreatment in bipolar disorder, or if they relate to presence of other clinical features associated with childhood maltreatment, e.g., elevated prevalence of comorbid substance use disorders. To investigate this, we compared young adults with a family history of bipolar disorder (n\u2009=\u200921), but who did not fulfill diagnostic criteria for bipolar disorder, with typically developing young adults without a family history of bipolar disorder (n\u2009=\u200926). Participants completed structural neuroimaging, clinical and family history interviews, and assessment of childhood maltreatment and recent alcohol and cannabis use patterns. We examined relations between childhood maltreatment and prefrontal-paralimbic GMV by modeling main effects of maltreatment and family history group by maltreatment interactions on prefrontal-paralimbic GMV. We also examined relations between maltreatment and associated GMV changes with recent alcohol and cannabis use. Childhood maltreatment correlated with lower ventral, rostral and dorsolateral prefrontal and insular cortical GMV across all participants regardless of the presence or absence of familial history of bipolar disorder. However, exploratory analyses did reveal greater maltreatment-related GMV differences in individuals with prodromal symptoms of depression. Lower insula GMV was associated with greater frequency of cannabis use across all participants and greater quantity of alcohol use only in those with familial risk for bipolar disorder. Results suggest familial risk for bipolar disorder, and presumably genetic risk, may relate to outcomes following childhood maltreatment and should be considered in prevention\/early intervention strategies.<\/jats:p>","DOI":"10.1038\/s41598-020-80407-w","type":"journal-article","created":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T11:13:01Z","timestamp":1610104381000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Childhood maltreatment, prefrontal-paralimbic gray matter volume, and substance use in young adults and interactions with risk for bipolar disorder"],"prefix":"10.1038","volume":"11","author":[{"given":"Dylan E.","family":"Kirsch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Tretyak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepeadeh","family":"Radpour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wade A.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles B.","family":"Nemeroff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Fromme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Strakowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth T. 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SMS consults for Sunovian and Otsuka and holds research grants with Janssen. ETCL received funding for a Janssen-sponsored study through UT. In the last 3\u00a0years, CN has consulted to Xhale, Takeda, Taisho Pharmaceutical Inc., Signant, Sunovion Pharmaceuticals Inc., Janssen Research & Development, Magstim, Inc., Navitor Pharmaceuticals, Inc., Actify Neurotherapies, Intra-Cellular Therapies, Inc. CN is a Stockholder of Xhale, Celgene, Seattle Genetics, Abbvie, Antares, BI Gen Holdings, Inc., Corcept Therapeutics Pharmaceuticals Company, TC MSO, Inc., and Trends in Pharma Development, LLC. CN is a member of the scientific advisory boards of the Brain and Behavior Research Foundation (BBRF), Xhale, Anxiety Disorder Association of America (ADAA), Skyland Trail, Signant Health, Laureate Institute for Brain Research (LIBR), Inc. and on the board of directors of AFSP, Gratitude America, Chale Smart and ADAA. CN has had income sources or equity of 10,000 USD or more from American Psychiatric Publishing, Xhale, Signant Health, CME Outfitters, Actify Neurotherapies, Intra-Cellular Therapies, Inc., and Magstim. CN holds the following patents: method and devices for transdermal delivery of lithium (US 6375990B1), Method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitter by ex vivo assay (US 7148027B2), and Compounds, Compositions, Methods of Synthesis, and Methods of Treatment (CRF Receptor Binding Ligand) (US 8551996 B2). All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"123"}}