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Tobacco and alcohol use are associated with increased BAG; however, no studies have compared global and regional BAG across substances other than alcohol and tobacco. This study aimed to compare global and regional estimates of brain age in individuals with substance use disorders and healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>This was a cross\u2010sectional study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>This is an Enhancing Neuro Imaging through Meta\u2010Analysis Consortium (ENIGMA) Addiction Working Group study including data from 38 global sites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>This study included 2606 participants, of whom 1725 were cases with a substance use disorder and 881 healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements<\/jats:title><jats:p>This study used the Kaufmann brain age prediction algorithms to generate global and regional brain age estimates using T1 weighted magnetic resonance imaging (MRI) scans. We used linear mixed effects models to compare global and regional (FreeSurfer lobestrict output) BAG (i.e. predicted minus chronological age) between individuals with one of five primary substance use disorders as well as healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>Alcohol use disorder (\u03b2\u2009=\u2009\u22125.49, <jats:italic>t<\/jats:italic>\u2009=\u2009\u22125.51, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) was associated with higher global BAG, whereas amphetamine\u2010type stimulant use disorder (\u03b2\u2009=\u20093.44, <jats:italic>t<\/jats:italic>\u2009=\u20092.42, <jats:italic>p<\/jats:italic>\u2009=\u20090.02) was associated with lower global BAG in the separate substance\u2010specific models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>People with alcohol use disorder appear to have a higher brain\u2010age gap than people without alcohol use disorder, which is consistent with other evidence of the negative impact of alcohol on the brain.<\/jats:p><\/jats:sec>","DOI":"10.1111\/add.16621","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T01:03:48Z","timestamp":1724288628000},"page":"1937-1946","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mega\u2010analysis of the brain\u2010age gap in substance use disorder: An ENIGMA Addiction working group study"],"prefix":"10.1111","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8898-8599","authenticated-orcid":false,"given":"Freda","family":"Scheffler","sequence":"first","affiliation":[{"name":"Neuroscience Institute University of Cape Town  Cape Town South Africa"},{"name":"Department of Psychiatry and Mental Health University of Cape Town  Cape Town South 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