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Background and Aims: The brain age gap (BAG), calculated as the difference between a machine learning model‐based predicted brain age and chronological age, has been increasingly investigated in psychiatric disorders. 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. Design: This was a cross‐sectional study. Setting: This is an Enhancing Neuro Imaging through Meta‐Analysis Consortium (ENIGMA) Addiction Working Group study including data from 38 global sites. Participants: This study included 2606 participants, of whom 1725 were cases with a substance use disorder and 881 healthy controls. Measurements: 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. Findings Alcohol use disorder (β = −5.49, t = −5.51, p < 0.001) was associated with higher global BAG, whereas amphetamine‐type stimulant use disorder (β = 3.44, t = 2.42, p = 0.02) was associated with lower global BAG in the separate substance‐specific models. Conclusions: People with alcohol use disorder appear to have a higher brain‐age gap than people without alcohol use disorder, which is consistent with other evidence of the negative impact of alcohol on the brain. [ABSTRACT FROM AUTHOR]

Neuroimaging studies have linked the methionine (Met) allele of the brain-derived neurotrophic factor ( BDNF) gene to abnormal regional brain volumes in several psychiatric and neurodegenerative diseases. However, no neuroimaging studies assessed the effects of this allele on brain morphology in alcohol use disorders and its demonstrated change during abstinence from alcohol. Here we assessed the effects of the BDNF Val66Met (rs6265) polymorphism on regional brain tissue volumes and their recovery during short-term abstinence in treatment-seeking alcohol-dependent individuals. 3D T1 weighted magnetic resonance images from 62 individuals were acquired at 1.5 T at one week of abstinence from alcohol; 41 of the participants were rescanned at 5 weeks of abstinence. The images were segmented into gray matter (GM), white matter (WM) and cerebrospinal fluid and parcellated into regional volumes. The BDNF genotype was determined from blood samples using the TaqMan technique. Alcohol-dependent Val (Valine)/Met heterozygotes and Val homozygotes had similar regional brain volumes at either time point. However, Val homozygotes had significant GM volume increases, while Val/Met heterozygotes increased predominantly in WM volumes over the scan interval. Longitudinal increases in GM but not WM volumes were related to improvements in neurocognitive measures during abstinence. The findings suggest that functionally significant brain tissue volume recovery during abstinence from alcohol is influenced by BDNF genotype. [ABSTRACT FROM AUTHOR]