Structural MRI data from 19 subjects did not pass our data quality standards and were excluded from further analysis. Reasons for exclusion included not passing the manual quality inspection due to structural abnormalities (N=4), poor quality of skull stripping (N=5), and poor gray matter image quality associated with extreme covariance parameters (N=10). The remaining 88 scans, 43 HR offspring (Mean age 27.4 ± 3.6 years) and 45 LR offspring (Mean age 24.5 ± 4.1 years) were available for the VBM analysis. Cumulative estimates of personal exposure to alcohol, drugs, and cigarettes along with diagnoses concerning alcohol abuse, alcohol dependence, drug abuse and drug dependence up to the time of the MRI scan were available for all 88 subjects who had participated in the longitudinal follow-up. Substance use disorder was defined as presence of either alcohol abuse or dependence, or drug abuse or dependence. The mothers’ use of alcohol, drugs, and cigarettes was not available for some participants (alcohol and drug exposure [N=8], cigarette use [N=5]). A total of 75 subjects (HR=36, LR=39) had complete prenatal use data for VBM analysis.