Associations Between Family History of Alcohol and/or Substance Use Problems and Frontal Cortical Development From 9 to 13 Years of Age: A Longitudinal Analysis of the ABCD Study.

Background: Previous investigations that have examined associations between family history (FH) of alcohol/substance use and adolescent brain development have been primarily cross-sectional. Here, leveraging a large population-based sample of youths, we characterized frontal cortical trajectories among 9- to 13-year-olds with (FH+) versus without (FH-) an FH and examined sex as a potential moderator.

Methods: We used data from 9710 participants in the Adolescent Brain Cognitive Development (ABCD) Study (release 4.0). FH+ was defined as having ≥1 biological parents and/or ≥2 biological grandparents with a history of alcohol/substance use problems ( = 2433). Our primary outcome was frontal cortical structural measures obtained at baseline (ages 9-11) and year 2 follow-up (ages 11-13). We used linear mixed-effects models to examine the extent to which FH status qualified frontal cortical development over the age span studied. Finally, we ran additional interactions with sex to test whether observed associations between FH and cortical development differed significantly between sexes.

Results: For FH+ (vs. FH-) youths, we observed increased cortical thinning from 9 to 13 years across the frontal cortex as a whole. When we probed for sex differences, we observed significant declines in frontal cortical thickness among boys but not girls from ages 9 to 13 years. No associations were observed between FH and frontal cortical surface area or volume.

Conclusions: Having a FH+ is associated with more rapid thinning of the frontal cortex across ages 9 to 13, with this effect driven primarily by male participants. Future studies will need to test whether the observed pattern of accelerated thinning predicts future substance use outcomes.