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

Abstract

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 (n = 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.

Keywords: Adolescence; Alcohol use; Cortical thickness; Family history; Frontal development; Substance use.

Figure 1

Development of frontal cortical thickness and family history of substance misuse. For example, at age 9, the overall mean of frontal cortical thickness (standardized mean) in the family history positive (FHP) group was 0.144 and family history negative (FHN) was 0.146, and at age 13, the FHP group had a standardized mean of −0.401 while the FHN group’s mean was −0.351, indicating a more rapid thinning of the overall frontal thickness in the FHP group. The model was adjusted by intracranial volume, and for the following baseline variables as fixed effects: sex assigned at birth, race/ethnicity, parental marital status, household income, and prenatal exposure to tobacco, alcohol, cannabis, and other substance use. The model was also adjusted to random effects of magnetic resonance imaging device, family relationship, and participant ID.

Figure 2

Development of frontal cortical thickness, family history of substance misuse, and sex assigned at birth. For example, for males at age 9, the overall mean of frontal cortical thickness (standardized mean) in the family history positive (FHP) group was 0.097 and family history negative (FHN), 0.075, and at age 13, the FHP group had a standardized mean of −0.408 while the FHN group’s mean was −0.341, indicating a more rapid thinning of the overall frontal thickness among males with a FHP. While for females, the FHP group was 0.194 and FHN, 0.219, and at age 13, the FHP group had a standardized mean of −0.325 while the FHN group’s mean was −0.297. The model was adjusted by intracranial volume and pubertal scale, and for the following baseline variables as fixed effects: race/ethnicity, parental marital status, household income, and prenatal exposure to tobacco, alcohol, cannabis, and substance use. The model was also adjusted to random effects of magnetic resonance imaging device, family relationship, and participant ID.