Effects of substance misuse and current family history of substance use disorder on brain structure in adolescents and young adults with attention-deficit/hyperactivity disorder

Background: Alterations in brain structure in attention-deficit/hyperactivity disorder (ADHD) show considerable overlap with those observed in substance use disorder (SUD). These overlapping structural alterations in ADHD and SUD might be explained by family history (FH-trait) effects of SUD, and/or substance misuse (state) effects. Our aim was to investigate effects of 1) current parental SUD (SUD-FH) and 2) recent substance misuse (SM) on brain structure in a cohort of ADHD patients and controls.

Design: Cortical thickness and subcortical volumes were measured using structural MRI. We compared ADHD subjects and controls with or without SUD-FH (aim 1) and additionally explored differences between SUD-FH- and SUD-FH + subjects with one versus two parents with SUD. We also compared ADHD groups with and without SM (ADHD + SM and ADHD-only, respectively) and controls (aim 2).

Findings: There was no association between SUD-FH and brain structure. Exploratory analysis on SUD-FH showed decreased IFG thickness (p = 0.032) and nucleus accumbens (NAcc) volume (p = 0.017) in subjects with two versus one SUD parent, regardless of ADHD. ADHD + SM showed decreased inferior frontal gyrus (IFG) thickness compared to controls (pars opercularis p = 0.025, pars orbitalis p = 0.010, pars triangularis p = 0.049), while no difference was found between ADHD-only and either ADHD + SM or controls.

Conclusions: Despite negative findings in the primary trait-analysis, exploratory trait-analysis on SUD-FH loading suggested potential SUD trait-effects on IFG thickness and NAcc volume. Substance misuse state effects in ADHD were linked to lower IFG thickness. Future studies should confirm these findings and investigate their clinical relevance, including the functional consequences of decreased IFG thickness.