Shapes of Subcortical Structures in Adolescents With and Without Familial History of Substance Use Disorder

Background: To explore if intergenerational transmission of risk for substance use disorder (SUD) manifests in brain anatomy of substance naive adolescents. Differences in anatomical shapes of subcortical structures (SSS) have been detected in neuroimaging studies, even in the absence of volume differences and SSS have been shown to be heritable. Therefore, we examined if the SSS of adolescents with a family history (FH+) of SUD differed from the SSS of adolescents without a family history of SUD (FH-).  Because risk for SUD is associated with anxiety and impulsivity, we also examined correlations between these psychological characteristics and SSS. Methods: Using structural MRI, we obtained indices of SSS from 64 FH+ and 58 FH- adolescents and examined group differences and correlations between shape indices, trait anxiety and impulsivity. Findings: FH+ adolescents had a significant inward deformation in the shape of the right anterior hippocampus compared to FH- adolescents, while the volume of the right anterior hippocampus did not differ. Compared to FH- adolescents, the shape deformation of the brainstem, amygdala, hippocampus, putamen, pallidum and nucleus accumbens of FH+ adolescents exhibited an inverted correlational pattern with trait anxiety and impulsivity. Interpretation: SSS appears to capture anatomical features that traditional volumetric analysis does not. The inward shape deformation in the right anterior hippocampus in the FH+ adolescents may be related to the known increased risk for behavioral dysregulation leading to SUD in FH+ offspring. This novel approach may reveal neural correlates of familial transmission of increased vulnerability to problematic substance use. Funding Statement: This study was supported in part by NIDA (5R01 DA038154, PI: Christina W. Hoven) Declaration of Interests: No authors report any financial relationships with commercial interests. Ethics Approval Statement: The New York State Psychiatric Institute’s Institutional Review Board approved this study, and informed consent/assent was obtained from every participant.