Shapes of subcortical structures in adolescents with and without familial history of substance use disorder

Abstract

It has been suggested that intergenerational transmission of risk for substance use disorder (SUD) manifests in the brain anatomy of substance naïve adolescents. While volume and shapes of subcortical structures (SSS) have been shown to be heritable, these structures, especially the pallidum, putamen, nucleus accumbens, and hippocampus, have also been associated with substance use disorders. However, it is not clear if those anatomical differences precede substance use or are the result of that use. Therefore, we examined if volume and SSS of adolescents with a family history (FH+) of SUD differed from adolescents without such a history (FH-). Because risk for SUD is associated with anxiety and impulsivity, we also examined correlations between these psychological characteristics and volume/SSS. Using structural MRI and FSL software, we segmented subcortical structures and obtained indices of SSS and volumes of 64 FH+ and 58 FH- adolescents. We examined group differences in volume and SSS, and the correlations between volume/SSS and trait anxiety and impulsivity. FH+ adolescents had a significant inward deformation in the shape of the right anterior hippocampus compared to FH- adolescents, while the volume of this structure did not differ between groups. Neither shape nor volume of the other subcortical structures differed between groups. In the FH+ adolescents, the left hippocampus shape was positively correlated with both trait anxiety and impulsivity, while in FH- adolescents a negative correlation pattern of SSS was seen in the hippocampus. SSS appears to capture local anatomical features that traditional volumetric analysis does not. The inward shape deformation in the right anterior hippocampus in FH+ adolescents may be related to the known increased risk for behavioral dysregulation leading to SUD in FH+ offspring. Hippocampus shape also exhibits opposite patterns of correlation with anxiety and impulsivity scores across the FH+ and FH- adolescents. These novel findings may reveal neural correlates, not captured by traditional volumetric analysis, of familial transmission of increased vulnerability to SUD.

Keywords: MRI; adolescents; familial risk for SUD; shape analysis; subcortical brain structures; substance use disorder (SUD).

FIGURE 1

Vertex‐based shape analysis results for the comparison between FH+ and FH− groups (FWE and TFCE‐corrected p < 0.05) controlling for age and sex. Blue arrows correspond to inward deformations and red arrows correspond to outward deformations. The x and y axes indicate the anatomical directions. (a) Mesh views, (b) 3D anterior view, and (c) 3D medial view

FIGURE 2

Differences between FH+ and FH− groups in the shape associations with psychological measures in the left hippocampus covarying for age and sex (FWE and TFCE‐corrected p < 0.05). Color bars: red to yellow colors indicate a positive difference of the correlations between the FH+ and FH− groups, whereas blue to purple colors indicate a negative difference of the correlations between the FH+ and FH− groups. This figure shows the differences of comparing FH+ to FH− groups of the correlations between the left hippocampus shape and (a) STAI trait score, (b) BIS‐11 attentional impulsivity score, and (c) BAS fun seeking score

FIGURE 3

Shape‐behavioral score correlations for FH+ group covarying for age and sex (FWE and TFCE‐corrected p < 0.05) in the left hippocampus. Color bars: red to yellow colors indicate a positive correlation, whereas blue to purple colors indicate a negative correlation. This figure shows the correlations in the FH+ group between the left hippocampus shape and (a) STAI trait score, (b) BIS‐11 attentional impulsivity score, and (c) BAS fun seeking score

FIGURE 4

Shape‐behavioral score correlations for FH− group covarying for age and sex (FWE and TFCE‐corrected p < 0.05) in the left hippocampus. Color bars: red to yellow colors indicate a positive correlation, whereas blue to purple colors indicate a negative correlation. This figure shows the correlations in the FH− group between the left hippocampus shape and (a) STAI trait score, (b) BIS‐11 attentional impulsivity score, and (c) BAS fun seeking score