Regional microstructural differences in ADHD youth with and without a family history of bipolar I disorder

Having a first-degree relative with bipolar I disorder (BD) in conjunction with prodromal attention deficit/hyperactivity disorder (ADHD) may represent a unique phenotype that confers greater risk for developing BD than ADHD alone. However, underlying neuropathoetiological mechanisms remain poorly understood. This cross-sectional study compared regional microstructure in psychostimulant-free ADHD youth with ('high-risk', HR) and without ('low-risk', LR) a first-degree relative with BD, and healthy controls (HC).

A total of 140 (high-risk, n = 44; low-risk, n = 49; and HC, n = 47) youth (mean age: 14.1 ± 2.5 years, 65 % male) were included in the analysis. Diffusion tensor images were collected and fractional anisotropy (FA) and mean diffusivity (MD) maps were calculated. Both tract-based and voxel-based analyses were performed. Correlations between clinical ratings and microstructural metrics that differed among groups were examined.

No significant group differences in major long-distance fiber tracts were observed. The high-risk ADHD group exhibited predominantly higher FA and lower MD in frontal, limbic, and striatal subregions compared with the low-risk ADHD group. Both low-risk and high-risk ADHD groups exhibited higher FA in unique and overlapping regions compared with HC subjects. Significant correlations between regional microstructural metrics and clinical ratings were observed in ADHD groups.

Prospective longitudinal studies will be required to determine the relevance of these findings to BD risk progression.

Psychostimulant-free ADHD youth with a BD family history exhibit different microstructure alterations in frontal, limbic, and striatal regions compared with ADHD youth without a BD family history, and may therefore represent a unique phenotype relevant to BD risk progression.