Aberrant White Matter Microstructure in Youth with a High Risk for Bipolar Disorder.

Background: Advances in neuroimaging of bipolar disorder (BD) have highlighted key structural and functional abnormalities in prefrontal-limbic circuits. Youth with a family history of BD often experience early onset of mood symptoms that may increase their risk for developing BD. However, etiological mechanisms underlying this risk remain poorly understood. We aimed to identify white matter connectivity abnormalities by comparing regional microstructure in high-risk youth and healthy controls (HC).

Methods: Depressed and/or anxious youth (n=108, age = 14.9±1.6) with a family history of BD but no prior antidepressant exposure and matched HC (n=45, age = 14.8±1.6) were recruited at two sites. Automated fiber quantification using Diffusion Tensor Imaging was used to calculate the diffusion properties of fiber tracks and identify microstructural abnormalities. Correlations between clinical ratings and diffusion properties that differed between groups were examined in high-risk youth.

Results: High-risk group showed higher fractional anisotropy in anterior thalamic radiation and corticospinal, higher axial diffusivity in anterior thalamic radiation, and lower mean diffusivity in corticospinal, lower radial diffusivity in corticospinal and callosum forceps minor compared with HC (p < 0.05, FWE-corrected). Significant positive correlations between regional microstructural metrics and both the Pediatric Anxiety Rating Scale and the Children's Global Assessment Scale were observed in high-risk youth (p < 0.05, FDR-corrected).

Conclusions: Compared to healthy youth, youth at risk for BD have altered integrity in the white matter of callosum forceps minor, anterior thalamic radiation, and corticospinal tracts. Damage to these tracts may be a structural basis for impaired emotional regulation in high-risk youth and a potential target for early intervention.