Cortical Thickness in Individuals at High Familial Risk of Mood Disorders as They Develop Major Depressive Disorder

BACKGROUND: Frontal and temporal cortical thickness abnormalities have been observed in mood disorders. However, it is unknown whether cortical thickness abnormalities reflect early adverse effects of genetic and environmental risk factors predisposing to mood disorders or emerge at illness onset. METHODS: Magnetic resonance imaging was conducted at baseline and after a 2-year follow-up interval in 111 initially unaffected young adults at high familial risk of mood disorders and 93 healthy control subjects (HC). During the follow-up period, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the remainder remaining well (HR-well). Cortical surface reconstruction was applied to measure cortical thickness of frontal and temporal regions of interest. Mixed-effects models were used to investigate differences and longitudinal changes in cortical thickness. RESULTS: Reduced cortical thickness in the right parahippocampal and fusiform gyrus across both time points was found in both high-risk groups. HR-MDD also had thinner parahippocampi than HR-well individuals. Over time, HR-well and HC individuals had progressive thickness reductions in the left inferior frontal and precentral gyrus, which were greater in HR-well subjects. HR-MDD showed left inferior frontal gyrus thickening relative to HR-well subjects and left precentral gyrus thickening relative to HR-well and HC individuals. CONCLUSIONS: Reduced right parahippocampal and fusiform gyrus thickness are familial trait markers for vulnerability to mood disorders. Increased risk for mood disorders is associated with progressive cortical thinning in the left inferior frontal and precentral gyri in subjects who remain well. In contrast, onset of depression is associated with increasing left inferior frontal and precentral thickness.