Structural brain imaging and cognitive function in individuals at high familial risk of mood disorders
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Bipolar disorder (BD) and major depressive disorder (MDD) are characterised by a fundamental disturbance of mood, with strong support for overlapping causal pathways. Structural brain and neurocognitive abnormalities have been associated with mood disorders, but it is unknown whether these reflect early adverse effects predisposing to mood disorders or emerge as a consequence of illness onset. The Bipolar Family Study is well-suited to examine the origin of structural brain and neuropsychological abnormalities in mood disorders further. The volumes of subcortical brain regions, cortical thickness and surface area measures of frontal and temporal regions of interest and neuropsychological performance over a two-year time interval was compared at baseline and longitudinally between three groups: young individuals at high risk of mood disorders who subsequently developed MDD during the follow-up period (HR-MDD), individuals at high risk of mood disorders who remained well (HR-well), and healthy control subjects (HC). The longitudinal analysis of cortical thickness revealed significant group effects for the right parahippocampal and right fusiform gyrus. Cortical thickness in both of these brain regions across the two time points was reduced in both high-risk groups relative to controls, with the HR-MDD group displaying a thinner parahippocampus gyrus than the HR-well group. Moreover, a significant interaction effect was observed for the left inferior frontal and left precentral gyrus. The HR-well subjects had progressive thickness reductions in these brain regions relative to controls, while the HR-MDD group showed cortical thickening of these areas. Finally, longitudinal analyses of neuropsychological performance revealed a significant group effect for long delay verbal memory and extradimensional set-shifting performance. Reduced neurocognitive performance during both tasks across the two time points was found in the HR-well group relative to controls, with the HR-MDD group displaying decreased extradimensional set-shifting abilities as compared to the HC group only. These findings indicate, that reduced left parahippocampal and fusiform thickness constitute a familial trait marker for vulnerability to mood disorders and may thus form potential neuroanatomic endophenotypes. Particularly strong thickness reductions of the parahippocampal gyrus appear be linked to an onset of MDD. Moreover, progressive thickness reductions in the left inferior frontal and precentral gyrus in early adulthood form a familial trait marker for vulnerability to mood disorders, potentially reflecting early neurodegenerative processes. By contrast, an absence of cortical thinning of these brain regions in early adulthood appears to be linked to the onset of MDD, potentially reflecting a lack or delay of normal synaptic pruning processes. Reduced long delay verbal memory and extradimensional set-shifting performance across time constitute a familial trait marker for vulnerability to mood disorders, likely representing disturbances of normal brain development predisposing to illness. These findings advance our understanding of the origin of structural brain and neurocognitive abnormalities in mood disorders.