Structural brain imaging and cognitive function in individuals at high familial risk of mood disorders
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Date
04/07/2015Author
Papmeyer, Martina
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Abstract
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.