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New structural brain imaging endophenotype in bipolar disorder.

K Matsuo1, M Kopecek, M A Nicoletti

  • 1Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.

Molecular Psychiatry
|February 16, 2011
PubMed
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Structural brain abnormalities in the anterior-limbic region are linked to bipolar disorder (BD). These brain differences, including gray matter reductions in the left anterior insula, are also observed in unaffected relatives, suggesting a genetic link to BD.

Area of Science:

  • Neuroimaging
  • Psychiatry
  • Genetics

Background:

  • Anterior-limbic structural brain abnormalities are implicated in bipolar disorder (BD).
  • Few studies have investigated these abnormalities in unaffected first-degree relatives (UAR) of BD patients, who carry a genetic risk.
  • Understanding these differences may illuminate BD pathophysiology and identify endophenotypes.

Purpose of the Study:

  • To investigate morphometric correlates of genetic risk for BD using voxel-based morphometry.
  • To compare brain structure in BD type I (BD-I) patients, UAR, and healthy controls.

Main Methods:

  • 3T magnetic resonance imaging (MRI) was performed on 35 BD-I patients, 20 UAR, and 40 healthy controls.
  • Voxel-based morphometry (VBM) using DARTEL in SPM8 was employed for image analysis.

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  • Whole-brain analysis examined gray matter (GM) and white matter (WM) volumes.

    • Main Results:

    • Significant main effect of diagnosis was found for GM volumes in the left anterior insula and right inferior frontal gyrus.
    • BD-I patients and UAR showed smaller left anterior insular GM volumes compared to controls.
    • BD-I patients had smaller right inferior frontal gyrus GM volumes than controls.
    • WM analysis revealed a significant main effect for the medial frontal gyrus.
    • UAR exhibited smaller right medial frontal WM volumes compared to controls.

    Conclusions:

    • Morphometric brain abnormalities in the anterior-limbic neural substrate are associated with a family history of BD.
    • These findings suggest that structural brain differences may represent a potential morphological endophenotype for BD.
    • The observed abnormalities in UAR provide insight into the neurobiological underpinnings of genetic susceptibility to BD.