Subcortical gray matter volume abnormalities in healthy bipolar offspring: potential neuroanatomical risk marker for bipolar disorder?

Abstract

Objective: A growing number of structural neuroimaging studies have shown that bipolar disorder (BD) is associated with gray matter (GM) volume abnormalities in brain regions known to support affect regulation. The goal of this study was to examine whole-brain regional GM volume in healthy bipolar offspring (HBO) relative to age-matched controls to identify possible structural abnormalities that may be associated with risk for BD.

Method: Participants were 20 youths (8-17 years old) with at least one parent diagnosed with BD, and 22 age-matched healthy individuals. All of them were free of Axis I diagnoses. High-resolution magnetic resonance imaging structural images were acquired using a 3-T Siemens scanner. Voxel-based morphometric analyses were conducted using SPM5.

Results: Relative to controls, HBO had significantly increased GM volume in left parahippocampal/hippocampal gyrus (p <.05 corrected), following whole-brain analyses. This increase was correlated with puberty but not age in HBO. Region-of-interest analyses on the amygdala and orbitomedial prefrontal cortex did not yield any significant group differences after conducting small volume correction.

Conclusions: The pattern of increased GM volume in parahippocampal/hippocampal gyrus in HBO suggests a potential marker for risk for BD. It can also be considered as a potential neuroprotective marker for the disorder because HBO were free of current psychopathology. Prospective studies examining the relationship between changes in GM volume in these regions and subsequent development of BD in HBO will allow us to elucidate further the role of this region in either conferring risk for or protecting against the development of BD.

Fig. 1

Anatomical localization of increased gray matter (GM) volume following whole-brain voxel-based morphometry analyses in healthy bipolar offspring (HBO) (n = 20) compared to control participants (n = 22). Color scale represents T scores, increasing from red to white. MNI coordinates. A, Left parahippocampal/hippocampal gyrus. Cluster size: 124 voxels, t = 3.93, Z = 3.57, p_uncorrected < .001 (x = −20, y = −18, z = −32); small volume correction: p < .05. B, Box plot of GM volume intensity (with SD) in the region of increased GM volume for the HBO and control groups.