Elsevier

Biological Psychiatry

Volume 55, Issue 12, 15 June 2004, Pages 1154-1162
Biological Psychiatry

Original article
Regional brain gray matter volume differences in patients with bipolar disorder as assessed by optimized voxel-based morphometry

https://doi.org/10.1016/j.biopsych.2004.02.026Get rights and content

Abstract

Background

Structural magnetic resonance imaging (MRI) studies of regions of interest in brain have been inconsistent in demonstrating volumetric differences in subjects with bipolar disorder (BD). Voxel-based morphometry (VBM) provides an unbiased survey of the brain, can identify novel brain areas, and validates previously hypothesized regions. We conducted both optimized VBM, comparing MRI gray matter volume, and traditional VBM, comparing MRI gray matter density, in 11 BD subjects and 31 healthy volunteers. To our knowledge, these are the first VBM analyses of BD.

Methods

Segmented MRI gray matter images were normalized into standardized stereotactic space, modulated to allow volumetric analysis (optimized only), smoothed, and compared at the voxel level with statistical parametric mapping.

Results

Optimized VBM showed that BD subjects had smaller volume in left ventromedial temporal cortex and bilateral cingulate cortex and larger volume in left insular/frontoparietal operculum cortex and left ventral occipitotemporal cortex. Traditional VBM showed that BD subjects had less gray matter density in left ventromedial temporal cortex and greater gray matter density in left insular/frontoparietal operculum cortex and bilateral thalamic cortex. Exploratory analyses suggest that these abnormalities might differ according to gender.

Conclusions

Bipolar disorder is associated with volumetric and gray matter density changes that involve brain regions hypothesized to influence mood.

Section snippets

Subjects

Subjects were referred from an outside clinic or responded to an advertisement. They were assessed by clinical history, chart review, Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) (First et al 1995), review of systems, physical examination, routine blood tests, pregnancy test, and urine toxicology. Study entrance criteria for BD subjects included 1) age 18–65 years; 2) DSM-IV criteria for BD; 3) absence of lifetime history of alcohol or substance abuse or dependence; 4)

Optimized VBM: volumetric differences in BD sbjects

Optimized VBM analyses showed that BD subjects had smaller volumes in cingulate bilaterally (x = 0, y = 27, z = 21 through x = −3, y = −8, z = 45; Z = 4.28, pcorrected = .003) and left ventromedial temporal cortex (x = −20, y = −21, z = −21; Z = 5.08, pcorrected < .001) (Figure 1, Table 2) when compared with healthy volunteers. Larger volumes in BD subjects were seen in left insular/frontoparietal cortex (x = −45, y = −18, z = 28; Z = 5.47, pcorrected = .028) (Figure 2, Table 2) and left

Neuroanatomical differences in BD subjects compared with healthy volunteers

Previous structural MRI studies in BD subjects have been inconsistent. Generally, BD subjects have smaller PFC structures, larger amygdala, and possibly larger basal ganglia structures. Other temporal lobe structures have failed to show consistent volumetric change (for a summary see Table 1). It has been proposed that neuroanatomical abnormalities in limbic structures might represent a disruption in limbic circuitry and a consequent predisposition for depression, mania, and/or cycling

Acknowledgements

Funding was provided by The Stanley Medical Research Institute, American Foundation for Suicide Prevention, U.S. Public Health Service grants National Institute of Mental Health P30 MH46745 and MH40695, and the National Alliance for Research on Schizophrenia and Depression.

We thank the staff of the Brain Imaging Division, and the Department of Neuroscience.

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