Paul Thompson's Research Publications

Cortical Abnormalities in Elderly Depressed Patients

Proc. Human Brain Mapping Conference, New York City, NY, USA, June 2003.

1Martina Ballmeier, 2Anand Kumar, 1Elizabeth R. Sowell, 1Paul M. Thompson, 1Rebecca E. Blanton, 2Helen Lavretsky, 1Suzanne E. Welcome, 1Jeff Peterson, 1Daniel Pham, 1Heather deLuca, 1Arthur W. Toga

1Laboratory of Neuro Imaging and Dept. of Neurology, UCLA School of Medicine, Los Angeles, CA
2UCLA Neuropsychiatric Institute, Los Angeles, CA


Despite the growing evidence for an involvement of the prefrontal cortex in younger as well as elderly patients with major depression, there have been relatively few structural magnetic resonance imaging (MRI) studies examining the prefrontal cortex. To provide insights for a more comprehensive understanding of distinct regional abnormalities involved in major depression, we used two approaches to analyze the morphometry of the cortex in a sample of elderly depressed patients with onset of illness during adulthood.

Subjects and Methods
Twenty four elderly patients with major depression (18 females, six males,mean age=65.85, SD=8.81) and 19 nondepressed comparison subjects (15 females, four males, mean age=66.24, SD=7.25) were studied using high resolution, 3D, structural MRI data. In the first approach, whole-brain surface-based image analysis procedures were used to provide detailed spatial mapping of brain size and gray matter density across the cortical surface. With surface-based methods, brain surface anatomy is carefully matched across individuals by defining cortical sulcal landmarks on the brain surface renderings of each subject, thereby ensuring accurate localization of group differences relative to gyral landmarks. The medial brain surface was not measured. In the second approach, volumetric image analysis methods were used to assess abnormalities in gray matter, white matter and CSF volumes independently in seven subregions of the prefrontal cortex, also including ventromedial areas, such as the anterior cingulate and the gyrus rectus.

Using whole-brain surface-based analysis, depressed patients showed: 1) a robust size reduction in the orbitofrontal cortex bilaterally, confirmed with permutation tests, without decreased size in any other region; 2) unexpected, but significant gray matter increases bilaterally within the parietal lobes, also confirmed with permutation tests. Interestingly, a relationship between the brain surface contraction in the orbitofrontal cortex and complex patterns of gray matter density decrease as well as gray matter density increase in the orbitofrontal cortex was found. The key findings of the volumetric MRI-based parcellation of the prefrontal cortex were: 1) a prominent reduction in left and right gray matter volumes in the orbitofrontal cortex, the anterior cingulate and the gyrus rectus; 2) significant decreases in white matter volume and a significant increase in CSF volume in the anterior cingulate and the gyrus rectus 3) a significant reduction in CSF volume in the orbitofrontal cortex of depressed patients. No significant abnormalities were found in inferior, middle and superior cortices as well as the precentral gyrus, observation consistent with the surface-based analysis.

By measuring gray matter density on a point-by-point basis, the surface-based methods increased spatial sensitivity, allowing us to detect distinct patterns of progressive and regressive cortical changes which may contribute to the pronounced brain size reduction in the orbitofrontal cortex. Furthermore, an additional link between orbitofrontal cortex and major depression might be implied in the connection between the orbitofrontal and the parietal cortices. Our analysis study showed that volumetric abnormalities occur in distinct tissue compartments of the orbitofrontal cortex, the anterior cingulate and the gyrus rectus, giving rise to additional hypotheses regarding etiopathological mechanisms underlying structural cortical abnormalities in major depression.

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    Paul Thompson, Ph.D.
    Assistant Professor of Neurology
    4238 Reed Neurology
    UCLA School of Medicine
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    Westwood, Los Angeles CA 90095-1769, USA.

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