Hippocampus shape analysis and late-life depression.

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Major depression in the elderly is associated with brain structural changes and vascular lesions. Changes in the subcortical regions of the limbic system have also been noted. Studies examining hippocampus volumetric differences in depression have shown variable results, possibly due to any volume differences being secondary to local shape changes rather than differences in the overall volume. Shape analysis offers the potential to detect such changes. The present study applied spherical harmonic (SPHARM) shape analysis to the left and right hippocampi of 61 elderly subjects with major depression and 43 non-depressed elderly subjects. Statistical models controlling for age, sex, and total cerebral volume showed a significant reduction in depressed compared with control subjects in the left hippocampus (F(1,103) = 5.26; p = 0.0240) but not right hippocampus volume (F(1,103) = 0.41; p = 0.5213). Shape analysis showed significant differences in the mid-body of the left (but not the right) hippocampus between depressed and controls. When the depressed group was dichotomized into those whose depression was remitted at time of imaging and those who were unremitted, the shape comparison showed remitted subjects to be indistinguishable from controls (both sides) while the unremitted subjects differed in the midbody and the lateral side near the head. Hippocampal volume showed no difference between controls and remitted subjects but nonremitted subjects had significantly smaller left hippocampal volumes with no significant group differences in the right hippocampus. These findings may provide support to other reports of neurogenic effects of antidepressants and their relation to successful treatment for depressive symptoms.





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Zhao, Zheen, Warren D Taylor, Martin Styner, David C Steffens, K Ranga R Krishnan and James R MacFall (2008). Hippocampus shape analysis and late-life depression. PLoS One, 3(3). p. e1837. 10.1371/journal.pone.0001837 Retrieved from https://hdl.handle.net/10161/4485.

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David Carl Steffens

Professor Emeritus of Psychiatry and Behavioral Sciences

Geriatric Affective Disorders

Geriatric Cognitive Disorders

Alzheimer's Disease



K. Ranga Rama Krishnan

Professor Emeritus of Psychiatry and Behavioral Sciences

I have validated in vivo methods of estimating volumes of subcortical structures utilizing MRI and sterology. These studies have suggested that depressed patients have smaller caudate, smaller putamen, altered water balance in the hippocampus, a smaller medulla and cerebellar vermis, and enlarged ventricles. Our group has demonstrated that late-life depression patients have increased MRI lesions in the fronto-parietal white matter and subcortical gray; and, have lesions in the caudate increase the risk of delirium with ECT and antidepressants. In the last year, we have developed high resolution MR proton spectroscopy methods to measure the concentration of a variety of physico-chemical moieties, including choline, lactic acid, water, glucose, N-acetylaspartate and glutamate in volumes of < one ml. We are utilizing this technique to study affective disorder, Alzheimer's disease and social phobia and the effect of psychotropic medications on these parameters. In an initial study, a state dependent increase in choline in depressed patients has been demonstrated; and, in Alzheimer's disease, a reduction in N-acetyl asparatate and an increase in Inositol which progresses as the disease advances. In addition, we are examining the relationship between fluoxetine concentrations in the brain using MRS and therapeutic efficacy. We currently use MR methods to assess drug efficacy in various disorders and in the development of new drugs. We have developed protocols to compare drugs developed for Alzheimer's disease based on their known effects on MRS parameters in dogs.

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