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Macromolecular White Matter Abnormalities in Geriatric Depression: A Magnetization Transfer Imaging Study

From the Institute of Geriatric Psychiatry and the Department of Psychiatry, Weill Medical College of Cornell University (FMG-D, CFM, SK, VL, MM-T, GSA), Weill Cornell Institute of Geriatric Psychiatry, White Plains; the Division of Clinical Research and the Center for Advanced Brain Imaging, Nathan S. Kline Institute for Psychiatric Research (MJH, JH, BAA), Orangeburg; Department of Psychiatry (MJH, BAA), New York University School of Medicine, NY; and the Department of Psychiatry, University of Minnesota (KOL), Minneapolis, MN.

Objective: Geriatric depression consists of complex and heterogeneous behaviors unlikely to be caused by a single brain lesion. However, abnormalities in specific brain structures and their interconnections may confer vulnerability to the development of late-life depression. The objective of this study was to identify subtle white matter abnormalities in late-life depression.

Design: The authors used magnetization transfer ratio (MTR) imaging, a technique that is thought primarily to reflect myelin integrity, to examine the hypothesis that individuals with late-life depression would exhibit white matter abnormalities in frontostriatal and limbic regions.

Setting: The study was conducted in a university-based, geriatric psychiatry clinic.

Participants: Fifty-five older patients with major depression and 24 elderly comparison subjects were assessed.

Measurement: Voxel-based analysis of MTR data were conducted with a general linear model using age as a covariate.

Results: Relative to comparison subjects, patients demonstrated lower MTR in multiple left hemisphere frontostriatal and limbic regions, including white matter lateral to the lentiform nuclei, dorsolateral and dorsomedial prefrontal, dorsal anterior cingulate, subcallosal, periamygdalar, insular, and posterior cingulate regions. Depressed patients had lower MTR in additional left hemisphere locales including the thalamus, splenium of the corpus callosum, inferior parietal, precuneus, and middle occipital white matter regions.

Conclusion: These findings suggest that geriatric depression may be characterized by reduced myelin integrity in specific aspects of frontostriatal and limbic networks, and complement diffusion tensor studies of geriatric depression that indicate decreased organization of white matter fibers in specific frontal and temporal regions.

Key Words: Geriatric depression • magnetization transfer imaging • white matter