Macromolecular white matter abnormalities in geriatric depression: A magnetization transfer imaging study

Faith M. Gunning-Dixon, Matthew J. Hoptman, Kelvin O. Lim, Christopher F. Murphy, Sibel Klimstra, Vassilios Latoussakis, Magdalena Majcher-Tascio, Jan Hrabe, Babak A. Ardekani, George S. Alexopoulos

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)255-262
Number of pages8
JournalThe American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
Issue number4
StatePublished - Dec 2008

Bibliographical note

Funding Information:
This work was supported by National Institute of Mental Health grants P30 MH68638, RO1 MH65653, and T32 MH19132 (to GSA), K23 MH074818 (to FGD), K23 MH067702 (to CFM), and RO1 MH64783 (to MJH) , the Sanchez Foundation and Forest Pharmaceuticals. GSA has received research grants by Forest Pharmaceuticals, Inc. and Cephalon and participated in scientific advisory board meetings of Forest Pharmaceuticals. He has given lectures supported by Forest, Cephalon, Bristol Meyers, Janssen, and Lilly and has received support by Comprehensive Neuroscience, Inc. for the development of treatment guidelines in late-life psychiatric disorders.


  • Geriatric depression
  • Magnetization transfer imaging
  • White matter


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