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Anand Kumar, MD; Rakesh Gupta, MD; Albert Thomas, PhD; Olusola Ajilore, MD, PhD; Gerhard Hellemann, PhD

Arch Gen Psychiatry. 2009;66(3):324-330.

Context  Major depressive disorder has been consistently identified in patients with type 2 diabetes. Despite its high prevalence and clinical effect, the neurobiological substrates underlying depression in patients with diabetes remain largely unknown.

Objective  To examine the biophysical integrity of proteins in critical white and gray matter regions in patients with type 2 diabetes and major depression to understand the pathophysiology of depression in diabetes.

Design  A cross-sectional magnetization transfer study using magnetic resonance imaging. Regions examined included the anterior cingulate, corpus callosum, frontal and occipital white matter, and the caudate and lenticular nuclei.

Setting  A tertiary care university hospital.

Participants  We studied 16 patients diagnosed with type 2 diabetes and major depression, 22 patients diagnosed with diabetes without depression (diabetic controls), and 30 controls without diabetes or major depression (healthy controls).

Main Outcome Measures  Magnetization transfer ratios, a measure of the biophysical structure of proteins in the gray and white matter.

Results  Magnetization transfer ratios were significantly lower bilaterally in the head of the caudate nucleus in the group with diabetes and depression compared with the other 2 groups (P < .001). Diabetic controls had values between the depressed diabetic and healthy control groups. There were no significant differences in magnetization transfer ratios between groups in the other regions examined.

Conclusions  These data indicate that there is an important subcortical biophysical component to depression in patients with type 2 diabetes. This finding has broad implications for the neuronal circuitry underlying mood disorders.

Author Affiliations: Departments of Psychiatry and Radiology and the Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles (UCLA) (Drs Kumar, Thomas, Ajilore, and Hellemann); and the Sanjay Gandhi Institute of Post Graduate Medical Education and Research, Lucknow, India (Dr Gupta).

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