Abstract # 2008 Event # 12:

Scheduled for Thursday, August 17, 2006 09:45 AM-10:00 AM: Session 2 (Regency East #2) Oral Presentation


NEUROBIOLOGICAL SUBSTRATES OF A RELATIONSHIP BETWEEN DEPRESSION AND ATHEROSCLEROSIS IN ADULT FEMALE CYNOMOLGUS MONKEYS (Macaca fascicularis)

C. A. Shively1,4, T. C. Register1,4, D. P. Friedman1,2, H. D. Gage1,3, M. C. Bounds1,3 and T. B. Clarkson1,4
1Wake Forest Univ. School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1040, USA, 2Department of Physiology & Pharmacology, 3Department of Radiology, 4Department of Pathology (Comparative Medicine)
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     Depression and coronary heart disease (CHD) are comorbid in human beings. Neural serotonergic function has been implicated in both diseases. Atherosclerosis is the major pathologic process underlying CHD. We investigated whether depressive behavior and atherosclerosis extent were related, and whether neural serotonergic function might be associated with these conditions. We recorded time spent in depressed behavior (operationally defined as a slumped or collapsed body posture, lack of responsiveness to environmental stimuli to which other monkeys are attending, and open eyes) for approximately 36 months in females housed in small social groups (n=4 each) and consuming a moderately atherogenic diet containing 0.28 mg cholesterol/calorie with 42% of calories from fat. Then, we examined serotonin (5-HT) 1a receptor binding potential (BP) in the cingulate cortex using positron emission tomography, and measured iliac artery atherosclerosis extent with histomorphometry. 5-HT1a receptor BP was lower in depressed monkeys (ANOVA, p<0.003, n=17). Percent time spent in depressive behavior was correlated with atherosclerosis extent (r=0.56, p<0.01, n=22, 2-sided test). 5-HT1a receptor BP in the cingulate cortex was significantly associated with atherosclerosis extent (r=0.69, p=0.007, n=14, 2-sided test). These observations suggest that, in primates, the relationship between depression and CHD risk extends back to early atherogenesis, and that there may be a direct relationship between central serotonergic function and atherogenesis, as well as depressive behavior. Supported by MH56881and the MacArthur Foundation.