Opportunities for research are in the general area of the role of social stress in disease susceptibility in nonhuman primates. Much of our work has addressed sex differences and women's health issues. Social status, social isolation and novel environments are some of the stressors that are being examined. Individual differences in behavioral, sympathetic nervous system, and hypothalamic-pituitary-adrenal responsivity to stress are being assessed. Evaluations of pathologic responses to social factors include atherosclerosis, coronary vasomotor reactivity, bone density and biochemistry, breast cancer risk, depression, lipid and carbohydrate metabolism, regional fat distribution and the metabolic syndrome, and immune system function. In addition, PET, quantitative receptor autoradiography, and unbiased stereology are used to assess the effects of stress on brain function.
Two current areas of research include social inequalities in health and modeling the comorbidity of coronary heart disease and depression in a primate model. Social inequalties in health are widely recognized to contribute to the global burden of disease. It is is critical for us to understand how low social status is translated into illness. Like human beings, a central organizing mechanism of macaque society is the social status hierarchy. Also like human beings, many aspects of health are inversely related to social status in macaques, and we are studying these relationships. Two diseases inversely related to social status in human beings are coronary heart disease (CHD) and depressive disorders. Depression and CHD are highly comorbid in the human population. CHD patients who experience depression after their first myocardial infarction (heart attack) are 4-6 times more likely to die of a second heart attack in the next 18 months. The mechanisms underlying this comorbidity are poorly understood. With funding from the National Heart, Lung, and Blood Institute of the National Institutes of Health we are currently studying this comorbidity in monkeys, and will treat depression pharmacologically to determine whether that improves CHD risk.
Figure Legend: An alert monkey compared with a monkey in depressed posture. These photographs were taken by the same photographer at approximately the same distance from each monkey. The nondepressed monkey was alert and orienting toward the photographer (a potential threat), whereas the depressed monkey seemed oblivious to the presence of a human being. The depressed monkey was sitting in a slumped or collapsed body posture, with open eyes directed downward, and was unresponsive to environmental events.
Shively CA, Register TC, Adams MR, Golden DL, Willard SL, Clarkson TB. Depressive behavior and coronary artery atherogenesis in adult female cynomolgus monkeys. Psychosomatic Medicine. In Press, Feb. 2008.
Shively CA, Wood CE, Register TC, Willard SL, Lees CJ, Chen H, Sitruk-Ware RL, Tsong YY, Cline JM. Hormone therapy effects on social behavior and activity levels of surgically postmenopausal cynomolgus monkeys. Psychoneuroendocrinology. 2007 Sep-Nov;32(8-10):981-90.
Shively CA, Mietus JE, Grant KA, Goldberger AL, Bennett AJ, Willard SL. Effects of chronic moderate alcohol consumption and novel environment on heart rate variability in primates (Macaca fascicularis). Psychopharmacology (Berl). 2007 Jun;192(2):183-91.
Shively CA, Friedman DP, Gage HD, Bounds MC, Brown-Proctor C, Blair JB, Henderson JA, Smith MA, Buchheimer N. Behavioral depression and positron emission tomography-determined serotonin 1A receptor binding potential in cynomolgus monkeys. Arch Gen Psychiatry. 2006 Apr;63(4):396-403.
Shively CA, Register TC, Friedman DP, Morgan TM, Thompson J, Lanier T. Social stress-associated depression in adult female cynomolgus monkeys (Macaca fascicularis). Biol Psychol. 2005 Apr;69(1):67-84.
Shively CA, Register TC, Grant KA, Johnson JL, Cline JM. Effects of social status and moderate alcohol consumption on mammary gland and endometrium of surgically postmenopausal monkeys. Menopause. 2004 Jul-Aug;11(4):389-99.
Shively CA, Bethea CL. Cognition, mood disorders, and sex hormones. ILAR J. 2004;45(2):189-99.
Ivester P, Shively CA, Register TC, Grant KA, Reboussin DM, Cunningham CC. The effects of moderate ethanol consumption on the liver of the monkey, Macaca fascicularis. Alcohol Clin Exp Res. 2003 Nov; 27(11): 1831-7.
Henderson JA, Shively CA. Triphasic oral contraceptive treatment alters the behavior and neurobiology of female cynomolgus monkeys. Psychoneuroendocrinology. 2004 Jan;29(1):21-34.
Register TC, Cline JM, Shively CA. Health issues in postmenopausal women who drink. Alcohol Res Health. 2002;26(4): 299-307.
Shively CA, Mirkes SJ, Lu NZ, Henderson JA, Bethea CL. Soy and social stress affect serotonin neurotransmission in primates. Pharmacogenomics J. 2003;3(2):114-21.
Abbott DH, Keverne EB, Bercovitch FB, Shively CA, Mendoza SP, Saltzman W, Snowdon CT, Ziegler TE, Banjevic M, Garland T, Sapolsky RM. Are subordinates always stressed? A comparative analysis of rank differences in cortisol levels among primates. Horm Behav. 2003 Jan;43(1):67-82.
Shively CA, Grant KA, Register TC. Effects of long-term moderate alcohol consumption on agonistic and affiliative behavior of socially housed female cynomolgus monkeys (Macaca fascicularis). Psychopharmacology (Berl). 2002 Dec;165(1):1-8.
Shively CA, Williams JK, Laber-Laird K, Anton RF. Depression and coronary artery atherosclerosis and reactivity in female cynomolgus monkeys. Psychosom Med. 2002 Sep-Oct;64(5):699-706.
Vivian JA, Green HL, Young JE, Majerksy LS, Thomas BW, Shively CA, Tobin JR, Nader MA, Grant KA. Induction and maintenance of ethanol self-administration in cynomolgus monkeys (Macaca fascicularis): long-term characterization of sex and individual differences. Alcohol Clin Exp Res. 2001 Aug;25(8):1087-97.
Bethea CL, Mirkes SJ, Shively CA, Adams MR. Steroid regulation of tryptophan hydroxylase protein in the dorsal raphe of macaques. Biol Psychiatry. 2000 Mar 15;47(6):562-76.
Wallace JM, Shively CA, Clarkson TB. Effects of hormone replacement therapy and social stress on body fat distribution in surgically postmenopausal monkeys. Int J Obes Relat Metab Disord. 1999 May;23(5):518-27.
Shively CA. Behavioral and neurobiological effects of estrogen replacement therapy and a history of triphasic oral contraceptive exposure. Psychoneuroendocrinology. 1998 Oct; 23(7):713-32.
Shively CA. Social subordination stress, behavior, and central monoaminergic function in female cynomolgus monkeys. Biol Psychiatry. 1998 Nov 1;44(9):882-91.
Watson SL, Shively CA, Kaplan JR, Line SW. Effects of chronic social separation on cardiovascular disease risk factors in female cynomolgus monkeys. Atherosclerosis. 1998 Apr;137(2):259-66.
Register TC, Shively CA, Lewis CE. Expression of estrogen receptor alpha and beta transcripts in female monkey hippocampus and hypothalamus. Brain Res. 1998 Mar 30;788(1-2):320-2.
Grant KA, Shively CA, Nader MA, Ehrenkaufer RL, Line SW, Morton TE, Gage HD, Mach RH. Effect of social status on striatal dopamine D2 receptor binding characteristics in cynomolgus monkeys assessed with positron emission tomography. Synapse. 1998 May;29(1):80-3.
Shively CA, Laber-Laird K, Anton RF. Behavior and physiology of social stress and depression in female cynomolgus monkeys. Biol Psychiatry. 1997 Apr 15;41(8):871-82.