The proposed research will study the Agitation-Depression reaction following social separation in monkeys as an animal model of human depression. It has been well documented that separations and losses are potent pathogens in both psychiatry and medicine generally. We believe one of the relevant mechanisms to be the disruption of an attachment bond, which leads to pathophysiological changes within the organism, increasing the organism's vulnerability. Three research areas are proposed. Emerging evidence suggests significant commonalities between disorders of eating and affective disorders. We will study the relationship between recently observed physiological changes accompanying alterations in nutritional status and the similar physiological changes accompanying maternal separation. We will assess infant milk intake and correlate degree of nutritional alteration following maternal separation with degree of physiological response in two environments, social group and individual cages. These studies will improve our understanding of the relationship between alterations in nutrition and response to separation and the relationship between social stress and the response to maternal separation. Physiological variables will include heart rate and rhythm, body temperature, circadian rhythms, sleep patterns, and EEG patterns. All physiological data will be obtained by means of totally implantable multichannel biotelemetry. The two major paradigms used as primate animal models of depression are maternal separation and peer separation. As of yet, there is no available data on the similarity of these two paradigms on a physiological level. We will study ten monkey infants who have been raised as peers, measuring behavioral, physiological, and immunological changes accompanying both peer separation and altered nutritional status produced by short term food restriction. These studies will also permit for the first time a direct test of the hypothesis that one function of attachment is to promote psychobiological synchrony between individuals. We will develop an electrochemical telemetry technology that will permit a better definition of imputed alterations in function of central catechol and indolamine neurotransmitter systems that accompany and/or underlie the separation induced depressive syndrome and the similar changes accompanying altered nutrition. The development of electrochemical biotelemetry capability should represent a powerful new research strategy for assessing CNS correlates of behavior in a nondestructive fashion in primates.
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