The overall goal of this project is to determine if growth hormone (GH) responsiveness is a physiological variable which may serve to identify individuals who are predisposed to the development of affective disorders. Blunted GH responsiveness to stimulation is one of the most reliable physiological correlates to affective disorders. However, it is not known if blunted GH responsiveness is an inherent characteristic of an individual, or whether it emerges after the onset of behavioral disorders. The mechanisms underlying the blunted GH responsiveness are also unknown. It is not possible to perform such studies with human subjects; however, nonhuman primates raised without their mothers during early development often display behaviors similar to those seen with depression and anxiety, and thus provide an appropriate animal model. In this proposal, GH responsiveness will be measured in monkeys shortly after birth, and the question of whether monkeys with low GH responses are more likely to display behavioral abnormalities when raised in the absence of their mothers, compared to individuals with high GH responsiveness will be addressed. This proposal will also examine whether blunted GH responsiveness, results from decreased levels of GH in the pituitary, due to trophic support of GHRH or increased somatostatin inhibitory input to the pituitary. Subsequent definition of the neuroendocrine system accounting for blunted GH responsiveness will then be the first step in identifying neural systems that underlie the altered GH responsiveness, which may also underlie a predisposition for the development of affective disorders.
Coleman, Kristine; Dahl, Ronald E; Ryan, Neal D et al. (2003) Growth hormone response to growth hormone-releasing hormone and clonidine in young monkeys: correlation with behavioral characteristics. J Child Adolesc Psychopharmacol 13:227-41 |