Growth hormone response to growth hormone-releasing hormone and clonidine in young monkeys: correlation with behavioral characteristics.

Abstract

Blunted growth hormone (GH) release in response to stimulation by a secretagogue has been widely reported in both children and adults with anxiety and depressive disorders. Blunted GH responsiveness appears to be a stable characteristic of an individual, suggesting that it may be useful as a biological marker that would allow early recognition of these disease processes. Another potential biological marker for anxiety disorders is the temperamental construct of behavioral inhibition. Children identified as being behaviorally inhibited early in life are more likely than less inhibited children to suffer from anxiety disorders later in life (Biederman et al. 1993; Hirshfeld et al. 1992). If blunted GH responsiveness to pharmacological challenge and behavioral inhibition are markers of anxiety and depressive disorders, then it would follow that they would coexist in a subset of individuals. However, such prospective studies in clinically normal young children are difficult to perform. Therefore, in this study, we examined GH responsiveness and temperament in a group of 38 young rhesus monkeys (ages 3-6 months). Monkeys received an intravenous dose of 10 microg/kg of growth hormone-releasing hormone (GHRH) and 5 microg/kg of clonidine, combined, to assess GH response to stimulation. Behavioral reactivity in a fearful situation was assessed using the Human Intruder Test developed by Kalin et al. (1991). This test measures response to a potentially threatening stimulus (a human stranger making direct eye contact). Results showed a population distribution of GH response to GHRH and clonidine ranging from 120 ng/mL/90 minutes to 3,000 ng/mL/90 minutes. There was no difference in GH response in males versus females or any significant effect of age on GH response. There was a significant correlation between GH responsiveness and the time spent reacting to the intruder in the Human Intruder Test. Monkeys with lower GH responsiveness reacted less to the intruder (p < 0.01). Additionally, when monkeys were classified based on their reactivity in the Human Intruder Test, behaviorally nonreactive monkeys had significantly lower GH responsiveness than behaviorally reactive monkeys (p < 0.005). These data provide evidence that there are inherent differences in GH responsiveness to stimulation in young rhesus monkeys and that low GH responsiveness is linked to low behavioral reactivity, which may be a form of behavioral inhibition. Further studies will be necessary to determine if the characteristics of low GH responsiveness and low behavioral reactivity predict an increased propensity to develop anxious or depressive behaviors over the course of the life span.