Depressive disorders are a leading global cause of disability. Although the incidence of depressive disorders is two-fold higher in women compared to men, the neurobiological basis for this disparity is unknown. Depressive disorders are often characterized by elevated blood levels of the glucocorticoid steroid hormone, cortisol. In both humans and rodents, females secrete greater levels of glucocorticoids than males in response to stress, which may at least partially explain the increased rates of affective disorders in women.
Dr. Nirupa Goel's research aims to elucidate the mechanisms behind the gender differences in stress responses. Previous studies suggest that deficits in serotonin neurotransmission may be a central cause for the increase in glucocorticoid secretion in depression. Most of these findings, however, come from research using male subjects. A critical first step for Dr. Goel is to identify how serotonin contributes to the gender difference in stress responses. The results of her preliminary studies indicate that blocking the serotonin 1A receptor reduces the glucocorticoid response to stress and that this effect is larger in male than in female rats. In brain tissue from the same animals, there were marked gender differences in stress-induced neuronal activation of the serotonin-producing dorsal raphe nucleus and of forebrain regions that regulate glucocorticoid release.
Based on the strength of her initial findings, Dr. Goel will further examine how stress, gender and serotonin intersect in the brain. To do this, she will measure biochemical markers of serotonin function in male and female rats under basal conditions and in response to repeated stress exposure. She will use serotonin receptor blockers to determine which receptors are involved in the gender differences in stress adaptation. Overall, these studies will elucidate the mechanisms by which serotonin mediates sex differences in stress responses. The findings have realistic clinical implications for discovering individual and sex-based differences in the development and potential treatments of affective disorders.