Project 4: Hormonal Interaction on the Neuroendocrine Axis
Depressive disorders are a major health issue in the United States resulting in significant social and economic problems. Studies have shown that women are twice as likely as men to develop depression and experience more recurrent depressive episodes. The observation that the onset of depression in many women occurs during menopause and increases in severity during postmenopausal life strongly suggests that decreasing levels of estrogen during the perimenopausal period are somehow involved in the onset or continuation of depression. This view is supported by findings that estrogen replacement therapy reduces depressive symptoms in perimenopausal women. Although these data suggest that estrogen has beneficial effects in alleviating depressive symptoms, the mechanisms by which estrogen achieves these effects are not known. Currently, most depressive disorders are treated with Selective Serotonin Reuptake Inhibitors (SSRIs) which cause an increase in a neurotransmitter known as serotonin. How this increased availability of serotonin causes beneficial effects is not clear, however, it appears that serotonin may stimulate a factor in the brain (Brain-Derived Neurotrophic Factor or BDNF) which in turn has been shown to enhance the growth and development of new neurons in the brain. It is thought that the establishment of appropriate neural networks is, at least in part, responsible for successful treatment of depression. The sites of action of SSRIs in the brain are not known. Thus, one goal of Project #4 is to identify the sites of action as well as the mechanisms by which SSRIs cause an enhancement of BDNF levels to stimulating neurogenesis. A second goal of this Project is to identify the estrogen-sensitive neurons that are regulated by serotonin to reveal the mechanisms by which estrogen reduces the frequency and severity of depressive episodes. The third goal is to determine if the SSRIs and estrogen act in an additive or synergistic fashion and to identify the underlying mechanisms.
Project 4 investigators: