This Mentored Research Scientist Development Award (MRSDA) is designed to promote the Candidate's long-term goal of becoming a women's health researcher with expertise in the etiology and treatment of depression in women. The training and research activities described in this MRSDA will facilitate the Candidate's training in the methods of acute stress research and neurohormonal assessment techniques, and the integration of these techniques within her own background in depression intervention research. This interdisciplinary training will provide the Candidate with the skills and experience needed to pursue an independent program of research testing biobehavioral mechanisms of stress sensitivity, depression vulnerability, and ultimately, depression treatment outcomes in women. Post-pubertal females are twice as likely as males to experience a lifetime episode of major depression, and are particularly likely to become depressed when faced with stressful life events. This gender-linked health disparity persists throughout women's reproductive lives, carrying deleterious consequences for both the woman herself and the children under her care. We (Cyranowski et al., 2000) have theorized that women's sensitivity to interpersonal life stress is mediated, in part, by the hypothalamic neurohormone, oxytocin. Oxytocin is known to play a key role in female reproductive processes. A growing body of animal research indicates that oxytocin is critically regulated by female reproductive hormones, and that oxytocin serves to facilitate female affiliative behaviors and down-regulate the hypothalamic-pituitary-adrenal (HPA) stress axis. The proposed pilot study was designed to provide a preliminary examination of the role of oxytocin in women's stress sensitivity and depression vulnerability. Twenty-two normal cycling, depressed females aged 21-40 and 22 age-matched never-depressed controls will be recruited to participate in a 3-hour laboratory experiment designed to stimulate, measure and compare peripheral oxytocin release and basal oxytocin concentrations within and between groups, and to examine whether peripheral oxytocin release is associated with a down-regulation of the HPA stress axis following an acute stress task. Subjects will also complete self-report measures of depression, anxiety, interpersonal function, trauma history, and recent life stress. Subjects will then be retested with the laboratory paradigm at 18 weeks follow-up, or for depressed subjects, following a course of interpersonal psychotherapy (IPT). The skills, training, and pilot data obtained from this MRSDA will subsequently be used to support the Candidate's development of an R0l application in Years 03-05 of the award period.
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