Our initial studies, demonstrated for the first time the short-term antidepressant efficacy of estradiol therapy in depression during the menopause transition, and that these beneficial effects on mood were independent of estradiols effects on vasomotor symptoms. Additionally, an ongoing longitudinal study demonstrated that episodes of depression clustered during the late menopause transition and the first year after the last menstrual period - phases of reproductive life accompanied by estrogen withdrawal and the onset of hypogonadism. Finally, we also demonstrated that depression during the menopause transition is not associated with an abnormal deficiency or excess of ovarian hormones. Our current studies focus on both the evaluation of alternative hormone-based therapies in women with depression during the menopause transition and, the identification of the hormonal events triggering the onset of depression in these women.? ? Our findings to date suggest a significant improvement in mood in women with depression during the menopause transition after short-term therapy with either estradiol or the selective estrogen receptor modulator (SERM), raloxifene, but not after either placebo or phytoestrogen treatment under double-blind, controlled conditions. Interestingly, raloxifene increases plasma estradiol levels in these women, suggesting both a mechanism underlying raloxifenes actions and its potential role as an effective and safer alternative to estradiol therapy in this condition. We also have preliminary evidence that women with a past depression during the menopause transition, but not those without such a history, experience a recurrence of depressive symptoms during short-term estradiol withdrawal under blinded, placebo-controlled conditions. These findings represent the first evidence of a direct association between a change in hormone level (estradiol) and the onset of depressive symptoms in women. Additionally, we have examined the clinical characteristics of women with depression during the menopause transition in order to identify potential risks for the development of depression during this phase of reproductive life. In contrast to clinical anectdote, there is no increased risk of postpartum depression, relative to community-based samples, in women with depression during the menopause transition; however, a higher than expected occurrence of prospectively confirmed severe premenstrual dysphoria was observed in women with depression during the menopause transition. Additionally, we have demonstrated the absence of a causal relationship between vasomotor symptoms (i.e., hot flushes) and depression in women during the menopause transition. Finally, in two new initiatives we work in collaboration with Investigators at the University of North Carolina in Chapel Hill, and Wake Forest University, to employ animal models to identify markers (e.g., candidate signaling systems and genomic variables) accompanying a susceptibility to develop depression in women transitioning through the menopause.? ? In collaboration with Investigators at the NICHD, we have studied the impact of ovarian failure on mood and behavior in women in whom declining ovarian function occurs at a young age. We have observed that women with Turner Syndrome have significantly higher scores on measures of shyness, depression and anxiety than asymptomatic controls but their scores do not differ from those in women with premature ovarian insufficiency (POI). However, women with POI report an increased lifetime frequency of major depression compared with community samples of women (i.e., 69.5% versus 20%, respectively), and the majority of these depressive episodes occurred after the onset of menstrual cycle irregularity but before the final menstrual period and the diagnosis of POI. Finally, testosterone augmentation of estrogen therapy has a significant mood-enhancing effect in women with POI under double-blind placebo-controlled conditions.
| Harsh, Veronica; Schmidt, Peter J; Rubinow, David R (2007) The menopause transition: the next neuroendocrine frontier. Expert Rev Neurother 7:S7-10 |
| Schmidt, Peter J; Cardoso, Graca M P; Ross, Judith L et al. (2006) Shyness, social anxiety, and impaired self-esteem in Turner syndrome and premature ovarian failure. JAMA 295:1374-6 |
| Morrison, John H; Brinton, Roberta D; Schmidt, Peter J et al. (2006) Estrogen, menopause, and the aging brain: how basic neuroscience can inform hormone therapy in women. J Neurosci 26:10332-48 |
| Richards, Misty; Rubinow, David R; Daly, Robert C et al. (2006) Premenstrual symptoms and perimenopausal depression. Am J Psychiatry 163:133-7 |
| Schmidt, Peter J; Rubinow, David R (2006) Reproductive ageing, sex steroids and depression. J Br Menopause Soc 12:178-85 |
| Rubinow, David R; Roca, Catherine A; Schmidt, Peter J et al. (2005) Testosterone suppression of CRH-stimulated cortisol in men. Neuropsychopharmacology 30:1906-12 |
| Bloch, Miki; Rubinow, David R; Schmidt, Peter J et al. (2005) Cortisol response to ovine corticotropin-releasing hormone in a model of pregnancy and parturition in euthymic women with and without a history of postpartum depression. J Clin Endocrinol Metab 90:695-9 |
| Schmidt, Peter J; Daly, Robert C; Bloch, Miki et al. (2005) Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry 62:154-62 |
| Roca, Catherine A; Schmidt, Peter J; Deuster, Patricia A et al. (2005) Sex-related differences in stimulated hypothalamic-pituitary-adrenal axis during induced gonadal suppression. J Clin Endocrinol Metab 90:4224-31 |
| Schmidt, Peter J (2005) Mood, depression, and reproductive hormones in the menopausal transition. Am J Med 118 Suppl 12B:54-8 |
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