The SBE investigates the relationship between sex steroids, stress, and mood by examining the pathophysiology of reproductive endocrine-related mood disorders (i.e., premenstrual-, perinatal-, and perimenopausal-related depressions) as well as the physiologic effects of sex steroids on systems relevant to affective modulation and social cognition. Alterations of gonadal steroids and adrenal androgens are implicated in the observed sex differences in the prevalence, course and treatment response characteristics of affective disorders. Sex steroids influence the response to stress (both short and long term) as well as several cognitive processes (e.g., working memory) relevant to affective adaptation. His clinical studies focus on mechanisms of the hormonal triggers and the substrates of susceptibility for developing reproductive endocrine-related mood disorders. Recently, the Section initiated a multidisciplinary collaborative study investigating puberty-related endocrine and metabolic events in normal brain development.
The original objective of the Section on Behavioral Endocrinology was to identify the occurrence and characterize the neurobiology of reproductive endocrine-related mood disorders. Concomitant with this emphasis, the subject of study expanded beyond menstrual cycle related mood disorders to include several examples of mood disturbances consequent to changes in levels of gonadal steroids.
We believe that several different reproductive endocrine-related mood disorders must be studied if we are to successfully elucidate the roles of reproductive hormones in affective dysregulation. Multiple disorders are studied because it is clear that the link between affect and alterations in reproductive hormones changes as a function of context. For example, estradiol can trigger symptoms of premenstrual dysphoria (PMD) in some women but not all; whereas, estradiol has antidepressant efficacy in depressions during the perimenopause and postpartum. There are several contextual variables that could dictate the nature of the relationship between reproductive steroids and affective dysregulation including the impact of age, duration of exposure to the presence or absence of ovarian hormones, and whether the hormone levels are stable or vary cyclically. There is no prototypic hormone-sensitive woman, and individual susceptibility varies from one reproductive endocrine-related mood disorder to another. We will better understand the processes of ovarian steroid-related triggers of affective dysregulation and susceptibility to reproductive endocrine-related mood disorders by taking advantage of the experiments of nature that these disorders present.
Dr. Peter Schmidt is Chief of the Section on Behavioral Endocrinology (SBE), NIMH. His laboratory studies the effect of sex steroids on brain function and behavior. He joined the National Institute of Mental Health’s Intramural Research Program in 1986 after completing his psychiatric residency at the University of Toronto. He chairs the Endocrine Society Advisory Panel on Ethics and Conflicts of Interest, and is an advisor to the American Psychiatric Association’s DSM-V workgroup on Premenstrual Dysphoric Disorder.
- Li HJ, Goff A, Rudzinskas SA, Jung Y, Dubey N, Hoffman J, Hipolito D, Mazzu M, Rubinow DR, Schmidt PJ, Goldman D. Altered estradiol-dependent cellular Ca2+ homeostasis and endoplasmic reticulum stress response in Premenstrual Dysphoric Disorder. Mol Psychiatry. 2021.
- Wei SM, Baller EB, Kohn PD, Kippenhan JS, Kolachana B, Soldin SJ, Rubinow DR, Schmidt PJ, Berman KF. Brain-derived neurotrophic factor Val66Met genotype and ovarian steroids interactively modulate working memory-related hippocampal function in women: a multimodal neuroimaging study. Mol Psychiatry. 2018;23(4):1066-1075.
- Dubey N, Hoffman JF, Schuebel K, Yuan Q, Martinez PE, Nieman LK, Rubinow DR, Schmidt PJ, Goldman D. The ESC/E(Z) complex, an effector of response to ovarian steroids, manifests an intrinsic difference in cells from women with premenstrual dysphoric disorder. Mol Psychiatry. 2017;22(8):1172-1184.
- Schmidt PJ, Martinez PE, Nieman LK, Koziol DE, Thompson KD, Schenkel L, Wakim PG, Rubinow DR. Premenstrual Dysphoric Disorder Symptoms Following Ovarian Suppression: Triggered by Change in Ovarian Steroid Levels But Not Continuous Stable Levels. Am J Psychiatry. 2017;174(10):980-989.
- Schmidt PJ, Ben Dor R, Martinez PE, Guerrieri GM, Harsh VL, Thompson K, Koziol DE, Nieman LK, Rubinow DR. Effects of Estradiol Withdrawal on Mood in Women With Past Perimenopausal Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2015;72(7):714-26.
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This page was last updated on Friday, August 26, 2022