Gonadal steroids are major neuroregulators and presumably underlie gender-related differences (sexual dimorphisms) in brain structure and function. We have studied reproductive endocrine-related mood disorders as well as developed endocrine models for these disorders in order to characterize the role of gonadal steroids in affective disturbance. Our major recent findings are as follows: 1) Demonstration of significant differences in the allele and genotype frequencies of the 5HTTLPR polymorphism in women with PMS (93) compared with controls (261); 2) Failure to replicate with CRH in women the luteal phase enhancement of stimulated pituitary-adrenal axis function seen with exercise; 3) Preliminary demonstration that continous administration of combined estradiol and progesterone eliminates premenstrual syndrome after the first stimulated episode (three of four subjects); 4) Failure to demonstrate, in preliminary data, reported menstrual cycle variation in the neurosteroid synthetic enzyme, 3-alpha hydroxysteroid oxido-reductase; 5) Preliminary demonstration that women with PMS differ from controls in progesterone metabolism, with increased levels of DHP and allopregnanolone relative to progesterone seen in patients; 6) Demonstration that patients with PMS differ from those with recurrent brief depression and controls in the standard deviation of prospectively obtained mood ratings but not in the depgree of approximate entropy (ApEn) manifested; 7) Demonstration that women with PMS, in contrast to controls, show strong menstrual cycle phase effects on discrimination of expressed emotion in faces, with more negative judgments seen in the luteal phase. These observations extend known differences between women with PMS and normal women in a manner that may help elucidate the pathophysiology of the differential sensitivity to gonadal steroids seen in this disorder. Additionally, the data with continous hormone administration may not only inform our understanding of the relevant hormonal stimuli that precipitate PMS, but as well may suggest a new therapeutic strategy for the millions of women who suffer from this disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002765-06
Application #
6671629
Study Section
(BEB)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2002
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Miller, Alexandra; Vo, Hoa; Huo, Liang et al. (2010) Estrogen receptor alpha (ESR-1) associations with psychological traits in women with PMDD and controls. J Psychiatr Res 44:788-94
Khine, Khursheed; Rosenstein, Donald L; Elin, Ronald J et al. (2006) Magnesium (mg) retention and mood effects after intravenous mg infusion in premenstrual dysphoric disorder. Biol Psychiatry 59:327-33
Rubinow, D R (2005) Reproductive steroids in context. Arch Womens Ment Health 8:1-5
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
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
Cardoso, Graca; Daly, Robert; Haq, Nazli A et al. (2004) Current and lifetime psychiatric illness in women with Turner syndrome. Gynecol Endocrinol 19:313-9
Smith, M J; Schmidt, P J; Su, T P et al. (2004) Gonadotropin-releasing hormone-stimulated gonadotropin levels in women with premenstrual dysphoria. Gynecol Endocrinol 19:335-43
Roca, Catherine A; Schmidt, Peter J; Altemus, Margaret et al. (2003) Differential menstrual cycle regulation of hypothalamic-pituitary-adrenal axis in women with premenstrual syndrome and controls. J Clin Endocrinol Metab 88:3057-63
Frye, Mark A; Pazzaglia, Peggy J; George, Mark S et al. (2003) Low CSF somatostatin associated with response to nimodipine in patents with affective illness. Biol Psychiatry 53:180-3

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