Prior research indicates that women with premenstrual dysphoric disorder (PMDD) have alterations in sympathetic nervous system (SNS) and adrenergic receptor (AR) function. Our work suggests that PMDD women with histories of sexual and physical abuse, especially childhood abuse (CA) show even greater adrenergic dysregulation, since they exhibit greater heart rate and blood pressure levels, greater B-AR responsivity and lower plasma norepinephrine (NE) relative to non-abused PMDD women. Animal studies clearly indicate a role for B-AR activation in producing hyperalgesia, while NE pathways and HPA-axis activation are involved in pain inhibition. Thus, alterations in B-AR function and diminished NE and cortisol output in PMDD women with abuse may have implications for the hyperalgesia that has been documented in PMDD. It is hypothesized that increased B-AR responsivity coupled with blunted NE will contribute to worse premenstrual symptoms and to hyperalgesia to experimental pain in PMDD women with prior CA. Sixty PMDD and 90 non-PMDD women will be tested in the luteal phase of the menstrual cycle for SNS (e.g., plasma NE, blood pressure) and HPA-axis (cortisol, ACTH, B-end) activation at rest and during stress, B-AR responsivity, and pain sensitivity to ischemic, thermal heat, and cold pain. Five groups will be compared for differences in pain sensitivity and relationship to physiological measures: 1) PMDD women with prior CA (n=30);2) never abused PMDD women (n=30);3) non-PMDD women with prior CA (n=30);4) never abused non-PMDD women (n=30);and 5) non-PMDD women with no abuse and no psychiatric histories (n=30) as a healthy control group. Since our prelim studies show that all women with abuse have lower cortisol and non- PMDD women with CA show some degree of adrenergic dysregulation, we predict a rank order of effects PMDD/CA+>non-PMDD/CA+>PMDD/CA->non-PMDD/CA- for adrenergic dysregulation and hyperalgesia. Following this testing, using double-blind, placebo-controlled, cross-over procedures, all women will be retested in 2 subsequent luteal phases for SNS measures, pain sensitivity, and dysphoric mood;once during a low dose, i.v. propranolol session (0.1 mg/kg) and once during placebo. Since propranolol is a B-AR blocker, we intend to use propranolol as a pharmacological probe to investigate SNS and adrenergic factors that contribute to hyperalgesia and dysphoric mood in PMDD. We hypothesize that propranolol will be associated with differentially greater normalization of SNS, NE and hyperalgesia measures, and greater reductions in dysphoria in PMDD women with CA. These results are intended to provide important insights into the pathophysiological significance of altered adrenergic activation in the subgroup of PMDD women with CA.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH051246-12
Application #
7796697
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Muehrer, Peter R
Project Start
1995-08-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
12
Fiscal Year
2010
Total Cost
$451,987
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Psychiatry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Fleischman, Diana S; Bunevicius, Adomas; Leserman, Jane et al. (2014) Menstrually related mood disorders and a history of abuse: moderators of pain sensitivity. Health Psychol 33:147-54
Klatzkin, Rebecca R; Bunevicius, Adomas; Forneris, Catherine A et al. (2014) Menstrual mood disorders are associated with blunted sympathetic reactivity to stress. J Psychosom Res 76:46-55
Bunevicius, Adomas; Hinderliter, Alan; Klatzkin, Rebecca et al. (2013) Beta-adrenergic receptor mechanisms and pain sensitivity in women with menstrually related mood disorders. J Pain 14:1349-60
Brownley, Kimberly A; Girdler, Susan S; Stout, Anna L et al. (2013) Chromium supplementation for menstrual cycle-related mood symptoms. J Diet Suppl 10:345-56
Bunevicius, Adomas; Rubinow, David R; Calhoun, Anne et al. (2013) The association of migraine with menstrually related mood disorders and childhood sexual abuse. J Womens Health (Larchmt) 22:871-6
Bunevicius, Adomas; Leserman, Jane; Girdler, Susan S (2012) Hypothalamic-pituitary-thyroid axis function in women with a menstrually related mood disorder: association with histories of sexual abuse. Psychosom Med 74:810-6
Girdler, Susan S; Lindgren, Monica; Porcu, Patrizia et al. (2012) A history of depression in women is associated with an altered GABAergic neuroactive steroid profile. Psychoneuroendocrinology 37:543-53
Klatzkin, Rebecca R; Mechlin, Beth; Girdler, Susan S (2010) Menstrual cycle phase does not influence gender differences in experimental pain sensitivity. Eur J Pain 14:77-82
Porcu, Patrizia; O'Buckley, Todd K; Alward, Sarah E et al. (2010) Differential effects of ethanol on serum GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in mice, rats, cynomolgus monkeys, and humans. Alcohol Clin Exp Res 34:432-42
Klatzkin, Rebecca R; Lindgren, Monica E; Forneris, Catherine A et al. (2010) Histories of major depression and premenstrual dysphoric disorder: Evidence for phenotypic differences. Biol Psychol 84:235-47

Showing the most recent 10 out of 29 publications