title: Histories of sexual abuse are associated with differential effects of clonidine on autonomic function in women with premenstrual dysphoric disorder.
abstract: In women meeting strict criteria for premenstrual dysphoric disorder (PMDD), we examined whether clonidine, an alpha2-adrenergic receptor (AR) agonist, would have different effects on sexually abused versus non-abused PMDD women for measures of autonomic nervous system function. Twelve women meeting prospective, DSM-IV criteria for PMDD, five of whom had a history of sexual abuse, participated in a randomized, placebo-controlled, double-blind, cross-over design study, comparing 2 months of on oral clonidine (0.3 mg/day) with 2 months on active placebo. During the luteal phase that preceded randomization and following each two-month challenge, women were tested for cardiovascular measures at rest and in response to mental stress, and for resting plasma norepinephrine (NE) concentrations as well as beta1 and beta2-AR responsivity using the isoproterenol sensitivity test. Results revealed that in comparison to placebo, clonidine significantly reduced plasma norepinephrine concentrations, increased both beta1- and beta2-AR responsivity, and reduced resting and stress heart rate (HR) and blood pressure (BP) (p < 0.05) in all PMDD women. With clonidine, sexually abused PMDD women exhibited greater decreases in resting and stress-induced HR (p < 0.01) and stress-induced systolic BP (p < 0.05), while non-abused PMDD women exhibited greater reductions in plasma NE concentration (p = 0.07), and greater increases in beta2-AR responsivity (p < 0.05) than abused PMDD women. These results suggest PMDD women with and without a history of sexual abuse respond differently to a clonidine challenge in measures reflecting autonomic nervous system functioning, indicating that abuse may modify presynaptic alpha2-AR function in PMDD.
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, CB# 7175, Medical Research Bldg A, Chapel Hill, NC 27599-7175, USA.
authors.forename: Robertas
authors.initials: R
authors.lastname: Bunevicius
authors.forename: Alan L
authors.initials: AL
authors.lastname: Hinderliter
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Light
authors.forename: Jane
authors.initials: J
authors.lastname: Leserman
authors.forename: Cort A
authors.initials: CA
authors.lastname: Pedersen
authors.forename: Susan S
authors.initials: SS
authors.lastname: Girdler
mesh_terms: D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000328:Adult; D001341:Autonomic Nervous System / Q000187:drug effects*; D002648:Child; D002650:Child Abuse, Sexual / Q000523:psychology* / Q000706:statistics & numerical data*; D002851:Chromatography, High Pressure Liquid; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D018592:Cross-Over Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019964:Mood Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D009638:Norepinephrine / Q000097:blood; D011293:Premenstrual Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D000316:Adrenergic alpha-Agonists; D003000:Clonidine; D009638:Norepinephrine