Women with premenstrual dysphoric disorder have altered sensitivity to allopregnanolone over the menstrual cycle compared to controls—a pilot study

Rationale In premenstrual dysphoric disorder (PMDD), a condition that afflicts 3–8 % of women in fertile ages, the cyclic recurrence of debilitating mood symptoms is restricted to the luteal phase of the menstrual cycle. The progesterone metabolite allopregnanolone is produced by the corpus luteum,...

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Veröffentlicht in:Psychopharmacology Jg. 233; H. 11; S. 2109 - 2117
Hauptverfasser: Timby, Erika, Bäckström, Torbjörn, Nyberg, Sigrid, Stenlund, Hans, Wihlbäck, Anna-Carin N., Bixo, Marie
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2016
Springer
Springer Nature B.V
Schlagworte:
Adolescent
Adult
Anxiety - psychology
Biomedical and Life Sciences
Biomedicine
Complications and side effects
Drug interactions
Electrooculography
Female
GABA
GABA Modulators - pharmacology
Gonadal Steroid Hormones - blood
Gonadal Steroid Hormones - pharmacology
Humans
Hypnotics and Sedatives - pharmacology
Medical disorders
Menstrual cycle
Menstrual Cycle - drug effects
Menstruation
Neurosciences
Neurosteroid
Observations
Original Investigation
Panic - drug effects
Pharmacology/Toxicology
Physiological aspects
Pilot Projects
Pregnanolone - blood
Pregnanolone - pharmacology
Premenstrual dysphoric disorder
Premenstrual Dysphoric Disorder - physiopathology
Premenstrual syndrome
Psychiatry
Psychopharmacology
Receptors, GABA-A - drug effects
Saccades - drug effects
Saccadic eye velocity
Steroids
Steroids (Drugs)
Young Adult
GABA
Saccadic eye velocity
Neurosteroid
Menstrual cycle
Premenstrual dysphoric disorder
ISSN:0033-3158, 1432-2072, 1432-2072
Online-Zugang:Volltext
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Zusammenfassung:Rationale In premenstrual dysphoric disorder (PMDD), a condition that afflicts 3–8 % of women in fertile ages, the cyclic recurrence of debilitating mood symptoms is restricted to the luteal phase of the menstrual cycle. The progesterone metabolite allopregnanolone is produced by the corpus luteum, and circulating levels are reflected in the brain. Allopregnanolone is a modulator of the GABA A receptor, enhancing the effect of γ-aminobutyric acid (GABA). Previous studies have demonstrated different sensitivity to other GABA A receptor agonists, i.e., benzodiazepines, alcohol, and pregnanolone, in PMDD patients compared to controls. Objectives This study aimed to investigate the sensitivity to intravenous allopregnanolone over the menstrual cycle in PMDD patients. Methods Allopregnanolone, 0.05 mg/kg, was administered intravenously once in the mid-follicular and once in the luteal phase of the menstrual cycle to 10 PMDD patients and 10 control subjects. The saccadic eye velocity (SEV) was recorded by electrooculography as a measurement of functional GABA A receptor activity, at baseline and repeatedly after the injection. A mixed model was used to analyze data. Results There was a highly significant group × phase interaction in the SEV response to allopregnanolone ( F (1,327.489) = 12.747, p  < 0.001). In the PMDD group, the SEV response was decreased in the follicular phase compared to the luteal phase ( F (1,168) = 7.776, p  = 0.006), whereas in the control group, the difference was opposite during the menstrual cycle ( F (1,158.45) = 5.70, p  = 0.018). Conclusions The effect of exogenous allopregnanolone is associated with menstrual cycle phase in PMDD patients and in controls. The results suggest an altered sensitivity to allopregnanolone in PMDD patients.
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ISSN:0033-3158
1432-2072
1432-2072
DOI:10.1007/s00213-016-4258-1