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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Vydáno v:	Psychopharmacology Ročník 233; číslo 11; s. 2109 - 2117
Hlavní autoři:	Timby, Erika, Bäckström, Torbjörn, Nyberg, Sigrid, Stenlund, Hans, Wihlbäck, Anna-Carin N., Bixo, Marie
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2016 Springer Springer Nature B.V
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23
ISSN:	0033-3158 1432-2072 1432-2072
DOI:	10.1007/s00213-016-4258-1