Neuroactive steroid levels are elevated in the follicular phase and predict premenstrual depression and anxiety symptom severity in women with menstrually related mood disorder.

Autor: Kimball A; Neuroendocrine Unit, Massachusetts General Hospital, 50 Staniford St., Suite 750B, Boston, MA, 02114, USA. akimball1@mgb.org.; Harvard Medical School, Boston, MA, USA. akimball1@mgb.org., Bourassa J; Neuroendocrine Unit, Massachusetts General Hospital, 50 Staniford St., Suite 750B, Boston, MA, 02114, USA., Chicote ML; Neuroendocrine Unit, Massachusetts General Hospital, 50 Staniford St., Suite 750B, Boston, MA, 02114, USA., Gerweck AV; Neuroendocrine Unit, Massachusetts General Hospital, 50 Staniford St., Suite 750B, Boston, MA, 02114, USA., Dichtel LE; Neuroendocrine Unit, Massachusetts General Hospital, 50 Staniford St., Suite 750B, Boston, MA, 02114, USA.; Harvard Medical School, Boston, MA, USA., Miller KK; Neuroendocrine Unit, Massachusetts General Hospital, 50 Staniford St., Suite 750B, Boston, MA, 02114, USA.; Harvard Medical School, Boston, MA, USA.
Jazyk: angličtina
Zdroj: Archives of women's mental health [Arch Womens Ment Health] 2024 Nov 27. Date of Electronic Publication: 2024 Nov 27.
DOI: 10.1007/s00737-024-01532-3
Abstrakt: Purpose: Menstrually related mood disorder (MRMD) is marked by severe affective symptoms in the late luteal phase of the menstrual cycle. We hypothesized that women with MRMD experience relative neuroactive steroid deficiency, specifically low allopregnanolone levels due to reduced conversion of progesterone, in association with the onset of affective symptoms in the late luteal phase.
Methods: Nine subjects with MRMD and 14 healthy controls were studied. Daily Record of Severity of Problems was used to diagnose MRMD by DSM-5 criteria for premenstrual dysphoric disorder. Depression and anxiety symptom severity (16-Item Quick Inventory of Depressive Symptomatology Self Report, Generalized Anxiety Disorder 7-Item Scale) and levels of plasma neuroactive steroids by mass spectrometry were assessed at the mid-follicular, mid-luteal, and late luteal phases.
Results: Depression severity was greater in women with MRMD than healthy controls in the late luteal phase only, as expected. In the mid-follicular phase, the mean allopregnanolone level and allopregnanolone/progesterone ratio were higher in women with MRMD than healthy controls. There were no differences between groups in luteal phase allopregnanolone levels. Higher follicular phase allopregnanolone sulfate and allopregnanolone levels were associated with greater depression severity in the mid-luteal and late luteal phases and greater anxiety severity in the late luteal phase.
Conclusion: Levels of allopregnanolone, which have antidepressant effects, were higher in the mid-follicular phase in women with MRMD compared to healthy controls. In MRMD, increased conversion of progesterone to allopregnanolone in the mid-follicular phase may be a compensatory response to luteal phase depression and anxiety, or increased allopregnanolone levels could paradoxically trigger depression and anxiety.
Competing Interests: Declarations. Competing interests: LED has received study medication from Pfizer, research support from Perspectum Ltd. and research support from Lumos Pharma, all per investigator-initiated request, and additional research support from Recordati and Novo Nordisk. She has equity in Marea Therapeutics and is a consultant for Lumos Pharma. She was a fellow at Third Rock Ventures through the Mass General Brigham’s Innovation Fellows Program but remained a full-time employee of Mass General Brigham during the course of this educational program (10/1/2022–9/30/2024). KKM has received study medication and investigator-initiated research grants from Amgen and has equity in Bristol-Myers Squibb (BMS), General Electric, Boston Scientific, and Becton Dickinson. The other authors declare no conflicts of interest.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
Databáze: MEDLINE
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