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Negative Association Between Allopregnanolone and Cerebral Serotonin Transporter Binding in Healthy Women of Fertile Age
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.ORCID iD: 0000-0002-2491-2042
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-2174-2068
Umea Univ, Dept Clin Sci Obstet & Gynecol, Umea, Sweden.
Umea Univ, Dept Clin Sci Obstet & Gynecol, Umea, Sweden.
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2019 (English)In: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 9, article id 2767Article in journal (Refereed) Published
Abstract [en]

Allopregnanolone is a metabolite of the sex hormone progesterone, with suggested relevance for female mood disorders. While allopregnanolone and serotonin are known to influence psychological well-being, the molecular and psychological specifics of their relationship are to date poorly understood, especially in women of fertile age who experience regular fluctuations of progesterone across the menstrual cycle. Availability of serotonin in the synaptic cleft is regulated by the serotonin transporter (SERT), which can be imaged in the living human brain by use of positron emission tomography (PET) and the radiotracer [C-11]DASB. To evaluate sex-specific allopregnanolone-SERT interactions, the present study investigated the relationship between cerebral SERT availability, serum allopregnanolone levels and psychological well-being in women of fertile age. Brain imaging data, self-reported symptoms of mental distress and emotion regulation, and biobank material from ninety healthy women were available from the Center for Integrated Molecular Brain Imaging (CIMBI) database. Age, BMI, and daylight minutes were included as covariates in the analyses and SERT genotype (5-HTTLPR) was considered a potential confounder. Lower serum allopregnanolone levels were associated with higher SERT binding in the prefrontal cortex. Moreover, allopregnanolone levels were negatively associated with measures of alertness, although this finding was not mediated by prefrontal cortex SERT binding. These findings suggest a link between the typical psychological well-being experienced in the follicular phase when allopregnanolone levels are low and higher SERT in the prefrontal cortex, a region for higher cognitive functions and top-down regulation of emotions.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2019. Vol. 9, article id 2767
Keywords [en]
allopregnanolone, brain, mood, PET, serotonin transporter, women, 5HTT
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:uu:diva-375873DOI: 10.3389/fpsyg.2018.02767ISI: 000455554400001PubMedID: 30687199OAI: oai:DiVA.org:uu-375873DiVA, id: diva2:1285265
Funder
Swedish Research CouncilEU, FP7, Seventh Framework Programme, INCA 600398Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceAvailable from: 2019-02-04 Created: 2019-02-04 Last updated: 2019-02-04Bibliographically approved

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