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Premenstrual dyspho...
Premenstrual dysphoric disorder : brain structure and function, GABAA-active neurosteroids and GABAA receptor plasticity
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- Stiernman, Louise, 1994- (författare)
- Umeå universitet,Obstetrik och gynekologi
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- Bixo, Marie, Professor (preses)
- Umeå universitet,Obstetrik och gynekologi
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- Johansson, Inga-Maj, Docent (preses)
- Umeå universitet,Kemiska institutionen,Obstetrik och gynekologi
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- Comasco, Erika, Docent (preses)
- Institutionen för kvinnors och barns hälsa, Uppsala University
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- Eriksson, Elias, Professor (opponent)
- Institutionen för Farmakologi, Sahlgrenska Akademin, Göteborg University
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(creator_code:org_t)
- ISBN 9789180704205
- Umeå : Umeå University, 2024
- Engelska 128 s.
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Serie: Umeå University medical dissertations, 0346-6612 ; 2310
- Relaterad länk:
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Abstract
Ämnesord
Stäng
- Background Premenstrual dysphoric disorder (PMDD) is an ovarian hormone-bound disorder, characterized by mood symptoms which occur exclusively during the luteal phase of the menstrual cycle. Previous neuroimaging studies of PMDD have primarily reported functional brain differences during the luteal phase in regions of the salience network (SN), which is commonly implicated in mood and anxiety disorders. SN dysfunction may mediate affective and behavioral deficits by leading to enhanced detection and inappropriate assignment of salience to stimuli. What drives altered brain function in PMDD is unknown. However, one influential hypothesis implicates the luteal phase hormone progesterone, and in particular its neurosteroid metabolites. Progesterone-derived neurosteroids increase transmission at the g- aminobutyric acid type A (GABAA) receptor, leading to increased inhibitory tone at the neuronal level. This thesis aimed to i) investigate structural and functional characteristics of the brain in PMDD, ii) relate functional measures to levels of neurosteroids during the luteal phase, and iii) investigate how gene expression of GABAA receptor subunits is altered across the menstrual cycle in PMDD.Results In Study I, we found that women with PMDD had thinner cortices in widespread brain regions, including regions of the SN. In Studies II and III, we found that increases in functional brain measures are most prominent during the symptomatic luteal phase in regions belonging to the SN and in other networks commonly involved in the psychopathology of mood disorders. Furthermore, we could show that increased activity in key nodes of the SN was apparent in the follicular phase and related to the severity of affective symptoms experienced during the luteal phase. Additionally, in Study II, we found that functional activity in the amygdala, a key region of the SN, was differentially associated with serum levels of GABAA receptor- active neurosteroids between PMDD and controls during the luteal phase. Lastly, in Study IV, we found seminal evidence of reduced mRNA expression of the d-GABAA subunit, which imbues GABAA receptors with increased sensitivity to progesterone’s neurosteroid metabolites. Lower expression of d subunits was related to higher amygdala reactivity.Conclusion In this thesis, I provide evidence for altered structure and function in multiple brain networks, particularly the SN in PMDD. Accentuated SN dysfunction during the symptomatic luteal phase may be mediated by the amygdala, and related to abnormal deficits in the expression of neurosteroid-sensitive d- GABAA receptors in response to ovarian hormone fluctuations.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)
Nyckelord
- Premenstrual dysphoric disorder
- GABAA receptor
- neurosteroids
- allopregnanolone
- isoallopregnanolone
- functional magnetic brain imaging
- salience network
- obstetrik och gynekologi
- Obstetrics and Gynaecology
Publikations- och innehållstyp
- vet (ämneskategori)
- dok (ämneskategori)
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