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Premenstrual dysphoric disorder and prefrontal reactivity during anticipation of emotional stimuli
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. (Reproduktiv hälsa/Sundström Poromaa)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Reproduktiv hälsa/Sundström Poromaa)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
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2013 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 23, no 11, 1474-1483 p.Article in journal (Refereed) Published
Abstract [en]

Premenstrual disorder (PMDD) affects around 5% of women in childbearing ages. An increased sensitivity in emotion processing areas of the brain to variations in ovarian steroid levels has been suggested as part of the pathophysiology in PMDD, but prior neuroimaging studies of emotion processing are yet inconclusive. Previous behavioral studies of women with PMDD have, however, reported enhanced luteal phase startle responsivity during emotional anticipation. Here we used functional magnetic resonance imaging (fMRI) to investigate central neural circuitry activity during anticipation of, and exposure to, emotional stimuli across the menstrual cycle in women with and without PMDD. As compared to healthy controls, women with PMDD displayed significantly enhanced reactivity in the prefrontal cortex during anticipation of, but not exposure to, negative emotional stimuli during the luteal phase. In PMDD patients, BOLD reactivity during anticipation or viewing of negative emotional stimuli was not dependent on absolute levels of estradiol or progesterone. However, progesterone levels were positively correlated with emotion-induced reactivity in the dorsolateral prefrontal cortex to positive emotional stimuli. These findings suggest that cortical emotional circuitry reactivity during anticipation is altered in PMDD during the luteal phase, which might be part of the pathophysiology behind the emotional symptoms or lack of emotional control reported by women with PMDD.

Place, publisher, year, edition, pages
2013. Vol. 23, no 11, 1474-1483 p.
Keyword [en]
fMRI, premenstrual dysphoric disorder, progesterone, estrogen, anticipation, emotion
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:uu:diva-199788DOI: 10.1016/j.euroneuro.2013.08.002ISI: 000328014700016PubMedID: 24001875OAI: oai:DiVA.org:uu-199788DiVA: diva2:621352
Available from: 2013-05-14 Created: 2013-05-14 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Ovarian Steroid Hormones, Emotion Processing and Mood
Open this publication in new window or tab >>Ovarian Steroid Hormones, Emotion Processing and Mood
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

It is known that some psychiatric disorders may deteriorate in relation to the menstrual cycle. However, in some conditions, such as premenstrual dysphoric disorder (PMDD), symptomatology is triggered mainly by the variations in ovarian steroid hormones. Although symptoms induced by fluctuations in ovarian steroids often are affective, little is known about how emotion processing in women is influenced by variations, or actual levels, of ovarian steroid hormones.

The general aim of this thesis was to evaluate menstrual cycle effects on reactivity in emotion generating and controlling areas in the corticolimbic system to emotional stimulation and anticipation, in healthy controls and women with PMDD. A second aim was to evaluate corticolimbic reactivity during long-term administration of exogenous ovarian steroids.

In study I, III and IV effects of the menstrual cycle on emotional reactivity in women with PMDD was studied. In study I, women with PMDD in displayed higher amygdala reactivity than healthy controls to emotional faces, not in the luteal phase as was hypothesised, but in the follicular phase. No difference between menstrual cycle phases was obtained in women with PMDD, while healthy controls had an increased reactivity in the luteal phase. The results of study I was further elaborated in study III, where women with PMDD were observed to have an increased anticipatory reactivity to negative emotional stimuli. However, no differences in amygdala reactivity to emotional stimuli were obtained across the menstrual cycle. Finally, in study IV the hypothesis that amygdala reactivity increase in the luteal phase in women with PMDD is linked to social stimuli rather than generally arousing stimuli was suggested, tested and supported.

In study II, re-exposure to COC induced mood symptoms de novo in women with a previous history of COC-induced adverse mood. Women treated with COC reported increased levels of mood symptoms both as compared to before treatment, and as compared to the placebo group. There was a relatively strong correlation between depressive scores before and during treatment. The effects of repeated COC administration on subjective measures and brain function were however dissociated with increased aversive experiences accompanied by reduced reactivity in the insular cortex.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 77 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 912
Keyword
premenstrual dysphoric disorder, menstrual cycle, combined oral contraceptives, estrogen, estradiol, progesterone, ethinyl-estradiol, levonorgestrel, randomized clinical trial, placebo, fMRI, amygdala, ACC, insula, dlPFC, mPFC, IFG, MFG
National Category
Obstetrics, Gynecology and Reproductive Medicine Psychiatry Radiology, Nuclear Medicine and Medical Imaging Psychology (excluding Applied Psychology)
Research subject
Medical Science; Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-199791 (URN)978-91-554-8693-8 (ISBN)
Public defence
2013-08-30, Auditorium Minus, Gustavianum, Museum Gustavianum Akademigatan 3, Uppsala, 09:15 (English)
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Supervisors
Available from: 2013-06-05 Created: 2013-05-14 Last updated: 2013-08-30Bibliographically approved

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Gingnell, MalinBannbers, ElinWikström, JohanFredrikson, MatsSundström Poromaa, Inger

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