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Ovarian Steroid Hormones, Emotion Processing and Mood
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
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 [en]
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: urn:nbn:se:uu:diva-199791ISBN: 978-91-554-8693-8 (print)OAI: oai:DiVA.org:uu-199791DiVA: diva2:621369
Public defence
2013-08-30, Auditorium Minus, Gustavianum, Museum Gustavianum Akademigatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2013-06-05 Created: 2013-05-14 Last updated: 2013-08-30Bibliographically approved
List of papers
1. Menstrual cycle effects on amygdala reactivity to emotional stimulation in premenstrual dysphoric disorder
Open this publication in new window or tab >>Menstrual cycle effects on amygdala reactivity to emotional stimulation in premenstrual dysphoric disorder
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2012 (English)In: Hormones and Behavior, ISSN 0018-506X, E-ISSN 1095-6867, Vol. 62, no 4, 400-406 p.Article in journal (Refereed) Published
Abstract [en]

Premenstrual dysphoric disorder (PMDD) with luteal phase related anxiety and mood swings compromise quality of life in around 4% of reproductive women. While anxiety is related to amygdala function, prior studies on amygdala reactivity both in healthy controls and women with PMDD are inconsistent with respect to menstrual cycle effects. Here women with PMDD and healthy controls were exposed to emotional faces during the mid-follicular and late luteal phase, and mean blood-oxygen-level dependence (BOLD) signal changes in the amygdala were determined with functional magnetic resonance imaging (fMRI). Women with PMDD had enhanced bilateral amygdala reactivity in the follicular phase in comparison with healthy controls, but there was no difference between groups during the luteal phase. In contrast, healthy controls displayed higher left amygdala reactivity in the luteal than in their follicular phase. However, among women with PMDD follicular phase progesterone serum concentrations were positively correlated with bilateral amygdala reactivity while depression scores were positively correlated with right amygdala reactivity in the luteal phase. In addition, women with PMDD and high scores on trait anxiety had increased right amygdala reactivity in the luteal as compared to the follicular phase. Finally, amygdala reactivity was more prone to habituation in women with PMDD, as they had enhanced amygdala reactivity in comparison with controls at the first, but not the second scanning session. Thus, while the study failed to indicate increased luteal phase amygdala reactivity in women with PMDD, our findings suggest that anxiety proneness and progesterone levels modulate menstrual cycle related amygdala reactivity in women with PMDD.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-183654 (URN)10.1016/j.yhbeh.2012.07.005 (DOI)000310654100006 ()22814368 (PubMedID)
Available from: 2012-10-31 Created: 2012-10-31 Last updated: 2017-12-07Bibliographically approved
2. Oral contraceptive use changes brain activity and mood in women with previous negative affect on the pill: A double-blinded, placebo-controlled randomized trial of a levonorgestrel-containing combined oral contraceptive
Open this publication in new window or tab >>Oral contraceptive use changes brain activity and mood in women with previous negative affect on the pill: A double-blinded, placebo-controlled randomized trial of a levonorgestrel-containing combined oral contraceptive
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2013 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 7, 1133-1144 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE:

Most women on combined oral contraceptives (COC) report high levels of satisfaction, but 4-10% complain of adverse mood effects. The aim of this randomized, double-blinded, placebo-controlled trial was to investigate if COC use would induce more pronounced mood symptoms than placebo in women with previous history of COC-induced adverse mood. A second aim was to determine if COC use is associated with changes in brain reactivity in regions previously associated with emotion processing.

METHODS:

Thirty-four women with previous experience of mood deterioration during COC use were randomized to one treatment cycle with a levonorgestrel-containing COC or placebo. An emotional face matching task (vs. geometrical shapes) was administered during functional magnetic resonance imaging (fMRI) prior to and during the COC treatment cycle. Throughout the trial, women recorded daily symptom ratings on the Cyclicity Diagnoser (CD) scale.

RESULTS:

During the last week of the treatment cycle COC users had higher scores of depressed mood, mood swings, and fatigue than placebo users. COC users also had lower emotion-induced reactivity in the left insula, left middle frontal gyrus, and bilateral inferior frontal gyri as compared to placebo users. In comparison with their pretreatment cycle, the COC group had decreased emotion-induced reactivity in the bilateral inferior frontal gyri, whereas placebo users had decreased reactivity in the right amygdala.

CONCLUSION:

COC use in women who previously had experienced emotional side effects resulted in mood deterioration, and COC use was also accompanied by changes in emotional brain reactivity. These findings are of relevance for the understanding of how combined oral contraceptives may influence mood. Placebo-controlled fMRI studies in COC sensitive women could be of relevance for future testing of adverse mood effects in new oral contraceptives.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-188504 (URN)10.1016/j.psyneuen.2012.11.006 (DOI)000320412400018 ()23219471 (PubMedID)
Available from: 2012-12-17 Created: 2012-12-17 Last updated: 2017-12-06Bibliographically approved
3. Premenstrual dysphoric disorder and prefrontal reactivity during anticipation of emotional stimuli
Open this publication in new window or tab >>Premenstrual dysphoric disorder and prefrontal reactivity during anticipation of emotional stimuli
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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.

Keyword
fMRI, premenstrual dysphoric disorder, progesterone, estrogen, anticipation, emotion
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-199788 (URN)10.1016/j.euroneuro.2013.08.002 (DOI)000328014700016 ()24001875 (PubMedID)
Available from: 2013-05-14 Created: 2013-05-14 Last updated: 2017-12-06Bibliographically approved
4. Social stimulation, amygdala reactivity and connectivity in premenstrual dysphoric disorder.
Open this publication in new window or tab >>Social stimulation, amygdala reactivity and connectivity in premenstrual dysphoric disorder.
Show others...
(English)Manuscript (preprint) (Other academic)
Keyword
premenstrual dysphoric disorder, estrogen, progesterone, amygdala, fMRI, emotion.
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-199789 (URN)
Available from: 2013-05-14 Created: 2013-05-14 Last updated: 2013-08-30

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