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The Effect of Steroid Hormones in the Female Brain During Different Reproductive States
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
2012 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Women are twice as likely as men to suffer from depression and anxiety disorders and have an increased risk of onset during periods associated with hormonal changes, such as the postpartum period and the menopausal transition. Furthermore, some women seem more sensitive to normal hormone fluctuations across the menstrual cycle, since approximately 3-5% suffers from premenstrual dysphoric disorder (PMDD). Why these disorders are so common in women has not been established but there is a probable involvement of the ovarian hormones.

The aim of this thesis was to investigate the effect of the ovarian hormones on the female brain during different reproductive states using psychological tests known to affect brain activity in different ways.

Paper one examined the effect of the ovarian hormones on prepulse inhibition (PPI) on the acoustic startle response (ASR) and comprised cycling women and postmenopausal women. The cycling women had lower levels of PPI compared to postmenopausal women and postmenopausal women with moderate estradiol levels had lower PPI compared to postmenopausal women with low estradiol levels.

Paper two examined the effect of anticipation and affective modulation on the ASR in women with PMDD and healthy controls. Women with PMDD have an increased modulation during anticipation of affective pictures compared to healthy controls during the luteal phase of the menstrual cycle.

Paper three examined brain activity during response inhibition among women with PMDD and healthy controls by the use of a Go/NoGo task and fMRI. Women with PMDD displayed a decreased activity in the left insula during follicular phase and an increased activity during the luteal phase compared to controls.

Paper four comprised women in the postpartum period and non-pregnant controls to examine brain activity during response inhibition. While this study revealed decreased activity at 4 weeks postpartum compared to 48 hours postpartum we cannot ascertain the role of the ovarian steroids, since none of the significant brain areas correlated with ovarian steroid or neurosteroid serum concentrations.

The results of this thesis demonstrate that the ovarian hormones, or at least various hormonal states, have a probable impact on how the female brain works.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2012. , s. 85
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 787
Emneord [en]
Premenstrual dysphoric disorder, Postpartum, Estradiol, Progesterone, Menstrual cycle, Functional magnetic resonance imaging, Response inhibition, Prepulse inhibition, Startle response
HSV kategori
Forskningsprogram
Medicinsk vetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-175409ISBN: 978-91-554-8402-6 (tryckt)OAI: oai:DiVA.org:uu-175409DiVA, id: diva2:531388
Disputas
2012-09-14, Gustavianum, Auditorium Minus, Akademigatan 3, Uppsala, 09:00 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2012-08-22 Laget: 2012-06-06 Sist oppdatert: 2013-07-22
Delarbeid
1. Lower levels of prepulse inhibition in luteal phase cycling women in comparison with postmenopausal women
Åpne denne publikasjonen i ny fane eller vindu >>Lower levels of prepulse inhibition in luteal phase cycling women in comparison with postmenopausal women
2010 (engelsk)Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 35, nr 3, s. 422-429Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Menopause denotes the end of the reproductive period in a woman's life and is characterized by gradually declining plasma levels of ovarian hormones. Mounting evidence suggests that prepulse inhibition (PPI) is sensitive to fluctuations in estradiol and progesterone. Deficits in PPI are associated with conditions characterized by increased levels of ovarian steroids, such as the mid-luteal phase of the menstrual cycle and the third trimester of pregnancy. The aim of the current study was to further elucidate ovarian steroid-related effects on PPI by examining 43 women with regular menstrual cycles, 20 healthy postmenopausal women without hormone replacement treatment (HRT) and 21 healthy postmenopausal women with ongoing estradiol-only or estradiol and progesterone therapy (EPT). Cycling women were tested during the late luteal phase of the menstrual cycle while postmenopausal women were tested on any arbitrary day. The PPI was measured by electromyography. Cycling women exhibited lower levels of PPI than postmenopausal women (p<0.05). There were no differences in PPI between postmenopausal HRT users and non-users. However, postmenopausal women with estradiol serum concentrations in the cycling range had lower PPI than postmenopausal women with low estradiol concentrations (groupxPPI interaction, p<0.05). In conclusion, the results further suggest a role for the ovarian steroids in PPI regulation as PPI is increased in postmenopausal women in comparison to regularly menstruating women examined during the late luteal phase. Furthermore, postmenopausal women with estradiol levels in the cycling range had lower PPI than postmenopausal women with low estradiol levels.

Emneord
Estradiol, Hormone replacement therapy, Menopause, Prepulse inhibition, Progesterone, Startle response
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-124853 (URN)10.1016/j.psyneuen.2009.08.004 (DOI)000275700000010 ()19735984 (PubMedID)
Tilgjengelig fra: 2010-05-06 Laget: 2010-05-06 Sist oppdatert: 2017-12-12bibliografisk kontrollert
2. Patients with premenstrual dysphoric disorder have increased startle modulation during anticipation in the late luteal phase period in comparison to control subjects
Åpne denne publikasjonen i ny fane eller vindu >>Patients with premenstrual dysphoric disorder have increased startle modulation during anticipation in the late luteal phase period in comparison to control subjects
Vise andre…
2011 (engelsk)Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 36, nr 8, s. 1184-1192Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The acoustic startle response (ASR) is a withdrawal reflex to sudden or noxious auditory stimuli and, most importantly, an unbiased measure of emotional processing of appetitive and aversive stimuli. By exposing subjects to fearful situations, such as aversive pictures, the ASR may be enhanced, suggesting that amygdala modulates the startle circuit during threat situations. As one previous study, investigating affective modulation of the ASR in women with premenstrual dysphoric disorder (PMDD), discovered no difference during picture viewing it is possible that the mood changes observed in PMDD relate to anxious anticipation rather than to direct stimulus responding. Hence we sought to examine the effects of PMDD on picture anticipation and picture response.

Sixteen PMDD patients and 16 controls watched slide shows containing pleasant and unpleasant pictures and positive and negative anticipation stimuli during the follicular and luteal phase of the menstrual cycle. Simultaneously, semi-randomized startle probes (105dB) were delivered and the ASR was assessed with electromyography.

Compared with control subjects, PMDD patients displayed an enhanced startle modulation by positive and negative anticipation stimuli in the luteal phase of the menstrual cycle. This finding was mainly driven by increased modulation in the luteal phase in comparison to the follicular phase among PMDD patients but also by an increased modulation in patients compared to controls during luteal phase. This suggests that the neural circuits underlying response to emotional anticipation are more sensitive during this period and emphasize the need of examining the neural correlates of anticipatory processes in women with PMDD.

HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-152022 (URN)10.1016/j.psyneuen.2011.02.011 (DOI)000295072300009 ()21435793 (PubMedID)
Tilgjengelig fra: 2011-04-20 Laget: 2011-04-20 Sist oppdatert: 2017-12-11bibliografisk kontrollert
3.
Posten ble ikke funnet. Det kan skyldes at posten ikke lenger er tilgjengelig eller det er feil id i adressefeltet.
4. Prefrontal activity during response inhibition decreases over time in postpartum women
Åpne denne publikasjonen i ny fane eller vindu >>Prefrontal activity during response inhibition decreases over time in postpartum women
Vise andre…
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-175276 (URN)
Tilgjengelig fra: 2012-06-04 Laget: 2012-06-04 Sist oppdatert: 2015-06-11

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