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  • 1.
    Ahlsson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Akerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Schijven, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Univ Groningen, Dept Behav Physiol, Groningen, Netherlands.;Karolinska Inst, Ctr Gender Med, Stockholm, Sweden..
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Gene Expression in Placentas From Nondiabetic Women Giving Birth to Large for Gestational Age Infants2015In: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 22, no 10, p. 1281-1288Article in journal (Refereed)
    Abstract [en]

    Gestational diabetes, obesity, and excessive weight gain are known independent risk factors for the birth of a large for gestational age (LGA) infant. However, only 1 of the 10 infants born LGA is born by mothers with diabetes or obesity. Thus, the aim of the present study was to compare placental gene expression between healthy, nondiabetic mothers (n = 22) giving birth to LGA infants and body mass index-matched mothers (n = 24) giving birth to appropriate for gestational age infants. In the whole gene expression analysis, only 29 genes were found to be differently expressed in LGA placentas. Top upregulated genes included insulin-like growth factor binding protein 1, aminolevulinate synthase 2, and prolactin, whereas top downregulated genes comprised leptin, gametocyte-specific factor 1, and collagen type XVII 1. Two enriched gene networks were identified, namely, (1) lipid metabolism, small molecule biochemistry, and organismal development and (2) cellular development, cellular growth, proliferation, and tumor morphology.

  • 2. Andersson, Liselott
    et al.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wulff, Marianne
    Åström, Monica
    Bixo, Marie
    Depression and anxiety during pregnancy and six months postpartum: a follow-up study2006In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 85, no 8, p. 937-944Article in journal (Refereed)
    Abstract [en]

    Aims. To investigate the relationship between antenatal and postpartum depression and anxiety and to explore associated maternal characteristics. Methods. From a population-based sample of 1,555 women attending two obstetric clinics in Sweden, all women with an antenatal psychiatric diagnosis (n = 220) and a random selection of healthy women (n = 500) were contacted for a second assessment three to six months postpartum. The Primary Care Evaluation of Mental Disorders was used for evaluation on both occasions. Results. Fewer cases of depressive and/or anxiety disorders were prevalent postpartum compared with the second trimester screening. Depression and/or anxiety were prevalent in 16.5% of postpartal women versus 29.2% of pregnant women. There was a significant shift from a majority of subthreshold diagnoses during pregnancy to full Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnoses during the postpartum period. A history of previous psychiatric disorder, living single, and obesity were significantly associated with a new-onset postpartum psychiatric disorder. The absence of a previous psychiatric disorder was significantly associated with a postpartum recovery of depression or anxiety. Conclusions. Depression and anxiety appear to be less common postpartum than during pregnancy.

  • 3. Andersson, Liselott
    et al.
    Sundström-Poromaa, Inger
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Wulff, Marianne
    Åström, Monica
    Bixo, Marie
    Implications of antenatal depression and anxiety for obstetric outcome.2004In: Obstet Gynecol, ISSN 0029-7844, Vol. 104, no 3, p. 467-76Article in journal (Refereed)
  • 4. Andersson, Liselott
    et al.
    Sundström-Poromaa, Inger
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Wulff, Marianne
    Åström, Monica
    Bixo, Marie
    Neonatal outcome following maternal antenatal depression and anxiety: a population-based study.2004In: Am J Epidemiol, ISSN 0002-9262, Vol. 159, no 9, p. 872-81Article in journal (Other scientific)
  • 5. Andreen, Lotta
    et al.
    Sundström Poromaa, Inger
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Bixo, Marie
    Nyberg, Sigrid
    Bäckström, Torbjörn
    Allopregnanolone concentration and mood--a bimodal association in postmenopausal women treated with oral progesterone.2006In: Psychopharmacology (Berl), ISSN 0033-3158, Vol. 187, no 2, p. 209-21Article in journal (Refereed)
  • 6.
    Arnadottir, Ragnheidur
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hudecova, Miriam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kunovac-Kallak, Theodora
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Poromaa, Inger Sundstrom
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Steroid hormone receptor expression, proliferative activity and microvessel density in the endometrium of women with polycystic ovary syndrome2012In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, p. 64-64Article in journal (Other academic)
  • 7.
    Axfors, Cathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Eckerdal, Patricia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Volgsten, Helena
    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), Obstetrics and Reproductive Health Research.
    Wikström, Anna-Karin
    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), Clinical Obstetrics.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Ramklint, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Sundström Poromaa, Inger
    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.
    Skalkidou, Alkistis
    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), Obstetrics and Reproductive Health Research.
    Neuroticism is not independently associated with adverse obstetric or neonatal outcomes: An observational studyIn: Article in journal (Refereed)
  • 8.
    Bannbers, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Gingnell, Malin
    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.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Kask, Kristiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Garavan, Hugh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    The effect of premenstrual dysphoric disorder and menstrual cycle phase on brain activity during response inhibition2012In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 142, no 1-3, p. 347-350Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Premenstrual dysphoric disorder (PMDD) has generally not been associated with impulsive behavior. However, some studies suggest that women with PMDD have higher impulsivity scores than healthy controls and that brain activity during response inhibition may vary across the menstrual cycle. Therefore, our aim was to unravel potentially important cognitive aspects of PMDD by investigating brain activity during response inhibition in women with PMDD and healthy controls in relation to menstrual cycle phase.

    METHODS:

    Fourteen PMDD patients and 13 healthy controls performed a Go/NoGo task to measure brain activity during response inhibition by use of event-related functional magnetic resonance imaging.

    RESULTS:

    Women with PMDD displayed decreased activity during both menstrual cycle phases compared to healthy controls in several task-related parietal areas. A significant group by phase interactions was found in the left insula, driven by enhanced activity among healthy controls in the follicular phase and by enhanced insula activity during the luteal phase among PMDD patients.

    LIMITATIONS:

    The limitations of the present study are the relatively limited sample size, the relatively small number of NoGo trials and the lack of a baseline contrast for the NoGo trials.

    CONCLUSIONS:

    During response inhibition women with PMDD have reduced activity in areas associated with attention and motor function which is unrelated to menstrual cycle phase. Insular cortex activity, involved in both affective and cognitive processing, was significantly activated during the luteal phase among PMDD women. These findings are relevant for the understanding of how ovarian steroids influence mood symptoms in women.

  • 9.
    Bannbers, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Gingnell, Malin
    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.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Morell, Arvid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sylvén, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kask, Kristiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bäckström, Torbjörn
    Department of Clinical Science, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Prefrontal activity during response inhibition decreases over time in the postpartum period2013In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 241, no 1, p. 132-138Article in journal (Refereed)
    Abstract [en]

    The postpartum period is characterized by complex hormonal changes, but human imaging studies in the postpartum period have thus far predominantly focused on the neural correlates of maternal behavior or postpartum depression, whereas longitudinal studies on neural correlates of cognitive function across the postpartum period in healthy women are lacking. The aim of this study was to longitudinally examine response inhibition, as a measure of executive function, and its neural correlates in healthy postpartum women and non-postpartum controls. Thirteen healthy postpartum women underwent event-related functional magnetic resonance imaging while performing a Go/NoGo task. The first assessment was made within 48hours of delivery, and the second at 4-7 weeks postpartum. In addition, 13 healthy women examined twice during the menstrual cycle were included as non-postpartum controls. In postpartum women region of interest analyses revealed task-related decreased activations in the right inferior frontal gyrus, right anterior cingulate, and bilateral precentral gyri at the late postpartum assessment. Generally, postpartum women displayed lower activity during response inhibition in the bilateral inferior frontal gyri and precentral gyri compared to non-postpartum controls. No differences in response inhibition performance were found between time-points or between groups. In conclusion, this study has discovered that brain activity in prefrontal areas during a response inhibition task decreases throughout the course of the first postpartum weeks and is lower than in non-postpartum controls. Further studies on the normal adaptive brain activity changes that occur during the postpartum period are warranted.

  • 10.
    Bannbers, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kask, Kristiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Risbrough, Victoria
    Department of Psychiatry, University of California, San Diego, CA, USA.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Patients with premenstrual dysphoric disorder have increased startle modulation during anticipation in the late luteal phase period in comparison to control subjects2011In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 36, no 8, p. 1184-1192Article in journal (Refereed)
    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.

  • 11.
    Baumgart, J
    et al.
    Department of Obstetrics and Gynecology, Örebro University Hospital, Sweden.
    Nilsson, K
    Department of Obstetrics and Gynecology, Örebro University Hospital, Sweden.
    Stavreus Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kallak, Theodora Kunovac
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kushnir, M M
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab. ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah, USA.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Pathology, University of Utah School of Medicine, Salt Lake City, USA.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Androgen levels during adjuvant endocrine therapy in postmenopausal breast cancer patients2014In: Climacteric, ISSN 1369-7137, E-ISSN 1473-0804, Vol. 17, no 1, p. 48-54Article in journal (Refereed)
    Abstract [en]

    Objective

    To investigate plasma steroid hormone levels in postmenopausal breast cancer patients with and without adjuvant endocrine therapy and in healthy postmenopausal women.

    Methods

    Steroid hormone levels in postmenopausal breast cancer patients treated with aromatase inhibitors (n = 32) were compared with breast cancer patients treated with tamoxifen (n = 34), breast cancer patients without adjuvant endocrine therapy (n = 15), and healthy postmenopausal women (n = 56). Pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, cortisone, dehydroepiandrosterone (DHEA), androstenedione, total testosterone, dihydrotestosterone, estrone and estradiol were measured using liquid chromatography-tandem mass spectrometry. Sex hormone binding globulin was measured by solid-phase chemiluminescent immunometric assays, and the free androgen index was calculated.

    Results

    Aromatase inhibitor users did not differ in dihydrotestosterone, total testosterone, androstenedione, DHEA, or free androgen index levels from healthy controls or untreated breast cancer patients. The highest total testosterone levels were found in tamoxifen-treated women, who had significantly higher plasma concentrations than both women treated with aromatase inhibitors and breast cancer patients without adjuvant treatment. Concentrations of cortisol and cortisone were significantly greater in aromatase inhibitor users as well as tamoxifen users, in comparison with healthy controls and untreated breast cancer patients. Aromatase inhibitor users had lower estrone and estradiol plasma concentrations than all other groups.

    Conclusion

    Adjuvant treatment with aromatase inhibitors or tamoxifen was associated with increased cortisol and cortisone plasma concentrations as well as decreased estradiol concentrations. Androgen levels were elevated in tamoxifen-treated women but not in aromatase inhibitor users.

  • 12.
    Baumgart, Juliane
    et al.
    Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro.
    Nilsson, Kerstin
    Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kallak, Theodora Kunovac
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer2013In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 20, no 2, p. 162-168Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    The goal of this study was to investigate sexual function in postmenopausal breast cancer patients treated with aromatase inhibitors.

    METHODS:

    A population-based, cross-sectional study was conducted among postmenopausal breast cancer patients on adjuvant endocrine treatment and age-matched controls with and without estrogen treatment. Sexual function was assessed with a standardized questionnaire.

    RESULTS:

    In all, 42.4% of aromatase inhibitor-treated breast cancer patients were dissatisfied with their sex life in general, and 50.0% reported low sexual interest; this was significantly more common than in tamoxifen-treated patients and controls (P < 0.05). Aromatase inhibitor-treated patients reported insufficient lubrication in 73.9% and dyspareunia in 56.5% of cases, which were significantly more common than in controls, irrespective of hormonal use (P < 0.05). Tamoxifen-treated patients reported significantly more dyspareunia (31.3%; P < 0.05) but resembled controls in all other concerns.

    CONCLUSIONS:

    Our findings suggest that sexual dysfunction in aromatase inhibitor-treated women is a greatly underestimated problem.

  • 13.
    Baumgart, Juliane
    et al.
    Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Kerstin
    Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro, Sweden.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kask, Kristiina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Villman, Kenneth
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Kallak, Theodora
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Urogenital disorders in women with adjuvant endocrine therapy after early breast cancer2011In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 204, no 1, p. 26.e1-7Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the prevalence of urogenital symptoms and vaginal atrophy in postmenopausal breast cancer patients on adjuvant endocrine therapy. STUDY DESIGN: A population-based, cross-sectional study on postmenopausal breast cancer patients on adjuvant endocrine treatment and age-matched control subjects. Vaginal atrophy was assessed by gynecologic examination and atrophy-related symptoms by validated questionnaires. RESULTS: In all, 57.6% of aromatase inhibitor-treated and 32.4% of tamoxifen-treated breast cancer patients rated at least 1 vaginal atrophy symptom as moderate/severe, which was significantly more common than in control subjects (P < .01). Aromatase inhibitor-treated patients more often had moderate or severe vaginal atrophy (P < .05), a more atrophic cytohormonal evaluation, and significantly higher vaginal pH (P < .05) than all control subjects, irrespective of hormonal use. CONCLUSION: Our findings indicate that the frequency of vaginal atrophy symptoms, particularly in aromatase inhibitor-treated women, might have been underestimated in previous clinical trials.

  • 14.
    Bengtsdotter, Hanna
    et al.
    Örebro Univ, Dept Obstet & Gynaecol, Örebro, Sweden..
    Lundin, Cecilia
    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.
    Danielsson, Kristina Gemzell
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Bixo, Marie
    Umea Univ, Dept Clin Sci, Umea, Sweden..
    Baumgart, Juliane
    Örebro Univ, Dept Obstet & Gynaecol, Örebro, Sweden..
    Marions, Lena
    Karolinska Inst Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden..
    Brynhildsen, Jan
    Linkoping Univ, Dept Obstet & Gynaecol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Malmborg, Agota
    Linköping Univ, Dept Obstet & Gynaecol, Linköping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Lindh, Ingela
    Gothenburg Univ, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Obstet & Gynaecol, Gothenburg, Sweden..
    Sundström Poromaa, Inger
    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.
    Ongoing or previous mental disorders predispose to adverse mood reporting during combined oral contraceptive use2018In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 23, no 1, p. 45-51Article in journal (Refereed)
    Abstract [en]

    Purpose: Previous studies have emphasised that women with pre-existing mood disorders are more inclined to discontinue hormonal contraceptive use. However, few studies have examined the effects of combined oral contraceptives (COC) on mood in women with previous or ongoing mental disorders. Materials and methods: This is a supplementary analysis of an investigator-initiated, double-blinded, randomised clinical trial during which 202 women were treated with either a COC (1.5mg estradiol and 2.5mg nomegestrolacetate) or placebo during three treatment cycles. The Mini International Neuropsychiatric Interview was used to collect information on previous or ongoing mental disorders. The primary outcome measure was the total change score in five mood symptoms on the Daily Record of Severity of Problems (DRSP) scale in the intermenstrual phase of the treatment cycle. Results: Women with ongoing or previous mood, anxiety or eating disorders allocated to COC had higher total DRSP -scores during the intermenstrual phase of the treatment cycle in comparison with corresponding women randomised to placebo, mean difference 1.3 (95% CI 0.3-2.3). In contrast, among women without mental health problems, no difference in total DRSP -scores between COC- and placebo users was noted. Women with a risk use of alcohol who were randomised to the COC had higher total DRSP -scores than women randomised to placebo, mean difference 2.1 (CI 95% 1.0-3.2). Conclusions: Women with ongoing or previous mental disorders or risk use of alcohol have greater risk of COC-induced mood symptoms. This may be worth noting during family planning and contraceptive counselling.

  • 15.
    Bhandage, Amol
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Ólafsson, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    The mRNA expression of GABA-A, GABA-B receptor subunits and chloride transporters in peripheral blood mononuclear cells is influenced by gender, pregnancy and depression2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 215, p. 91-91Article in journal (Other academic)
  • 16.
    Bhandage, Amol K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Olafsson, Einar B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Expression of GABA receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, no 3, p. 575-585Article in journal (Refereed)
    Abstract [en]

    AIM: The concept of nerve-driven immunity recognizes a link between the nervous and the immune system. γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain and receptors activated by GABA can be expressed by immune cells. Here we examined if the expression of GABA receptors and chloride transporters in human peripheral mononuclear cells (PBMCs) were influenced by gender, pregnancy or mental health.

    METHODS: We used RT-qPCR to determine the mRNA expression level in men (n=16), non-pregnant women (n=19), healthy pregnant women (n=27) and depressed pregnant women (n=15).

    RESULTS: The ρ2 subunit had the most prominent expression level of the GABA-A receptor subunits in all samples. The δ and ρ2 subunits were up-regulated by pregnancy whereas the ε subunit was more frequently expressed in healthy pregnant women than non-pregnant women who, in-turn, commonly expressed the α6 and the γ2 subunits. The β1 and ε subunits expression was altered by depression in pregnant women. The GABA-B1 receptor was up-regulated by depression in pregnant women while the transporters NKCC1 and KCC4 were down-regulated by pregnancy. The changes recorded in the mRNA expression levels imply participation of GABA receptors in establishing and maintaining tolerance in pregnancy. Importantly, the correlation of mental health with the expression of specific receptor subunits reveals a connection between the immune cells and the brain. Biomarkers for mental health may be identified in PBMCs.

    CONCLUSION: The results demonstrate the impact gender, pregnancy and mental health have on expression of GABA receptors plus chloride transporters expressed in human PBMCs.

  • 17.
    Bhandage, Amol K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Olafsson, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Sundström, Iinger Poromaa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    GABA-A receptor subunit expression in human peripheral blood mononuclear cells2014In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 211, no S696, p. 86-86, article id P45Article in journal (Other academic)
  • 18.
    Bhandage, Amol K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Korol, Sergiy V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Nowak, Krzysztof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Williamsson, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women2017In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 305, p. 51-58Article in journal (Refereed)
    Abstract [en]

    The amino acid glutamate opens cation permeable ion channels, the iGlu receptors. These ion channels are abundantly expressed in the mammalian brain where glutamate is the main excitatory neurotransmitter. The neurotransmitters and their receptors are being increasingly detected in the cells of immune system. Here we examined the expression of the 18 known subunits of the iGlu receptors families; alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, N-methyl-D-aspartate (NMDA) and delta in human peripheral blood mononuclear cells (PBMCs). We compared the expression of the subunits between four groups: men, non-pregnant women, healthy pregnant women and depressed pregnant women.

    Out of 18 subunits of the iGlu receptors, mRNAs for 11 subunits were detected in PBMCs from men and nonpregnant women; AMPA: GluA3, GluA4, kainate: GluK2, GluK4, GluK5, NMDA: GluN1, GluN2C, GluN2D, GluN3A, GluN3B, and delta: GluD1. In the healthy and the depressed pregnant women, in addition, the delta GluD2 subunit was identified. The mRNAs for GluK4, GluK5, GluN2C and GluN2D were expressed at a higher level than other subunits. Gender, pregnancy or depression during pregnancy altered the expression of GluA3, GluK4, GluN2D, GluN3B and GluD1 iGlu subunit mRNAs. The greatest changes recorded were the lower GluA3 and GluK4 mRNA levels in pregnant women and the higher GluN2D mRNA level in healthy but not in depressed pregnant women as compared to non-pregnant individuals. Using subunit specific antibodies, the GluK4, GluK5, GluNl, GluN2C and GluN2D subunit proteins were identified in the PBMCs. The results show expression of specific iGlu receptor subunit in the PBMCs and support the idea of physiology-driven changes of iGlu receptors subtypes in the immune cells.

  • 19.
    Billström, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Poromaa, Inger Sundström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Stålberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Asplund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hellberg, Dan
    Socioeconomic characteristics, housing conditions and criminal behavior in women with cervical intraepithelial neoplasia (CIN) between 1960 and 20062012In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, p. 68-69Article in journal (Other academic)
  • 20.
    Billström, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stålberg, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Asplund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Socioeconomic characteristics, housing conditions and criminal offences among women with cervical neoplasia2013In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 8, p. 888-894Article in journal (Refereed)
    Abstract [en]

    Objective. To investigate the association between cervical neoplasia and socioeconomic factors, housing conditions and criminal offences. Design. Longitudinal observational study. Setting. Falun county hospital, Sweden. Population. A total of 1331 women diagnosed with cervical intraepithelial neoplasia I-III or cervical cancer between 1967 and 1978 were compared with 2604 age-matched controls from the same geographical area in Sweden. Methods. The Population and Housing Censuses were used for information about civil status, education, housing conditions, employment and socioeconomic status. The Swedish Register of Conviction Decisions was used to access information on criminal offences. Main outcome measures. Socioeconomic status, housing conditions, criminal offences. Results. Women with cervical neoplasia had a lower socioeconomic status and a lower educational level than their age-matched controls. They were more often divorced and did not own their home as often as controls. A significant association with criminal offences was observed, and it persisted after adjustment for socioeconomic status. Differences in socioeconomic factors between women with cervical neoplasia and their controls had not diminished in the younger, compared with the older, part of the study population. Conclusions. The results indicate that women with cervical neoplasia belong to a socioeconomically disadvantaged group. Furthermore, the study provides information about an association with criminal offences.

  • 21.
    Bixo, Marie
    et al.
    Umea Univ, Dept Clin Sci, SE-90185 Umea, Sweden..
    Ekberg, Karin
    Asarina Pharma AB, Fogdevreten 2, SE-17165 Solna, Sweden..
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hirschberg, Angelica Linden
    Karolinska Inst, Dept Womens & Childrens Hlth, SE-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Dept Obstet & Gynecol, SE-17176 Stockholm, Sweden..
    Jonasson, Aino Fianu
    Karolinska Univ Hosp, Kvinnoforskningsenheten, SE-14146 Huddinge, Sweden..
    Andreen, Lotta
    Sundsvall Hosp, Dept Obstet & Gynecol, SE-85186 Sundsvall, Sweden..
    Timby, Erika
    Umea Univ, Dept Clin Sci, SE-90185 Umea, Sweden..
    Wulff, Marianne
    Slottsstadens Lakarhus Malmo, Fagelbacksgatan 11, SE-21744 Malmo, Sweden..
    Ehrenborg, Agneta
    Specialistlakarna Kungsbacka Qvinnolivet, Sodra Torggatan 18, SE-43430 Kungsbacka, Sweden..
    Bäckström, Torbjörn
    Umea Univ, Dept Clin Sci, SE-90185 Umea, Sweden..
    Treatment of premenstrual dysphoric disorder with the GABA(A) receptor modulating steroid antagonist Sepranolone (UC1010)-A randomized controlled trial2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, p. 46-55Article in journal (Refereed)
    Abstract [en]

    Context: Allopregnanolone is a metabolite from progesterone and a positive modulator of the GABA(A) receptor. This endogenous steroid may induce negative mood in sensitive women when present in serum levels comparable to the premenstrual phase. Its endogenous isomer, isoallopregnanolone, has been shown to antagonize allopregnanolone effects in experimental animal and human models.

    Objective: The objective was to test whether inhibition of allopregnanolone by treatment with the GABA(A) modulating steroid antagonist (GAMSA) Sepranolone (UC1010) during the premenstrual phase could reduce symptoms of the premenstrual dysphoric disorder (PMDD). The pharmacokinetic parameters of UC1010 when given as a subcutaneous injection were measured in healthy women prior to the study in women with PMDD.

    Design: This was an explorative randomized, double-blind, placebo-controlled study.

    Setting: Swedish multicentre study with 10 centers.

    Participants: Participants were 26 healthy women in a pharmacokinetic phase I study part, and 126 women with PMDD in a phase II study part. Diagnosis followed the criteria for PMDD in DSM-5 using Daily Record of Severity of Problems (DRSP) and Endicott's algorithm.

    Intervention: Subjects were randomized to treatment with UC1010 (10 or 16 mg) subcutaneously every second day during the luteal phase or placebo during one menstrual cycle.

    Outcome measures: The primary outcome measure was the sum of all 21 items in DRSP (Total DRSP score). Secondary outcomes were Negative mood score i.e. the ratings of the 4 key symptoms in PMDD (anger/irritability, depression, anxiety and lability) and impairment (impact on daily life).

    Results: 26 healthy women completed the pharmacokinetic phase I study and the dosing in the following trial was adjusted according to the results. 106 of the 126 women completed the phase II study. Within this group, a significant treatment effect with UC1010 compared to placebo was obtained for the Total DRSP score (p = 0.041) and borderline significance (p = 0.051) for the sum of Negative mood score. Nineteen participants however showed symptoms during the follicular phase that might be signs of an underlying other conditions, and 27 participants had not received the medication as intended during the symptomatic phase. Hence, to secure that the significant result described above was not due to chance, a post hoc sub-group analysis was performed, including only women with pure PMDD who completed the trial as intended (n =60). In this group UC1010 reduced Total DRSP scores by 75% compared with 47% following placebo; the effect size 0.7 (p = 0.006), and for sum of Negative mood score (p=0.003) and impairment (p =0.010) with the effect size 0.6. No severe adverse events were reported during the treatment and safety parameters (vital signs and blood chemistry) remained normal during the study.

    Conclusions: This explorative study indicates promising results for UC1010 as a potential treatment for PMDD. The effect size was comparable to that of SSRIs and drospirenone containing oral contraceptives. UC1010 was well tolerated and deemed safe.

  • 22.
    Bjersand, Kathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Andreasson, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Drug Sensitivity Testing in Cytoreductive Surgery and Intraperitoneal Chemotherapy of Pseudomyxoma Peritonei2015In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 22, p. S810-S816Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) is an established therapy for pseudomyxoma peritonei (PMP). However, the role of IPC is unclear. By ex vivo assessment of PMP tumor cell sensitivity to cytotoxic drugs, we investigated the basis for IPC drug selection and the role of IPC in the management of PMP.

    METHODS: Tumor cells were prepared by collagenase digestion of tumor tissue from 133 PMP patients planned for CRS and IPC. Tumor cell sensitivity to oxaliplatin, 5FU, mitomycin C, doxorubicin, irinotecan, and cisplatin was assessed in a 72-h cell-viability assay. Drug sensitivity was correlated to progression-free survival (PFS) and overall survival (OS).

    RESULTS: Samples from 92 patients were analyzed successfully. Drug sensitivity varied considerably between samples. Peritoneal mucinous carcinomatosis (PMCA), compared with PMCA intermediate or disseminated peritoneal adenomucinosis, was slightly more resistant to platinum and 5FU and tumor cells from patients previously treated with chemotherapy were generally less sensitive than those from untreated patients. Multivariate analysis showed patient performance status and completeness of CRS to be prognostic for OS. Among patients with complete CRS (n = 61), PFS tended to be associated with sensitivity to mitomycin C and cisplatin (p ≈ 0.06). At the highest drug concentration tested, the hazard ratio for disease relapse increased stepwise with drug resistance for all drugs.

    CONCLUSIONS: Ex vivo assessment of drug sensitivity in PMP provides prognostic information. The results suggest a role for IPC as therapeutic adjunct to CRS and for individualization of IPC by pretreatment assessment of drug sensitivity.

  • 23.
    Bjersand, Kathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Poromaa, Inger Sundström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pseudomyxoma Peritone: symptoms, treatment, prognosis and sensitivity to cytostatic drugs in vitro2012In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, no S159, p. 71-71Article in journal (Other academic)
  • 24.
    Bjersand, Kathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Seidal, Tomas
    Department of Pathology, Halmstad Medical Center Hospital, Halmstad, Sweden.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Skírnisdottir, Ingiridur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    The clinical and prognostic correlation of HRNPM and SLC1A5 in pathogenesis and prognosis in epithelial ovarian cancer2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0179363Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the prognostic effect of the Heterogeneous nuclear ribonucleoprotein type M (HNRPM) and Solute carrier 1A5 (SLC1A5) in FIGO-stages I-II epithelial ovarian cancer.

    METHODS: A retrospective cohort study was designed to investigate the prognostic effect of HNRPM and SLC1A5, and the association with clinical-pathologic characteristics in 131 patients with FIGO-stages I-II epithelial ovarian cancer. Tissue microarrays were constructed and protein levels were assessed by immunohistochemistry (IHC).

    RESULTS: Positive HRNPM status was associated with positive staining for PUMA (P = 0.04), concomitant PUMA and p21 staining (P = 0.005), and VEGF-R2 (P = 0.003). Positive SLC1A5 staining was associated with positive staining of p27 (P = 0.030), PUMA (P = 0.039), concomitant PUMA and p27 staining, and VEGF-R2 (P = 0.039). In non-serous tumors (n = 72), the SLC1A5 positivity was associated with recurrent disease (P = 0.01). In a multivariable logistic regression analysis FIGO-stage (OR = 12.4), tumor grade (OR = 5.1) and SLC1A5 positivity (OR = 0.1) were independent predictive factors for recurrent disease. Disease-free survival (DFS) in women with SLC1A5-positive non-serous tumors was 92% compared with of 66% in patients with SLC1A5-negative non-serous tumors (Log-rank = 15.343; P = 0.008). In Cox analysis with DFS as endpoint, FIGO-stage (HR = 4.5) and SLC1A5 status (HR = 0.3) were prognostic factors.

    CONCLUSIONS: As the proteins HRNPM and SLC1A5 are associated with the cell cycle regulators p21 or p27, the apoptosis regulators PTEN and PUMA, and the VEGF-R2 it is concluded that both proteins have role in the pathogenesis of ovarian cancer. In patients with non-serous ovarian cancer SLC1A5 protects from recurrent disease, presumably by means of biological mechanisms that are unrelated to cytotoxic drug sensitivity.

  • 25. Björn, I
    et al.
    Bäckström, T
    Lalos, A
    Sundström Poromaa, I
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health.
    Adverse mood effects during postmenopausal hormone treatment in relation to personality traits.2006In: Climacteric, ISSN 1369-7137, Vol. 9, no 4, p. 290-7Article in journal (Refereed)
  • 26.
    Bolin, Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wiberg-Itzel, Eva
    Department of Clinical Science and Education, Section of Obstetrics and Gynecology, Karolinska Institute, Södersjukhuset, Stockholm, Sweden.
    Olsson, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ringvall, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Axelsson, Ove
    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 Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i D län (CKFD).
    Thilaganathan, Basky
    Division of Clinical Development Sciences, Department of Obstetrics and Gynecology, St George’s University of London, England.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Prediction of Preeclampsia by Combining Serum Histidine-Rich Glycoprotein and Uterine Artery Doppler2012In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 25, no 12, p. 1305-1310Article in journal (Refereed)
    Abstract [en]

    Background

    Preeclampsia is associated with both maternal and perinatal morbidity and mortality. Histidine-rich glycoprotein (HRG) is a protein interacting with angiogenesis, coagulation, and inflammatory responses, processes known to be altered in preeclamptic pregnancies. Significantly lower levels of HRG have been demonstrated as early as in the first trimester in women later developing preeclampsia compared with normal pregnancies. The aim of this study was to investigate whether the combination of HRG and uterine artery Doppler ultrasonography can be used as a predictor of preeclampsia.

    Methods

    A total of 175 women were randomly selected from a case-control study; 86 women had an uncomplicated pregnancy and 89 women later developed preeclampsia. Blood samples and pulsatility index (PI) were obtained from both cases and controls in gestational week 14.

    Results

    HRG levels were significantly lower in women who developed preterm preeclampsia compared with controls, but not for women developing preeclampsia in general. PI was significantly higher in the preeclampsia group compared with controls, especially in preterm preeclampsia. The combination of HRG and PI revealed a sensitivity of 91% and a specificity of 62% for preterm preeclampsia.

    Conclusions

    The combination of HRG and uterine artery Doppler may predict preterm preeclampsia in early pregnancy.

  • 27.
    Bränn, Emma
    et al.
    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), Obstetrics and Reproductive Health Research.
    Fransson, Emma
    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), Obstetrics and Reproductive Health Research. Karolinska Institutet, Stockholm, Sweden..
    White, Richard A
    Norwegian Institute of Public Health, Oslo, Norway.
    Papadopoulos, Fotios C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Edvinsson, Åsa
    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.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Cunningham, Janet L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Sundström Poromaa, Inger
    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.
    Skalkidou, Alkistis
    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), Obstetrics and Reproductive Health Research.
    Inflammatory markers in women with postpartum depressive symptoms2018In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547Article in journal (Refereed)
    Abstract [en]

    Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.

  • 28.
    Bränn, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Papadopoulos, Fotios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Fransson, Emma
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.; Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden .
    White, Richard
    Norwegian Inst Publ Hlth, Oslo, Norway.
    Edvinsson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Boström, Adrian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Inflammatory markers in late pregnancy in association with postpartum depression-A nested case-control study.2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 79, p. 146-159Article in journal (Refereed)
    Abstract [en]

    Recent studies indicate that the immune system adaptation during pregnancy could play a significant role in the pathophysiology of perinatal depression. The aim of this study was to investigate if inflammation markers in a late pregnancy plasma sample can predict the presence of depressive symptoms at eight weeks postpartum. Blood samples from 291 pregnant women (median and IQR for days to delivery, 13 and 7-23days respectively) comprising 63 individuals with postpartum depressive symptoms, as assessed by the Edinburgh postnatal depression scale (EPDS≥12) and/or the Mini International Neuropsychiatric Interview (M.I.N.I.) and 228 controls were analyzed with an inflammation protein panel using multiplex proximity extension assay technology, comprising of 92 inflammation-associated markers. A summary inflammation variable was also calculated. Logistic regression, LASSO and Elastic net analyses were implemented. Forty markers were lower in late pregnancy among women with depressive symptoms postpartum. The difference remained statistically significant for STAM-BP (or otherwise AMSH), AXIN-1, ADA, ST1A1 and IL-10, after Bonferroni correction. The summary inflammation variable was ranked as the second best variable, following personal history of depression, in predicting depressive symptoms postpartum. The protein-level findings for STAM-BP and ST1A1 were validated in relation to methylation status of loci in the respective genes in a different population, using openly available data. This explorative approach revealed differences in late pregnancy levels of inflammation markers between women presenting with depressive symptoms postpartum and controls, previously not described in the literature. Despite the fact that the results do not support the use of a single inflammation marker in late pregnancy for assessing risk of postpartum depression, the use of STAM-BP or the novel notion of a summary inflammation variable developed in this work might be used in combination with other biological markers in the future.

  • 29.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Frokjaer, Vibe G
    Department of Neurology, Center for Integrated Molecular Brain Imaging and Neurobiology Research Unit 6931, Copenhagen University Hospital, Denmark.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Functional and molecular neuroimaging of menopause and hormone replacement therapy2014In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 8, p. 388-Article, review/survey (Refereed)
    Abstract [en]

    The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. The present review summarizes the findings of thirty-five studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri- and postmenopausal women treated with estrogen, or estrogen-progestagen replacement therapy. Seven studies using gonadotropin-releasing hormone agonist intervention as a model of hormonal withdrawal are also included. Cognitive paradigms are employed by the majority of studies evaluating the effect of unopposed estrogen or estrogen-progestagen treatment on peri- and postmenopausal women's brain. In randomized-controlled trials, estrogen treatment enhances activation of fronto-cingulate regions during cognitive functioning, though in many cases no difference in cognitive performance was present. Progestagens seems to counteract the effects of estrogens. Findings on cognitive functioning during acute ovarian hormone withdrawal suggest a decrease in activation of the left inferior frontal gyrus, thus essentially corroborating the findings in postmenopausal women. Studies of the cholinergic and serotonergic systems indicate these systems as biological mediators of hormonal influences on the brain. More, hormonal replacement appears to increase cerebral blood flow in several cortical regions. On the other hand, studies on emotion processing in postmenopausal women are lacking. These results call for well-powered randomized-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal variations on the brain.

  • 30.
    Comasco, Erika
    et al.
    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 Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Gulinello, Maria
    Albert Einstein Coll Med, Dept Neurosci, Behav Core Facil, Bronx, NY USA..
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sylven, Sara
    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 Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sleep duration, depression, and oxytocinergic genotype influence prepulse inhibition of the startle reflex in postpartum women2016In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 26, no 4, p. 767-776Article in journal (Refereed)
    Abstract [en]

    The postpartum period is characterized by a post-withdrawal hormonal status, sleep deprivation, and susceptibility to affective disorders. Postpartum mothering involves automatic and attentional processes to screen out new external as well as internal stimuli. The present study investigated sensorimotor gating in relation to sleep duration, depression, as well as catecholaminergic and oxytocinergic genotypes in postpartum women. Prepulse inhibition (PPI) of the startle reflex and startle reactivity were assessed two months postpartum in 141 healthy and 29 depressed women. The catechol-O-methyltransferase (COMT) Val158Met, and oxytocin receptor (OXTR) rs237885 and rs53576 polymorphisms were genotyped, and data on sleep duration were collected. Short sleep duration (less than four hours in the preceding night) and postpartum depression were independently associated with lower PPI. Also, women with postpartum depression had higher startle reactivity in comparison with controls. The OXTR rs237885 genotype was related to PPI in an allele dose-dependent mode, with T/T healthy postpartum women carriers displaying the lowest PPI. Reduced sensorimotor gating was associated with sleep deprivation and depressive symptoms during the postpartum period. Individual neurophysiological vulnerability might be mediated by oxytocinergic genotype which relates to bonding and stress response. These findings implicate the putative relevance of lower PPI of the startle response as an objective physiological correlate of liability to postpartum depression.

  • 31.
    Comasco, Erika
    et al.
    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 Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hahn, Andreas
    Ganger, Sebastian
    Gingnell, Malin
    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.
    Bannbers, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Epperson, C Neill
    Lanzenberger, Rupert
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Emotional fronto-cingulate cortex activation and brain derived neurotrophic factor polymorphism in premenstrual dysphoric disorder2014In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 35, no 9, p. 4450-4458Article in journal (Refereed)
    Abstract [en]

    Premenstrual dysphoric disorder (PMDD) is the prototypical sex-specific disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. The present study investigated brain emotion processing in PMDD and healthy controls, as well as functional polymorphisms in two candidate genes for PMDD, the serotonin transporter (5-HTT) and brain derived neurotrophic factor (BDNF). The 5-HTT linked polymorphic region (5-HTTLPR) and BDNF Val66Met polymorphisms were genotyped in 31 patients with PMDD and 31 healthy controls. A subset of 16 patients and 15 controls participated in two functional magnetic resonance imaging-sessions performing an emotion processing task; once in the mid-follicular, and once in the late luteal phase which corresponds with maximum severity of mood symptoms. Genotypes were not directly associated with PMDD. A main effect of group was found in the whole brain analysis, with patients having lower activation of the pre-genual anterior cingulate and ventro-medial prefrontal cortex, independent of menstrual cycle phase. Post-hoc functional ROI analyses in the fronto-cingulate cluster showed no effect of 5-HTTLPR genotype but a genotype-by-group-by-phase interaction effect of BDNF Val66Met. Women with PMDD who were carriers of the Met-allele had lower fronto-cingulate cortex activation in the luteal phase compared to Met-allele carrying controls. The results provide suggestive evidence of impaired emotion-induced fronto-cingulate cortex activation in PMDD patients. Although limited by a small sample, the potential influence of BDNF Val66Met in PMDD is in line with preclinical findings. Hum Brain Mapp, 2014. 

  • 32.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien D A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Supraphysiological hormonal status, anxiety disorders, and COMT Val/Val genotype are associated with reduced sensorimotor gating in women2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 60, p. 217-23Article in journal (Refereed)
    Abstract [en]

    Pregnancy is a period characterized by a supraphysiological hormonal status, and greater anxiety proneness, which can lead to peripartum affective symptoms with dramatic consequences not only for the woman but also for the child. Clinical psychiatry is heavily hampered by the paucity of objective and biology-based intermediate phenotypes. Prepulse inhibition (PPI) of the startle response, a neurophysiological measure of sensorimotor gating, has been poorly investigated in relation to anxiety and in pregnant women. In the present study, the PPI of healthy non-pregnant women (n=82) and late pregnant women (n=217) was investigated. Age, BMI, depression and anxiety symptoms, tobacco use, and antidepressant medication were considered. We investigated and provided evidence of lower PPI: (i) in healthy pregnant women compared to healthy non-pregnant controls, (ii) in pregnant women with anxiety disorders compared to healthy pregnant women, (iii) in pregnant women with anxiety disorders using SSRI compared to un-medicated pregnant women with anxiety disorders, and (iv) in healthy pregnant women carrying the COMT Val158Met Val/Val genotype compared to Met carriers. Altogether, a reduced sensorimotor gating as an effect of supraphysiological hormonal status, anxiety disorders, SSRIs, and catecholaminergic genotype, implicate the putative relevance of lower PPI as an objective biological correlate of anxiety proneness in pregnant women. These findings call for prospective studies to dissect the multifactorial influences on PPI in relation to mental health of pregnant women.

  • 33.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Influence of COMT val158met polymorphism on startle response during pregnancy2012In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 27, no S1Article in journal (Other academic)
  • 34.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Influence of catechol-O-methyltransferase Val158Met polymorphism on startle response in the presence of high estradiol levels2013In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 23, no 7, p. 629-635Article in journal (Refereed)
    Abstract [en]

    Introduction: both human and animal studies have shown a somewhat complex COMT-by-sex interaction effect on brain function and dysfunction. A functional variation in the gene coding for the catechol-O-methyltransferase (COMT) enzyme, which metabolizes dopamine and noradrenaline, has been related to executive and emotional functions, and to sex dimorphism. Aim: to investigate if COMT Val158Met genotype influences startle response in pregnant women, given their physiologically elevated estradiol levels. Methods: seventy-three pregnant women were assessed in gestational week 38 for acoustic startle response, measured by electromyography of the blink reflex, during control condition, positive and negative anticipation stimuli, and pleasant and unpleasant image stimuli. A blood sample was taken for measurement of estradiol levels and genetic analysis. Results: the results indicated a COMT Val158Met effect on startle response across all conditions (main effect of genotype, F(2,70=3.58), p=0.033), where Val/Val women displayed higher startle magnitudes than Val/Met carriers (Cohen's d=0.71). No significant difference by genotype was found in affective modulation. The findings also suggested an estrogen dose-dependent effect of COMT Val158Met on startle reflex. Among women with higher pregnancy-induced estradiol levels, Val/Val carriers had markedly higher startle response across conditions than heterozygotes (Cohen's d=1.36; F(4,21=11.07); p=0.003), while this effect was not present in women with estradiol levels under the median concentration. Conclusions: the observed effect of COMT Val158Met by estradiol on overall startle response is likely to be due to a variable noradrenergic transmission depending on COMT activity in a possible interaction with estradiol. 

  • 35.
    Comasco, Erika
    et al.
    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 Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hellgren, Chorlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Poromaa, Inger Sundström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Pregnancy, anxiety symptoms and catecholaminergic genotype are associated with prepulse inhibition of the startle response in women2015In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 25, p. S216-S216Article in journal (Other academic)
  • 36.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Iliadis, Stavros I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Adipocytokines levels at delivery, functional variation of TFAP2 beta, and maternal and neonatal anthropometric parameters2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 10, p. 2130-2137Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    Adipocytokines participate in the regulation of glucose metabolism and foetal development. The transcription factor activating protein 2B (TFAP2β) has been associated with adipocytokine regulation, and gene variations with type 2 diabetes and obesity. This study investigated associations between maternal TFAP2B variation, adipocytokines levels and maternal and neonatal anthropometric characteristics.

    DESIGN AND METHODS

    A population-based sample of women was followed from delivery to six months postpartum. Adiponectin, leptin and interleukin-6 levels at delivery, and maternal as well as neonatal anthropometric variables were assessed. The TFAP2β intron 1 variable number tandem repeat (VNTR) was genotyped.

    RESULTS

    Maternal interleukin-6 correlated positively with leptin at delivery, with peripartum weight changes and weight of newborn males, adjusted for potential confounders. Leptin at delivery was associated with TFAP2β intron 1 VNTR genotype, adjusted for confounders, maternal weight and negatively with birth weight among female neonates. A path model suggested a link between TFAP2β genotype, leptin levels and newborn females' weight.

    CONCLUSIONS

    The present results stress a role for the TFAP2 β in adiposity-related conditions and intrauterine growth. The association between neonatal birth weight and maternal adipocytokine levels, together with the observed sex effect, call for further studies on the mechanisms behind neuro-endocrine foetal programming.

  • 37.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Neuroimaging the Menstrual Cycle and Premenstrual Dysphoric Disorder2015In: Current Psychiatry Reports, ISSN 1523-3812, E-ISSN 1535-1645, Vol. 17, no 10, article id 77Article, review/survey (Refereed)
    Abstract [en]

    Knowledge of gonadal hormone-related influences on human brain anatomy, function, and chemistry is scarce. The present review scrutinized organizational and functional neuroimaging correlates of the menstrual cycle and premenstrual dysphoric disorder (PMDD). Supportive evidence of cyclic short-term structural and functional brain plasticity in response to gonadal hormonal modulation is provided. The paucity of studies, sparsity and discordance of findings, and weaknesses in study design at present hinder the drawing of firm conclusions. Ideal study designs should comprise high-resolution multimodal neuroimaging (e.g., MRI, DTI, rsfMRI, fMRI, PET), hormones, genetic, and behavioral longitudinal assessments of healthy women and PMDD patients at critical time points of the menstrual cycle phase (i.e., early follicular phase, late follicular phase, mid-luteal phase) in a counter-balanced setup. Studies integrating large-scale brain network structural, functional, and molecular neuroimaging, as well as treatment data, will deepen the understanding of neural state, disorder, and treatment markers.

  • 38.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Sylvén, Sara M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Papadopoulos, Fotios C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Postpartum depressive symptoms and the BDNF Val66Met functional polymorphism: effect of season of delivery:  2011In: Archives of Women's Mental Health, ISSN 1434-1816, E-ISSN 1435-1102, Vol. 14, no 6, p. 453-463Article in journal (Refereed)
    Abstract [en]

    Postpartum depression (PPD) is an often underdiagnosed and undertreated mood disorder, with negative impact on the mother's and infant's health. Seasonal variation has been discussed as a risk factor for PPD. Candidate genes, such as those encoding for the brain-derived neurotrophic factor (BDNF), serotonin transporter (5-HTT), and Period2 (PER2), have been associated with depression and seasonal disorders. The present study is aimed to examine whether functional polymorphic variants, BDNF Val66Met, 5-HTTLPR, or PER2 SNP 10870, are associated with PPD symptoms and whether these genetic polymorphisms interact with season in predicting PPD symptoms. This case-control study comprised of 275 women from a population-based cohort of delivering women in Sweden, who completed a questionnaire containing the Edinburgh postnatal depression scale (EPDS) at 6 weeks and 6 months postpartum. Stressful life events (SLEs) and maternity stressors were also assessed. The results did not reveal any statistically significant overall association between the studied genetic polymorphisms and PPD symptoms. However, a significant association between BDNF Met66 carrier status and development of PPD symptoms at 6 weeks postpartum, even when controlling for prepartum and postpartum environmental risk factors, was evident among mothers delivering during autumn/winter. No gene-gene interactions were found but a cumulative effect was detected with carriers of a greater number of 5-HTTLPR S and BDNFVal66Met Met alleles reporting higher EPDS scores, if delivered during autumn/winter. Our findings propose a role of the BDNF gene in the development of PPD symptoms, potentially mediated by season of delivery.

  • 39.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Sylvén, Sara M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Papadopoulos, Fotios C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Postpartum depression symptoms: a case-control study on monoaminergic functional polymorphisms and environmental stressors2011In: Psychiatric Genetics, ISSN 0955-8829, E-ISSN 1473-5873, Vol. 21, no 1, p. 19-28Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Postpartum depression (PPD) is an under diagnosed and under treated mood disorder, with negative impact on both the mother and the infant's health. The aim of this study is to examine whether genetic variations in the monoaminergic neurotransmitter system, together with environmental stressors, contribute to the development of PPD symptoms.

    METHODS:

    This nested case-control study included 275 women from a population-based cohort of delivering women in Sweden. A questionnaire containing the Edinburgh Postnatal Depression Scale was collected at 6 weeks and 6 months postpartum. Three functional polymorphisms were genotyped, catechol-O-methyltransferase (COMT)-ValMet, monoamine oxidase A (MAOA)-upstream variable number tandem repeat (uVNTR) and serotonin transporter linked polymorphic region (5HTT-LPR). Stressful life events, maternity stressors and previous psychiatric contact were considered as potential risk factors.

    RESULTS:

    COMT-ValMet was significantly associated with PPD symptoms at 6 weeks, but not at 6 months postpartum. A significant gene-gene interaction effect was present between COMT-ValMet and MAOA-uVNTR. In a gene-environment multivariate model, COMT-ValMet, psychiatric contact and maternity stressors were significantly associated with PPD symptoms. Among those with history of psychiatric problems, the COMT-ValMet and 5HTT-LPR risk variants were associated with PPD symptoms, whereas in the absence of previous psychiatric contact only maternity stressors were related to PPD symptoms.

    CONCLUSION:

    The interaction effect between monoaminergic genes and environmental stressors is likely to contribute to vulnerability for PPD. The different patterns of association according to history of psychiatric problems, if replicated, might be helpful in screening strategies.

  • 40.
    Dabo, Fatimah
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Grönbladh, Alfhild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Different SNP combinations in the GCH1 gene and use of labor analgesia2010In: Molecular pain, ISSN 1744-8069, Vol. 6, p. 41-Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to investigate if there is an association between different SNP combinations in the guanosine triphosphate cyclohydrolase (GCH1) gene and a number of pain behavior related outcomes during labor. A population-based sample of pregnant women (n = 814) was recruited at gestational week 18. A plasma sample was collected from each subject. Genotyping was performed and three single nucleotide polymorphisms (SNP) previously defined as a pain-protective SNP combination of GCH1 were used. Results: Homozygous carriers of the pain-protective SNP combination of GCH1 arrived to the delivery ward with a more advanced stage of cervical dilation compared to heterozygous carriers and non-carriers. However, homozygous carriers more often used second line labor analgesia compared to the others. Conclusion: The pain-protective SNP combination of GCH1 may be of importance in the limited number of homozygous carriers during the initial dilation of cervix but upon arrival at the delivery unit these women are more inclined to use second line labor analgesia.

  • 41.
    Dabo, Fatimah
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Zhou, Qin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Plasma Levels of beta-Endorphin During Pregnancy and Use of Labor Analgesia2010In: Reproductive Sciences, ISSN 1933-7191, Vol. 17, no 8, p. 742-747Article in journal (Refereed)
    Abstract [en]

    beta-endorphins are endogenous opioid substances produced by the pituitary gland and placenta. The aims of this project were to longitudinally follow plasma levels of beta-endorphin during pregnancy in women with a healthy pregnancy and to investigate whether plasma levels of beta-endorphin in late pregnancy are associated with need for additional pain medication beyond nitrous oxide during labor. Plasma samples from 45 women were collected at gestational weeks 10, 25, 28, 33 and 37, and beta-endorphin was analyzed by radioimmunoassay (RIA). Plasma levels of beta-endorphin displayed a significant decrease in gestational weeks 28 and 33 compared to week 10, followed by a subsequent increase between gestational weeks 28 and 37. However, there was no change in levels of beta-endorphin between gestational weeks 10 and 37. Low levels of beta-endorphin at the end of pregnancy were associated with need for additional pain medication beyond nitrous oxide during labor, although the causal relationship is unclear.

  • 42.
    Dabo Pettersson, Fatimah
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Grönblad, Alhild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    The A118G Single Nucleotide Polymorphism of Human μ–Opioid Receptor Gene and Use of Labor Analgesia2012In: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 19, no 9, p. 962-967Article in journal (Refereed)
    Abstract [en]

    The human µ-opioid receptor (MOR) is the major site of action of endogenous opioids and most of the clinically used opioid analgesics. The single-nucleotide polymorphism (SNP), A118G of the MOR 1 gene (OPRM1), has been associated with altered pain perception. The aim of this study was to investigate whether this polymorphism of OPRM1 is associated with a number of pain-related behaviors during labor. In this observational retrospective population-based study, pregnant women (n = 814) were recruited at gestational week 18. A plasma sample was collected from each participant and an SNP genotyping assay was performed. No differences in sociodemographic variables or labor pain-related outcomes, such as stage of cervical dilation on arrival at the delivery unit or use of any type of second-line analgesia during spontaneous labor, were found between noncarriers and G-allele carriers of OPRM1. We conclude that there is no association between the A118G polymorphism of OPRM1 regarding pain-related behavior during labor.

  • 43.
    Dabo Pettersson, Fatimah
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Anxiety, Depressed Mood and the Use of Labor Analgesia2016In: Archives of Women's Mental Health, ISSN 1434-1816, E-ISSN 1435-1102, Vol. 19, no 1, p. 11-16Article in journal (Refereed)
    Abstract [en]

    Relatively little is known about mental health and labor pain. The aim of this study was to assess if self-rated antenatal depressed mood and anxiety are associated with pain-related behaviors and self-reported labor pain. We also wanted to replicate our previous finding of altered labor pain behavior in carriers of a specific guanosine triphosphate cyclohydrolase 1 gene (GCH1) haplotype. Ninety-nine women in gestational weeks 37 to 40 filled out questionnaires on depression and anxiety symptoms and later rated their labor pain by use of visual analog scales. Each subject was also genotyped for GCH1. Following adjustment for relevant confounders, women who arrived early to the delivery unit (cervical dilation < 5 cm) had a significantly higher antenatal Montgomery-sberg Depression Rating Scale (MADRS-S) score, p < 0.05, than late arrivers (cervical dilation > 5 cm). Women with increased Spielberger State-Trait Anxiety Inventory (STAI-T) scores reported higher self-rated pain prior to labor analgesia, p < 0.05, than women with low STAI-T scores. No association between the GCH1 pain-protective haplotype and cervical dilation was found, but a previously demonstrated association with increased use of second-line analgesia was confirmed. Depressed mood during pregnancy is associated with early arrival to the delivery department, whereas antenatal anxiety is associated with increased self-rated pain prior to labor analgesia.

  • 44.
    Edvinsson, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Dept Womens & Childrens Hlth, S-75185 Uppsala, Sweden..
    Bränn, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Freyhult, Eva
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    White, Richard
    Norwegian Inst Publ Hlth, Oslo, Norway..
    Kamali-Moghaddam, Masood
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Olivier, Jocelien
    Univ Groningen, Groningen Inst Evolutionary Life Sci, Unit Behav Neurosci, Dept Neurobiol, Groningen, Netherlands..
    Bergquist, Jonas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Boström, Adrian E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, p. 15-25Article in journal (Refereed)
    Abstract [en]

    Background: Antenatal depression and use of serotonin reuptake inhibitors (SSRI) in pregnancy have both been associated with an increased risk of poor pregnancy outcomes, such as preterm birth and impaired fetal growth. While the underlying biological pathways for these complications are poorly understood, it has been hypothesized that inflammation may be a common physiological pathway. The aim of the present study was to assess peripheral inflammatory markers in healthy women, women with antenatal depression, and in women using SSRI during pregnancy.

    Methods: 160 healthy pregnant controls, 59 women with antenatal depression and 39 women on treatment with SSRIs were included. The relative levels of 92 inflammatory proteins were analyzed by proximity extension assay technology.

    Results: Overall, 23 of the inflammatory markers were significantly lower in women with antenatal depression and in women on treatment with SSRIs in comparison with the healthy controls. No difference in any of the inflammatory markers was observed between women with antenatal depression and those who were using SSRI. Top three inflammatory markers that were down-regulated in women with antenatal depression were TNF-related apoptosis-inducing ligand (TRAIL), p = 0.000001, macrophage colony-stimulating factor 1 (CSF-1), p = 0.000004, and fractalkine (CX3CL1), p =0.000005. Corresponding inflammatory markers in SSRI users were CSF-1, p = 0.000011, vascular endothelial growth factor A (VEGF-A), p =0.000016, and IL-15 receptor subunit alpha (IL-15RA), p = 0.000027. The inflammatory markers were negatively correlated with cortisone serum concentrations in controls, but not in the cases. Differential DNA methylation of was found for seven of these inflammatory markers in an independent epigenetics cohort.

    Conclusion: Women with antenatal depression or on SSRI treatment have lower levels of a number of peripheral inflammatory markers than healthy pregnant controls. Hypothetically, this could be due to dysregulated switch to the pro-M2 milieu that characterizes normal third trimester pregnancy. However, longitudinal blood sampling is needed to elucidate whether the presumably dysregulated M2 shift is driving the development of antenatal depression or is a result of the depression.

  • 45.
    Edvinsson, Åsa
    et al.
    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.
    Skalkidou, Alkistis
    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), Obstetrics and Reproductive Health Research.
    Hellgren, Charlotte
    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.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Willebrand, Mimmie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Uppsala Univ, Dept Neurosci, Psychiat, Uppsala, Sweden..
    Sundström Poromaa, Inger
    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.
    Different patterns of attentional bias in antenatal and postpartum depression2017In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 7, no 11, article id e00844Article in journal (Refereed)
    Abstract [en]

    BackgroundBiased information processing in attention, memory, and interpretation is proposed to be central cognitive alterations in patients with major depressive disorder, but studies in women with peripartum depression are scarce. Because of the many similarities with depression in nonperipartum states as regards symptom profile and risk factors, we hypothesized that women with antenatal and postpartum depression would display attentional bias to negatively and positively valenced words. MethodsOne hundred and seventy-seven pregnant and 157 postpartum women were included. Among these, 40 suffered from antenatal depressive disorder and 33 from postpartum depressive disorder. An emotional Stroop task with neutral, positive, negative, and negatively valenced obstetric words was used. ResultsNo significant difference in emotional interference scores was noted between women with antenatal depression and nondepressed pregnant women. In contrast, women with postpartum depression displayed shorter reaction times to both positive (p=.028) and negative (p=.022) stimuli, compared with neutral words. Pregnant women on antidepressant treatment displayed longer reaction times to negatively valenced obstetric words in comparison with untreated depressed women (p=.012), and a trend toward greater interference in comparison with controls (p=.061). ConclusionsIn contrast with the hypothesis, we found no evidence of attentional bias to emotionally valenced stimuli in women with untreated peripartum depression. However, the shorter reaction times to emotional stimuli in women with postpartum depression may indicate emotional numbing, which in turn, is a functional impairment that may have repercussions for child development and well-being. Our findings emphasize the need to identify and treat women with postpartum depression at the earliest possible time point to ensure swift recovery and support for the family.

  • 46.
    Elenis, Evangelia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Lindgren, Karin E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Karypidis, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hosseini, Frida
    Bremme, Katarina
    Landgren, Britt-Marie
    Skjoldebrand-Sparre, Lottie
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    The histidine-rich glycoprotein A1042G polymorphism and recurrent miscarriage: a pilot study2014In: Reproductive Biology and Endocrinology, ISSN 1477-7827, E-ISSN 1477-7827, Vol. 12, p. 70-Article in journal (Refereed)
    Abstract [en]

    Background: Histidine-rich Glycoprotein (HRG) has previously been shown to have an impact on implantation and fertility. The aim of this study was to investigate if there is an association between the HRG A1042G single nucleotide polymorphism (SNP) and recurrent miscarriage. Methods: The study was designed as a case-control study and the women were included at University Hospitals in Sweden. 186 cases with recurrent miscarriage were compared with 380 pregnant controls with no history of miscarriage. Each woman was genotyped for the HRG A1042G SNP. Results: The results indicated that the frequency of heterozygous HRG A1042G carriers was higher among controls compared to cases (34.7% vs 26.3%; p < 0.05). In a bivariate regression analysis, a negative association was found between recurrent miscarriage and heterozygous A/G carriers both in the entire study population (OR 0.67, 95% CI 0.45 - 0.99; p < 0.05) as well as in a subgroup of women with primary recurrent miscarriage (OR 0.37, 95% CI 0.16 - 0.84; p < 0.05). These results remained even after adjustment for known confounders such as age, BMI and thyroid disease (OR 0.36, 95% CI 0.15 - 0.84; p < 0.05). Conclusions: Women who are heterozygous carriers of the HRG A1042G SNP suffer from recurrent miscarriage more seldom than homozygous carriers. Thus, analysis of the HRG A1042G SNP might be of importance for individual counseling regarding miscarriage.

  • 47.
    Engman, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Moby, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredriksson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State Networks in Women with Previous Affective Side Effects on the Pill.2018In: Neuropsychopharmacology, ISSN 0893-133X, E-ISSN 1740-634X, Vol. 43, no 3, p. 555-563Article in journal (Refereed)
    Abstract [en]

    The mechanisms linking ovarian hormones to negative affect are poorly characterized, but important clues may come from the examination of the brain's intrinsic organization. Here, we studied the effects of both the menstrual cycle and oral contraceptives (OCs) on amygdala and salience network resting-state functional connectivity using a double-blind, randomized, and placebo-controlled design. Hormone levels, depressive symptoms, and resting-state functional connectivity were measured in 35 healthy women (24.9±4.2 years) who had previously experienced OC-related negative affect. All participants were examined in the follicular phase of a baseline cycle and in the third week of the subsequent cycle during treatment with either a combined OC (30 μg ethinyl estradiol/0.15 mg levonorgestrel) or placebo. The latter time point targeted the midluteal phase in placebo users and steady-state ethinyl estradiol and levonorgestrel concentrations in OC users. Amygdala and salience network connectivity generally increased with both higher endogenous and synthetic hormone levels, although amygdala-parietal cortical connectivity decreased in OC users. When in the luteal phase, the naturally cycling placebo users demonstrated higher connectivity in both networks compared with the women receiving OCs. Our results support a causal link between the exogenous administration of synthetic hormones and amygdala and salience network connectivity. Furthermore, they suggest a similar, potentially stronger, association between the natural hormonal variations across the menstrual cycle and intrinsic network connectivity.

  • 48.
    Esscher, Annika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Essén, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Innala, Eva
    Department of Clinical Sciences, Obstetrics and Gynaecology, Umeå University.
    Papadopoulos, Fotios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Högberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Suicides during pregnancy and one year postpartum in Sweden, 1980–20072016In: British Journal of Psychiatry, ISSN 0007-1250, E-ISSN 1472-1465, Vol. 208, no 5, p. 462-469Article in journal (Refereed)
    Abstract [en]

    Background

    Although the incidence of suicide among women who havegiven birth during the past 12 months is lower than that ofwomen who have not given birth, suicide remains one of themost common causes of death during the year followingdelivery in high-income countries, such as Sweden.

    Aims

    To characterise women who died by suicide duringpregnancy and postpartum from a maternal careperspective.

    Method

    We traced deaths (n = 103) through linkage of the SwedishCause of Death Register with the Medical Birth and NationalPatient Registers. We analysed register data and obstetricmedical records.

    Results

    The maternal suicide ratio was 3.7 per 100 000 live births forthe period 1980–2007, with small magnitude variation overtime. The suicide ratio was higher in women born inlow-income countries (odds ratio 3.1 (95% CI 1.3–7.7)).Violent suicide methods were common, especially during thefirst 6 months postpartum. In all, 77 women had receivedpsychiatric care at some point, but 26 women had nodocumented psychiatric care. Antenatal documentationof psychiatric history was inconsistent. At postpartumdischarge, only 20 women had a plan for psychiatricfollow-up.

    Conclusions

    Suicide prevention calls for increased clinical awareness andcross-disciplinary maternal care approaches to identify and support women at risk.

  • 49.
    Gingnell, Malin
    et al.
    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.
    Ahlstedt, Victoria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bannbers, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Social stimulation and corticolimbic reactivity in premenstrual dysphoric disorder: a preliminary study2014In: Biology of Mood & Anxiety Disorders, ISSN 2045-5380, Vol. 4, no 1, p. 3-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Premenstrual dysphoric disorder (PMDD), characterized by luteal phase-induced negative affect and loss of impulse control, often results in compromised social interactions. Although amygdala activation is generally linked to negative affect, increased amygdala reactivity to aversive stimuli in the luteal phase has not been consistently reported in PMDD. We tested the hypothesis that amygdala hyper-reactivity in PMDD is symptom specific, rather than generalized, and linked to socially relevant stimuli. Blood oxygenation level dependent signal changes during exposure to negative images with social and non-social content were evaluated in the mid-follicular and late luteal phase of the menstrual cycle. Fourteen women with PMDD and 13 healthy controls participated.

    RESULTS:

    When compared with healthy controls, women with PMDD in the luteal phase had enhanced reactivity to social stimuli compared to non-social stimuli in the amygdala and insula, but attenuated reactivity in the anterior cingulate cortex. Functional couplings between emotion processing and controlling areas were significantly different, being positive in women with PMDD and negative in healthy controls. Changes in progesterone levels in women with PMDD correlated positively with altered amygdala reactivity.

    CONCLUSIONS:

    Socially relevant aversive stimulation elicited enhanced activity in affective processing brain regions that were functionally coupled to compromised activity in cognitive control areas. Because increased reactivity correlated positively with alterations in ovarian steroid levels, data preliminary support the hypothesis that enhanced progesterone sensitivity in PMDD affects corticolimbic processing of social emotions.

  • 50.
    Gingnell, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bannbers, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frick, Andreas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Moby, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    The effect of combined hormonal contraceptives use on brain reactivity during response inhibition2016In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 21, no 2, p. 150-157Article in journal (Refereed)
    Abstract [en]

    Objectives Cognitive control, which can be described as the ability to moderate impulses, has not previously been investigated in users of combined hormonal contraception (CHC). Given the suggested modulatory role of ovarian steroids in prefrontal dopaminergic function, which in turn taps into cognitive control, this randomised, double-blinded, placebo-controlled oral contraceptive trial set out to investigate the brain activity pattern during response inhibition in CHC users. Methods Thirty-four women were randomised to one treatment cycle with a levonorgestrel-containing CHC or placebo. The women performed a Go/NoGo task to measure brain activity during response inhibition by use of event-related functional magnetic resonance imaging (fMRI) prior to and during the CHC/placebo treatment cycle. Results No differences between CHC and placebo users in number of correct inhibitions were found during treatment, but only women on CHC significantly improved their performance between the baseline and treatment assessments. During the treatment cycle CHC users displayed decreased activity in the right middle frontal gyrus in comparison with placebo users. No other significant activations were evident between treatment groups or within groups. Conclusion Overall, CHC use had marginal effects on brain activity during response inhibition. If anything, the findings of the study may suggest reduced effort or increased efficiency in maintaining orbitofrontal cortex inhibitory cognitive control when using a combined oral contraceptive.

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