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  • 1.
    Axfors, Cathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    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.
    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.
    Skoog Svanberg, Agneta
    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.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    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.
    Ramklint, Mia
    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, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    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.
    Neuroticism is associated with higher antenatal care utilization in obstetric low-risk women2019In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 98, no 4, p. 470-478Article in journal (Refereed)
    Abstract [en]

    Introduction

    Elevated neuroticism is associated with higher health care utilization in the general population. This study aimed to investigate the association between neuroticism and the use of publicly financed antenatal care in obstetric low‐risk women, taking predisposing and need factors for health care utilization into consideration.

    Material and methods

    Participants comprised 1052 obstetric low‐risk women (no chronic diseases or adverse pregnancy conditions) included in several obstetrics/gynecology studies in Uppsala, Sweden. Neuroticism was self‐rated on the Swedish universities Scales of Personality. Medical records of their first subsequent pregnancy were scanned for antenatal care use. Associations between antenatal care use and neuroticism were analyzed with logistic regression (binary outcomes) or negative binomial regression (count outcomes) comparing the 75th and 25th neuroticism percentiles. Depending on the Akaike information criterion the exposure was modeled as either linear or with restricted cubic splines. Analyses were adjusted for predisposing (sociodemographic and parity) and need factors (body mass index and psychiatric morbidity).

    Results

    After adjustment, women with higher neuroticism had more fetal ultrasounds (incidence rate ratio = 1.09, 95% confidence interval (CI) 1.02‐1.16), more emergency visits to an obstetrician/gynecologist (incidence rate ratio = 1.22, 95% CI 1.03‐1.45) and were more likely to visit a fear‐of‐childbirth clinic (odds ratio = 2.71, 95% CI 1.71‐4.29). Moreover, they more often consulted midwives in specialized antenatal care facilities (significant J‐shaped association).

    Conclusions

    Neuroticism was associated with higher utilization of publicly financed antenatal care in obstetric low‐risk women, even after adjusting for predisposing and need factors. Future studies should address the benefits of interventions as a complement to routine antenatal care programs to reduce subclinical anxiety.

  • 2.
    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)
  • 3.
    Bhandage, Amol
    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.
    Korol, Sergiy V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Tafreshiha, Atieh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Gohel, Priya
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
    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.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    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.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0208981Article in journal (Refereed)
    Abstract [en]

    Calcium (Ca2+) is an important ion in physiology and is found both outside and inside cells. The intracellular concentration of Ca2+ is tightly regulated as it is an intracellular signal molecule and can affect a variety of cellular processes. In immune cells Ca2+ has been shown to regulate e.g. gene transcription, cytokine secretion, proliferation and migration. Ca2+ can enter the cytoplasm either from intracellular stores or from outside the cells when Ca2+ permeable ion channels in the plasma membrane open. The Ca2+ release-activated (CRAC) channel is the most prominent Ca2+ ion channel in the plasma membrane. It is formed by ORAI1-3 and the channel is opened by the endoplasmic reticulum Ca2+ sensor proteins stromal interaction molecules (STIM) 1 and 2. Another group of Ca-2(+) channels in the plasma membrane are the voltage-gated Ca2+ (Ca-V) channels. We examined if a change in immunological tolerance is accompanied by altered ORAI, STIM and Ca-V gene expression in peripheral blood mononuclear cells (PBMCs) in pregnant women and in type 1 diabetic individuals. Our results show that in pregnancy and type 1 diabetes ORAI1-3 are up-regulated whereas STIM1 and 2 are down-regulated in pregnancy but only STIM2 in type 1 diabetes. Expression of L-, P/Q-, R- and T-type voltage-gated Ca2+ channels was detected in the PBMCs where the Ca(V)2.3 gene was up-regulated in pregnancy and type 1 diabetes whereas the Ca(V)2.1 and Ca(V)3.2 genes were up-regulated only in pregnancy and the Ca(V)1.3 gene in type 1 diabetes. The results are consistent with that expression of ORAI, STIM and Ca-V genes correlate with a shift in immunological status of the individual in health, as during pregnancy, and in the autoimmune disease type 1 diabetes. Whether the changes are in general protective or in type 1 diabetes include some pathogenic components remains to be clarified.

  • 4.
    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.

  • 5.
    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)
  • 6.
    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.

  • 7.
    Breedh, Julia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Comasco, Erika
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.
    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.
    Papadopoulos, Fotios C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    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.
    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.
    Hypothalamic-pituitary-adrenal axis responsiveness, startle response, and sensorimotor gating in late pregnancy2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 106, p. 1-8Article in journal (Refereed)
    Abstract [en]

    During pregnancy, the hypothalamic-pituitary-adrenal (HPA) axis, the main regulator of the stress response, undergoes dramatic changes. The acoustic startle response (ASR) and the prepulse inhibition (PPI) of the startle response are neurophysiological research tools and objective measures of an individual's response to an emotional context or stressor. The ASR and PPI are influenced by psychiatric diseases characterized by anxiety symptoms and are sensitive to cortisol. Hence, the ASR and the PPI can be used to investigate the effects of pregnancy-induced endocrine changes and their contribution to affective disorders. The present study sought to investigate the association between measures of HPA-axis responsiveness, startle reactivity and sensorimotor gating during pregnancy that to date remains unknown. The eye-blink component of the ASR, and its prepulse inhibition, were measured in 107 late third trimester pregnant women. Saliva samples were collected to assess the cortisol awakening response (CAR), a measure of HPA-axis activity. Blood was sampled to measure serum levels of cortisol, cortisone and the cortisone to cortisol ratio. Ongoing anxiety disorders, sleep duration, smoking, and age were considered as potential confounders in the statistical analyses. CAR reactivity, measured as area under the curve (AUC) increase and above baseline, was positively associated with baseline startle magnitude [Cohen's d = 0.27; F (1, 105) = 4.99; p = 0.028, and Cohen's d = 0.30; F (1, 105) = 6.25; p = 0.014, respectively] as well as PPI at 86 dB [Cohen's d = 0.29; F (1, 105) = 5.93; p = 0.017; and Cohen's d = 0.34; F (1, 105) = 8.38; p = 0.005, respectively]. The observed positive correlation between startle magnitude in pregnant women and greater increase in cortisol during the awakening response may be interpreted as heightened neurophysiological reactivity, likely associated with dysregulation of the stress system.

  • 8.
    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.

  • 9.
    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.

  • 10.
    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.

  • 11.
    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)
  • 12.
    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. 

  • 13.
    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)
  • 14.
    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.

  • 15.
    Eckerdal, Patricia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kollia, Natasa
    Department of Biostatistics, Harokopio University, Athens, Greece.
    Löfblad, Johanna
    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, Obstetrics and Gynaecology.
    Karlsson, Linnea
    Department of Child Psychiatry, Turku University Hospital, Turku, Finland .
    Högberg, Ulf
    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.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Delineating the Association between Heavy Postpartum Haemorrhage and Postpartum Depression2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 1, article id e0144274Article in journal (Refereed)
    Abstract [en]

    Objectives

    To explore the association between postpartum haemorrhage (PPH) and postpartum depression (PPD), taking into account the role of postpartum anaemia, delivery experience and psychiatric history.

    Methods

    A nested cohort study (n = 446), based on two population-based cohorts in Uppsala, Sweden. Exposed individuals were defined as having a bleeding of ≥1000ml (n = 196) at delivery, and non-exposed individuals as having bleeding of <650ml (n = 250). Logistic regression models with PPD symptoms (Edinburgh Postnatal Depression scale (EPDS) score ≥ 12) as the outcome variable and PPH, anaemia, experience of delivery, mood during pregnancy and other confounders as exposure variables were undertaken. Path analysis using Structural Equation Modeling was also conducted.

    Results

    There was no association between PPH and PPD symptoms. A positive association was shown between anaemia at discharge from the maternity ward and the development of PPD symptoms, even after controlling for plausible confounders (OR = 2.29, 95%CI = 1.15–4.58). Path analysis revealed significant roles for anaemia at discharge, negative self-reported delivery experience, depressed mood during pregnancy and postpartum stressors in increasing the risk for PPD.

    Conclusion

    This study proposes important roles for postpartum anaemia, negative experience of delivery and mood during pregnancy in explaining the development of depressive symptoms after PPH.

  • 16.
    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.
    Bränn, 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), Reproductive Health. 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.
    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.

  • 17.
    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.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kallak, Theodora Kunovac
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Reproductive Biology in Uppsala (CRU).
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    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.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institute.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institute.
    Spigset, Olav
    Department of Clinical Pharmacology, St. Olav University Hospital.
    Lager, Susanne
    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.
    Olivier, Jocelien
    Neurobiology, unit Behavioral Neuroscience, Groningen Institute for Evolutionary Life Sciences, University of Groningen, the Netherlands.
    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.
    The effect of antenatal depression and antidepressant treatment on placental tissue: a protein-validated gene expression studyManuscript (preprint) (Other academic)
  • 18.
    Edvinsson, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Olivier, Jocelien
    Univ Groningen, Groningen Inst Evolutionary Life Sci, Dept Neurobiol, Unit Behav Neurosci, Groningen, Netherlands.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kallak, Theodora Kunovac
    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 Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Victorin, Elisabeth Stener
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Fornes, Romina
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Spigset, Olav
    St Olavs Univ Hosp, Dept Clin Pharmacol, Trondheim, Norway;Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Lager, Susanne
    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.
    Antenatal Depression and Placental Function: A Protein Validated Gene Expression Study2018In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 69, p. E62-E62Article in journal (Other academic)
  • 19.
    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.

  • 20.
    Hannerfors, Anna-Karin
    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.
    Schijven, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Iliadis, Stavros I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    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.
    Skalkidou, Alkistis
    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.
    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.
    Treatment with serotonin reuptake inhibitors during pregnancy is associated with elevated corticotropin-releasing hormone levels2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 58, p. 104-113Article in journal (Refereed)
    Abstract [en]

    Treatment with serotonin reuptake inhibitors (SSRI) has been associated with an increased risk of preterm birth, but causality remains unclear. While placental CRH production is correlated with gestational length and preterm birth, it has been difficult to establish if psychological stress or mental health problems are associated with increased CRH levels. This study compared second trimester CRH serum concentrations in pregnant women on SSRI treatment (n=207) with untreated depressed women (n=56) and controls (n=609). A secondary aim was to investigate the combined effect of SSRI treatment and CRH levels on gestational length and risk for preterm birth. Women on SSRI treatment had significantly higher second trimester CRH levels than controls, and untreated depressed women. CRH levels and SSRI treatment were independently associated with shorter gestational length. The combined effect of SSRI treatment and high CRH levels yielded the highest risk estimate for preterm birth. SSRI treatment during pregnancy is associated with increased CRH levels. However, the elevated risk for preterm birth in SSRI users appear not to be mediated by increased placental CRH production, instead CRH appear as an independent risk factor for shorter gestational length and preterm birth.

  • 21.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Physiological Stress Reactivity in Late Pregnancy2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    During pregnancy, the basal activity is increased in both of our major stress response systems: the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. At the same time, the reactivity towards stressors is reduced. These alterations sustain maternal and fetal homeostasis, and are involved in the regulation of gestational length. Although the feto-placental hormone synthesis produces the main endocrinological changes, also the central nervous system undergoes adaptation. Together, these profound adjustments have been suggested to make women’s mental health more vulnerable during pregnancy and postpartum period. The aim of this thesis was to examine factors connected to physiological stress responses during the late pregnancy in relation to pain, labour onset, emotional reactivity, and mental health.

    The first study examined the pain and sympathetic response during cold stress, in relation to time to delivery. Women with fewer days to spontaneous delivery had lower sympathetic reactivity, while no pain measure was associated with time to delivery.

    In the second study, acoustic startle response modulation was employed to study emotional reactivity during late gestation, and at four to six weeks postpartum. The startle response was measured by eye-blink electromyography, while the participants watched pleasant and unpleasant pictures, and positive and negative anticipation stimuli. A significant reduction in startle modulation by anticipation was found during the postpartum assessment. However, no startle modulation by pleasant, or unpleasant, pictures was detected at either time-point.

    The serum level of allopregnanolone, a neurosteroid implied in pregnancy-induced hyporeactivity, was analysed in relation to self-reported symptoms of anxiety and depression. Although the participants reported low levels of depression, the women with the highest depression scores had significantly lower levels of serum allopregnanolone. There was no correlation between allopregnanolone and anxiety scores.

    In the fourth study, the cortisol awakening response was compared between women with depression during pregnancy, women with depression prior to pregnancy, and women who had never suffered from depression. No group differences in cortisol awakening response during late pregnancy were found.

    The results are in line with the previously described pregnancy-induced hyporesponsiveness, and add to the knowledge on maternal stress hyporeactivity, gestational length, and maternal mental health.

    List of papers
    1. Sympathetic reactivity in late pregnancy is related to labour onset in women
    Open this publication in new window or tab >>Sympathetic reactivity in late pregnancy is related to labour onset in women
    2011 (English)In: Stress, ISSN 1025-3890, E-ISSN 1607-8888, Vol. 14, no 6, p. 627-633Article in journal (Refereed) Published
    Abstract [en]

    Stress regulation during pregnancy is considered to be connected to the timing of labour initiation. Although increasing knowledge is emerging on the regulation of parturition, there is currently no way to predict the start of spontaneous labour in women. The main aim of this study was to assess pain threshold and the sympathetic nervous system response to cold pain in relation to the onset of labour in healthy pregnant women. Ninety-three pregnant women were recruited and assessed for skin conductance (SC) activity during a cold pressor test in gestational week 38. Pain threshold and cold endurance were also measured and the results were compared with data obtained from hospital records. Seventy-four women had a spontaneous labour onset and a valid SC measurement. SC activity during the cold pressor test decreased significantly with the number of days left to spontaneous parturition. This may indicate a gradual decrease in sympathetic autonomic nervous system reactivity even during the last weeks of pregnancy. Measuring SC activity during mild stress provocation is a rapid and non-invasive means to study variation in sympathetic reactivity during pregnancy, and may be useful in research on stress regulation in pregnancy and its relation to labour initiation.

    Keywords
    Cold pressor test, initiation of labour, pain threshold, pregnancy, skin conductance, sympathetic activity
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-161450 (URN)10.3109/10253890.2011.614662 (DOI)000295891600006 ()
    Available from: 2011-11-15 Created: 2011-11-14 Last updated: 2017-12-08Bibliographically approved
    2. Decreased startle modulation during anticipation in the postpartum period in comparison to late pregnancy
    Open this publication in new window or tab >>Decreased startle modulation during anticipation in the postpartum period in comparison to late pregnancy
    Show others...
    2012 (English)In: Archives of Women's Mental Health, ISSN 1434-1816, E-ISSN 1435-1102, Vol. 15, no 2, p. 87-94Article in journal (Refereed) Published
    Abstract [en]

    Knowledge about healthy women's psychophysiological adaptations during the large neuroendocrine changes of pregnancy and childbirth is essential in order to understand why these events have the potential to disrupt mental health in vulnerable individuals. This study aimed to compare startle response modulation, an objective psychophysiological measure demonstrated to be influenced by anxiety and depression, longitudinally across late pregnancy and the postpartum period. The acoustic startle response modulation was assessed during anticipation of affective images and during image viewing in 31 healthy women during gestational weeks 36-39 and again at 4 to 6 weeks postpartum. No startle modulation by affective images was observed at either time point. Significant modulation during anticipation stimuli was found at pregnancy assessment but was reduced in the postpartum period. The women rated the unpleasant images more negative and more arousing and the pleasant images more positive at the postpartum assessment. Self-reported anxiety and depressive symptoms did not change between assessments. The observed postpartum decrease in modulation of startle by anticipation suggests a relatively deactivated defense system in the postpartum period.

    Keywords
    Acoustic startle response, Affective modulation, Anticipation, Postpartum, Pregnancy
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-175634 (URN)10.1007/s00737-012-0261-7 (DOI)000304169100002 ()
    Available from: 2012-06-12 Created: 2012-06-11 Last updated: 2017-12-07Bibliographically approved
    3. Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy
    Open this publication in new window or tab >>Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy
    Show others...
    2014 (English)In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 69, no 3, p. 147-153Article in journal (Refereed) Published
    Abstract [en]

    Allopregnanolone (3α-hydroxy-5α-pregnan-20-one) is a neurosteroid which has inhibitory function through interaction with the GABAA receptor. This progesterone metabolite has strong sedative and anxiolytic properties, and low endogenous levels have been associated with depressed mood. This study aimed to investigate whether the very high serum allopregnanolone levels in late pregnancy co-vary with concurrent self-rated symptoms of depression and anxiety.

    Ninety-six women in pregnancy weeks 37 - 40 rated symptoms of depression and anxiety with the Montgomery-Åsberg Depression Rating Scale (MADRS-S) and Spielberger State-Trait Anxiety Inventory (STAI-S and STAI–T). Their serum allopregnanolone was analyzed by celite chromatography and radioimmunoassay.

    Ten women had elevated depression scores (MADRS-S ≥ 13), and this group had significantly lower allopregnanolone levels compared to women with MADRS-S scores in the lower range (39.0 ± 17.9 nmol/l vs. 54.6 ± 18.7 nmol/l, p = 0.014). A significant negative correlation was found between self-rated depression scores and allopregnanolone concentrations (Pearson’s correlation coefficient = -0.220, p = 0.031). The linear association between self-rated depression scores and allopregnanolone serum concentrations remained significant when adjusted for gestational length, progesterone levels, and parity. Self-rated anxiety, however, was not associated with allopregnanolone serum concentrations during pregnancy. In conclusion, high allopregnanolone serum concentrations may protect against depressed mood during pregnancy.

    Keywords
    allopregnanolone, anxiety, depression, MADRS-S, neurosteroid, pregnancy, STAI
    National Category
    Neurosciences Physiology Obstetrics, Gynecology and Reproductive Medicine
    Research subject
    Obstetrics and Gynaecology; Medical Science; Neuroscience
    Identifiers
    urn:nbn:se:uu:diva-197611 (URN)10.1159/000358838 (DOI)000337267300003 ()
    Available from: 2013-04-02 Created: 2013-04-01 Last updated: 2018-01-11Bibliographically approved
    4. Cortisol awakening response in late pregnancy in women with previous or ongoing depression
    Open this publication in new window or tab >>Cortisol awakening response in late pregnancy in women with previous or ongoing depression
    2013 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 12, p. 3150-54Article in journal (Other academic) Published
    Abstract [en]

    Pregnancy involves an increase in basal cortisol, and a decrease in the hypothalamic-pituitary-adrenal (HPA) axis reactivity. The cortisol awakening response is a measure of HPA axis reactivity which has been reported to be altered in patients with an ongoing depressive episode, as well as in individuals with remitted depression.

    This study aimed to use the cortisol awakening response to study the HPA axis reactivity in relation to previous and ongoing depression in women during the third trimester of pregnancy. Based on structured interviews, and repeated questionnaires during pregnancy, 134 women were included in one of three groups: never depressed (n=57), depressed prior to the current pregnancy (n=39), and depressed during the current pregnancy (n=38). The hypothesis was that the women with ongoing, or previous, depression would have a higher cortisol awakening response than women who have never suffered from depression.

    Linear mixed models analysis revealed no group differences in the absolute cortisol levels or in the shape of the cortisol awakening response. We conclude that the difference in cortisol awakening response between women with and without experience of a depressive episode is not evident in late pregnancy.

    Keywords
    cortisol awakening response, pregnancy, depression
    National Category
    Neurosciences Physiology Obstetrics, Gynecology and Reproductive Medicine
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-197612 (URN)
    Available from: 2013-04-02 Created: 2013-04-01 Last updated: 2018-01-11Bibliographically approved
  • 22.
    Hellgren, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Bannbers, Elin
    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.
    Risbrough, Victoria
    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.
    Decreased startle modulation during anticipation in the postpartum period in comparison to late pregnancy2012In: Archives of Women's Mental Health, ISSN 1434-1816, E-ISSN 1435-1102, Vol. 15, no 2, p. 87-94Article in journal (Refereed)
    Abstract [en]

    Knowledge about healthy women's psychophysiological adaptations during the large neuroendocrine changes of pregnancy and childbirth is essential in order to understand why these events have the potential to disrupt mental health in vulnerable individuals. This study aimed to compare startle response modulation, an objective psychophysiological measure demonstrated to be influenced by anxiety and depression, longitudinally across late pregnancy and the postpartum period. The acoustic startle response modulation was assessed during anticipation of affective images and during image viewing in 31 healthy women during gestational weeks 36-39 and again at 4 to 6 weeks postpartum. No startle modulation by affective images was observed at either time point. Significant modulation during anticipation stimuli was found at pregnancy assessment but was reduced in the postpartum period. The women rated the unpleasant images more negative and more arousing and the pleasant images more positive at the postpartum assessment. Self-reported anxiety and depressive symptoms did not change between assessments. The observed postpartum decrease in modulation of startle by anticipation suggests a relatively deactivated defense system in the postpartum period.

  • 23.
    Hellgren, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    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.
    Allopregnanolone levels and depressive symptoms during pregnancy in relation to single nucleotide polymorphisms in the allopregnanolone synthesis pathway2017In: Hormones and Behavior, ISSN 0018-506X, E-ISSN 1095-6867, Vol. 94, p. 106-113Article in journal (Refereed)
    Abstract [en]

    Allopregnanolone, a neurosteroid whose levels rise throughout gestation, putatively stabilizes antenatal mood. The present study aimed to investigate associations of plasma allopregnanolone to antenatal depressive symptoms, as well as to genetic and obstetric factors. Allopregnanolone plasma levels from 284 pregnant women were measured around gestational week 18. Haplotype tag single nucleotide polymorphisms in the aldo-keto reductase family 1, members C2 and C4 (AKR1C2, AKR1C4), and steroid 5 alpha-reductase 1 and 2 (SRD5A1, and SRD5A2) genes were genotyped in a larger sample of pregnant women (n=1351). The Edinburgh Postnatal Depression Scale (EPDS) was administered via web-questionnaires in gestational weeks 17 and 32. Demographic and obstetric data was retrieved from web-questionnaires and medical records. There was no association between allopregnanolone levels and depressive symptoms. Furthermore, no associations between allopregnanolone level and synthesis pathway genotypes were found after accounting for multiple comparisons. However, exploratory analyses suggested that the women who were homozygous for the minor allele of the AKR1C2 polymorphism rs1937863 had nominally lower allopregnanolone levels and lower depression scores in gestational week 17, but also the highest increase in depression scores between week 17 and 32. Additionally, higher body mass index was associated with lower allopregnanolone levels. The results do not support second trimester plasma allopregnanolone as a mood stabilizing factor. However, we speculate that AKR1C2 variation may alter the susceptibility to depressive symptoms through effects on central allopregnanolone synthesis. Another implication of this study is that the relationship between neuroactive steroids and obesity in pregnancy deserves to be investigated.

  • 24.
    Hellgren, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Edvinsson, Åsa
    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.
    Univ Groningen, Groningen Inst Evolutionary Life Sci, Dept Neurobiol, Unit Behav Neurosci, NL-9700 AB Groningen, Netherlands..
    Fornes, Romina
    Karolinska Inst, Dept Physiol & Pharmacol, S-10401 Stockholm, Sweden..
    Stener-Victorin, Elisabet
    Karolinska Inst, Dept Physiol & Pharmacol, S-10401 Stockholm, Sweden..
    Ubhayasekera, S. J. Kumari A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Bergquist, Jonas
    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.
    Tandem mass spectrometry determined maternal cortisone to cortisol ratio and psychiatric morbidity during pregnancy-interaction with birth weight2016In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 69, p. 142-149Article in journal (Refereed)
    Abstract [en]

    Maternal serum cortisol has been suggested to be influenced by psychiatric morbidity, and may also influence fetal growth. However, several studies found equal cortisol levels in depressed and healthy pregnant women. Placental 11-beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) shields the fetus from maternal cortisol by conversion to cortisone, a function that may be compromised by maternal stress. We aimed to compare the serum ratio of cortisone to cortisol, in women with and without psychiatric morbidity during pregnancy. A secondary aim was to investigate whether fetal growth, approximated by infant birth weight, was associated with the cortisone to cortisol ratio. We performed tandem mass spectrometry analysis of serum cortisol and cortisone in late pregnancy in 94 women with antenatal psychiatric morbidity and 122 controls (cohort 1). We also compared the placental gene expression of HSD11B1 and 2 in another group of 69 women with psychiatric morbidity and 47 controls (cohort 2). There were no group differences in cortisol to cortisone ratio, absolute levels of cortisone and cortisol (cohort 1), or expression of HSD11B1 or 2 (cohort 2). However, cortisone to cortisol ratio was positively associated with birth weight in women with psychiatric morbidity, also after adjustment for gestational length, fetal sex, maternal height, smoking, SSRI use, and time of blood sampling (standardized beta = 0.35, p < 0.001), with no association in the healthy controls Thus, the maternal serum cortisone to cortisol ratio does not seem to be affected by psychiatric morbidity, but psychiatric morbidity may increase fetal exposure to cortisol or other metabolic factors influencing fetal growth.

  • 25.
    Hellgren, Charlotte
    et al.
    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.
    Jonsson, Maria
    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.
    Sympathetic reactivity in late pregnancy is related to labour onset in women2011In: Stress, ISSN 1025-3890, E-ISSN 1607-8888, Vol. 14, no 6, p. 627-633Article in journal (Refereed)
    Abstract [en]

    Stress regulation during pregnancy is considered to be connected to the timing of labour initiation. Although increasing knowledge is emerging on the regulation of parturition, there is currently no way to predict the start of spontaneous labour in women. The main aim of this study was to assess pain threshold and the sympathetic nervous system response to cold pain in relation to the onset of labour in healthy pregnant women. Ninety-three pregnant women were recruited and assessed for skin conductance (SC) activity during a cold pressor test in gestational week 38. Pain threshold and cold endurance were also measured and the results were compared with data obtained from hospital records. Seventy-four women had a spontaneous labour onset and a valid SC measurement. SC activity during the cold pressor test decreased significantly with the number of days left to spontaneous parturition. This may indicate a gradual decrease in sympathetic autonomic nervous system reactivity even during the last weeks of pregnancy. Measuring SC activity during mild stress provocation is a rapid and non-invasive means to study variation in sympathetic reactivity during pregnancy, and may be useful in research on stress regulation in pregnancy and its relation to labour initiation.

  • 26.
    Hellgren, Charlotte
    et al.
    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.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Backstrom, T.
    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.
    Low serum allopregnanolone is associated with elevated depressive symptoms in late pregnancy2012In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 22, no S2, p. S228-S228Article in journal (Other academic)
  • 27.
    Hellgren, Charlotte
    et al.
    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.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå Neurosteroid Research Center, Department of Clinical Science, Obstetrics and Gynecology, Umeå University, Umeå, 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.
    Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy2014In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 69, no 3, p. 147-153Article in journal (Refereed)
    Abstract [en]

    Allopregnanolone (3α-hydroxy-5α-pregnan-20-one) is a neurosteroid which has inhibitory function through interaction with the GABAA receptor. This progesterone metabolite has strong sedative and anxiolytic properties, and low endogenous levels have been associated with depressed mood. This study aimed to investigate whether the very high serum allopregnanolone levels in late pregnancy co-vary with concurrent self-rated symptoms of depression and anxiety.

    Ninety-six women in pregnancy weeks 37 - 40 rated symptoms of depression and anxiety with the Montgomery-Åsberg Depression Rating Scale (MADRS-S) and Spielberger State-Trait Anxiety Inventory (STAI-S and STAI–T). Their serum allopregnanolone was analyzed by celite chromatography and radioimmunoassay.

    Ten women had elevated depression scores (MADRS-S ≥ 13), and this group had significantly lower allopregnanolone levels compared to women with MADRS-S scores in the lower range (39.0 ± 17.9 nmol/l vs. 54.6 ± 18.7 nmol/l, p = 0.014). A significant negative correlation was found between self-rated depression scores and allopregnanolone concentrations (Pearson’s correlation coefficient = -0.220, p = 0.031). The linear association between self-rated depression scores and allopregnanolone serum concentrations remained significant when adjusted for gestational length, progesterone levels, and parity. Self-rated anxiety, however, was not associated with allopregnanolone serum concentrations during pregnancy. In conclusion, high allopregnanolone serum concentrations may protect against depressed mood during pregnancy.

  • 28.
    Hellgren, Charlotte
    et al.
    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.
    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.
    Cortisol awakening response in late pregnancy in women with previous or ongoing depression2013In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 12, p. 3150-54Article in journal (Other academic)
    Abstract [en]

    Pregnancy involves an increase in basal cortisol, and a decrease in the hypothalamic-pituitary-adrenal (HPA) axis reactivity. The cortisol awakening response is a measure of HPA axis reactivity which has been reported to be altered in patients with an ongoing depressive episode, as well as in individuals with remitted depression.

    This study aimed to use the cortisol awakening response to study the HPA axis reactivity in relation to previous and ongoing depression in women during the third trimester of pregnancy. Based on structured interviews, and repeated questionnaires during pregnancy, 134 women were included in one of three groups: never depressed (n=57), depressed prior to the current pregnancy (n=39), and depressed during the current pregnancy (n=38). The hypothesis was that the women with ongoing, or previous, depression would have a higher cortisol awakening response than women who have never suffered from depression.

    Linear mixed models analysis revealed no group differences in the absolute cortisol levels or in the shape of the cortisol awakening response. We conclude that the difference in cortisol awakening response between women with and without experience of a depressive episode is not evident in late pregnancy.

  • 29.
    Hellgren, Charlotte
    et al.
    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.
    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.
    Cortisol awakening response in late pregnancy in women with previous or ongoing depression2013In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 38, no 12, p. 3150-3154Article in journal (Refereed)
    Abstract [en]

    Pregnancy is associated with increased basal cortisol levels, and decreased hypothalamic-pituitary-adrenal (HPA) axis reactivity. The cortisol awakening response (CAR) is a measure of HPA-axis reactivity which has been reported to be increased in patients with ongoing depressive disorder and in individuals with remitted depression. In this study, we investigated HPA-axis reactivity in pregnant women with ongoing or previous depression. The CAR was assessed by measurement of salivary cortisol at awakening and 15, 30, and 45min post-awakening. Based on structured psychiatric interviews and repeated measurements of depressive symptoms during pregnancy, 134 women were included in one of the three groups: never depressed (n=57), depressed prior to the current pregnancy (n=39), and depressed during the current pregnancy (n=38). Given the prior findings of increased CAR in non-pregnant depressed subjects, we hypothesized that an ongoing or previous depression would result in a higher CAR. Contrary to our hypothesis, a mixed models analysis failed to yield significant group differences. Thus, our results suggest that never depressed pregnant women and women with depression during pregnancy have similar cortisol awakening responses. Furthermore, our findings suggest that the cortisol awakening response does not differ between currently healthy women with and without experience of a depressive episode during late pregnancy.

  • 30.
    Iliadis, Stavros I.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. 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.
    Kollia, N.
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece.
    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.
    Associations between a polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene, neuroticism and postpartum depression2017In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 207, p. 141-147Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: This study examined the association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene and neuroticism, as well as the possible mediatory role of neuroticism in the association between the polymorphism and postpartum depressive symptoms.

    METHODS: 769 women received questionnaires containing the Edinburgh Postnatal Depression Scale (EPDS) at six weeks postpartum and demographic data at pregnancy week 17 and 32 and at six weeks postpartum, as well as the Swedish universities Scales of Personality at pregnancy week 32.

    RESULTS: Linear regression models showed an association between the GG genotype and depressive symptoms. When neuroticism was introduced in the model, it was associated with EPDS score, whereas the association between the GG genotype and EPDS became borderline significant. A path analysis showed that neuroticism had a mediatory role in the association between the polymorphism and EPDS score.

    LIMITATIONS: The use of the EPDS, which is a self-reporting instrument.

    CONCLUSIONS: Neuroticism was associated with the polymorphism and had a mediatory role in the association between the polymorphism and postpartum depression. This finding elucidates the genetic background of neuroticism and postpartum depression.

  • 31.
    Iliadis, Stavros I.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    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.
    Sylven, Sara
    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.
    Sundström, Inger Poromaa
    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.
    Prenatal and Postpartum Evening Salivary Cortisol Levels in Association with Peripartum Depressive Symptoms2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 8, article id e0135471Article in journal (Refereed)
    Abstract [en]

    Background The biology of peripartum depression remains unclear, with altered stress and the Hypothalamus- Pituitary-Adrenal axis response having been implicated in its pathophysiology. Methods The current study was undertaken as a part of the BASIC project (Biology, Affect, Stress, Imaging, Cognition), a population-based longitudinal study of psychological wellbeing during pregnancy and the postpartum period in Uppsala County, Sweden, in order to assess the association between evening salivary cortisol levels and depressive symptoms in the peripartum period. Three hundred and sixty-five pregnant women from the BASIC cohort were recruited at pregnancy week 18 and instructed to complete a Swedish validated version of the Edinburgh Postnatal Depression Scale at the 36th week of pregnancy as well as the sixth week after delivery. At both times, they were also asked to provide evening salivary samples for cortisol analysis. A comprehensive review of the relevant literature is also provided. Results Women with postpartum EPDS score >= 10 had higher salivary evening cortisol at six weeks postpartum compared to healthy controls (median cortisol 1.19 vs 0.89 nmol/L). A logistic regression model showed a positive association between cortisol levels and depressive symptoms postpartum (OR = 4.1; 95% CI 1.7-9.7). This association remained significant even after controlling for history of depression, use of tobacco, partner support, breastfeeding, stressful life events, and sleep problems, as possible confounders (aOR = 4.5; 95% CI 1.5-14.1). Additionally, women with postpartum depressive symptoms had higher postpartum cortisol levels compared to both women with depressive symptoms antenatally and controls (p = 0.019 and p = 0.004, respectively). Conclusions Women with depressive symptoms postpartum had higher postpartum cortisol levels, indicating an altered response of the HPA-axis in postpartum depression.

  • 32.
    Iliadis, Stavros I
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sylvén, Sara
    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
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Dept. of Behavioural Neuroscience, Groningen Institute for Evolutionary Life Sciences, Nijenborgh, 7, 9747 AG, University of Groningen, Groningen, The Netherlands.
    Schijven, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Dept. of Neuroscience, Uppsala University, 751 24, Uppsala, Sweden.
    Chrousos, George P
    Dept. of Pediatrics, Athens University Medical School, Athens, Greece.
    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.
    Mid-pregnancy corticotropin-releasing hormone levels in association with postpartum depressive symptoms2016In: Depression and anxiety (Print), ISSN 1091-4269, E-ISSN 1520-6394, Vol. 33, no 11, p. 1023-1030Article in journal (Refereed)
    Abstract [en]

    Background: Peripartum depression is a common cause of pregnancy and postpartum related morbidity. The production of corticotropin-releasing hormone (CRH) from the placenta alters the profile of hypothalamus-pituitary-adrenal axis hormones and may be associated with postpartum depression. The purpose of this study was to assess, in non-depressed pregnant women, the possible association between CRH levels in pregnancy and depressive symptoms postpartum.

    Methods: A questionnaire containing demographic data and the Edinburgh Postnatal Depression Scale was filled in gestational weeks 17 and 32, and six weeks postpartum. Blood samples were collected in week 17 for assessment of CRH. A logistic regression model was constructed, using postpartum Edinburgh Postnatal Depression Scale score as the dependent variable and log transformed CRH levels as the independent variable. Confounding factors were included in the model. Sub-analyses after exclusion of study subjects with preterm birth, small for gestational age newborns, and women on corticosteroids were performed.

    Results: 535 women without depressive symptoms during pregnancy were included. Logistic regression showed an association between high CRH levels in gestational week 17 and postpartum depressive symptoms, before and after controlling for several confounders (unadjusted Odds Ratio = 1.11; 95% CI 1.01 – 1.22, adjusted Odds Ratio = 1.13; 95% CI 1.02 – 1.26, per 0.1 unit increase in log corticotropin-releasing hormone). Exclusion of women with preterm birth and newborns small for gestational age as well as women who used inhalation corticosteroids during pregnancy did not alter the results.

    Conclusions: This study suggests an association between high CRH levels in gestational week 17 and the development of postpartum depressive symptoms, among women without depressive symptoms during pregnancy.

  • 33.
    Jonsson, Maria
    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.
    Wiberg-Itzel, Eva
    Department of Obstetrics and Gynaecology, Söder Hospital, Stockholm, Sweden.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Assessment of pain in women randomly allocated to speculum or digital insertion of the Foley catheter for induction of labor2011In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 90, no 9, p. 997-1004Article in journal (Refereed)
    Abstract [en]

    Objective

    The primary aim was to assess pain subjectively and objectively in women during insertion of a Foley catheter for induction of labor. A secondary aim was to assess pain during cervical ripening and to evaluate maternal satisfaction.

    Design

    Randomized controlled trial. Setting. University hospital, Sweden. Population. Forty-two women undergoing induction of labor and cervical ripening with a Foley catheter.

    Methods

    Women were randomly allocated to digital (n=21) or to speculum (n=21) placement of a Foley catheter. A visual analogue scale (VAS) was used for subjective assessment of pain and, for objective measurements, a skin conductance algesimeter was used and the area under the curve (AUC) was calculated (mu Ss). Maternal satisfaction was evaluated in a questionnaire. Main outcome measures. Pain sensation during placement of the Foley catheter.

    Results

    There was a significant difference between groups in pain measurements during insertion of the Foley catheter. The speculum group had higher median pain scores than the digital group, VAS=5 vs. = 3 (p=0.03) and greater median AUC measurements: 1840 vs. 823 mu Ss (p=0.04). There was no difference in pain assessments during cervical ripening. Overall satisfaction scores were high and comparable between groups.

    Conclusion

    Digital placement of the Foley catheter is subjectively and objectively less painful compared to the use of a speculum. Digital placement should therefore be considered as an alternative in the management of these patients. Ripening of the cervix with the Foley catheter is well tolerated and the overall satisfaction rate among patients induced with this method is high.

  • 34.
    Kallak, Theodora Kunovac
    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.
    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.
    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.
    Sandelin-Francke, Lotta
    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.
    Ubhayasekera, Kumari
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). 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.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Campbell, Rebecca E
    Centre for Neuroendocrinology, Department of Physiology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
    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.
    Maternal and female fetal testosterone levels are associated with maternal age and gestational weight gain2017In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 177, no 4, p. 379-388Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Prenatal androgen exposure has been suggested to play a role in polycystic ovary syndrome. Given the limited information on what maternal characteristics influence maternal testosterone levels, and the even less explored routes by which female fetus androgen exposure would occur, the aim of this study was to investigate the impact of maternal age, BMI, weight gain, depressed mood and aromatase SNPs on testosterone levels in maternal serum and amniotic fluid of female fetuses.

    METHODS: Blood samples from pregnant women (n = 216) obtained in gestational weeks 35-39, and pre-labor amniotic fluid samples from female fetuses (n = 56), taken at planned Caesarean section or in conjunction with amniotomy for induction of labor, were analyzed. Maternal serum testosterone and amniotic fluid testosterone and cortisol were measured by tandem mass spectrometry.

    RESULTS: Multiparity (β = -0.28, P < 0.001), self-rated depression (β = 0.26, P < 0.001) and weight gain (β = 0.18, P < 0.05) were independent explanatory factors for the maternal total testosterone levels. Maternal age (β = -0.34, P < 0.001), weight gain (β = 0.19, P < 0.05) and amniotic fluid cortisol levels (β = 0.44, P < 0.001) were independent explanatory factors of amniotic fluid testosterone in female fetuses, explaining 64.3% of the variability in amniotic fluid testosterone.

    WIDER IMPLICATIONS OF THE FINDINGS: Young maternal age and excessive maternal weight gain may increase the prenatal androgen exposure of female fetuses. Further studies are needed to explore this finding.

  • 35.
    Skalkidou, Alkistis
    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.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Sylvén, Sara
    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.
    Biological aspects of postpartum depression2012In: Women's health, ISSN 1745-5065, Vol. 8, no 6, p. 659-671Article in journal (Refereed)
    Abstract [en]

    In comparison with the vast epidemiological literature on postpartum depression (PPD), relatively few studies have examined the biological aspects of the disorder. However, research into the biological mechanisms of PPD is a challenging task, as normal pregnancy and the postpartum period cause adaptive endocrine changes, which would otherwise be considered pathological in nonpregnant women. This review focuses on the adaptive changes of childbearing and nursing, which ultimately may put women at increased risk of PPD. In light of the normal physiology, the authors also attempt to describe the current evidence of the biological changes associated with the development of depression in the postpartum period, including ovarian steroids, the hypothalamic-pituitary-adrenal axis, the serotonergic neurotransmitter system, the thyroid system and inflammatory markers. In addition, current knowledge on candidate genes associated with PPD is reviewed.

  • 36.
    Skalkidou, Alkistis
    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.
    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.
    Iliadis, Stavros I.
    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.
    Huizink, Anja C.
    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.
    Freyhult, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Stress-related genetic polymorphisms in association with peripartum depression symptoms and stress hormones: A longitudinal population-based study2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 103, p. 296-305Article in journal (Refereed)
    Abstract [en]

    Individual differences in the response of the stress system to hormonal changes during pregnancy and the postpartum period render some women susceptible to developing depression. The present study sought to investigate peripartum depression and stress hormones in relation to stress-related genotypes. The Edinburgh Postnatal Depression Scale was used to assess peripartum depressive symptoms in a sample of 1629 women, followed from pregnancy week seventeen to six months postpartum. Genotypes of ninety-four haplotype-tag single nucleotide polymorphisms (SNPs) in sixteen genes of the hypothalamus-pituitary-adrenal axis pathway were analyzed and data on psychosocial and demographic factors was collected. In sub-studies, salivary cortisol awakening response in gestational week 35-39, salivary evening cortisol levels in gestational week 36 and postpartum week 6, and blood cortisol and cortisone levels in gestational week 35-39 were analyzed. SNP-set kernel association tests were performed at the gene-level, considering psychosocial and demographic factors, followed by post-hoc analyses of SNPs of significant genes. Statistically significant findings at the 0.05 p-level included SNPs in the hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) gene in relation to self-rated depression scores in postpartum week six among all participants, and serpin family A member 6 (SERPINA6) gene at the same time-point among women with de novo onset of postpartum depression. SNPs in these genes also associated with stress hormone levels during pregnancy. The present study adds knowledge to the neurobiological basis of peripartum depression by systematically assessing SNPs in stress-regulatory genes and stress-hormone levels in a population-based sample of women.

  • 37.
    Wallström, Tove
    et al.
    Sodersjukhuset Hosp, Karolinska Inst, Sect Obstet & Gynaecol, Dept Clin Sci & Educ, S-11883 Stockholm, Sweden..
    Hellgren, Charlotte
    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.
    Wiberg-Itzel, Eva
    Sodersjukhuset Hosp, Karolinska Inst, Sect Obstet & Gynaecol, Dept Clin Sci & Educ, S-11883 Stockholm, Sweden..
    Skin conductance activity in post-term pregnancies2015In: The Journal of Maternal-Fetal & Neonatal Medicine, ISSN 1476-7058, E-ISSN 1476-4954, Vol. 28, no 16, p. 1912-1916Article in journal (Refereed)
    Abstract [en]

    Objective: The pain threshold in humans rises during late pregnancy, and the woman becomes less sensitive to stress. The aim of this study was to investigate whether monitoring the sympathetic nervous system response to stimuli by skin conductance activity might be a useful predictor of spontaneous onset of labour in post-term pregnancies. Study design: A prospective observational study. Fifty-two healthy pregnant women were consecutively asked for inclusion in the study at their post-term pregnancy examination. Initially, a Ctg (cardiotocography) registration was performed, followed by 5 min of skin conductance measurement including a ''cold pressor test''. Finally, a vaginal examination with a cervical assessment were performed according to clinical guidelines. Results: A statistically significant lower pain reaction during the period of provocation was seen in deliveries close to spontaneous onset of labour compared with induced deliveries with an non-spontaneous onset of labour before 294 days (p = 0.02). Sixty-three per cent (19/30) of the women with spontaneous onset had a negative value at provocation compared with 30% (6/20) in the induced group. Conclusions: Decreased response to pain stimuli, as an indication of decreased activity in the sympathetic nervous system, has a correlation to spontaneous onset of labour in post-term pregnancies.

1 - 37 of 37
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