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  • 1.
    Bränn, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    Edvinsson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Rostedt Punga, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Sundström Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartumIngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322Artikel i tidskrift (Refereegranskat)
  • 2.
    Bränn, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    Edvinsson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Rostedt Punga, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Sundström Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartum2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 1863Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    During pregnancy, the woman's body undergoes tremendous changes in immune system adaptation. The immunological shifts that occur in pregnancy can partially be explained by alterations in hormonal levels. Furthermore, during pregnancy, many autoimmune diseases go into remission, only to flare again in the early postpartum period. Given these important changes in the clinical course of a number of autoimmune disorders, surprisingly little has been done to investigate the inflammatory profile changes across pregnancy and the postpartum period. Thus, the aim of this study was to describe how inflammatory and anti-inflammatory markers change from late pregnancy to the early postpartum period, using a multiplexed assay consisting of both well-known as well as exploratory proteins. Two-hundred-and-ninety women were included in this study and donated a total of 312 blood samples; 198 in late pregnancy (similar to gw38) and 114 in the postpartum period (similar to w8). The plasma blood samples were analyzed for 92 immune system related protein markers using Proseek Multiplex Inflammation I panel, a high-sensitivity assay based on proximity extension assay technology. Fifty-six inflammatory and anti-inflammatory markers were significantly different between pregnancy and the postpartum, of which 50 survived corrections for multiple comparisons. Out of these 50 markers, 41 decreased from pregnancy to postpartum, while the remaining 9 increased in the postpartum period. The top five markers with the greatest decrease in the postpartum period were Leukemia inhibitory factor receptor (LIF-R), Latency-associated peptide Transforming growth factor beta-1 (LAP TGF-beta-1), C-C motif chemokine 28 (CCL28), Oncostatin M (OSM) and Fibroblast growth factor 21 (FGF21). Top three markers that increased in the postpartum period were Tumor necrosis factor ligand superfamily member 11 (TRANCE), Tumor necrosis factor ligand superfamily member 12 (TWEAK), and C-C motif chemokine/Eotaxin (CCL11). This study revealed that the majority of the markers decreased from pregnancy to postpartum, and only a few increased. Several of the top proteins that were higher in pregnancy than postpartum have anti-inflammatory and immune modulatory properties promoting pregnancy progress. These results clearly reflect the tremendous change in the immune system in the pregnancy to postpartum transition.

  • 3.
    Bränn, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    Fransson, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning. Karolinska Institutet, Stockholm, Sweden..
    White, Richard A
    Norwegian Institute of Public Health, Oslo, Norway.
    Papadopoulos, Fotios C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Edvinsson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Kamali-Moghaddam, Masood
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Cunningham, Janet L
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Sundström Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    Inflammatory markers in women with postpartum depressive symptoms2018Ingår i: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 4.
    Bränn, Emma
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Papadopoulos, Fotios
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Hellgren, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Kamali-Moghaddam, Masood
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Boström, Adrian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Sundström-Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Inflammatory markers in late pregnancy in association with postpartum depression-A nested case-control study.2017Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 79, s. 146-159Artikel i tidskrift (Refereegranskat)
    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.

  • 5.
    Edvinsson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Biological Aspects of Peripartum Depression2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Peripartum depression affects around 12% of women in pregnancy and postpartum, and about 2–3% of European pregnant women use antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). An increased risk of poor pregnancy outcomes has been described in women with antenatal depression and SSRI treatment during pregnancy. The biological mechanisms behind these complications are not fully understood and here we investigated several biological correlates of peripartum depression, and discriminated between the effects of antidepressant treatment and depression itself.

    In Paper I, attentional biases in pregnant and postpartum women were studied by using the Emotional Stroop Task, measuring reaction times to different stimuli. The major finding was shorter reaction times in postpartum depressed women, for emotionally valenced stimuli, which can be interpreted as emotional numbing.

    In Paper II, peripheral inflammatory markers were assessed by proximity extension assay technology in depressed, SSRI-treated and healthy pregnant women. Lower levels of 23 markers were found in women with antenatal depression, independent of treatment, compared with healthy controls. These findings suggest a dysregulated switch to the anti-inflammatory M2 milieu characterizing a normal third trimester.

    In Paper III, normal changes in inflammatory markers across pregnancy and postpartum were assessed in healthy pregnant and postpartum women. The majority (41) of the 50 markers that differed between groups were lower postpartum. These results clearly reflect the change in the immune system in pregnancy to postpartum transition.

    In Paper IV, placental gene and protein expression were investigated and nominally significant findings were noted for serotonin receptor 1A (HTR1A) and neuropeptide Y2 receptor (NPY2R), where women with untreated depression displayed higher gene expression than healthy controls. Protein expression analyses revealed higher levels of HTR1A in placentas from SSRI-treated women, compared with healthy controls and women with untreated depression. This suggests possible involvement of HTR1A in the effect of antenatal depression on the placenta.

    Overall, peripartum depression is associated with altered cognitive-emotional processing, lower levels of several mostly anti-inflammatory markers, and altered placental gene and protein expression. However, we found no major differences between untreated and treated depression.

    Delarbeten
    1. Different patterns of attentional bias in antenatal and postpartum depression
    Öppna denna publikation i ny flik eller fönster >>Different patterns of attentional bias in antenatal and postpartum depression
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    2017 (Engelska)Ingår i: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 7, nr 11, artikel-id e00844Artikel i tidskrift (Refereegranskat) Published
    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.

    Nyckelord
    antenatal depression, attentional bias, emotional Stroop, postpartum depression, pregnancy, women
    Nationell ämneskategori
    Reproduktionsmedicin och gynekologi Psykiatri
    Identifikatorer
    urn:nbn:se:uu:diva-342913 (URN)10.1002/brb3.844 (DOI)000416063200009 ()29201545 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet
    Tillgänglig från: 2018-02-26 Skapad: 2018-02-26 Senast uppdaterad: 2018-12-05Bibliografiskt granskad
    2. Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction
    Öppna denna publikation i ny flik eller fönster >>Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction
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    2017 (Engelska)Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, s. 15-25Artikel i tidskrift (Refereegranskat) Published
    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.

    Ort, förlag, år, upplaga, sidor
    PERGAMON-ELSEVIER SCIENCE LTD, 2017
    Nyckelord
    Antenatal depression, Pregnancy, Inflammatory markers, Proximity extension assay, Selective serotonin reuptake inhibitors
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-326211 (URN)10.1016/j.psyneuen.2017.02.027 (DOI)000402352200003 ()28292683 (PubMedID)
    Tillgänglig från: 2017-08-08 Skapad: 2017-08-08 Senast uppdaterad: 2019-11-11Bibliografiskt granskad
    3. Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartum
    Öppna denna publikation i ny flik eller fönster >>Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartum
    Visa övriga...
    (Engelska)Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322Artikel i tidskrift (Refereegranskat) Submitted
    Nationell ämneskategori
    Reproduktionsmedicin och gynekologi
    Identifikatorer
    urn:nbn:se:uu:diva-367092 (URN)
    Anmärkning

    Emma Bränn and Åsa Edvinsson are shared first authors.

    Tillgänglig från: 2018-11-30 Skapad: 2018-11-30 Senast uppdaterad: 2018-12-05
    4. The effect of antenatal depression and antidepressant treatment on placental tissue: a protein-validated gene expression study
    Öppna denna publikation i ny flik eller fönster >>The effect of antenatal depression and antidepressant treatment on placental tissue: a protein-validated gene expression study
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    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Reproduktionsmedicin och gynekologi
    Identifikatorer
    urn:nbn:se:uu:diva-367376 (URN)
    Anmärkning

    Jocelien Olivier and Inger Sundström-Poromaa are shared last authors.

    Tillgänglig från: 2018-11-30 Skapad: 2018-11-30 Senast uppdaterad: 2018-12-05
  • 6.
    Edvinsson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Is peripartum depression just another depression?2016Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Depressive symptoms in pregnancy are common, reported by approximately 20% of pregnant women worldwide. Of these, around 4-7% fulfill the criteria for major depressive episode (MDE).

    The prevalence rates of MDE seem no different from those in non-pregnant women of childbearing ages, or may even be lower. Further, the clinical presentation of depressive symptoms in women of childbearing age does not differ depending on whether women are pregnant, postpartum or outside the peripartum period. For this reason, some researchers argue that peripartum depression is just another depression, merely occurring at a stressful point in life.  

    Antenatal depression and antidepressant treatment have been associated with an increased risk of poor pregnancy outcomes, such as preterm birth, impaired placental function, decreased fetal body and head growth. Nevertheless, little is known about the biological mechanisms behind these complications and more research is needed to elucidate the underlying pathways.

    In this thesis we have studied 1) attentional bias in antenatal and postpartum depression, with or without antidepressant treatment and 2) peripheral inflammatory markers in pregnancy (depressed, SSRI-treated, healthy controls).

    The title for this thesis is: Is peripartum depression just another depression? Based on the findings we have obtained thus far, the answer would be no. One argument would be that, as presented in study I, women who suffer from antenatal and postpartum depression do not display the typical attentional bias to negative words that is characteristic of depressive states in the non-pregnant population. Whether this is due to protective mechanisms of pregnancy or due to features that distinguish antenatal and postpartum depression from non-peripartum depression remains to be demonstrated.

    Secondly, study II describes that women with antenatal depression had significantly lower levels of peripheral inflammatory markers than healthy pregnant controls. Hypothetically, this could be due to dysregulated switch to the antiinflammatory pro-M2 milieu that characterizes normal third trimester pregnancy. These findings are clearly at odds with the literature in non-pregnant samples, where depression has been associated with increased levels of proinflammatory cytokines, but should be interpreted in the context of pregnancy-induced changes in inflammatory response.

    Moreover, treatment for antenatal depression is not as straightforward as it is in non-pregnant patients. When considering treatment, the expecting mother has to be aware of the risk-benefit profile for herself and the child. While antidepressant therapy clearly improves the mood of treated women, our findings do not indicate that antidepressant treatment has any positive impact on their inflammatory profile.

  • 7.
    Edvinsson, Åsa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Bränn, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    Hellgren, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Freyhult, Eva
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    White, Richard
    Norwegian Inst Publ Hlth, Oslo, Norway..
    Kamali-Moghaddam, Masood
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Olivier, Jocelien
    Univ Groningen, Groningen Inst Evolutionary Life Sci, Unit Behav Neurosci, Dept Neurobiol, Groningen, Netherlands..
    Bergquist, Jonas
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Boström, Adrian E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Schiöth, Helgi B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Funktionell farmakologi.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Cunningham, Janet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Sundström Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction2017Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, s. 15-25Artikel i tidskrift (Refereegranskat)
    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.

  • 8.
    Edvinsson, Åsa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Hellgren, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Kallak, Theodora Kunovac
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för reproduktionsbiologi i Uppsala (CRU).
    Åkerud, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    Olivier, Jocelien
    Neurobiology, unit Behavioral Neuroscience, Groningen Institute for Evolutionary Life Sciences, University of Groningen, the Netherlands.
    Sundström Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    The effect of antenatal depression and antidepressant treatment on placental tissue: a protein-validated gene expression studyManuskript (preprint) (Övrigt vetenskapligt)
  • 9.
    Edvinsson, Åsa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Olivier, Jocelien
    Univ Groningen, Groningen Inst Evolutionary Life Sci, Dept Neurobiol, Unit Behav Neurosci, Groningen, Netherlands.
    Hellgren, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Kallak, Theodora Kunovac
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Åkerud, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Sundström Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Antenatal Depression and Placental Function: A Protein Validated Gene Expression Study2018Ingår i: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 69, s. E62-E62Artikel i tidskrift (Övrigt vetenskapligt)
  • 10.
    Edvinsson, Åsa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    Hellgren, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Gingnell, Malin
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Ekselius, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Willebrand, Mimmie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset. Uppsala Univ, Dept Neurosci, Psychiat, Uppsala, Sweden..
    Sundström Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Different patterns of attentional bias in antenatal and postpartum depression2017Ingår i: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 7, nr 11, artikel-id e00844Artikel i tidskrift (Refereegranskat)
    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.

  • 11.
    Hellgren, Charlotte
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Edvinsson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    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 universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Bergquist, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Sundström-Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Tandem mass spectrometry determined maternal cortisone to cortisol ratio and psychiatric morbidity during pregnancy-interaction with birth weight2016Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 69, s. 142-149Artikel i tidskrift (Refereegranskat)
    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.

  • 12.
    Piltonen, Terhi T.
    et al.
    Univ Oulu, Oulu Univ Hosp, Dept Obstet & Gynecol, PEDEGO Res Unit,Med Res Ctr, Aapistie 5,Box 5000, Oulu 90014, Finland.
    Giacobini, Paolo
    INSERM, Jean Pierre Aubert Res Ctr, Lab Dev & Plast Neuroendocrine Brain, Lille, France;Univ Lille, Sch Med, Federat Hosp Univ, Lille, France.
    Edvinsson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Hustad, Steinar
    Univ Bergen, Dept Clin Sci, Bergen, Norway;Univ Bergen, Core Facil Metabol, Bergen, Norway.
    Lager, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning.
    Morin-Papunen, Laure
    Univ Oulu, Oulu Univ Hosp, Dept Obstet & Gynecol, PEDEGO Res Unit,Med Res Ctr, Aapistie 5,Box 5000, Oulu 90014, Finland.
    Tapanainen, Juha S.
    Univ Oulu, Oulu Univ Hosp, Dept Obstet & Gynecol, PEDEGO Res Unit,Med Res Ctr, Aapistie 5,Box 5000, Oulu 90014, Finland;Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland;Helsinki Univ Cent Hosp, Helsinki, Finland.
    Sundström-Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Arffman, Riikka K.
    Univ Oulu, Oulu Univ Hosp, Dept Obstet & Gynecol, PEDEGO Res Unit,Med Res Ctr, Aapistie 5,Box 5000, Oulu 90014, Finland.
    Circulating antimüllerian hormone and steroid hormone levels remain high in pregnant women with polycystic ovary syndrome at term2019Ingår i: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 111, nr 3, s. 588-596.e1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate plasma antimullerian hormone (AMH) concentration and its relation to steroid hormone levels in pregnant women with polycystic ovary syndrome (PCOS) and controls at term.

    Design: Case-control study.

    Setting: University-affiliated hospital.

    Patient(s): A total of 74 pregnant women at term: 25 women with PCOS (aged 31.6 ± 3.9 years [mean ± standard deviation], body mass index 24.0 ± 3.9 kg/m2, mean gestational length 279 ± 9 days) and 49 controls (aged 31.7 ± 3.3 years, body mass index 24.0 ± 3.3 kg/m2, mean gestational length 281 ± 9 days).

    Intervention(s): None.

    Main Outcome Measure(s): Plasma AMH and steroid hormone levels.

    Result(s): Antimullerian hormone, T, and androstenedione levels were higher in women with PCOS at term compared with controls, whereas estrogen and P levels were similar. The differences were pronounced in women carrying a female fetus. Testosterone and AMH levels correlated positively in both groups, but E2 levels only in women with PCOS.

    Conclusion(s): Pregnant women with PCOS present with elevated AMH and androgen levels even at term, suggesting a hormonal imbalance during PCOS pregnancy. Differences were detected especially in pregnancies with a female fetus, raising the question of whether female pregnancies are more susceptible to AMH and steroid hormone actions.

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