| 1. |
- Axfors, Cathrine, et al.
(author)
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Cohort profile : the Biology, Affect, Stress, Imaging and Cognition (BASIC) study on perinatal depression in a population-based Swedish cohort
- 2019
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In: BMJ Open. - : BMJ. - 2044-6055. ; 9:10
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Journal article (peer-reviewed)abstract
- PURPOSE: With the population-based, prospective Biology, Affect, Stress, Imaging and Cognition (BASIC) cohort, we aim to investigate the biopsychosocial aetiological processes involved in perinatal depression (PND) and to pinpoint its predictors in order to improve early detection.PARTICIPANTS: From September 2009 to November 2018, the BASIC study at Uppsala University Hospital, Sweden, has enrolled 5492 women, in 6478 pregnancies, of which 46.3% first-time pregnancies and with an average age of 31.5 years. After inclusion around gestational week 16-18, participants are followed-up with data collection points around gestational week 32, at childbirth, as well as three times postpartum: after 6 weeks, 6 months and 1 year. At the last follow-up, 70.8% still remain in the cohort.FINDINGS TO DATE: In addition to internet-based surveys with self-report instruments, participants contribute with biological samples, for example, blood samples (maternal and from umbilical cord), biopsies (umbilical cord and placenta) and microbiota samples. A nested case-control subsample also takes part in cognitive and emotional tests, heart rate variability tests and bioimpedance tests. Subprojects have identified various correlates of PND of psychological and obstetric origin in addition to factors of the hypothalamic-pituitary-adrenal axis and immune system.FUTURE PLANS: In parallel with the completion of data collection (final follow-up November 2019), BASIC study data are currently analysed in multiple subprojects. Since 2012, we are conducting an ongoing follow-up study on the participants and their children up to 6 years of age (U-BIRTH). Researchers interested in collaboration may contact Professor Alkistis Skalkidou (corresponding author) with their request to be considered by the BASIC study steering committee.
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| 2. |
- Axfors, Cathrine, et al.
(author)
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Neuroticism is associated with higher antenatal care utilization in obstetric low-risk women
- 2019
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 98:4, s. 470-478
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Journal article (peer-reviewed)abstract
- IntroductionElevated 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 methodsParticipants 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).ResultsAfter 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).ConclusionsNeuroticism 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.
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| 3. |
- Bhandage, Amol, 1988-, et al.
(author)
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Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes
- 2018
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Bhandage, Amol K., 1988-, et al.
(author)
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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 women
- 2017
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In: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 305, s. 51-58
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Journal article (peer-reviewed)abstract
- 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.
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| 5. |
- Bhandage, Amol K., 1988-, et al.
(author)
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Expression of GABA receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health
- 2015
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In: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 213:3, s. 575-585
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Journal article (peer-reviewed)abstract
- AimThe concept of nerve-driven immunity recognizes a link between the nervous and the immune system. -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 whether the expression of GABA receptors and chloride transporters in human peripheral blood mononuclear cells (PBMCs) was influenced by gender, pregnancy or mental health. MethodsWe used RT-qPCR to determine the mRNA expression level in PBMCs from men (n=16), non-pregnant women (n=19), healthy pregnant women (n=27) and depressed pregnant women (n=15). ResultsThe 2 subunit had the most prominent expression level of the GABA-A receptor subunits in all samples. The and 2 subunits were up-regulated by pregnancy, whereas the epsilon subunit was more frequently expressed in healthy pregnant women than non-pregnant women who, in turn, commonly expressed the 6 and the 2 subunits. The 1 and epsilon 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. ConclusionThe results demonstrate the impact gender, pregnancy and mental health have on the expression of GABA receptors and chloride transporters expressed in human PBMCs.
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| 6. |
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| 7. |
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| 8. |
- Breedh, Julia, et al.
(author)
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Hypothalamic-pituitary-adrenal axis responsiveness, startle response, and sensorimotor gating in late pregnancy
- 2019
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 106, s. 1-8
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Journal article (peer-reviewed)abstract
- 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.
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| 9. |
- Bränn, Emma, et al.
(author)
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Inflammatory markers in late pregnancy in association with postpartum depression-A nested case-control study.
- 2017
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 79, s. 146-159
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Journal article (peer-reviewed)abstract
- 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.
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| 10. |
- Comasco, Erika, et al.
(author)
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Influence of catechol-O-methyltransferase Val158Met polymorphism on startle response in the presence of high estradiol levels
- 2013
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In: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 23:7, s. 629-635
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Journal article (peer-reviewed)abstract
- 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.
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| 11. |
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| 12. |
- Comasco, Erika, et al.
(author)
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Sleep duration, depression, and oxytocinergic genotype influence prepulse inhibition of the startle reflex in postpartum women
- 2016
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In: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 26:4, s. 767-776
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Journal article (peer-reviewed)abstract
- 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.
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| 13. |
- Comasco, Erika, 1982-, et al.
(author)
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Supraphysiological hormonal status, anxiety disorders, and COMT Val/Val genotype are associated with reduced sensorimotor gating in women
- 2015
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 60, s. 217-23
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Journal article (peer-reviewed)abstract
- 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.
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| 14. |
- Dabo Pettersson, Fatimah, 1975-, et al.
(author)
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Anxiety, Depressed Mood and the Use of Labor Analgesia
- 2016
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In: Archives of Women's Mental Health. - : Springer Science and Business Media LLC. - 1434-1816 .- 1435-1102. ; 19:1, s. 11-16
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Journal article (peer-reviewed)abstract
- 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.
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| 15. |
- Daka, Bledar, 1976, et al.
(author)
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Circulating concentrations of endothelin-1 predict coronary heart disease in women but not in men: A longitudinal observational study in the Vara-Skövde Cohort
- 2015
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In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 15:1
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Journal article (peer-reviewed)abstract
- © 2015 Daka et al.Background: The vasoconstricting peptide endothelin-1 has been proposed to be a marker of cardiovascular disease. Our aim was to investigate whether circulating endothelin-1 levels predict coronary heart disease (CHD) in Sweden. Methods: In 2002-2005, 2816 adult participants (30-74 years) were randomly selected from two municipalities in south-western Sweden. Cardiovascular risk factors and endothelin-1 levels were assessed at baseline, and incident CHD was followed-up in all participants through 2011. After exclusion of 50 participants due to known CHD at baseline and 21 participants because of unsuccessful analysis of endothelin-1, 2745 participants were included in the study. In total, 72 CHD events (52 in men and 20 in women) were registered during the follow-up time. Results: We showed that baseline circulating endothelin-1 levels were higher in women with incident CHD than in women without CHD (3.2 pg/ml, SE: 0.36 vs 2.4 pg/ml, SE: 0.03, p = 0.003) whereas this difference was not observed in men (2.3 pg/ml, SE: 0.16 vs 2.3 pg/ml, SE: 0.04, p = 0.828). An age-adjusted Cox proportional regression analysis showed an enhanced risk of CHD with increasing baseline endothelin-1 levels in women (hazard ratio (HR) = 1.51, 95 % CI = 1.1-2.1, p = 0.015) but not in men (HR = 0.98, 95 % CI = 0.8-1.2, p = 0.854). Furthermore, the predictive value of endothelin-1 for incident CHD in women was still significant after adjustments for age, HOMA-IR, apolipoprotein (apo)B/apoA1 and smoking (HR = 1.53, CI = 1.1-1.2, p = 0.024). Conclusion: Circulating endothelin-1 levels may predict CHD in women.
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| 16. |
- Eckerdal, Patricia, 1972-, et al.
(author)
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Delineating the Association between Heavy Postpartum Haemorrhage and Postpartum Depression
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Journal article (peer-reviewed)abstract
- ObjectivesTo explore the association between postpartum haemorrhage (PPH) and postpartum depression (PPD), taking into account the role of postpartum anaemia, delivery experience and psychiatric history.MethodsA 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.ResultsThere 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.ConclusionThis study proposes important roles for postpartum anaemia, negative experience of delivery and mood during pregnancy in explaining the development of depressive symptoms after PPH.
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| 17. |
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| 18. |
- Edvinsson, Åsa, 1982-
(author)
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Biological Aspects of Peripartum Depression
- 2019
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Doctoral thesis (other academic/artistic)abstract
- 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.
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| 19. |
- Edvinsson, Åsa, et al.
(author)
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Different patterns of attentional bias in antenatal and postpartum depression
- 2017
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In: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279. ; 7:11
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Journal article (peer-reviewed)abstract
- 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.
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| 20. |
- Edvinsson, Åsa, 1982-, et al.
(author)
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Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction
- 2017
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In: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 80, s. 15-25
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Journal article (peer-reviewed)abstract
- 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.
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| 21. |
- Edvinsson, Åsa, 1982-, et al.
(author)
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The effect of antenatal depression and antidepressant treatment on placental tissue : a protein-validated gene expression study.
- 2019
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In: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393 .- 1471-2393. ; 19
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Journal article (peer-reviewed)abstract
- BACKGROUND: Antenatal depression affects 10-20% of pregnant women. Around 2-4% of European pregnant women use antidepressant treatment, most commonly selective serotonin reuptake inhibitors (SSRIs). Poor pregnancy outcomes, such as preterm birth and low birth weight, have been described in women with antenatal depression and in pregnant women on SSRI treatment. However, the effects of antenatal depression and antidepressant treatment on the placenta are largely unknown. The aim of this work was to compare placental gene and protein expression in healthy women, women with untreated antenatal depression and women on antidepressant treatment during pregnancy.METHODS: Placental samples from 47 controls, 25 depressed and 45 SSRI-treated women were analysed by means of qPCR using custom-designed TaqMan low-density arrays (TLDAs) for 44 genes previously known to be involved in the pathophysiology of depression, and expressed in the placenta. Moreover, placental protein expression was determined by means of immunohistochemistry in 37 healthy controls, 13 women with untreated depression and 21 women on antidepressant treatment. Statistical comparisons between groups were performed by one-way ANOVA or the Kruskal-Wallis test.RESULTS: Nominally significant findings were noted for HTR1A and NPY2R, where women with untreated depression displayed higher gene expression than healthy controls (p < 0.05), whereas women on antidepressant treatment had similar expression as healthy controls. The protein expression analyses revealed higher expression of HTR1A in placentas from women on antidepressant treatment, than in placentas from healthy controls (p < 0.05).CONCLUSION: The differentially expressed HTR1A, both at the gene and the protein level that was revealed in this study, suggests the involvement of HTR1A in the effect of antenatal depression on biological mechanisms in the placenta. More research is needed to elucidate the role of depression and antidepressant treatment on the placenta, and, further, the effect on the fetus.
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| 22. |
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| 23. |
- Filipek-Gorniok, Beata, et al.
(author)
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Expression of chondroitin/dermatan sulfate glycosyltransferases during early zebrafish development
- 2013
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In: Developmental Dynamics. - : Wiley. - 1058-8388 .- 1097-0177. ; 242:8, s. 964-975
-
Journal article (peer-reviewed)abstract
- Background: Chondroitin/dermatan sulfate (CS/DS) proteoglycans present in the extracellular matrix have important structural and regulatory functions. Results: Six human genes have previously been shown to catalyze CS/DS polymerization. Here we show that one of these genes, chpf, is represented by two copies in the zebrafish genome, chpfa and chpfb, while the other five human CS/DS glycosyltransferases csgalnact1, csgalnact2, chpf2, chsy1, and chsy3 all have single zebrafish orthologues. The putative zebrafish CS/DS glycosyltransferases are spatially and temporally expressed. Interestingly, overlapping expression of multiple glycosyltransferases coincides with high CS/DS deposition. Finally, whereas the relative levels of the related polysaccharide HS reach steady-state at around 2 days post fertilization, there is a continued relative increase of the CS amounts per larvae during the first 6 days of development, matching the increased cartilage formation. Conclusions: There are 7 CS/DS glycosyltransferases in zebrafish, which, based on homology, can be divided into the CSGALNACT, CHSY, and CHPF families. The overlap between intense CS/DS production and the expression of multiple CS/DS glycosyltransferases suggests that efficient CS/DS biosynthesis requires a combination of several glycosyltransferases.
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| 24. |
- Hannerfors, Anna-Karin, et al.
(author)
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Treatment with serotonin reuptake inhibitors during pregnancy is associated with elevated corticotropin-releasing hormone levels
- 2015
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 58, s. 104-113
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Journal article (peer-reviewed)abstract
- 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.
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| 25. |
- Hellgren, Charlotte, 1985-, et al.
(author)
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Allopregnanolone levels and depressive symptoms during pregnancy in relation to single nucleotide polymorphisms in the allopregnanolone synthesis pathway
- 2017
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In: Hormones and Behavior. - : Elsevier. - 0018-506X .- 1095-6867. ; 94, s. 106-113
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Journal article (peer-reviewed)abstract
- 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.
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| 26. |
- Hellgren, Charlotte, 1985-, et al.
(author)
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Cortisol awakening response in late pregnancy in women with previous or ongoing depression
- 2013
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 38:12, s. 3150-3154
-
Journal article (peer-reviewed)abstract
- 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.
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| 27. |
- Hellgren, Charlotte, 1985-, et al.
(author)
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Cortisol awakening response in late pregnancy in women with previous or ongoing depression
- 2013
-
In: Psychoneuroendocrinology. - 0306-4530 .- 1873-3360. ; 38:12, s. 3150-54
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Journal article (other academic/artistic)abstract
- 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.
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| 28. |
- Hellgren, Charlotte, et al.
(author)
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Decreased startle modulation during anticipation in the postpartum period in comparison to late pregnancy
- 2012
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In: Archives of Women's Mental Health. - : Springer Science and Business Media LLC. - 1434-1816 .- 1435-1102. ; 15:2, s. 87-94
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Journal article (peer-reviewed)abstract
- 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.
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| 29. |
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| 30. |
- Hellgren, Charlotte, et al.
(author)
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Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy
- 2014
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In: Neuropsychobiology. - : S. Karger AG. - 0302-282X .- 1423-0224. ; 69:3, s. 147-153
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Journal article (peer-reviewed)abstract
- 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.
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| 31. |
- Hellgren, Charlotte, 1985-
(author)
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Physiological Stress Reactivity in Late Pregnancy
- 2013
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Doctoral thesis (other academic/artistic)abstract
- 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.
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| 32. |
- Hellgren, Charlotte, et al.
(author)
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Reducing workload by navigational support in dynamic situations
- 2012
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In: Proceedings of the 9th International ISCRAM Conference. ; , s. 1-9
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Conference paper (peer-reviewed)abstract
- By presenting continuously updated heading and distance information on a small head-mounted display (HMD), as a supplement to a GPS-receiver, we examined if workload could be reduced and performance increased, when navigating in a demanding situation. The purpose was to present limited but sufficient information to facilitate navigation. The technique was tested on ground troops, but could also be used by rescue services and police in situations that require navigation in unknown environments. The main findings were that the workload was reduced in one aspect (during navigation) but increased in another (looking for foot placement). There were no clear differences in performance, except that participants stopped fewer times to look at the GPS-receiver if they had updated heading and distance information. This suggests that a supplement display with minimal information could be useful when navigating with a GPS-receiver in an unknown environment.
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| 33. |
- Hellgren, Charlotte, et al.
(author)
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Sympathetic reactivity in late pregnancy is related to labour onset in women
- 2011
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In: Stress. - : Informa UK Limited. - 1025-3890 .- 1607-8888. ; 14:6, s. 627-633
-
Journal article (peer-reviewed)abstract
- 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.
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| 34. |
- Hellgren, Charlotte, et al.
(author)
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Tandem mass spectrometry determined maternal cortisone to cortisol ratio and psychiatric morbidity during pregnancy-interaction with birth weight
- 2016
-
In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 69, s. 142-149
-
Journal article (peer-reviewed)abstract
- 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.
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| 35. |
- Hellgren, Margareta, 1955, et al.
(author)
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C-Reactive Protein Concentrations and Level of Physical Activity in Men and Women With Normal and Impaired Glucose Tolerance: A Cross-Sectional Population-Based Study in Sweden
- 2016
-
In: Journal of Physical Activity & Health. - : Human Kinetics. - 1543-3080 .- 1543-5474. ; 13:6, s. 625-631
-
Journal article (peer-reviewed)abstract
- Background: We aimed to explore the association between self-reported leisure time physical activity (LTPA) and C-reactive protein (CRP) concentrations in men and women with and without impaired glucose tolerance (IGT). Methods: In a cross-sectional study, a random sample (n = 2,816) was examined with an oral glucose tolerance test, CRP and information about LTPA. Those with IGT or normal glucose tolerance (NGT) and CRP value <= 10 mg/L were selected (n = 2,367) for the study. Results: An inverse association between LTPA and CRP concentrations was observed in the population (P < .001), though, only in men with IGT (P = .023) and in women with NGT. Men with IGT, reporting slight physical activity up to 4 hours a week presented significantly higher CRP concentrations than normoglycemic men (Delta 0.6 mg/L, P = .004). However, this difference could not be found in men with IGT reporting more intense physical activity (Delta 0.01 mg/L, P = .944). Conclusions: Physical inactivity seems to have greater inflammatory consequences for men (vs. women) with IGT. More importantly, although 4 hours of physical activity per week is more than the usual minimum recommendation, an even greater intensity of LTPA appears to be required to limit subclinical inflammation in men with IGT.
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| 36. |
- Hellgren, Margareta, et al.
(author)
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HbA1c räcker inte vid screening för störd glukosmetabolism - Även glukosbelastning behövs, visar svensk prospektiv epidemiologisk studie.
- 2015
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In: Läkartidningen. - 1652-7518. ; 112
-
Journal article (peer-reviewed)abstract
- An HbA1c threshold of ≥42 mmol/mol has been proposed to diagnose prediabetes. The sensitivity, specificity and positive predictive value of the proposed threshold for detection of individuals with prediabetes was examined in a study of 573 randomly selected individuals from Vara and Skövde. In addition, the utility of the FINDRISC questionnaire and of a fasting glucose test in combination with three short questions concerning BMI, heredity for type 2 diabetes and known hypertension was examined. Results from an oral glucose tolerance test were used as reference. The sensitivity of HbA1c and FINDRISC to detect individuals with IGT was 16 and 26 per cent respectively. Questions regarding BMI, heredity and hypertension together with a fasting glucose test yielded a sensitivity of 50%, but a lower specificity and positive predictive value. We conclude that HbA1c inefficiently detected individuals with impaired glucose tolerance and that oral glucose tolerance tests can still preferably be recommended.
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| 37. |
- Hellgren, Margareta, 1955, et al.
(author)
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Insulin resistance predicts early cardiovascular morbidity in men without diabetes mellitus, with effect modification by physical activity
- 2015
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In: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 22:7, s. 940-949
-
Journal article (peer-reviewed)abstract
- Aim: to assess how well insulin resistance predicts cardiovascular disease (CVD) in non-diabetic men and women and to explore the influence of physical activity. Methods: in this prospective study 2563 men and women without diabetes were examined with an oral glucose tolerance test, anthropometric measurements and blood pressure assessment. Questionnaires about lifestyle and physical activity were completed. Insulin resistance was estimated by fasting concentrations of plasma insulin and by HOMA index for insulin resistance. Participants were followed up for cardiovascular morbidity and mortality during an 8-year period, using information from the National Swedish Inpatient and Mortality registers. Results: at follow-up, HOMAir predicted CVD morbidity in males (50 events) and females (28 events) combined (HRage/sex-adj 1.4, 95% CI 1.1-1.7); however, when stratified by gender HOMAir was predictive solely in men (HRage-adj 1.8, 95% CI 1.3-2.4), whereas no association was found in women (HRage-adj 1.1, 95% CI 0.8-1.5). When stratifying the data for high and low physical activity, the predictive value of insulin resistance became stronger in sedentary men (HRage-adj 2.3, 95% CI 1.5-3.4) but was abolished in men performing moderate to vigorous physical activity (HRage-adj 1.0, 95% CI 0.6-1.6). The results remained when step-wise adjusted also for BMI, ApoB/ApoA1 and hypertension, as well as for smoking, alcohol consumption and education. Outcome for fasting plasma insulin was similar to HOMAir. Conclusions: insulin resistance predicts CVD in the general population; however, men may be more vulnerable to increased insulin resistance than women, and physically inactive men seem to be at high risk.
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| 38. |
- Iliadis, Stavros I, 1983-, et al.
(author)
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1843 – Depression in the peripartum period in association with salivary cortisol levels
- 2013
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In: European psychiatry. - : Elsevier. - 0924-9338 .- 1778-3585. ; 28:Supplement 1, s. 1-1
-
Journal article (other academic/artistic)abstract
- IntroductionThe Hypothalamic-Pituitary-Adrenal Axis (HPA axis) has been implicated in the pathogenesis of many affective disorders. Peripartum depression is a condition that includes depressive episodes occurring during pregnancy and the postpartum period. During uncomplicated pregnancy, mean cortisol levels rise substantially, mostly due to high levels of corticotropin releasing hormone produced by the placenta (p-CRH). The latter also suppresses hypothalamic CRH, leading to hypo-cortisolemia after partus. Cortisol concentration is usually normalised within two weeks after delivery. Failure of the above process results in continuing hypo-cortisolemia, which might increase susceptibility to PPD.Objectives/aimsThe current study aims to investigate the relationship between evening salivary cortisol levels and depression during the peripartum period.MethodsThree hundred and forty six pregnant women were asked to participate in the study. They completed the Edinburgh Postnatal Depression Scale (EPDS) and the Spielberger State-Trait Anxiety Inventory-State version (STAI-S) at the 36th week of pregnancy and the 6th week after delivery. At both times, study subjects were also asked to collect evening salivary samples by using a mail-delivered kit. Moreover, they were interviewed at the 36th week of pregnancy using the Mini International Neuropsychiatric Interview (MINI).ResultsPreliminary results indicate significantly higher evening salivary cortisol levels in depressed women during late pregnancy compared to healthy controls. No difference in cortisol levels was found between women with postpartum depression and healthy controls.ConclusionsOur study results support the hypothesis that depression during pregnancy resembles melancholic depression characterized by hyperactivity of the HPA-axis and hyper-cortisolemia.
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| 39. |
- Iliadis, Stavros I, et al.
(author)
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Association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene and postpartum depression symptoms: the role of neuroticism
-
Other publication (other academic/artistic)abstract
- BackgroundPostpartum depression is a common psychiatric disorder and numerous studies have assessed its association with psychosocial and biological factors. However, the contribution of genetic factors remains largely unknown. A dysregulated hypothalamus-pituitary-adrenal (HPA) axis and neuroticism associate with depressive symptoms after childbirth. A common genetic variant in the hydroxysteroid (11-beta) dehydrogenase 1 gene (HSD11B1), a component of the HPA-axis, has been recently associated with postpartum depressive symptoms. AimTo examine the association between the single nucleotide polymorphism (SNP) rs12565406 in HSD11B1 and neuroticism, as well as the possible mediatory role of neuroticism in the association between the polymorphism and postpartum depressive symptoms. Materials and MethodsThe present study was conducted as part of the BASIC-project and included 771 women. Self-administered questionnaires were sent to study participants, containing the Edinburgh Postnatal Depression Scale (EPDS) at six weeks postpartum and questions on demographic variables at pregnancy week 17 and 32 and at six weeks postpartum, as well as the Swedish universities Scale of Personality (SSP) at pregnancy week 32. Blood samples for genetic analyses were collected. ResultsSixty-five women (8.6%) reported depressive symptoms six weeks postpartum. Study subjects with EPDS ≥ 12 had higher scores on neuroticism compared to controls. Women who were homozygous for the major allele (GG) presented with higher EPDS score postpartum and scored higher in neuroticism, compared to T carriers. Linear regression models with log transformed EPDS score as the dependent variable and the rs12565406 genotype (GG vs. TG/TT) as the independent variable 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. Results were unaltered after adjustment for possible confounders. A path analysis on these variables revealed that neuroticism had a mediatory role in the association between the SNP and EPDS score. ConclusionsNeuroticism had a mediatory role in the association between the HSD11B1 rs12565406 SNP and postpartum depression. Future studies are needed to ascertain whether neuroticism can be used as an easily assessed intermediate phenotype that can reflect the genetic risk of PPD.
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| 40. |
- Iliadis, Stavros I., et al.
(author)
-
Associations between a polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene, neuroticism and postpartum depression
- 2017
-
In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 207, s. 141-147
-
Journal article (peer-reviewed)abstract
- 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.
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| 41. |
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| 42. |
- Iliadis, Stavros I, et al.
(author)
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Mid-pregnancy corticotropin-releasing hormone levels in association with postpartum depressive symptoms
- 2016
-
In: Depression and anxiety (Print). - : Hindawi Limited. - 1091-4269 .- 1520-6394. ; 33:11, s. 1023-1030
-
Journal article (peer-reviewed)abstract
- 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.
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| 43. |
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| 44. |
- Iliadis, Stavros I., et al.
(author)
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Prenatal and Postpartum Evening Salivary Cortisol Levels in Association with Peripartum Depressive Symptoms
- 2015
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
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Journal article (peer-reviewed)abstract
- 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.
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- Johansson, Björn, 1973-, et al.
(author)
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Hand-Held Support for Spatial Awareness for the Dismounted Soldier
- 2014
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In: HCI Posters 1. - Cham : Springer International Publishing. - 9783319078564 ; , s. 335-340
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Conference paper (other academic/artistic)abstract
- This contribution presents a summary of activities performed in an ongoing military research project aiming at investigating the impact of navigational support on spatial awareness. Investigated tasks are e.g. indication of direction to objects beyond visual range with and without navigational support, display size, performance time, and use of GPS device in darkness. The results indicate that the ability to keep track of targets in the terrain without a technical aid is very poor, but with a GPS device targets can be indicated with relatively high precision. Precision on target indication is slightly better with a larger display, it seems possible to indicate as fast as 5 seconds with a GPS device without impairments of precision, and a GPS device can be used for target indication in darkness. Spatial ability measured by PTSOT can discriminate important aspects of spatial ability with direct relevance for navigation and target indication.
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| 46. |
- Johansson, Björn, 1973-, et al.
(author)
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Supporting situation awareness on the move - the role of technology for spatial orientation in the field
- 2013
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In: Proceedings of the 10th International ISCRAM Conference. ; , s. 442-451
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Conference paper (peer-reviewed)abstract
- The study presented in this paper has investigated how technology can support spatial awareness when moving in wooded terrain. By “spatial awareness”, we refer to the ability to point in the approximate direction of several objects while navigating in unknown terrain. The ability to localize objects in the terrain has importance for emergency operations, for example firefighting and search and rescue operations. A field experiment was conducted with two conditions, one with technical support and one without. The results show that technical support in terms of GPS, digital maps and electronic compass can dramatically improve the ability to accurately indicate directions to objects. Further, findings concerning use of tests on spatial orientation to predict the ability to indicate directions to objects in the terrain when having no technical support are presented.
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- Jonsson, Maria, 1966-, et al.
(author)
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Assessment of pain in women randomly allocated to speculum or digital insertion of the Foley catheter for induction of labor
- 2011
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In: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 90:9, s. 997-1004
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Journal article (peer-reviewed)abstract
- ObjectiveThe 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.DesignRandomized controlled trial. Setting. University hospital, Sweden. Population. Forty-two women undergoing induction of labor and cervical ripening with a Foley catheter.MethodsWomen 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.ResultsThere 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.ConclusionDigital 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.
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