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Personality and the HPA-axis in Association with Postpartum Depression
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Postpartum depression is a psychiatric disorder affecting a substantial proportion of newly delivered women, and remains a significant cause of childbirth-related morbidity. The aim of the present thesis was to examine psychological, endocrine and genetic aspects of postpartum depression in a large, population-based sample of women in Uppsala, Sweden. All included studies were undertaken as parts of the BASIC-project, a longitudinal study on psychological wellbeing during pregnancy and the postpartum period. Study participants were screened for depressive symptoms in pregnancy week 17 and 32 as well as at six weeks and six months postpartum, mainly by use of the Swedish version of the Edinburgh Postnatal Depression Scale (EPDS). Furthermore, personality was assessed with the Swedish universities Scale of Personality (SSP) in pregnancy week 32. Evening cortisol levels in saliva were measured in pregnancy week 36 and at six weeks postpartum. Blood samples were obtained to measure corticotropin-releasing hormone levels (CRH) and to perform genetic analyses. The results of this thesis demonstrate that neuroticism is a strong and independent predictive factor of depressive symptoms at six weeks and six months postpartum, and has a significant mediatory role in the association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene (HSD11B1) and postpartum depression. Furthermore, women with postpartum depressive symptoms present with a dysregulated hypothalamic-pituitary-adrenal axis activity in terms of elevated cortisol levels postpartum, as well as elevated CRH levels in mid-gestation. In conclusion, this thesis develops current knowledge on several attributes of postpartum depression. Further studies are required to replicate and expand on these results, which would further contribute to early identification of women at risk of postpartum depression and adoption of proper interventions that may moderate the short- and long-term consequences of the disorder.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 81 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1178
Keyword [en]
Corticotropin-releasing hormone, cortisol, HPA-axis, HSD11B1, hydroxysteroid (11-beta) dehydrogenase 1, neuroticism, peripartum depression, personality, postpartum depression, rs12565406, stress
National Category
Obstetrics, Gynecology and Reproductive Medicine Psychiatry
Research subject
Obstetrics and Gynaecology; Psychiatry
Identifiers
URN: urn:nbn:se:uu:diva-274956ISBN: 978-91-554-9474-2 (print)OAI: oai:DiVA.org:uu-274956DiVA: diva2:899842
Public defence
2016-03-24, Rosénsalen, Kvinnokliniken, Ingång 95/96, Akademiska Sjukhuset, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2016-03-03 Created: 2016-01-26 Last updated: 2016-03-03
List of papers
1. Personality and risk for postpartum depressive symptoms
Open this publication in new window or tab >>Personality and risk for postpartum depressive symptoms
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2015 (English)In: Archives of Women's Mental Health, ISSN 1434-1816, E-ISSN 1435-1102, Vol. 18, no 3, 539-546 p.Article in journal (Refereed) Published
Abstract [en]

Postpartum depression (PPD) is a common childbirth complication, affecting 10-15 % of newly delivered mothers. This study aims to assess the association between personality factors and PPD. All pregnant women during the period September 2009 to September 2010, undergoing a routine ultrasound at Uppsala University Hospital, were invited to participate in the BASIC study, a prospective study designed to investigate maternal well-being. Depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS) while the Depression Self-Rating Scale (DSRS) was used as a diagnostic tool for major depression. Personality traits were evaluated using the Swedish Universities Scale of Personality (SSP). One thousand thirty-seven non-depressed pregnant women were included in the study. Non-depressed women reporting high levels of neuroticism in late pregnancy were at high risk of developing postpartum depressive symptoms (PPDSs) at 6 weeks and 6 months after delivery, even after adjustment for confounders (adjusted odds ratio (aOR) = 3.4, 95 % confidence interval (CI) 1.8-6.5 and adjusted odds ratio (aOR) = 3.9, 95 % CI 1.9-7.9). The same was true for a DSRS-based diagnosis of major depression at 6 months postpartum. Somatic trait anxiety and psychic trait anxiety were associated with increased risk for PPDS at 6 weeks (aOR = 2.1, 95 % CI 1.2-3.5 and aOR = 1.9, 95 % CI 1.1-3.1), while high scores of mistrust were associated with a twofold increased risk for PPDS at 6 months postpartum (aOR 1.9, 95 % CI 1.1-3.4). Non-depressed pregnant women with high neuroticism scores have an almost fourfold increased risk to develop depressive symptoms postpartum, and the association remains robust even after controlling for most known confounders. Clinically, this could be of importance for health care professionals working with pregnant and newly delivered women.

National Category
Obstetrics, Gynecology and Reproductive Medicine Psychiatry
Identifiers
urn:nbn:se:uu:diva-240437 (URN)10.1007/s00737-014-0478-8 (DOI)000354707100012 ()25369905 (PubMedID)
Funder
Swedish Research Council, 521-2010-3293
Available from: 2015-01-07 Created: 2015-01-07 Last updated: 2017-12-05
2. Prenatal and Postpartum Evening Salivary Cortisol Levels in Association with Peripartum Depressive Symptoms
Open this publication in new window or tab >>Prenatal and Postpartum Evening Salivary Cortisol Levels in Association with Peripartum Depressive Symptoms
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 8, e0135471Article in journal (Refereed) Published
Abstract [en]

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

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-262975 (URN)10.1371/journal.pone.0135471 (DOI)000360435500006 ()26322643 (PubMedID)
Funder
Swedish Research Council, 521-2013-2339Marianne and Marcus Wallenberg Foundation, MMW2011.0115
Available from: 2015-09-23 Created: 2015-09-23 Last updated: 2017-12-01Bibliographically approved
3. Mid-pregnancy corticotropin-releasing hormone levels in association with postpartum depressive symptoms
Open this publication in new window or tab >>Mid-pregnancy corticotropin-releasing hormone levels in association with postpartum depressive symptoms
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2016 (English)In: Depression and anxiety (Print), ISSN 1091-4269, E-ISSN 1520-6394, Vol. 33, no 11, 1023-1030 p.Article in journal (Refereed) Published
Abstract [en]

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

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

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

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

National Category
Psychiatry Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-274951 (URN)10.1002/da.22529 (DOI)000387396300005 ()27232288 (PubMedID)
Available from: 2016-01-26 Created: 2016-01-26 Last updated: 2017-11-30Bibliographically approved
4. Association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene and postpartum depression symptoms: the role of neuroticism
Open this publication in new window or tab >>Association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene and postpartum depression symptoms: the role of neuroticism
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background

Postpartum 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.

 

Aim

To 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 Methods

The 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.

 

Results

Sixty-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.

 

Conclusions

Neuroticism 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.

National Category
Psychiatry Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-274953 (URN)
Available from: 2016-01-26 Created: 2016-01-26 Last updated: 2016-02-09

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Iliadis, Stavros I

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