Sara Sylvén

Risk of postpartum depression in association with serum leptin and interleukin-6 levels at delivery: A nested case–control study within the UPPSAT cohort

Although postpartum depression (PPD) is a common condition, it often goes undiagnosed and untreated, with devastating consequences for the womans ability to perform daily activities, to bond with her infant and to relate to the infants father. Leptin, a protein synthesised in the adipose tissue and involved in regulation of food intake and energy expenditure has been related to depressive disorders, but studies report conflicting results. The aim of this study was to evaluate the association between serum leptin levels at the time of delivery and the subsequent development of postpartum depression in women, using data from a population-based cohort of delivering women in Uppsala, Sweden. Three hundred and forty seven women from which serum was obtained at the time of delivery filled out at least one of three structured questionnaires containing the Edinburgh Scale for Postnatal Depression (EPDS) at five days, six weeks and six months after delivery. Mean leptin levels at delivery did not significantly differ between the 67 cases of PPD and the 280 controls. Using linear regression analysis and adjusting for maternal age, body-mass index, smoking, interleukin-6 levels, duration of gestation and gender of the newborn, the EPDS scores at six weeks and six months after delivery were found to be negatively associated with leptin levels at delivery (p<0.05). Serum leptin levels at delivery were found to be negatively associated with self-reported depression during the first six months after delivery. No such association was found concerning serum IL-6 levels at delivery. If these finding are replicated by other studies, leptin levels at delivery could eventually serve as a biological marker for the prediction of postpartum depression.

Postpartum depression symptoms: a case–control study on monoaminergic functional polymorphisms and environmental stressors

Objective Postpartum depression (PPD) is an under diagnosed and under treated mood disorder, with negative impact on both the mother and the infants health. The aim of this study is to examine whether genetic variations in the monoaminergic neurotransmitter system, together with environmental stressors, contribute to the development of PPD symptoms. Methods This nested case–control study included 275 women from a population-based cohort of delivering women in Sweden. A questionnaire containing the Edinburgh Postnatal Depression Scale was collected at 6 weeks and 6 months postpartum. Three functional polymorphisms were genotyped, catechol-O-methyltransferase (COMT)-Val158Met, monoamine oxidase A (MAOA)-upstream variable number tandem repeat (uVNTR) and serotonin transporter linked polymorphic region (5HTT-LPR). Stressful life events, maternity stressors and previous psychiatric contact were considered as potential risk factors. Results COMT-Val158Met was significantly associated with PPD symptoms at 6 weeks, but not at 6 months postpartum. A significant gene–gene interaction effect was present between COMT-Val158Met and MAOA-uVNTR. In a gene–environment multivariate model, COMT-Val158Met, psychiatric contact and maternity stressors were significantly associated with PPD symptoms. Among those with history of psychiatric problems, the COMT-Val158Met and 5HTT-LPR risk variants were associated with PPD symptoms, whereas in the absence of previous psychiatric contact only maternity stressors were related to PPD symptoms. Conclusion The interaction effect between monoaminergic genes and environmental stressors is likely to contribute to vulnerability for PPD. The different patterns of association according to history of psychiatric problems, if replicated, might be helpful in screening strategies.

Prenatal and Postpartum Evening Salivary Cortisol Levels in Association with Peripartum Depressive Symptoms.

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.

Seasonality patterns in postpartum depression.

OBJECTIVE To investigate the possible association between postpartum depressive symptoms and season of delivery. STUDY DESIGN During 1 year, delivering women in the Uppsala University Hospital were asked to participate in the study by filling out 3 postpartum questionnaires containing the Edinburgh Postnatal Depression scale and questions assessing life style, medical history, breastfeeding, and social support. RESULTS Two thousand three hundred eighteen women participated. Women delivering in the last 3 months of the year had a significantly higher risk of self-reported depressive symptomatology both at 6 weeks (odds ratio, 2.02, 95% confidence interval, 1.32-3.10) and at 6 months after delivery (odds ratio, 1.82, 95% confidence interval, 1.15-2.88), in comparison to those delivering April-June, both before and after adjustment for possible confounders. CONCLUSION Women delivering during the last quartile of the year had a significantly higher risk for depressive symptoms 6 weeks and 6 months postpartum and would thus benefit from a closer support and follow-up after delivery.

Thyroid function tests at delivery and risk for postpartum depressive symptoms

Postpartum depression (PPD) is a common childbirth complication, which can have negative effects on both the newly delivered woman and her family. This condition is underdiagnosed and inadequately treated, while a biological diagnostic test is not yet available. Furthermore, postpartum thyroid dysfunction is common among new mothers, and some evidence point to an association between PPD and thyroid function disturbances. The aim of this study was to evaluate the possible association between serum levels of thyroid hormones at the time of delivery, and the later development of depressive symptoms, using data from a population based cohort of Swedish women. Blood samples were collected during delivery from 347 participating women, delivering at Uppsala University Hospital. The participating women filled in at least one of three structured questionnaires, containing the Edinburgh Postnatal Depression Scale (EPDS), at five days, six weeks and six months postpartum. A cut-off of 12 or more was applied on the EPDS, to identify cases of self-reported PPD and controls. Using a binary logistic regression model (adjusting for previous psychiatric contact, smoking during pregnancy, pre-pregnancy body mass index (BMI) and sleep), having a thyroid stimulating hormone (TSH) level over the clinical cut-off level of 4.0 mU/L was associated with increased risk for depressive symptoms at six months postpartum (OR 11.30, 95% CI 1.93-66.11). A ROC analysis revealed that the predictive variable (PV) had significant predictive ability for PPD at 6 months postpartum, given that the AUC was 0.764, and at a PV cut-off value of 6.33, the sensitivity and specificity were 76.2% and 69.4%, respectively. If these findings are replicated in future studies, they can have important clinical implications, since TSH determination is an inexpensive routine blood test, and its inclusion in a biological screening test for PPD involving other parameters would be tempting.

Premenstrual syndrome and dysphoric disorder as risk factors for postpartum depression

To investigate a possible association between postpartum depression and premenstrual symptoms.

Emotion Reactivity Is Increased 4-6 Weeks Postpartum in Healthy Women: A Longitudinal fMRI Study

Marked endocrine alterations occur after delivery. Most women cope well with these changes, but the postpartum period is associated with an increased risk of depressive episodes. Previous studies of emotion processing have focused on maternal–infant bonding or postpartum depression (PPD), and longitudinal studies of the neural correlates of emotion processing throughout the postpartum period in healthy women are lacking. In this study, 13 women, without signs of post partum depression, underwent fMRI with an emotional face matching task and completed the MADRS-S, STAI-S, and EPDS within 48 h (early postpartum) and 4–6 weeks after delivery (late postpartum). Also, data from a previous study including 15 naturally cycling controls assessed in the luteal and follicular phase of the menstrual cycle was used. Women had lower reactivity in insula, middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) in the early as compared to the late postpartum assessment. Insular reactivity was positively correlated with anxiety in the early postpartum period and with depressive symptoms late postpartum. Reactivity in insula and IFG were greater in postpartum women than in non-pregnant control subjects. Brain reactivity was not correlated with serum estradiol or progesterone levels. Increased reactivity in the insula, IFG, and MFG may reflect normal postpartum adaptation, but correlation with self-rated symptoms of depression and anxiety in these otherwise healthy postpartum women, may also suggest that these changes place susceptible women at increased risk of PPD. These findings contribute to our understanding of the neurobiological aspects of the postpartum period, which might shed light on the mechanisms underlying affective puerperal disorders, such as PPD.

Depressive symptoms postpartum among parents are associated with marital separation : A Swedish cohort study

Aims: To study whether there is an association between dyadic consensus, depressive symptoms, and parental stress during early parenthood and marital separation 6–8 years after childbirth, among couples in Sweden. Methods: At baseline, 393 couples were included. The couples answered three questionnaires, including: Dyadic consensus at 1 week post-partum, depressive symptoms at 3 months post-partum and parental stress at 18 months post-partum. The parents’ addresses were followed up after 6–8 years, to study the marital separation rate. Results: We found, 6–8 years after childbirth, that 20% of study couples were separated. Separation was associated with less dyadic consensus (mothers p < 0.001; fathers p < 0.001), depressive symptoms (mothers p = 0.022; fathers p = 0.041) and parental stress (mothers p = 0.002; fathers p = 0.040). The hazard ratio (HR) for marital separation was related to dyadic consensus for fathers (HR 0.51; 95% CI 0.28–0.92), depressive symptoms for mothers (HR 1.69; 95% CI 1.01–2.84) and fathers (HR 1.92; 95% CI 1.12–3.28), and the mother’s parental stress (HR 2.16; 95% CI 1.14–4.07). Conclusions: Understanding how dyadic consensus, depressive symptoms and parental stress are associated with marital separation is important for health professionals. It could be useful in developing interventions to provide parents with adequate support during pregnancy and early parenthood. This knowledge is also important for the public. Parents should get support in pregnancy and while bringing up children, which may help prevent marital separation and optimize conditions for the children.

Prefrontal activity during response inhibition decreases over time in the postpartum period

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

Sleep duration, depression, and oxytocinergic genotype influence prepulse inhibition of the startle reflex in postpartum women

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.