| 1. |
- Axfors, Cathrine, et al.
(författare)
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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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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:10
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Tidskriftsartikel (refereegranskat)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. |
- Castro, Rita Amiel, et al.
(författare)
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Pregnancy-related hormones and COMT genotype : Associations with maternal working memory
- 2021
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 132
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Tidskriftsartikel (refereegranskat)abstract
- Women experience different degrees of subjective cognitive changes during pregnancy. The exact mechanism underlying these changes is unknown, although endocrine alterations and genetics may be contributing factors. We investigated whether multiple pregnancy-related hormones were associated with working memory function assessed with the Digit Span Test (DST) in late pregnancy. Moreover, we examined whether the catechol-Omethyltransferase (COMT) genotype, previously related to working memory, was an effect modifier in this association. In this population-based panel study, we recorded psychiatric history, medication use, socio-demographic characteristics, and psychological well-being, gathered blood and saliva samples, and administered the DST at gestational weeks 35-39 (N = 216). We conducted multivariate linear regressions with DST as outcome, with different hormones and COMT genotype, adjusting for covariates including maternal age, BMI, education, depressive symptoms, and parity. We repeated these analyses excluding women with elevated depressive symptoms. Higher DST total scores were associated with increased free estradiol concentrations (B = 0.01, p = 0.03; B = 0.01, p = 0.02) in all participants and in participants without depressive symptoms, respectively, whereas DST forward was positively associated with free estradiol only in women without depressive symptoms (B = 0.01, p = 0.04). Lower total testosterone concentrations (B = -0.03, p = 0.01) enhanced DST backward performance in non-depressed women. Maternal higher education was significantly associated with the DST subscales in all participants. No significant differences emerged when considering the COMT genotype. Our results suggest differential associations of free estradiol and total testosterone levels with working memory function in late pregnancy.
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| 3. |
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| 4. |
- Edvinsson, Åsa, 1982-, et al.
(författare)
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Placental glucocorticoid receptors are not affected by maternal depression or SSRI treatment.
- 2020
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 125:1, s. 30-36
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prenatal depression is common, with an estimate that up to one in five pregnant women suffers from depressive symptoms. Maternal depression is associated with poor pregnancy outcomes such as preterm birth and low birth-weight. Such outcomes possibly affect offspring development. Previous studies suggest placental RNA levels of the glucocorticoid receptor are altered by maternal depression or anxiety; this stress may affect the placenta of male and female foetuses differently. However, it is unknown if the protein levels and activity of this receptor are additionally affected in women with depressive symptoms or being pharmacologically treated for depression.Methods: In this study, we investigated whether the glucocorticoid receptor (NR3C1) in the placenta is affected by maternal depression and/or selective serotonin reuptake inhibitor (SSRIs) treatment. Placentas from 45 women with singleton, term pregnancies were analysed by Western blot to determine glucocorticoid receptor levels, and by DNA-binding capacity to measure glucocorticoid receptor activation.Results: There were no differences in levels of the glucocorticoid receptor or activity between groups (control, depressive symptoms, and SSRI treatment; n = 45). Similarly, there was no difference in placental glucocorticoid receptor levels or activity dependent upon foetal sex.Conclusion: Maternal depression and SSRI treatment do not affect the glucocorticoid receptors in the placenta.
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| 5. |
- Edvinsson, Åsa, 1982-, et al.
(författare)
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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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Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393 .- 1471-2393. ; 19
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Tidskriftsartikel (refereegranskat)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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| 6. |
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| 7. |
- Kunovac Kallak, Theodora, 1985-, et al.
(författare)
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Differential gene expression in two consecutive pregnancies between same sex siblings and implications on maternal constraint
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate how placental gene expression differs in two consecutive pregnancies in same sex siblings, and its possible association with the "maternal constraint" hypothesis. Material was gathered from the BASIC study (Biological, Affect, Stress, Imaging, and Cognition in Pregnancy and the Puerperium), a population based prospective study that was started in 2009 in Uppsala. Over 900 specimens of placenta biopsies were collected and out of these 10 women gave birth twice, to the same sex child, and were included in this study. The total RNA was isolated and prepared from frozen villous tissue from the placenta and further analyzed by use of Ion AmpliSeq Human Transcriptome Gene Expression kit. A total of 234 genes differed significantly between the first and second pregnancy placentas, when adjusting for delivery mode, maternal BMI and gestational age. Of special interest was the down-regulated group of genes in the second pregnancy. Exemplified by Pentraxin 3, SRY-Box Transcription Factor 9, and Serum Amyloid A1, which all were associated with biological processes involved in the immune system and inflammation. Further, protein-protein interaction analysis visualized them as hub genes interacting with several of the other differentially expressed genes. How these altered gene expressions affect maternal constraint during pregnancy needs further validation in lager study cohorts and also future validation in functional assays.
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| 8. |
- Kunovac Kallak, Theodora, 1985-, et al.
(författare)
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DNA methylation in cord blood in association with prenatal depressive symptoms
- 2021
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Ingår i: Clinical Epigenetics. - : BioMed Central (BMC). - 1868-7083 .- 1868-7075. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prenatal symptoms of depression (PND) and anxiety affect up to every third pregnancy. Children of mothers with mental health problems are at higher risk of developmental problems, possibly through epigenetic mechanisms together with other factors such as genetic and environmental. We investigated DNA methylation in cord blood in relation to PND, taking into consideration a history of depression, co-morbidity with anxiety and selective serotonin reuptake inhibitors (SSRI) use, and stratified by sex of the child. Mothers (N = 373) prospectively filled out web-based questionnaires regarding mood symptoms and SSRI use throughout pregnancy. Cord blood was collected at birth and DNA methylation was measured using Illumina MethylationEPIC array at 850 000 CpG sites throughout the genome. Differentially methylated regions were identified using Kruskal-Wallis test, and Benjamini-Hochberg adjusted p-values < 0.05 were considered significant.Results: No differential DNA methylation was associated with PND alone; however, differential DNA methylation was observed in children exposed to comorbid PND with anxiety symptoms compared with healthy controls in ABCF1 (log twofold change - 0.2), but not after stratification by sex of the child. DNA methylation in children exposed to PND without SSRI treatment and healthy controls both differed in comparison with SSRI exposed children at several sites and regions, among which hypomethylation was observed in CpGs in the promoter region of CRBN (log2 fold change - 0.57), involved in brain development, and hypermethylation in MDFIC (log2 fold change 0.45), associated with the glucocorticoid stress response.Conclusion: Although it is not possible to assess if these methylation differences are due to SSRI treatment itself or to more severe depression, our findings add on to existing knowledge that there might be different biological consequences for the child depending on whether maternal PND was treated with SSRIs or not.
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| 9. |
- Kunovac Kallak, Theodora, 1985-, et al.
(författare)
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Maternal prenatal depressive symptoms and toddler behavior : an umbilical cord blood epigenome-wide association study
- 2022
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Children of mothers with prenatal depressive symptoms (PND) have a higher risk of behavioral problems; fetal programming through DNA methylation is a possible underlying mechanism. This study investigated DNA methylation in cord blood to identify possible "at birth" signatures that may indicate susceptibility to behavioral problems at 18 months of age. Cord blood was collected from 256 children of mothers who had self-reported on symptoms of depression during pregnancy and the behavior of their child at 18 months of age. Whole genome DNA methylation was assessed using Illumina MethylationEPIC assay. The mother and child pairs were categorized into four groups, based on both self-reported depressive symptoms, PND or Healthy control (HC), and scores from the Child Behavior checklist (high or low for internalizing, externalizing, and total scores). Adjustments were made for batch effects, cell-type, and clinical covariates. Differentially methylated sites were identified using Kruskal-Wallis test, and Benjamini-Hochberg adjusted p values < 0.05 were considered significant. The analysis was also stratified by sex of the child. Among boys, we observed higher and correlated DNA methylation of one CpG-site in the promoter region of TPP1 in the HC group, with high externalizing scores compared to HC with low externalizing scores. Boys in the PND group showed lower DNA methylation in NUDT15 among those with high, compared to low, internalizing scores; the DNA methylation levels of CpGs in this gene were positively correlated with the CBCL scores. Hence, the differentially methylated CpG sites could be of interest for resilience, regardless of maternal mental health during pregnancy. The findings are in a relatively healthy study cohort, thus limiting the possibility of detecting strong effects associated with behavioral difficulties. This is the first investigation of cord blood DNA methylation signs of fetal programming of PND on child behavior at 18 months of age and thus calls for independent replications.
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| 10. |
- Lager, Susanne, et al.
(författare)
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Alcohol consumption habits and associations with anxiety or depressive symptoms postpartum in women with high socioeconomic status in Sweden.
- 2022
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Ingår i: Archives of Women's Mental Health. - : Springer Nature. - 1434-1816 .- 1435-1102.
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Tidskriftsartikel (refereegranskat)abstract
- Postpar tum depression and anxiety are common among new mothers. It is well-established that in the general population alcohol use is associated with depression and anxiety. Linking alcohol consumption to symptoms of postpartum depression (PPDS) or postpartum anxiety (PPAS) is presently less established. This study aims to determine if alcohol consumption pre-pregnancy, 6 weeks postpartum, 6 months postpartum, or changes in alcohol consumption are associated with PPDS or PPAS. Longitudinal data on 3849 women from a Swedish perinatal cohort were analyzed using logistic regression analyses for associations between alcohol consumption and symptoms of anxiety or depression, as assessed with the Edinburgh Postnatal Depression Scale. There was no association between pre-pregnancy drinking habits and PPDS (p = 0.588, n = 2479) or PPAS (p = 0.942; n = 2449) at 6 weeks postpartum. Similarly, no associations were observed between concurrent drinking habits at 6 weeks postpartum and PPAS (p = 0.070, n = 3626), 6 months postpartum and PPDS (0.647, n = 3461) or PPAS (p = 0.700, n = 3431). However, there was an association between drinking habits at 6 weeks postpartum and concurrent PPDS (p = 0.047, n = 3659). In conclusion, robust associations were not found between postpartum alcohol consumption and mood symptoms. This lack of association between poor mental health and risk behaviors in new mothers could be interpreted as a result of long-term policy work and high participation in Swedish maternity care. Future studies need to address these research questions in more diverse socio-cultural contexts.
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