Dataset Information

The effects of antenatal depression and antidepressant treatment on placental gene expression.

ABSTRACT: The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene expression study on the fetal side of the placenta to investigate gene expression patterns in mothers with antenatal depression and in mothers using antidepressant treatment during pregnancy. Placental samples from mothers with normal pregnancies, from mothers with antenatal depression, and from mothers using antidepressants were collected. We performed a pilot microarray study to investigate alterations in the gene expression and selected several genes from the microarray for biological validation with qPCR in a larger sample. In mothers with antenatal depression 108 genes were differentially expressed, whereas 109 genes were differentially expressed in those using antidepressants. Validation of the microarray revealed more robust gene expression differences in the seven genes picked for confirmation in antidepressant-treated women than in depressed women. Among the genes that were validated ROCK2 and C12orf39 were differentially expressed in both depressed and antidepressant-treated women, whereas ROCK1, GCC2, KTN1, and DNM1L were only differentially expressed in the antidepressant-treated women. In conclusion, antenatal depression and antidepressant exposure during pregnancy are associated with altered gene expression in the placenta. Findings on those genes picked for validation were more robust among antidepressant-treated women than in depressed women, possibly due to the fact that depression is a multifactorial condition with varying degrees of endocrine disruption. It remains to be established whether the alterations found in the gene expression of the placenta are found in the fetus as well.

SUBMITTER: Olivier JD

PROVIDER: S-EPMC4292720 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The effects of antenatal depression and antidepressant treatment on placental gene expression.

Olivier Jocelien D A JD Åkerud Helena H Skalkidou Alkistis A Kaihola Helena H Sundström-Poromaa Inger I

Frontiers in cellular neuroscience 20150113

The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene expression study on the fetal side of the placenta to investigate gene expression patterns in mothers with antenatal depression and in mothers using antidepressant treatment during pregnancy. Placental samp ...[more]

PMID: 25628539

Similar Datasets

Project description: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.

Project description:Adverse experiences and chronic stress are well-known risk factors for the development of major depression, and an impaired stress response regulation is frequently observed in acute depression. Impaired glucocorticoid receptor (GR) signalling plays an important role in these alterations, and a restoration of GR signalling appears to be a prerequisite of successful antidepressant treatment. Variants in genes of the stress response regulation contribute to the vulnerability to depression in traumatized subjects. Consistent findings point to an important role of FKBP5, the gene expressing FK506-binding protein 51 (FKBP51), which is a strong inhibitor of the GR, and thus, an important regulator of the stress response. We investigated the role of FKBP5 and FKB51 expression with respect to stress response regulation and antidepressant treatment outcome in depressed patients. This study included 297 inpatients, who participated in the Munich Antidepressant Response Signature (MARS) project and were treated for acute depression. In this open-label study, patients received antidepressant treatment according to the attending doctor's choice. In addition to the FKBP5 genotype, changes in blood FKBP51 expression during antidepressant treatment were analyzed using RT-PCR and ZeptoMARKTM reverse phase protein microarray (RPPM). Stress response regulation was evaluated in a subgroup of patients using the combined dexamethasone (dex)/corticotropin releasing hormone (CRH) test. As expected, increased FKBP51 expression was associated with an impaired stress response regulation at baseline and after six weeks was accompanied by an elevated cortisol response to the combined dex/CRH test. Further, we demonstrated an active involvement of FKBP51 in antidepressant treatment outcome. While patients responding to antidepressant treatment had a pronounced reduction of FKBP5 gene and FKBP51 protein expression, increasing expression levels were observed in nonresponders. This effect was moderated by the genotype of the FKBP5 single nucleotide polymorphism (SNP) rs1360780, with carriers of the minor allele showing the most pronounced association. Our findings demonstrate that FKBP5 and, specifically, its expression product FKBP51 are important modulators of antidepressant treatment outcome, pointing to a new, promising target for future antidepressant drug development.

Project description:While maternal mental health strongly influences neurodevelopment and health in the offspring, little is known about the determinants of inter-individual variation in the mental health of mothers. Likewise, the in utero biological pathways by which variation in maternal mental health affects offspring development remain to be defined. Previous studies implicate lipids, consistent with a known influence on cognitive and emotional function, but the relevance for maternal mental health and offspring neurodevelopment is unclear. This study characterizes the placental and circulatory lipids in antenatal depression, as well as socio-emotional outcomes in the offspring. Targeted liquid chromatography-mass spectrometry covering 470 lipid species was performed on placenta from 186 women with low (n = 70) or high (n = 116) levels of antenatal depressive symptoms assessed using the Edinburgh Postnatal Depression Scale at 26 weeks' gestation. Child socio-emotional outcomes were assessed from the Child Behavior Check List (CBCL) at 48 months. Seventeen placental lipid species showed an inverse association with antenatal EPDS scores. Specifically, lower levels of phospholipids containing LC-PUFAs: omega-3 docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and omega-6 arachidonic acid (AA) were significantly associated with depressive symptoms. Additional measurement of LC-PUFA in antenatal plasma samples at mid-gestation confirmed the reduced circulation of these specific fatty acids in mothers. Reduced concentration of the placental phospholipids also predicted poorer socio-emotional outcomes in the offspring. This study provides new insights into the role of the materno-fetal lipid cross-talk as a mechanism linking maternal mental health to that of the offspring. These findings show the potential utility of nutritional approaches among pregnant women with depressive symptoms to reduce offspring risk for later socio-emotional problems.

Dataset Information

The effects of antenatal depression and antidepressant treatment on placental gene expression.

Publications

The effects of antenatal depression and antidepressant treatment on placental gene expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets