Hormonal transitions such as across pregnancy and postpartum may trigger depressive episodes in some women. It is not known why, but estrogen sensitivity may play a critical role. A preclinical human risk model showed that depressive symptoms induced by pharmacological sex-hormone manipulation is linked to increases in serotonin transporter (SERT) brain binding, which lowers serotonergic brain tone. It is currently unknown if these findings translates to women across pre- to postpartum transitions. This longitudinal project studies a group of women who will deliver by planned caesarian, thus permitting the collection of cerebrospinal fluid (csf) containing central markers of serotonergic signaling, at the latest point in pregnancy. The women are followed across late pregnancy, delivery and 6 months postpartum to illuminate relations between sex-hormones, stress-regulation, estradiol sensitivity, csf markers of neurotransmission, serotonin transporter genotype variance, and potential development of subclinical or manifest depressive symptoms. Further, markers of relevance for the infant brain development and stress-regulation will be obtained from placenta tissue and umbilical cord blood. A subgroup of 70 women will participate in a brain imaging program early postpartum (week 3-5), which includes an evaluation of brain activity and structure and in vivo molecular brain imaging serotonergic markers. Thus, serotonergic markers in csf can be combined with postpartum molecular brain imaging of key features of serotonin signaling. Women in the imaging program are selected based on variation in their level of mental distress immediately postpartum (day 2-5). The study's main hypothesis is that women with high-expressing SERT genotypes are more sensitive to peripartum hormonal transition in terms of changes in serotonergic tone and emergence of depressive symptoms and that such an association will be stronger in the presence of candidate gene transcript biomarkers of oestrogen sensitivity. A further hypothesis is that in vivo molecular brain imaging and csf based serotonergic markers will be associated with depressive symptoms both early and later postpartum. Ideally, this project will provide a rationale for future targeted prevention and/or treatment of perinatal depression in women at high risk, which holds grand potential to protect not only mother but also infant brain health long-term.
Motivation: Major depressive disorder (MDD) affects twice as many women as men and women are at an increased risk during hormonal transition phases such as pregnancy and birth. A highly relevant subpopulation within the mixed MDD diagnostic category comprises women who develop perinatal depression (PND). PND is defined as a depressive episode with onset during pregnancy or up to 4 weeks postpartum, however epidemiological studies show that the risk of developing depression is heightened for 6 months postpartum. PND affects 10-15% of mothers postpartum. Why certain women are at high risk of developing perinatal depression (PND) remains unclear but recent studies suggest that these women might be particularly sensitive to the transition from high levels of placenta-produced sex-steroids in pregnancy to the hormone withdrawal phase postpartum. Further, pharmacologically induced changes in ovarian sex-hormones can produce depressive symptoms in a subgroup of otherwise healthy women and that the emergence of depressive symptoms is linked to both estrogen fluctuations and increases in serotonin transporter (SERT) brain binding (which putatively lowers serotonergic brain tone). Intriguingly, common gene variants that index SERT expression levels show "gene BY environment" associations with risk for depression, such that high-expressing SERT genotypes render women more vulnerable to depressive symptoms early - but not late - postpartum in a "gene-dose" dependent manner. Further, DNA methylation and gene expression markers of estradiol sensitivity predispose to PND and are linked to the estradiol stimulation phase in the pharmacological manipulation of sex-steroids risk model, thus constituting a candidate biomarker for PND. It is currently unknown if estradiol sensitivity during pregnancy confers to PND risk through mechanism that (transiently) affect serotonergic tone in susceptible women. Changes in brain function late in pregnancy may extend to the early postpartum and shape how the brain integrates additional neurobiological changes that are associated with the postpartum hormonal withdrawal phase. This study will examine these mechanisms in a group of pregnant women that are followed from late pregnancy across early to late postpartum up to 6 month. Natural variation in SERT-genotypes provides a unique opportunity to specifically address the interaction between SERT-gene expression-capacity and estradiol exposure through pregnancy in processes driving changes in serotonergic tone, brain structure and activity, and mental health from late pregnancy to 6 months postpartum. The time-points comprise: basic program: 2-5 days postpartum, 6 weeks postpartum and 6 months postpartum for all participants and for the imaging program participants: 2-5 days postpartum, 3-5 weeks postpartum, 12 weeks postpartum, 6 months postpartum. By including women who undergo planned caesarean section, cerebrospinal fluid (CSF) can be obtained and thus, for the first time combine CSF markers of serotonergic tone and other transmitter systems (serotonin, 5-hydroxyindolacetic acid, other monoamines, γ-aminobutyric acid) with molecular brain imaging methods that index serotonergic tone (i.e. serotonin 4 receptor binding) Aims: * Determine if depressive symptoms from late pregnancy to 6 months postpartum map onto molecular brain imaging markers of serotonin signaling early postpartum (week 3-5), and evaluate if such markers and/or symptoms are dependent on serotonin transporter genotype and/or predicted by candidate gene transcription biomarkers for estrogen sensitivity. * Evaluate how markers of stress-regulation capacity, brain activity, brain structure (hippocampal volume) and central markers of neurotransmission are associated with the emergence of depressive symptoms in women postpartum. * Map the association between serotonin-4 receptor binding and cerebrospinal fluid markers of serotonergic tone (serotonin and 5-hydroxyindolacetic acid levels). * Determine if markers of mental distress in women during pregnancy and the postpartum period are associated with infant markers of stress-regulation and serotonergic signaling in placenta and umbilical cord blood. Hypotheses: * Women with high-expressing SERT genotypes are more sensitive to estradiol exposure in late pregnancy in terms of changes in proxies for serotonergic tone (PET imaging or csf based) and emergence of depressive symptoms in late pregnancy and/or postpartum and such an association will be stronger in the presence of candidate gene transcript PND biomarkers. * CSF levels of 5-hydroxyindolacetic acid are associated with serotonin 4 receptor brain PET (Positron Emission Tomography) binding. Study design: 150 pregnant women between 18-40 years of age who deliver by planned caesarean section, due to breech presentation of the fetus or previous caesarean section, will be included in a longitudinal study. Participants will be recruited at the midwife clinic of Rigshospitalet, Copenhagen, Denmark. Based on natural variation in European populations the expected distribution of high vs. low expressing SERT genotypes is 40/60, respectively, thus genotype status can be included in the analysis structure. Self-reported psychometrics and questionnaires will be collected online at inclusion, across the pre- to postpartum transition and up to 6 months postpartum (basic program: 2-5 days postpartum, 6 weeks postpartum and 6 months postpartum; imaging program: 2-5 days postpartum, 3-5 weeks postpartum, 12 weeks postpartum, 6 months postpartum). CSF will be collected as part of the anesthetic procedures for a planned caesarean section, thus avoiding any additional invasive procedures. CSF markers of serotonergic tone (serotonin and its main metabolite, 5-HIAA) will be measured by HPLC techniques. Corresponding blood samples for determining relevant biomarkers (sex-steroids, DNA, mRNA and microRNA) and saliva for hypothalamic-pituitary-adrenal axis dynamics, will be taken just before the planned caesarean section. Hair from mother and infant will be collected around delivery for further cortisol analyses. Placenta tissue and umbilical cord blood will also be collected for determining relevant markers of serotonergic and hypothalamic-pituitary-adrenal axis functioning. A subgroup of the study cohort selected towards high (N=35) or low risk for later manifest PND (N=35), based on symptoms of mental distress 2-5 days postpartum (in-house interview, high-risk scores correspond to at least 12 on the Kennerley Maternity Blues Questionnaire and at least 8 on Stein's Maternity Blues Scale), will participate in an extended brain imaging program. This program will include 5-HT4R (\[11C\]SB207145) PET, structural MRI, functional MRI (including emotional processing, reward processing and resting state fMRI), neuropsychological testing and face to face rating of mental state with a semi-structured interview (HAM-D17). The study includes long-term follow-up at six months. Collected data will enter the Center for Integrated Molecular Brain Imaging database, thus providing a basis for longitudinal follow-up, data sharing and crossvalidation. Statistics: Power calculations based on inter-subject variability of the 5-HT4R show that an imaging group size of 35 is required to detect a 15% difference with a power of 0.8 for the brain regions of interest. With the full cohort number of 150 and due to oversampling of high and low risk women, about 25 women are expected to develop manifest PND episodes and more will display subclinical depressive symptoms, which will allow for correlation analyses with relevant outcome parameters including the candidate gene transcript based biomarker of estrogen sensitivity. Highly correlated self-reported psychometric outcomes will be included in a latent variable construct of self-reported mental state (composite measure) using structural equation modelling. Ethics: The PET scans convey no known risk for adults. Infants will not be exposed to radiation and will be nursed by special staff or a close relative while the mother is scanned. Participants who develop levels of mental distress or depressive symptoms that approach clinical thresholds will be referred to relevant and timely psychiatric care. The study has been approved by the local ethics committee.
Study Type
OBSERVATIONAL
Enrollment
100
Peripartum transition from pregnant to postpartum state
Rigshospitalet
Copenhagen, Denmark
Depressive symptoms
Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Total group
Time frame: Week 3-6 postpartum
Depressive symptoms
Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group
Time frame: Week 3-6 postpartum
Gene transcript and DNA methylation markers of estrogen sensitivity
116 a priori defined gene transcripts, which where differentially expressed in third trimester of women who later developed perinatal depression with postpartum onset relative to pregnant women who did not and to other depressed (reference Mehta et al, 2014, Psychological Medicine) and confirmed to be coupled to estrogen fluctuations (Mehtaet al. 2018 British Journal of Psychiatry) will be evaluated in the total group. Also DNA methylation of the genes of these transcripts will be determined and analysed in terms of their predictive value (above chance) for perinatal depression.
Time frame: Prior to caesarean section
Cerebral serotonin 4 receptor binding postpartum
Latent variable construct of brain 5-HT4R level based on quantification of 5-HT4R binding from 11C-SB207145 positron emission tomography in primary volumes of interest; neocortex, nucleus caudatus, putamen and hippocampus. Assessed in imaging group.
Time frame: Week 3-6 postpartum
CSF levels of GABA
Assessed in total group
Time frame: On day of caesarean section
CSF levels of serotonin metabolite (5-HIAA)
Assessed in total group
Time frame: On day of caesarean section
Cortisol awakening response
Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.
Time frame: Week 3-6 postpartum
Hair cortisol level mothers
Provides an estimate of cortisol exposure up to 6 months prior to delivery, total group
Time frame: On day of caesarean section.
Hair cortisol level newborns
Provides an estimate of fetal cortisol exposure, infants from total group
Time frame: Day 0-5 postpartum.
Hippocampal volumes
Hippocampal brain volume (including hippocampus) from structural MRI, imaging group.
Time frame: Week 3-6 postpartum.
functional MRI response to reward
fMRI (BOLD response) based assessment of brain activity in response to reward, relative to non-reward, stimuli. Assessed in imaging cohort
Time frame: Week 3-6 postpartum.
Resting state functional connectivity MRI
rsfMRI based spontaneous co-fluctuations in low frequency BOLD signal, (functional connectivity). Assessed with rsfMRI scan in the resting state, i.e. non-goal oriented spontaneous thought and awake. Assessed in imaging group.
Time frame: Week 3-6 postpartum
Change in epigenetic SERT status
Change in epigenetic SERT status from late pregnancy to postpartum week 3-6.
Time frame: From just before delivery to 3-6 weeks postpartum
Concentration of inflammatory markers, i.e hsCRP and immunoactive cytokines, in peripheral blood
Composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group
Time frame: At week 3-6
functional MRI response to emotional faces
fMRI (BOLD response) based assessment of brain activity to emotionally salient, relative to neutral, stimuli. Assessed in imaging cohort.
Time frame: Week 3-6 postpartum.
Depressive symptoms
Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group
Time frame: Day 3-5 postpartum
Depressive symptoms
Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group
Time frame: Week 12 postpartum
Depressive symptoms
Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Assessed in total group
Time frame: Day 3-5 postpartum
Depressive symptoms
Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Assessed in all
Time frame: 6 months postpartum
CSF levels of serotonin
Assessed in total group
Time frame: On day of caesarean section
CSF levels of dopamine metabolites
Assessed in total group
Time frame: On day of caesarean section
CSF levels of noradrenaline metabolites
Assessed in total group
Time frame: On day of caesarean section
CSF levels of inflammatory markers
Composite measure of IFN-c, IFN-alfa TNF-alfa og IL-6, in total group
Time frame: On day of caesarean section
Estradiol level
Estradiol level in peripheral blood, total group
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Time frame: Prior to caesarean section.
Estradiol level
Estradiol level peripheral blood, total group
Time frame: At week 3-6 postpartum.
Change in estradiol level
Estradiol change pre- to postpartum, peripheral blood total group
Time frame: From baseline (caesarean section to week 3-6 postpartum)
Progesterone level
Progesterone level in peripheral blood
Time frame: Prior to caesarean section.
Progesterone level
Progesterone level in peripheral blood
Time frame: At week 3-6 postpartum.
Change in progesterone level
Progesterone change pre- to postpartum, peripheral blood total group
Time frame: From baseline (caesarean section to week 3-6 postpartum)
Allopregnanolone level
Allopregnanolone level in peripheral blood
Time frame: Prior to caesarean section.
Allopregnanolone level
Allopregnanolone level in peripheral blood
Time frame: At week 3-6 postpartum.
Change in allopregnanolone level
Change in allopregnanolone level in peripheral blood
Time frame: From baseline (caesarean section to week 3-6 postpartum)
Change in cortisol level
Cortisol change pre- to postpartum, peripheral blood total group
Time frame: From baseline (caesarean section to week 3-6 postpartum)
Cortisol awakening response
Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.
Time frame: Week 12 postpartum
Cortisol awakening response
Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.
Time frame: Prior to caesarean section
Change in cortisol awakening response
Change in cortisol awakening response, from caesarean section to 3-6 weeks postpartum.
Time frame: ´From baseline (caesarean section to week 3-6 postpartum)
DNA methylation of the SERT gene
Methylation status for the SERT gene, total group
Time frame: Prior to caesarean section
DNA methylation of the SERT gene
DNA Methylation status for the SERT gene, total group
Time frame: Week 3-6 postpartum
DNA methylation of the FK506-binding protein 51 (FKBP5) gene
Methylation status for the FK506-binding protein 51 (FKBP5) gene, total group
Time frame: Prior to caesarean section.
DNA methylation of the FK506-binding protein 51 (FKBP5) gene
Methylation status for the FK506-binding protein 51 (FKBP5) gene, total group
Time frame: Week 3-6 postpartum
Change in DNA methylation of the FK506-binding protein 51 (FKBP5) gene
Change in methylation status for the FK506-binding protein 51 (FKBP5) gene from late pregnancy to postpartum week 3-6.
Time frame: From baseline (caesarean section to week 3-6 postpartum)
DNA methylation of the glucocorticoid receptor gene
Methylation status for the glucocorticoid receptor gene, total group
Time frame: Prior to caesarean section.
DNA methylation of the glucocorticoid receptor gene
Methylation status for the glucocorticoid receptor gene, total group
Time frame: Week 3-6 postpartum
Change in DNA methylation of the glucocorticoid receptor gene
Change in methylation status for the glucocorticoid receptor gene from late pregnancy to postpartum week 3-6.
Time frame: From baseline (caesarean section to week 3-6 postpartum)
DNA methylation of the COMT gene
Methylation status for the COMT gene, total group
Time frame: Prior to caesarean section.
DNA methylation of the COMT gene
Methylation status for the COMT gene, total group
Time frame: Week 3-6 postpartum
Change in DNA methylation of the COMT gene
Change in methylation status for the COMT gene from just before delivery to 3-6 weeks postpartum
Time frame: From baseline (caesarean section to week 3-6 postpartum)
DNA methylation of the MAO-A gene
Methylation status for the MAO-A gene, total group
Time frame: Prior to caesarean section.
Change in DNA methylation of the MAO-A gene
Change in methylation status for the MAO-A gene, total group
Time frame: From baseline (caesarean section to week 3-6 postpartum)
DNA methylation of the MAO-A gene
Methylation status for the MAO-A gene, total group
Time frame: Week 3-6 postpartum
DNA methylation of the oxytocin receptor gene
Methylation status for the oxytocin receptor gene, total group
Time frame: Prior to caesarean section.
DNA methylation of the oxytocin receptor gene
Methylation status for the oxytocin receptor gene, total group
Time frame: Week 3-6 postpartum
Change in DNA methylation of the oxytocin receptor gene
Change in methylation status for the oxytocin receptor gene, total group
Time frame: From baseline (caesarean section to week 3-6 postpartum)
DNA methylation of the oxytocin gene
Methylation status for the oxytocin gene, total group
Time frame: Prior to caesarean section.
DNA methylation of the oxytocin gene
Methylation status for the oxytocin gene, total group
Time frame: Week 3-6 postpartum
Change in DNA methylation of the oxytocin gene
Change methylation status for the oxytocin gene, total group
Time frame: From baseline (caesarean section to week 3-6 postpartum)
Systemic inflammation peripheral blood hsCRP and immunoactive cytokines
Composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group
Time frame: Prior to caesarean section.
Change in systemic inflammation peripheral blood hsCRP and immunoactive cytokines
Change in composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group
Time frame: From baseline (caesarean section to week 3-6 postpartum
Self reported family history of mood disorders
Family History Assessment Module (OS-FHAM). Number of first degree relatives with a history of depressive episodes or bipolar disorder. Total group.
Time frame: Day 3-5 postpartum or before
Self reported impulsiveness score
Barratt Impulsiveness Scale (BIS-11), self-reported. Range: 30-120. Total group.
Time frame: Day 3-5 postpartum or before
Self reported Neuroticism score from NEO personality questionnaire
NEO-PI-R - Revised NEO Personality Inventory, self-reported. Participants may score 20-80 for each of the personality traits: openness, conscientiousness, extraversion, agreeableness, and neuroticism. The higher the score, the more prominent is the personality trait. Total group.
Time frame: Day 3-5 postpartum or before
Self reported parental bonding quality
Parental bonding instrument (PBI), both parents, self-reported. Total group.
Time frame: Day 3-5 postpartum or before
Self-reported perceived stress
Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.
Time frame: Day 3-5 postpartum
Self-reported perceived stress
Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.
Time frame: Week 3-6 postpartum
Change in self-reported perceived stress
Change in Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.
Time frame: Change from day 3-5 to week 3-6 postpartum
Self-reported anhedonia
Snaith-Hamilton Pleasure Scale (SHAPS), range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.
Time frame: Day 3-5 postpartum
Self-reported anhedonia
Snaith-Hamilton Pleasure Scale (SHAPS), range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.
Time frame: Week 3-6 postpartum
Change in self-reported anhedonia
Change in Snaith-Hamilton Pleasure Scale (SHAPS) score, range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.
Time frame: Change from day 3-5 to week 3-6 postpartum
Self-reported rumination
Rumination Response Scale (RRS), range 22-88, a score of 22 indicates no ruminative symptoms. Total group.
Time frame: Day 3-5 postpartum
Self-reported rumination
Rumination Response Scale (RRS), range 22-88, a score of 22 indicates no ruminative symptoms. Total group.
Time frame: Week 3-6 postpartum
Change in elf-reported rumination
Change in Rumination Response Scale (RRS) score, range 22-88, a score of 22 indicates no ruminative symptoms. Total group.
Time frame: Change from day 3-5 to week 3-6 postpartum
Self-reported mood
Profile of Mood States (POMS), range 0-260, a score of 0 indicates no mood disturbance. Total group.
Time frame: Day 3-5 postpartum
Self-reported mood
Profile of Mood States (POMS), range 0-260, a score of 0 indicates no mood disturbance. Total group.
Time frame: Week 3-6 postpartum
Change in self-reported mood
Change in Profile of Mood States (POMS) score, range 0-260, a score of 0 indicates no mood disturbance. Total group.
Time frame: Change from day 3-5 to week 3-6 postpartum
Self-reported sleep quality
Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.
Time frame: Day 3-5 postpartum
Self-reported sleep quality
Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.
Time frame: Week 3-6 postpartum
Change in self-reported sleep quality
Change in Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.
Time frame: Change from day 3-5 to week 3-6 postpartum
Self-reported psychiatric symptoms
Brief symptom Inventory-53 item (BSI-53), range 0-212, increasing score means worsening of symptoms.Total group.
Time frame: Day 3-5 postpartum
Self-reported psychiatric symptoms
Brief symptom Inventory-53 item (BSI-53), range 0-212, increasing score means worsening of symptoms.Total group.
Time frame: Week 3-6 postpartum
Change in self-reported psychiatric symptoms
Change in Brief symptom Inventory-53 item (BSI-53) score, range 0-212, increasing score means worsening of symptoms.Total group.
Time frame: Change from day 3-5 to week 3-6 postpartum
Self-reported well-being
WHO-5 well-being index, range 0-100, low score means less well-being. Total group.
Time frame: Day 3-5 postpartum
Self-reported well-being
WHO-5 well-being index, range 0-100, low score means less well-being. Total group.
Time frame: Week 3-6 postpartum
Change in self-reported well-being
Change in WHO-5 well-being index, range 0-100, low score means less well-being. Total group.
Time frame: Change from day 3-5 to week 3-6 postpartum
Self-reported anxiety
State Trait Anxiety Inventory (STAI-AD-D), state and trait subscales each have a range of 20-80, 20 means no anxiety. Total group.
Time frame: Day 3-5 postpartum
Self-reported anxiety
State Trait Anxiety Inventory (STAI-AD-D), state subscale range 20-80, 20 means no anxiety. Total group.
Time frame: Week 3-6 postpartum
Change in self-reported anxiety
Change in State Trait Anxiety Inventory (STAI-AD-D) score, state subscale range 20-80, 20 means no anxiety. Total group.
Time frame: Change from day 3-5 to week 3-6 postpartum
Self-reported obsessive and compulsive symptoms
Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.
Time frame: Day 3-5
Self-reported obsessive and compulsive symptoms
Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.
Time frame: Week 3-6 postpartum
Change in self-reported obsessive and compulsive symptoms
Change in Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.
Time frame: Change from day 3-5 to week 3-6 postpartum
Performance on Simple Reaction Time
Performance on Simple Reaction Time, in imaging cohort.
Time frame: Week 3-6 postpartum
Gray matter brain volume prefrontal cortex and anterior cingulate cortex
Gray matter brain volume prefrontal cortex and anterior cingulate cortex
Time frame: At week 3-6 postpartum
Serotonergic turnover in placenta
Composite measure of serotonin, tryptophan og tryptofan hydroxylase levels relative to 5-HIAA, in placenta sample. Infants from total group
Time frame: At delivery.
11-beta-hydroxysteroid dehydrogenase type 2 activity in placenta
11-beta-hydroxysteroid dehydrogenase type 2 activity in placenta. Infants from total group
Time frame: At delivery
Methylation status of genes relevant for stress-hormone regulation in placenta
Composite measure of methylation status for the FKBP5, glucocorticoid receptor, 11-beta hydroxysteroid dehydrogenase type 2 genes. Infants from total group
Time frame: At delivery
Methylation status of genes related to serotonergic signaling in placenta
Composite measure of the methylation status for monoamine oxidase, serotonin receptor and serotonin transporter genes. Infants from total group
Time frame: At delivery
Methylation status and gene transcript profiles of relevance for early brain development and stress regulation in newborn infants
Composite measure of methylation status and gene transcript profiles of Glucocorticoid receptor, FKBP5, oxytocin and oxytocin receptors, Brain-derived neurotrophic factor (BDNF) genes. Assessed in blood from umbilical cord blood sample from infants, total group.
Time frame: At delivery.