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Completed

NCT Number: NCT03795688

The Role of Sex Steroids and Serotonin Brain Dynamics in Perinatal Mental Health

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.

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Key information

Conditions

Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders Perinatal Depression

Age range

18 year–40 year

Sex eligibility

Female

Study type

Observational

Primary location

Rigshospitalet

Copenhagen, 2100, Denmark

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18-40 years
  • Healthy pregnant women planned to deliver by caesarean section due to breech position of the fetus or previous caesarean section.

Exclusion criteria

  • Current or previous severe psychiatric disorder such as psychotic disorders, eating disorder and bipolar disorder or current or previous psychiatric disorder requiring hospitalization.
  • Current or previous neurological diseases, severe somatic disease, severe postpartum hemorrhage or use of medication that can interfere with study outcomes
  • Severe disease or malformations in infants
  • Obesity or underweight (pre-gestational BMI below 18 or above 35)
  • Not fluent in Danish or severe visual or hearing impairments
  • Earlier or present learning disabilities
  • MRI contraindications (claustrophobia, metal implants)
  • Previous exposure to radioactivity > 10 millisievert (mSv) within the last year
  • Alcohol or drug abuse

Treatment and study plan

Pregnancy

Other

Peripartum transition from pregnant to postpartum state

Primary outcomes

  1. Depressive symptoms

    Time frame: Week 3-6 postpartum

    Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Total group

  2. Depressive symptoms

    Time frame: Week 3-6 postpartum

    Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group

  3. Gene transcript and DNA methylation markers of estrogen sensitivity

    Time frame: Prior to caesarean section

    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.

  4. Cerebral serotonin 4 receptor binding postpartum

    Time frame: Week 3-6 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.

  5. CSF levels of GABA

    Time frame: On day of caesarean section

    Assessed in total group

  6. CSF levels of serotonin metabolite (5-HIAA)

    Time frame: On day of caesarean section

    Assessed in total group

  7. Cortisol awakening response

    Time frame: Week 3-6 postpartum

    Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.

  8. Hair cortisol level mothers

    Time frame: On day of caesarean section.

    Provides an estimate of cortisol exposure up to 6 months prior to delivery, total group

  9. Hair cortisol level newborns

    Time frame: Day 0-5 postpartum.

    Provides an estimate of fetal cortisol exposure, infants from total group

  10. Hippocampal volumes

    Time frame: Week 3-6 postpartum.

    Hippocampal brain volume (including hippocampus) from structural MRI, imaging group.

  11. functional MRI response to reward

    Time frame: Week 3-6 postpartum.

    fMRI (BOLD response) based assessment of brain activity in response to reward, relative to non-reward, stimuli. Assessed in imaging cohort

  12. Resting state functional connectivity MRI

    Time frame: Week 3-6 postpartum

    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.

  13. Change in epigenetic SERT status

    Time frame: From just before delivery to 3-6 weeks postpartum

    Change in epigenetic SERT status from late pregnancy to postpartum week 3-6.

  14. Concentration of inflammatory markers, i.e hsCRP and immunoactive cytokines, in peripheral blood

    Time frame: At week 3-6

    Composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group

  15. functional MRI response to emotional faces

    Time frame: Week 3-6 postpartum.

    fMRI (BOLD response) based assessment of brain activity to emotionally salient, relative to neutral, stimuli. Assessed in imaging cohort.

Secondary outcomes

  1. Depressive symptoms

    Time frame: Day 3-5 postpartum

    Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group

  2. Depressive symptoms

    Time frame: Week 12 postpartum

    Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group

  3. Depressive symptoms

    Time frame: Day 3-5 postpartum

    Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Assessed in total group

  4. Depressive symptoms

    Time frame: 6 months postpartum

    Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Assessed in all

  5. CSF levels of serotonin

    Time frame: On day of caesarean section

    Assessed in total group

  6. CSF levels of dopamine metabolites

    Time frame: On day of caesarean section

    Assessed in total group

  7. CSF levels of noradrenaline metabolites

    Time frame: On day of caesarean section

    Assessed in total group

  8. CSF levels of inflammatory markers

    Time frame: On day of caesarean section

    Composite measure of IFN-c, IFN-alfa TNF-alfa og IL-6, in total group

  9. Estradiol level

    Time frame: Prior to caesarean section.

    Estradiol level in peripheral blood, total group

  10. Estradiol level

    Time frame: At week 3-6 postpartum.

    Estradiol level peripheral blood, total group

  11. Change in estradiol level

    Time frame: From baseline (caesarean section to week 3-6 postpartum)

    Estradiol change pre- to postpartum, peripheral blood total group

  12. Progesterone level

    Time frame: Prior to caesarean section.

    Progesterone level in peripheral blood

  13. Progesterone level

    Time frame: At week 3-6 postpartum.

    Progesterone level in peripheral blood

  14. Change in progesterone level

    Time frame: From baseline (caesarean section to week 3-6 postpartum)

    Progesterone change pre- to postpartum, peripheral blood total group

  15. Allopregnanolone level

    Time frame: Prior to caesarean section.

    Allopregnanolone level in peripheral blood

  16. Allopregnanolone level

    Time frame: At week 3-6 postpartum.

    Allopregnanolone level in peripheral blood

  17. Change in allopregnanolone level

    Time frame: From baseline (caesarean section to week 3-6 postpartum)

    Change in allopregnanolone level in peripheral blood

  18. Change in cortisol level

    Time frame: From baseline (caesarean section to week 3-6 postpartum)

    Cortisol change pre- to postpartum, peripheral blood total group

  19. Cortisol awakening response

    Time frame: Week 12 postpartum

    Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.

  20. Cortisol awakening response

    Time frame: Prior to caesarean section

    Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.

  21. Change in cortisol awakening response

    Time frame: ´From baseline (caesarean section to week 3-6 postpartum)

    Change in cortisol awakening response, from caesarean section to 3-6 weeks postpartum.

  22. DNA methylation of the SERT gene

    Time frame: Prior to caesarean section

    Methylation status for the SERT gene, total group

  23. DNA methylation of the SERT gene

    Time frame: Week 3-6 postpartum

    DNA Methylation status for the SERT gene, total group

  24. DNA methylation of the FK506-binding protein 51 (FKBP5) gene

    Time frame: Prior to caesarean section.

    Methylation status for the FK506-binding protein 51 (FKBP5) gene, total group

  25. DNA methylation of the FK506-binding protein 51 (FKBP5) gene

    Time frame: Week 3-6 postpartum

    Methylation status for the FK506-binding protein 51 (FKBP5) gene, total group

  26. Change in DNA methylation of the FK506-binding protein 51 (FKBP5) gene

    Time frame: From baseline (caesarean section to week 3-6 postpartum)

    Change in methylation status for the FK506-binding protein 51 (FKBP5) gene from late pregnancy to postpartum week 3-6.

  27. DNA methylation of the glucocorticoid receptor gene

    Time frame: Prior to caesarean section.

    Methylation status for the glucocorticoid receptor gene, total group

  28. DNA methylation of the glucocorticoid receptor gene

    Time frame: Week 3-6 postpartum

    Methylation status for the glucocorticoid receptor gene, total group

  29. Change in DNA methylation of the glucocorticoid receptor gene

    Time frame: From baseline (caesarean section to week 3-6 postpartum)

    Change in methylation status for the glucocorticoid receptor gene from late pregnancy to postpartum week 3-6.

  30. DNA methylation of the COMT gene

    Time frame: Prior to caesarean section.

    Methylation status for the COMT gene, total group

  31. DNA methylation of the COMT gene

    Time frame: Week 3-6 postpartum

    Methylation status for the COMT gene, total group

  32. Change in DNA methylation of the COMT gene

    Time frame: From baseline (caesarean section to week 3-6 postpartum)

    Change in methylation status for the COMT gene from just before delivery to 3-6 weeks postpartum

  33. DNA methylation of the MAO-A gene

    Time frame: Prior to caesarean section.

    Methylation status for the MAO-A gene, total group

  34. Change in DNA methylation of the MAO-A gene

    Time frame: From baseline (caesarean section to week 3-6 postpartum)

    Change in methylation status for the MAO-A gene, total group

  35. DNA methylation of the MAO-A gene

    Time frame: Week 3-6 postpartum

    Methylation status for the MAO-A gene, total group

  36. DNA methylation of the oxytocin receptor gene

    Time frame: Prior to caesarean section.

    Methylation status for the oxytocin receptor gene, total group

  37. DNA methylation of the oxytocin receptor gene

    Time frame: Week 3-6 postpartum

    Methylation status for the oxytocin receptor gene, total group

  38. Change in DNA methylation of the oxytocin receptor gene

    Time frame: From baseline (caesarean section to week 3-6 postpartum)

    Change in methylation status for the oxytocin receptor gene, total group

  39. DNA methylation of the oxytocin gene

    Time frame: Prior to caesarean section.

    Methylation status for the oxytocin gene, total group

  40. DNA methylation of the oxytocin gene

    Time frame: Week 3-6 postpartum

    Methylation status for the oxytocin gene, total group

  41. Change in DNA methylation of the oxytocin gene

    Time frame: From baseline (caesarean section to week 3-6 postpartum)

    Change methylation status for the oxytocin gene, total group

  42. Systemic inflammation peripheral blood hsCRP and immunoactive cytokines

    Time frame: Prior to caesarean section.

    Composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group

  43. Change in systemic inflammation peripheral blood hsCRP and immunoactive cytokines

    Time frame: From baseline (caesarean section to week 3-6 postpartum

    Change in composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group

  44. Self reported family history of mood disorders

    Time frame: Day 3-5 postpartum or before

    Family History Assessment Module (OS-FHAM). Number of first degree relatives with a history of depressive episodes or bipolar disorder. Total group.

  45. Self reported impulsiveness score

    Time frame: Day 3-5 postpartum or before

    Barratt Impulsiveness Scale (BIS-11), self-reported. Range: 30-120. Total group.

  46. Self reported Neuroticism score from NEO personality questionnaire

    Time frame: Day 3-5 postpartum or before

    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.

  47. Self reported parental bonding quality

    Time frame: Day 3-5 postpartum or before

    Parental bonding instrument (PBI), both parents, self-reported. Total group.

  48. Self-reported perceived stress

    Time frame: Day 3-5 postpartum

    Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.

  49. Self-reported perceived stress

    Time frame: Week 3-6 postpartum

    Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.

  50. Change in self-reported perceived stress

    Time frame: Change from day 3-5 to week 3-6 postpartum

    Change in Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.

  51. Self-reported anhedonia

    Time frame: Day 3-5 postpartum

    Snaith-Hamilton Pleasure Scale (SHAPS), range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.

  52. Self-reported anhedonia

    Time frame: Week 3-6 postpartum

    Snaith-Hamilton Pleasure Scale (SHAPS), range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.

  53. Change in self-reported anhedonia

    Time frame: Change from day 3-5 to week 3-6 postpartum

    Change in Snaith-Hamilton Pleasure Scale (SHAPS) score, range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.

  54. Self-reported rumination

    Time frame: Day 3-5 postpartum

    Rumination Response Scale (RRS), range 22-88, a score of 22 indicates no ruminative symptoms. Total group.

  55. Self-reported rumination

    Time frame: Week 3-6 postpartum

    Rumination Response Scale (RRS), range 22-88, a score of 22 indicates no ruminative symptoms. Total group.

  56. Change in elf-reported rumination

    Time frame: Change from day 3-5 to week 3-6 postpartum

    Change in Rumination Response Scale (RRS) score, range 22-88, a score of 22 indicates no ruminative symptoms. Total group.

  57. Self-reported mood

    Time frame: Day 3-5 postpartum

    Profile of Mood States (POMS), range 0-260, a score of 0 indicates no mood disturbance. Total group.

  58. Self-reported mood

    Time frame: Week 3-6 postpartum

    Profile of Mood States (POMS), range 0-260, a score of 0 indicates no mood disturbance. Total group.

  59. Change in self-reported mood

    Time frame: Change from day 3-5 to week 3-6 postpartum

    Change in Profile of Mood States (POMS) score, range 0-260, a score of 0 indicates no mood disturbance. Total group.

  60. Self-reported sleep quality

    Time frame: Day 3-5 postpartum

    Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.

  61. Self-reported sleep quality

    Time frame: Week 3-6 postpartum

    Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.

  62. Change in self-reported sleep quality

    Time frame: Change from day 3-5 to week 3-6 postpartum

    Change in Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.

  63. Self-reported psychiatric symptoms

    Time frame: Day 3-5 postpartum

    Brief symptom Inventory-53 item (BSI-53), range 0-212, increasing score means worsening of symptoms.Total group.

  64. Self-reported psychiatric symptoms

    Time frame: Week 3-6 postpartum

    Brief symptom Inventory-53 item (BSI-53), range 0-212, increasing score means worsening of symptoms.Total group.

  65. Change in self-reported psychiatric symptoms

    Time frame: Change from day 3-5 to week 3-6 postpartum

    Change in Brief symptom Inventory-53 item (BSI-53) score, range 0-212, increasing score means worsening of symptoms.Total group.

  66. Self-reported well-being

    Time frame: Day 3-5 postpartum

    WHO-5 well-being index, range 0-100, low score means less well-being. Total group.

  67. Self-reported well-being

    Time frame: Week 3-6 postpartum

    WHO-5 well-being index, range 0-100, low score means less well-being. Total group.

  68. Change in self-reported well-being

    Time frame: Change from day 3-5 to week 3-6 postpartum

    Change in WHO-5 well-being index, range 0-100, low score means less well-being. Total group.

  69. Self-reported anxiety

    Time frame: Day 3-5 postpartum

    State Trait Anxiety Inventory (STAI-AD-D), state and trait subscales each have a range of 20-80, 20 means no anxiety. Total group.

  70. Self-reported anxiety

    Time frame: Week 3-6 postpartum

    State Trait Anxiety Inventory (STAI-AD-D), state subscale range 20-80, 20 means no anxiety. Total group.

  71. Change in self-reported anxiety

    Time frame: Change from day 3-5 to week 3-6 postpartum

    Change in State Trait Anxiety Inventory (STAI-AD-D) score, state subscale range 20-80, 20 means no anxiety. Total group.

  72. Self-reported obsessive and compulsive symptoms

    Time frame: Day 3-5

    Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.

  73. Self-reported obsessive and compulsive symptoms

    Time frame: Week 3-6 postpartum

    Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.

  74. Change in self-reported obsessive and compulsive symptoms

    Time frame: Change from day 3-5 to week 3-6 postpartum

    Change in Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.

  75. Performance on Simple Reaction Time

    Time frame: Week 3-6 postpartum

    Performance on Simple Reaction Time, in imaging cohort.

  76. Gray matter brain volume prefrontal cortex and anterior cingulate cortex

    Time frame: At week 3-6 postpartum

    Gray matter brain volume prefrontal cortex and anterior cingulate cortex

  77. Serotonergic turnover in placenta

    Time frame: At delivery.

    Composite measure of serotonin, tryptophan og tryptofan hydroxylase levels relative to 5-HIAA, in placenta sample. Infants from total group

  78. 11-beta-hydroxysteroid dehydrogenase type 2 activity in placenta

    Time frame: At delivery

    11-beta-hydroxysteroid dehydrogenase type 2 activity in placenta. Infants from total group

  79. Methylation status of genes relevant for stress-hormone regulation in placenta

    Time frame: At delivery

    Composite measure of methylation status for the FKBP5, glucocorticoid receptor, 11-beta hydroxysteroid dehydrogenase type 2 genes. Infants from total group

  80. Methylation status of genes related to serotonergic signaling in placenta

    Time frame: At delivery

    Composite measure of the methylation status for monoamine oxidase, serotonin receptor and serotonin transporter genes. Infants from total group

  81. Methylation status and gene transcript profiles of relevance for early brain development and stress regulation in newborn infants

    Time frame: At delivery.

    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.

Other outcomes

  1. COMT-genotype (rs4680) variant, i.e met/met vs other polymorphisms

    Time frame: Prior to caesarean section.

    val158met (rs4680) status, binary variable, i.e. "val/val, val/met" vs "met/met" variants

  2. BDNF genotype (rs6265) status, i.e. val/val versus met-carrier variants

    Time frame: Prior to caesarean section.

    BDNF val66met (rs6265) status, binary variable, i.e. "val/val" versus "met-carrier" status

  3. 5-HTT genotype status, i.e LALA vs low-expressing (S or LG) variants

    Time frame: Prior to caesarean section.

    5-HTTLPR genotype status (binary), i.e. high-expressing LALA vs low-expressing (S or LG) variants, based on SLC6A4, i.e. L or S variants, and further subtyping on rs25531 haplotype L(A)L(A) vs LGLA, LGLG or variants containing as S as specified above.

  4. Postpartum blues symptoms

    Time frame: Day 3-5 postpartum.

    In house interview based on Kennerley Maternity Blues Questionnaire, range: 0-28, higher score indicates more severe postpartum blues symptoms. High blues score is associated with greater risk for perinatal depression at week 3-6.

  5. Postpartum blues symptoms

    Time frame: Day 3-5 postpartum.

    In house interview based on Stein's Maternity Blues Scale, range 0-26. High blues score is associated with greater risk for perinatal depression at week 3-6.

Sponsors and collaborators

Lead sponsor

Vibe G Frøkjær, MD, PhD

Other

Collaborators

  • Center for Integrated Molecular Brain Imaging, Copenhagen, Denmak
  • Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital
  • University of Copenhagen

Registry information

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Jan 8, 2019
Registry last updated
Dec 17, 2020

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View the official ClinicalTrials.gov record (opens in a new tab)

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