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

Summary

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.

Conditions

• Major Depressive Disorder
• Perinatal Depression

Interventions

OTHER

Pregnancy

Peripartum transition from pregnant to postpartum state

Sponsors & Collaborators

• Center for Integrated Molecular Brain Imaging, Copenhagen, Denmak

  collaborator OTHER

• Mental Health Services in the Capital Region, Denmark

  collaborator OTHER

• University of Copenhagen

  collaborator OTHER

• Vibe G Frøkjær, MD, PhD

  lead OTHER

Principal Investigators

• Vibe Frokjaer, MD, PhD · Rigshospitalet, Denmark

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-01-24

Primary Completion

2020-12-01

Completion

2020-12-01

Countries

• Denmark

Study Locations