Back to Search
Start Over
Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study
- Source :
- Biological psychiatry. 78(8)
- Publication Year :
- 2015
-
Abstract
- Background An adverse response to acute and pronounced changes in sex-hormone levels during, for example, the perimenopausal or postpartum period appears to heighten risk for major depression in women. The underlying risk mechanisms remain elusive but may include transiently compromised serotonergic brain signaling. Here, we modeled a biphasic ovarian sex hormone fluctuation using a gonadotropin-releasing hormone agonist (GnRHa) and evaluated if emergence of depressive symptoms was associated with change in cerebral serotonin transporter (SERT) binding following intervention. Methods A double-blind, randomized, placebo-controlled study included 63 healthy female volunteers (mean age 24.3 ± 4.9 years) with regular menstrual cycles between 23 and 35 days. Participants were randomized to active (goserelin [GnRHa] 3.6 mg implant) or placebo intervention. Sixty women completed follow-up and entered the analyses. Primary outcome measures were changes from baseline in depressive symptoms assessed on the 17-item Hamilton Depression Rating Scale and SERT binding as imaged by [ 11 C]DASB positron emission tomography. Outcome measures were acquired at baseline in the follicular phase (cycle day 6.6 ± 2.2) and at follow-up (16.2 ± 2.6 days after intervention start). Results Sex hormone manipulation with GnRHa significantly triggered subclinical depressive symptoms within-group ( p = .003) and relative to placebo ( p = .02), which were positively associated with net decreases in estradiol levels ( p = .02) from baseline within the GnRHa group. Depressive symptoms were associated with increases in neocortical SERT binding in the GnRHa group relative to placebo ( p = .003). Conclusions Our data imply both serotonergic signaling and estradiol in the mechanisms by which sex-steroid hormone fluctuations provoke depressive symptoms and thus provide a rationale for future preventive strategies in high-risk groups.
- Subjects :
- Adult
medicine.medical_specialty
medicine.drug_class
DASB
Placebo
chemistry.chemical_compound
Young Adult
Double-Blind Method
Gonadotropin-releasing hormone agonist
Internal medicine
Follicular phase
Outcome Assessment, Health Care
medicine
Humans
Gonadal Steroid Hormones
Biological Psychiatry
Serotonin transporter
Menstrual Cycle
Psychiatric Status Rating Scales
Serotonin Plasma Membrane Transport Proteins
Depressive Disorder, Major
biology
Goserelin
Postpartum Period
Brain
Endocrinology
chemistry
Sex steroid
Positron-Emission Tomography
biology.protein
Female
Psychology
Postpartum period
medicine.drug
Subjects
Details
- ISSN :
- 18732402
- Volume :
- 78
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Biological psychiatry
- Accession number :
- edsair.doi.dedup.....6d730dc3e82a0fdea811661024654542