Neuropsychobiological Correlates of Sex-steroid Hormone Manipulation in Healthy Women: a Risk Model for Depression

Summary

The project aimed at identifying neuropsychobiological signatures of pharmacological sex-steroid hormone manipulations in healthy women as a risk model for depression.

The study is a double-blind, randomized, placebo-controlled study. Investigators included 63 healthy female volunteers with regular menstrual cycles between 23 and 35 days. Participants were randomized to active Gonadotrophin-Releasing-Hormone agonist (GnRHa) (goserelin 3.6 mg implant) or placebo (saline injection) intervention, which was initiated in the mid follicular phase (i.e. cycle day 22.6 ±2.5). Sixty women completed follow-up and entered the analyses, except for a few drop outs on some domains. The following domains were addressed at baseline and at follow-up (16±3 days post intervention), (which corresponded to the early ovarian suppression phase of the biphasic hormone response to GnRHa): 1) serotonin transporter binding as imaged by 11CDASB Positron Emission Tomography (PET), 2) functional Magnetic Resonance Imaging (fMRI) emotional processing, 3) fMRI reward processing, 3) rating state fMRI (rsfMRI), 4) structural MRI, 5) Neuropsychology, 6) Psychophysiology, 7) Hypothalamus-Pituitary-Adrenal cortex (HPA)-axis dynamics, 8) Peripheral markers of immunoactive cell responses, 9) Epigenetic factors.

Psychometrics in terms of self reported mental distress and interview based ratings were monitored across the intervention period to monitor potential symptoms of mental distress and psychopathology. Also ovarian hormone responses, peripheral blood markers, and side effects scores were collected across the intervention period.

Conditions

• Postpartum Depression
• Major Depressive Disorder
• Postpartum Psychosis
• Menopause
• Neurodegeneration
• Schizophrenia

Interventions

DRUG

Goserelin 3.6 mg implant

Pharmacologically induced biphasic sex-steroid hormone fluctuation

DRUG

Placebo

Injection of saline

Sponsors & Collaborators

• Center for Integrated Molecular Brain Imaging, Copenhagen, Denmak

  collaborator OTHER

• Fertility Clinic Rigshospitalet

  collaborator UNKNOWN

• CNSR, Glostrup Psychiatric Center

  collaborator UNKNOWN

• Danish Multiple Sclerosis Center Rigshospitalet

  collaborator UNKNOWN

• Dept. of Clinical Immunology, Rigshospitalet

  collaborator UNKNOWN

• Gitte Moos Knudsen

  lead OTHER

Principal Investigators

• Vibe G Frokjaer, MD, Phd · Neurobiology Research Unit

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2011-01-31

Primary Completion

2012-12-31

Completion

2012-12-31

Countries

• Denmark

Study Locations