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.
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Changes from baseline in symptoms of depression
Timeframe: Baseline to follow-up 16±3 days after intervention
Changes from baseline in serotonin transporter binding in volumes of interest (VOIs)
Timeframe: Baseline to follow-up 16±3 days after intervention
Changes from baseline in fMRI response to emotional faces
Timeframe: Baseline to follow-up 16±3 days after intervention
Changes from baseline in fMRI response to gambling paradigm
Timeframe: Baseline to follow-up 16±3 days after intervention
Changes from baseline in rsfMRI changes in functional connectivity
Timeframe: Baseline to follow-up 16±3 days after intervention
Changes from baseline in affective cognition (VAMT-24 test)
Timeframe: Baseline to follow-up 16±3 days after intervention
Changes from baseline in reaction time
Timeframe: Baseline to follow-up 16±3 days after intervention
Serial mood fluctuations (SD of total mood disturbance (TMD) score of daily POMS across intervention period)
Timeframe: Intervention start to follow-up 16±3 days after intervention
Changes from baseline in hippocampal volume
Timeframe: Baseline to follow-up 16±3 days after intervention
Changes in pre-pulse-inhibition (PPI) from baseline
Timeframe: Baseline to follow-up 16±3 days after intervention
Changes in a set of markers of immunoactivity across study period
Timeframe: Baseline, intervention time, flare-up phase and follow-up
Changes in epigenetic markers of estrogen sensitivity
Timeframe: Baseline to follow-up 16±3 days after intervention
Changes in HPA-axis dynamics (the cortisol awakening response)
Timeframe: Baseline to follow-up 16±3 days after intervention
Changes in sensorimotor gating (P50 suppression) from baseline
Timeframe: Baseline to follow-up 16±3 days after intervention
Changes from baseline in hippocampal microstructure
Timeframe: Baseline to follow-up 16±3 days after intervention