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

Gitte Moos Knudsen1 个研究点分布在 1 个国家目标入组 63 人开始时间: 2011年1月最近更新: 2016年1月22日

适应症

干预措施

试验速览

阶段: 不适用
状态: 已完成
发起方
入组人数: 63
试验地点: 1
主要终点: Changes from baseline in fMRI response to gambling paradigm

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

详细描述

Aims and hypotheses:

Gender matters in normal brain function as well as in neuropsychiatric disorders. E.g. the vulnerability to mood and anxiety disorders is considerably greater in women. Among other factors, this possibly reflects gender differences in central serotonergic function since dysfunction of serotonergic neurotransmission is critically involved in the pathophysiology of mood and anxiety disorders, schizophrenia, and Alzheimer's disease. In particular, women going through phases in life where sex hormones decline rapidly from high levels or fluctuate, have a higher frequency of severe mood state changes and are more vulnerable to psychiatric disorders, e.g. across the pre to postpartum and menopausal transition. Interestingly, this risk is associated with increased variability of the plasma levels of the sex-hormone estradiol. Therefore, sex-hormone manipulation with a pharmacologically induced biphasic ovarian hormone response serve as a unique opportunity to study how sex-hormone fluctuations provoke mood state changes and increase vulnerability to neuropsychiatric disorders.

In this project investigators aimed at investigating whether sex-hormone manipulation affects: 1. Molecular imaging markers of serotonergic neurotransmission in vivo, 2. Brain structure, architecture and functional connectivity, 3. Stress and inflammatory responses, and 4. Cognitive functions, emotional processing, and information filtering, of importance in the pathophysiology of neuropsychiatric disorders.

Mentally healthy female volunteers were assessed at baseline (i.e cycle day 6.6 ±2.2) and at follow-up (i.e 16.2 ±2.6 days post intervention) in the early ovarian suppression phase af a Gonadotrophin-Releasing-Hormone agonist response in a placebo-controlled, double-blinded design (cohort size aim: N=30x2).

Research in neurobiological correlates of vulnerability related to sex-hormone changes is pivotal to improve the etiological understanding of brain disorders with gender differences in their incidence and/or nature. Such research may contribute to ameliorate fertility treatment, to improve treatment of mood disorders and schizophrenia, and, ideally, shed light on possible preventive strategies in vulnerable phases of women's lives such as the pre- to post-partum and menopausal transition period.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Basic Science
盲法: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围: 18 Years 至 40 Years（Adult）
性别: Female
接受健康志愿者: 是

入选标准

•Healthy women
•Regular menstrual cycles (23 -35 days cycle length)
•No systemic or intrauterine steroid hormone use

排除标准

•Psychiatric disorder (DSM IV Axis I or WHO ICD-10 diagnostic classification).
•Prior or present neurological or other severe medical condition including substance abuse.
•No drug intake suspected to influence results
•Conditions that may increase risk by participating in the study program including ovarian cysts
•Pregnancy during the last year
•Delivery during the last 2 years
•Presently wishing to obtain pregnancy
•Breast feeding
•Not fluent in Danish or severe visual or hearing impairments
•Earlier or present learning disabilities
•Claustrophobia (due to MRI scans)
•Metal implants (excludes MRI)

研究组 & 干预措施

GnRHa

Active Comparator

Goserelin 3.6 mg implant

干预措施: Goserelin 3.6 mg implant (Drug)

Placebo

Placebo Comparator

Injection of saline

干预措施: Placebo (Drug)