Stress, Inflammation and Neuroimaging in Major Depressive Disorder as Compared to Premenstrual Dysphoric Disorder
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 75
- 试验地点
- 2
- 主要终点
- neural stress reactivity / activation of the CCN (cognitive control network) during stress-related tasks
研究概览
简要总结
Premenstrual dysphoric disorder (PMDD) is a sex-specific depressive disorder where depressive symptom severity drastically changes in relation to menstrual cycle phase. It is characterized by late luteal phase symptoms of affective lability, irritability, depressed mood, and anxiety. A lot remains unclear and further studies are needed in order to improve the understanding of PMDD and to differentiate it from major depressive disorder (MDD). To date, and in contrast to MDD, the neural correlates of PMDD have been sparsely and poorly investigated. The aim of this study is therefore to investigate the neural correlates of PMDD as compared to MDD and to relate them to stress reactivity. Therefore, three groups of naturally cycling women will be investigated and compared, namely (1) women with MDD, (2) women with PMDD, and (3) healthy control women.
Stress and HPA axis activity are assumed to play a crucial role in the development of many mental disorders, including MDD. How stress reactivity and HPA axis activity are connected to PMDD still needs to be investigated. Furthermore, the HPA axis can affect or suppress the activity of the hypothalamic-pituitary-gonadal (HPG) axis, which is involved mainly in the reproductive, but also the immune system, making it an important candidate for the investigation of sex-specific differences in stress reactivity.
There are sex-specific differences in stress reactivity, but also in the prevalence of stress-related diseases. Women are twice as likely to suffer from depression than men and the first onset of MDD usually peaks during the reproductive years. As to why these differences exist, a recent theory suggests that ovarian hormone fluctuations function as modulators of women's susceptibility to stress and that altered reactivity to stressors during different cycle phases plays a role in the etiology of depressive disorders. This hypothesis extends the Social Signal Transduction Theory of Depression which first and foremost relates depression to inflammation. They postulate a critical role of cytokines for understanding the pathogenesis of depression. Therefore, ovarian hormone fluctuations, but also inflammation in regard to MDD and PMDD and stress reactivity will be investigated in this study.
详细描述
In the proposed study the investigators aim to investigate in more detail how women with MDD and women with PMDD differ in their stress response from healthy women. The investigators are directly comparing three groups of 1) women with MDD, 2) women with PMDD and 3) healthy women. All women will be measured in two different cycle phases to disentangle the effects of the menstrual cycle on stress reactivity. Furthermore, including inflammatory markers will help to shed light on the connection between stress, depressive disorders and the immune system.
The overall aim of this study is to elucidate the influence of stress on inflammation as well as on brain function in women with MDD in contrast to PMDD. Therefore, the behavioral, neural, immunological, and endocrine profiles of women with MDD as well as women with PMDD will be compared to the ones of naturally cycling women. The goal is to delineate the psychobiological characteristics of reproductive states and mental disorders. The results will provide the basis to develop more targeted treatments in the framework of precision medicine.
Open questions:
- How do women with MDD, women with PMDD, and healthy women differ in their stress reactivity on a neural level, as measured by fMRI activity?
- How do women with MDD, women with PMDD, and healthy women differ in their stress reactivity in their HPA axis response, as measured via cortisol levels?
- How do women with MDD, women with PMDD, and healthy women differ in their stress reactivity on an immunological level, as measured by inflammation markers?
The investigators hypothesize that after an acute psychosocial stressor,
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
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
- •age between 18 and 40 years (no menopausal women),
- •regular menstrual cycles (25-31 days),
- •normal body mass index (18-35 kg/m2),
- •German language fluency
排除标准
- •any neurological or mental disease (only for healthy participants)
- •hormonal, metabolic or chronical diseases
- •pregnancy
- •women who gave birth or were breastfeeding within the last year
- •women with any kind of steroid hormonal treatment
- •oral contraceptive treatment in the last three months
- •psychotropic treatment, only if regular
- •engagement in competitive sports
- •shift work
研究组 & 干预措施
major depressive disorder group
female MDD patients with moderate levels of depressive symptoms, mostly recruited from psychotherapist offices and the outpatient clinic of the university.
premenstrual dysphoric disorder group
female participants suffering from premenstrual dysphoric disorder, as confirmed by prospective ratings of premenstrual symptoms via an app during two consecutive menstrual cycles.
healthy controls
healthy controls
结局指标
主要结局
neural stress reactivity / activation of the CCN (cognitive control network) during stress-related tasks
时间窗: during the MIST (20 minutes)
activity in stress-circuits of the brain, especially DLPFC activity
TNF-alpha in response to stress-related task
时间窗: blood sample before and after the MIST (approx. 120 minutes)
TNF-alpha in blood before / after the MIST
stress-related cortisol reactivity
时间窗: five cortisol measurements at MRI arrival, before the MIST, 50 minutes after the MIST, 70 minutes after the MIST, 120 minutes after the MIST
cortisol level change in saliva between before and after the MIST
IL-6 in response to stress-related task
时间窗: blood sample before and after the MIST (approx. 120 minutes)
IL-6 in blood before / after the MIST
activity of parasympathetic nervous system (PNS) in response to stress-related task
时间窗: change of pNN50 of HRV during MIST (20 minutes)
pNN50 of HRV
activity of sympathetic nervous system (SNS)
时间窗: change of skin conductance during MIST (20 minutes)
skin conductance: galvanic skin response
chronic stress
时间窗: measured at the first MRI and 2 weeks later at the second MRI
cortisol in hair
CRP in response to stress-related task
时间窗: blood sample before and after the MIST (approx. 120 minutes)
CRP in blood before / after the MIST
activity of parasympathetic nervous system (PNS) in response to stress-related task
时间窗: change of RMSSD in relation to HRV during MIST (20 minutes)
RMSSD (Root Mean Square of Successive Differences) of HRV
次要结局
- changes in stress-reactivity induced by varying levels of sex hormones(MIST at T1 (follicular) and T2 (luteal phase) (2 weeks))
- different levels of inflammation in Major Depressive Disorder, Premenstrual Dysphoric Disorder and Healthy Controls(Baseline (T1))
研究者
Dr. Ann-Christine Ehlis
Leader of the Research Group Psychophysiology & Optical Imaging Techniques
University Hospital Tuebingen