Stress, Inflammation and Neuroimaging in Major Depressive Disorder as Compared to Premenstrual Dysphoric Disorder

NCT06130371 | Recruiting

• 1 other identifier: 340/2023BO2
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

MDD; PMDD

Keywords

MDD; PMDD; Stress; Inflammation; Cytokines; fMRI; MIST

Outcome Measures

Primary Outcomes (9)

• neural stress reactivity / activation of the CCN (cognitive control network) during stress-related tasks

  activity in stress-circuits of the brain, especially DLPFC activity

  during the MIST (20 minutes)

• stress-related cortisol reactivity

  cortisol level change in saliva between before and after the MIST

  five cortisol measurements at MRI arrival, before the MIST, 50 minutes after the MIST, 70 minutes after the MIST, 120 minutes after the MIST

• TNF-alpha in response to stress-related task

  TNF-alpha in blood before / after the MIST

  blood sample before and after the MIST (approx. 120 minutes)

• CRP in response to stress-related task

  CRP in blood before / after the MIST

  blood sample before and after the MIST (approx. 120 minutes)

• IL-6 in response to stress-related task

  IL-6 in blood before / after the MIST

  blood sample before and after the MIST (approx. 120 minutes)

• activity of parasympathetic nervous system (PNS) in response to stress-related task

  RMSSD (Root Mean Square of Successive Differences) of HRV

  change of RMSSD in relation to HRV during MIST (20 minutes)

• activity of parasympathetic nervous system (PNS) in response to stress-related task

  pNN50 of HRV

  change of pNN50 of HRV during MIST (20 minutes)

• activity of sympathetic nervous system (SNS)

  skin conductance: galvanic skin response

  change of skin conductance during MIST (20 minutes)

• chronic stress

  cortisol in hair

  measured at the first MRI and 2 weeks later at the second MRI

Secondary Outcomes (4)

• different levels of inflammation in Major Depressive Disorder, Premenstrual Dysphoric Disorder and Healthy Controls

  Baseline (T1)

• different levels of inflammation in Major Depressive Disorder, Premenstrual Dysphoric Disorder and Healthy Controls

  Baseline (T1)

• different levels of inflammation in Major Depressive Disorder, Premenstrual Dysphoric Disorder and Healthy Controls

  Baseline (T1)

• changes in stress-reactivity induced by varying levels of sex hormones

  MIST at T1 (follicular) and T2 (luteal phase) (2 weeks)

Study Arms (3)

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

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Participants will be recruited by newspaper/social media advertisements, e-mails ("Rundmail") and posting notices ("Aushänge") at different places at the University Hospital Tübingen as well as the University of Tübingen and in social networks.

You may qualify if:

• Women,
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Hospital Tübingen, Klinik für Psychiatrie und Psychotherapie

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood

MeSH Terms

Conditions

Inflammation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Andreas Fallgatter, Prof. Dr.

  Universitätsklinikum Tübingen, Klinik für Psychiatrie und Psychotherapie

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elise Bücklein, M.Sc.

CONTACT

+497071-2982627; elise.buecklein@uni-tuebingen.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Leader of the Research Group Psychophysiology & Optical Imaging Techniques

Study Record Dates

• First Submitted: September 5, 2023
• First Posted: November 14, 2023
• Study Start: January 4, 2024
• Primary Completion: June 1, 2025
• Study Completion: July 1, 2025
• Last Updated: February 22, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)