Clinical trial NCT04714671: Social Stress and Suicide
Official title: Effect of Social Stress in the Physiology and Cognition of Suicide Attempters: Heart Rate, Endocrine and Inflammatory Response, Decision Making
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Past Major Depressive Episode
Euthymic
Keywords: Suicide
Social stress
Cardiovascular
Decision making
Neuroendocrinology
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2021-01-19
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Only vulnerable patients, when facing environmental stressors, attempt or commit suicide. Previous research demonstrated that suicide attempters usually misunderstand the social context and show impairments in decision making. Heart activity, endocrine and inflammatory response to stress were related with these features. For that, suicide attempters, in a context of social stress, would have maladaptive physiological response impacting the following decision making. The main aim is to identify the physiological response (autonomous nervous system, endocrine and inflammatory response) of suicide attempters under social stress conditions and to investigate the association of this response with the posterior decision making.

The study aims to compare physiological response to social stress and posterior decision-making response in 80 euthymics women with a past mood disorder according to their history of suicide attempt

Detailed description: Hypothesis: 1. suicide attempters will have a lower cortisol, and, greater alpha-amylase and peripheral inflammatory response after a social stressor, compared to non-attempters 2. suicide attempters will have a hyper-activation of the cardiovascular response during the social stressor and a slower recovery to basal levels, compared with non-attempters.

3. With respect to decision-making, suicide attempters will demonstrate riskier decision-making than non-attempters after the social stressor, compared to non-attempters. Risk-taking behavior will be related with lower cortisol and higher testosterone levels after the stressor.

Measures: electrocardiogram (ECG) and impedance cardiography (IKG) will be used to analyse cardiovascular function during social stressor. Salivary samples to analyze cortisol, testosterone and α-amylase. Blood samples to analyze several peripheral inflammatory proteins. The Iowa Gambling Task a neuropsychologial task to evaluate decision making. Several questionnaires of mood, anxiety and psychological pain during the stressor. And a comprehensive battery of clinical measures for screening and assessment of construct of suicide, and psychiatric and social status.

Procedures: Depressed females will be screened and assigned to 2 groups: 1) 40 depressed with suicide attempt history. 2) 40 depressed without suicide attempt history. Participants will confront a virtual version of the Trier Social Stress Test (V-TSST). This test consists in a preparation and execution of a presentation in front of a virtual tribunal for obtain a job position followed by an arithmetic mental task. During the procedure, ECG and IKG will be performed, 5 salivary samples and 5 blood samples (before and after the stressor) and some self-reports of mood, anxiety and pain. After procedure decision making will be assessed. Their participation will consist of 3 visits : inclusion visit (psychiatric interview), visit between 1 to 8 days (social stressor procedure), at 12 months (follow up).

Potential impact and next steps: Identifying differences between the two depressed groups in the physiological response to social stress and their subsequent decision making will advance the understanding of the pathophysiological mechanisms of suicide. As social stress is present in several life events during lifetime, know how suicidal people respond to these issues may help in the implementation of preventive interventions.

Eligibility criteria: Inclusion Criteria:

* past major depressive episode according to the DSM-5 criteria (Diagnostic and Statistical Manual of Mental Disorders)
* euthymic (IDSC \< 14 and YMRS \< 7)
* ability to understand experimental procedures
* able to speak, read and understand French
* able to give written informed consent
* for suicide attempters only: Lifetime history of suicide attempt.
* for affective controls only: No lifetime history of suicide attempt

Exclusion Criteria:

* Lifetime diagnosis of schizoaffective disorder, schizophrenia or social phobia throughout
* Menopause
* Alcohol or illicit substance use disorder in the last 6 months;
* Diagnosis of current cardiovascular (arrhythmia, hypertension, heart valve problems, past heart attack or stroke, congenital heart disease), respiratory (chronic obstructive pulmonary disease, asthma, cystic fibrosis, tuberculosis, lung tumor) endocrine (adrenal disorder, cushing syndrome, adrenal tumor, type-2 diabetes, androgen deficiency, congenital adrenal hyperplasia, hypogonadism, polycystic ovarian syndrome) or neurological disease (dementia, brain stroke, epilepsia, multiple sclerosis, huntington disease, muscular dystrophy, brain or spinal cord tumor, meningitis) based on the first interview, which can interfere with the cardiovascular, endocrine or neurocognitive outcomes of the study;
* current cardiovascular medication which directly affects heart or arterial function or corticoids intake; anticoagulants, antiplatelet agents and dual antiplatelet therapy, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, angiotensin-receptor neprilysin inhibitors, beta blockers, calcium channel blockers, vasodilators.
* Pregnancy (urine pregnancy test) or breastfeeding
* refusing to participate
* being in exclusion period for another study
* not being affiliated to the French National Social Security System
* having reached 4500€ annual compensation for participating to clinical trials
* being protected by law or deprived of liberty

Primary outcomes:
measure: Change in salivary cortisol
timeFrame: at visit between 1 to 8 days
Secondary outcomes:
measure: Changes in cardiovascular response (heart rate)
timeFrame: at visit between 1 to 8 days
measure: Changes in cardiovascular response (Cardiac output)
timeFrame: at visit between 1 to 8 days
measure: Changes in cardiovascular response (Total peripheral resistance)
timeFrame: at visit between 1 to 8 days
measure: Changes in cardiovascular response ((time between the two R peaks)
timeFrame: at visit between 1 to 8 days
measure: Changes in cardiovascular response (pre-ejection period)
timeFrame: at visit between 1 to 8 days
measure: Changes in cardiovascular response ( Vascular contractibility)
timeFrame: at visit between 1 to 8 days
measure: Changes in cardiovascular response (High frequency)
timeFrame: at visit between 1 to 8 days
measure: Changes in cardiovascular response (Low frequency)
timeFrame: at visit between 1 to 8 days
measure: Changes in cardiovascular response (Very low frequency)
timeFrame: at visit between 1 to 8 days
measure: Changes in cardiovascular response (Root mean squared of successive R-R interval differences)
timeFrame: at visit between 1 to 8 days
measure: Changes in salivary testosterone
timeFrame: at visit between 1 to 8 days
measure: Changes in salivary α-amylase
timeFrame: at visit between 1 to 8 days
measure: Risk Taking decision making after V-TSST
timeFrame: at visit between 1 to 8 days
measure: Sense of fairness/unfairness after V-TSST
timeFrame: at visit between 1 to 8 days
measure: Domination/submission after V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in anxiety level induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in depression level induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in psychological pain level induced by V-TSST
timeFrame: at inclusion
measure: Changes in suicidal ideation level induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in social distress level induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in C-Reactive Protein (CRP) induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in Interleukin (IL) - 1b induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in IL-6 induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in IL1β induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in IL2 induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in IL4 induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in IL8 induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in IL10 induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in IL13 induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in IL27 induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in NF-KB protein induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in IKB protein induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in Tumor necrosis factor (TNF) - α protein induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in Interferon (IFN) - γ induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in Vascular endothelial growth factor (VEGF) induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in kyrunenine induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in sCD62P induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in sCD40L induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in Platelet factor (PF) 4 induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in RANTES induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in Brain derived neurotrophic factor (BDNF) induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in sOx40L induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in Microparticle induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Changes in Mitochondrial deoxyribonucleic acid (DNA) of platelet origin induced by V-TSST
timeFrame: at visit between 1 to 8 days
measure: Suicidal behavior evaluated with the C-SSRS
timeFrame: at 12 months post V-SST
Other outcomes:
Locations:
city: Montpellier
country: France
facility: University Hospital, Montpellier
state: Hérault
Study officials:
References: