Social Stress and Suicide

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

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