Biomarkers of Social Sensitivity in Major Depression

Study Overview
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Brief Summary
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Major depression disorder (MDD) is a frequent and disabling mental disorder with great risk of recurrence and chronicity. Interpersonal factors are among the strongest predictors of the course and duration of an episode of depression. More specifically, social rejection is one of the most environmental risk factors of MDD. Targeted rejection predicts hastened onset of major depression. On the other hand, healthy subject show prosocial behavior after social rejection to reconnect to new source of social interaction. In addition to the potential impact of social exclusion on MDD onset, depressed patients may be more prone to be rejected as they encounter interpersonal difficulties and may less be able to reconnect to the social group after rejection. Recent neuroimaging data show that brain processing of social exclusion activate brain regions that are central to the pathophysiology of MDD. Some of these regions are also known to be activated during physical pain and may contribute to the aversive dimension of the experienced rejection. Pro-inflammatory cytokines are involved in MDD physiopathology and can induce social withdrawal behavior. Inflammation can modulate social interactions in mammals. Moreover, after a social stress such as social rejection, blood cytokines increase. At a cognitive level, self-esteem can modulate the sensitivity to social rejection. The major objective of the trial is to study sensitivity to social signals in MDD patient compared to healthy subject. The investigators hypothesize in MDD patient : (1) decrease of rapid facial reactions (RFR) to dynamic emotional faces expressing joy, (2) increase of RFR to dynamic emotional faces expressing sadness, (3) decrease of prosocial reaction after experimental social rejection. Secondary objective is to identify psychological and biological mediators We hypothetize in MDD patient: (1)mediating effect of systemic inflammatory cytokines, an (2) mediating effect of state self esteem 30 MDD patients and 60 healthy subject will be included. They will encounter psychiatric and psychometric evaluation. Their facial EMG will be recorded to assess RFR to dynamic emotional faces created by photo morphing from KDEF emotional faces database, coupled to occulometric recording. Subjects will perform cyberball game as an experimental inclusion or exclusion task and the trustgame task as an implicit evaluation of their prosocial behavior. Questionnaires will assess explicit measurement of social rejection pain and desire of affiliation. Inflammatory markers will be measured in a blood sample before the cyberball task for every subjects and 6 hours later for 20 healthy volunteers. Dosage of IL-6, IL-10, TNFa, IP-10, MCP-1, MIP-1b, Rantes, sIL-6Ra, IL1ra, VEGF, Leptin, PECAM1, sTie2, sVEGFR1, sVEGFR2 will be performed by luminex technique and usCRP, srIL2 ans sCD14 by ELISA technique.

Official Title
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Etude de la sensibilité Aux Signaux Sociaux Dans la dépression, Modulateurs Psychologiques, Comportementaux et Inflammatoires.

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Behavioral: emotional facial stimuli
* Behavioral: Cyberball game


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For everybody : benefit social health insurance french speaker and reader can stop smoking one day volunteer to participate For 1st group : actual MDD diagnosed by a psychiatrist and meet the DSM IV criterias of MDD no antidepressant treatment or antidepressant treatment for less than 7 days. Exclusion Criteria: BMI > 40 weekly sport > 3 hours pregnancy fever or other infection symptoms during the last month significant or unstable disease, especially neurologic or inflammatory. recent history of coronary disease, ulcer, COPD, severe dyslipemia, kidney or liver failure. severe smoking addiction (fagerström > 8) antiinflammatory or immunomodulatory treatment during last month For 1st group : no psychiatric treatment except benzodiazepin if no severe vigilance trouble and antidepressant treatment more than 7 days subjects under legal protection constraint hospitalization significant suicidal risk resistant MDD psychiatric comorbidity For 2nd group : - psychiatric disease, actual or past according to DSM IV criterias

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MDD patients<br>emotional facial stimuli cyberball game | Behavioral: emotional facial stimuli<br>* Subjects watch passively dynamic facial emotions obtained by emotionnal faces photos morphing. Their rapid facial reactions are recorded by faciel EMG device as eye movement by occulometric device.<br>Behavioral: Cyberball game<br>* Ball tossing computer game to manipulate social inclusion status : rejection or inclusion. Social behavior, social pain and inflammatory modification will be assessed after the game.<br>|
| healthy subjects<br>emotional facial stimuli cyberball game | Behavioral: emotional facial stimuli<br>* Subjects watch passively dynamic facial emotions obtained by emotionnal faces photos morphing. Their rapid facial reactions are recorded by faciel EMG device as eye movement by occulometric device.<br>Behavioral: Cyberball game<br>* Ball tossing computer game to manipulate social inclusion status : rejection or inclusion. Social behavior, social pain and inflammatory modification will be assessed after the game.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rapid facial reactions : milliVolts amplitude of electromyographic signal of zygomaticus, corrugator, depressor & frontalis muscles | During passive watching of dynamic emotional faces, electromyographic signal is recorded with skin electrodes facing zygomaticus, corrugator, depressor & frontalis muscles. | During stimuli presentation (emotional faces) at Day 1 from 9:40 to 10:30 am | 
| Implicit pro-social behavior : invested money during a 4-round trust game | Total amount of money invested by the subject during a 4-round trust game without feedback. | At Day 1 from 11:40 to 11:50 am | 
| Explicit pro-social behavior : affiliation desire measured by a questionnaire | Affiliation desire questionnaire from Park and Manner assessing total affiliation desire and affiliation desire towards close relationship or strangers. | At Day 1 from 11:50 to 12:00 am | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self esteem assessed by questionnaires mediates social pain after rejection and pro-social behavior | Scoring of questionnaires of state and trait self esteem (state self esteem scale and Rosenberg scale) | 2 assessments at Day 1 : at 8:30 and at 11:50 am | 
| Systemic inflammation mediates social pain after rejection and pro-social behavior | Inflammatory dosage in blood : IL-6, IL-10, TNFa, IP-10, MCP-1, MIP-1b, Rantes, sIL-6Ra, IL1ra, VEGF, Leptin, PECAM1, sTie2, sVEGFR1, sVEGFR2 by luminex technique usCRP, srIL2 ans sCD14 by ELISA technique. | At day 1 : at 11:30 am and 5:30 pm | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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major depressive disorder, social rejection, rapid facial reaction, facial mimicry, prosocial behavior, inflammation, self esteem