Biomarkers of Social Sensitivity in Major Depression
Condition: Major Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Observational

Summary: 
      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.
    


Intervention name(s): emotional facial stimuli; Cyberball game
Intervention type(s): Behavioral; Behavioral
Intervention description(s): 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.; 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.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        1. st group : major depression disorder patients

          2. nd group : healthy volunteers
      
Biospecimen description: 
      Blood samples to explore inflammatory cytokines. 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.
    
Keywords: major depressive disorder; social rejection; rapid facial reaction; facial mimicry; prosocial behavior; inflammation; self esteem