Cerebral Neuroinflammation During Major Depressive Episode

Cerebral Neuroinflammation During Major Depressive Episode: Multicentric Comparative Study.

the investigators make the following assumptions: 1) neuroinflammation in MDD can be measured by the [18 F ] DPA- 714 ; 2) it is accompanied by anatomical and functional changes in the frontal subcortical loops, strongly involved in MDD ; 3) neuroinflammation in patients might be a biomarker related to resistance to treatment in patients with MDD. If this assumptions are validated, then this study will enable a better understanding of the neuroinflammatory processes. This breakthrough could have a long term therapeutic impact, helping to target more specifically antidepressant drugs with anti-inflammatory action and / or drugs targeting neuroinflammation.

The most widespread pathophysiological hypothesis in major depressive disorder (MDD), is the hypothesis of monoamine deficit. The most used antidepressants in everyday clinical practice act by inhibiting the reuptake of monoamines. However, meta-analyzes evaluating the efficacy of antidepressants suggest that they are ineffective in 30 to 40% of patients. Inflammatory mechanisms might be related to the deficiency of monoamines, compromising the effectiveness of conventional antidepressants. Newly developed specific radiotracers allow the use of positron emission tomography (PET) imaging techniques to evaluate neuroinflammation. It has recently demonstrated the relevance of the [18F] DPA- 714 as a biomarker of neuroinflammation in humans in several neurological diseases.

• Inclusion criteria for all groups:

  • Written agreement for participation
  • Able to understand instructions and information data

• Inclusion criteria for the experimental group:

  • Responding to MDD criteria (DSM-5)
  • MADRS score> 20
  • Antidepressant medication considered ineffective and before the introduction of a new treatment according to the recommendations (unchanged dosage for at least a week and plasma levels within the therapeutic range)

• Inclusion criteria for the pathological control group :

  • Having met MDD criteria (DSM-5)
  • In remission for 8 weeks according to the DSM-5
  • MADRS score <10
  • Treated with antidepressants (unchanged dosage for at least week)

• Inclusion criteria for the control group :

  • Without any neurological or psychiatric previous disorder
  • CRPus < 5mg/L

• Exclusion criteria for all groups:

  • Patients without public insurance regime.
  • Specific contraindication to the use of MRI (metallic material) or PET (specific allergy related to the ligand).
  • Pregnant and breastfeeding women
  • Persons deprived of liberty by judicial or administrative decision
  • People hospitalized without consent, or subject to legal protection
  • Persons unable to consent
  • Patients with a neurodegenerative disease, bipolar disease, chronic psychotic disorder, addictive disorder, Obsessive Compulsive Disorder, Post-Traumatic Stress disorder (PCL-S> ou =45), known system pathology
  • Patients with a history of stroke
  • Patients with an acute infectious disease
  • Patients with chronic inflammatory pathology.
  • Patients treated with anti-inflammatory and/or immunosuppressive, and/or antipsychotics, and/or diazepam

• Exclusion criteria for control group:

  • No significant psychiatric or somatic history.
  • No psychotropic treatment
  • Suicidal risk (C-SSRS)
  • Anxiety Disorders (MINI)