Peripheral Immunomarker Validation in Treatment-resistant Depression
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Observational

Summary: 
      This is a study to characterise the role of inflammatory processes in depression. There is
      compelling evidence that inflammation is often associated with, and can cause, depression. It
      is currently less clear that antiinflammatory drugs have meaningful antidepressant effect.
      One of the goals is to identify the subset of depressed patients that is most likely to
      respond better to an antiinflammatory drug than to a conventional antidepressant. The
      investigators will therefore undertake a study of patients with a diagnosis of major
      depressive disorder including four groups: i) incompletely responsive patients who have
      demonstrated failure to respond consistently or completely to standard treatment, ii) those
      who have responded well to treatment and are not currently depressed, iii) untreated patients
      who are currently depressed, iv) healthy volunteers with no history of depression.
      Participants will undergo a clinical assessment, an interview with a trained member of the
      research team and will complete self-rated questionnaires. Investigators will collect blood
      and saliva samples to measure certain immune markers. They will also perform magnetic
      resonance imaging (MRI) scans to look for MRI markers in the brain and investigate brain
      inflammation in a subsample of these patients using positron emission topography (PET) and
      cerebrospinal fluid (CSF) sampling (also called lumbar puncture).
    

Detailed description: 
      The hypotheses are (i) that therapeutic resistance to monoaminergic (MA) antidepressant drugs
      is associated with peripheral biomarkers indicating abnormal activation of the innate immune
      system; and (ii) that peripheral inflammation, defined by blood levels of C-reactive protein
      (CRP), is associated with central nervous system inflammation and abnormal brain structure
      and function.

      The objectives are to test these two hypotheses by collecting clinical, immunological and
      neuroimaging data on patients with depression (DEP+) recruited from a network of clinical
      research sites in the United Kingdom.

      Primary objective:

      To measure peripheral immunophenotypes in healthy volunteers (at least N=50) and 3 groups of
      depressed patients, categorised by their exposure and therapeutic response to monoaminergic
      antidepressants (up to N=200):

        -  Incompletely responsive patients (approximately N ~100) who are currently depressed
           after greater than 6 weeks of treatment with one or more monoaminergic antidepressants
           (DEP+MA+);

        -  Responsive patients (approximately N~50) who are not currently depressed after greater
           than 6 weeks of treatment with a monoaminergic antidepressant (DEP-MA+);

        -  Untreated patients (approximately N~50) who are currently depressed but have not been
           treated with monoaminergic antidepressants in the previous 6 weeks (DEP+MA-);

        -  Healthy volunteers (approximately N~50) who have no personal history of depression
           requiring treatment with either monoaminergic antidepressants or other clinical
           interventions including psychotherapy (DEP-MA-).

      Secondary objective:

      To measure brain and cognitive phenotypes in a subsample of up to N=100 depressed patients
      recruited, preferably from the primary cohort, on the basis of their CRP levels:

        -  Low CRP patients (N~45) will have CRP <= 3 mg/L

        -  High CRP patients (N~45) will have CRP > 3 mg/L

        -  Healthy volunteers (at least N=45).

      All subjects in this sample will be assessed using structural and functional magnetic
      resonance imaging (MRI) and subjects providing additional specific consents will also be
      assessed using positron emission tomography (PET-MR), and/or lumbar puncture (LP) for
      cerebrospinal fluid (CSF) sampling.
    

Intervention name(s): MA; DEP
Intervention type(s): Other; Other
Intervention description(s): Monoaminergic antidepressant use; Depression measured using the Hamilton Depression (HAM-D) questionnaire
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        People with depression and healthy controls
      
Biospecimen description: 
      Blood and saliva samples will be stored in a linked anonymised form for immunophenotyping and
      DNA analysis
    
Keywords: Depression; Major depressive disorder; MDD