Exploring Effects of Electroconvulsive Therapy on the Human Brain in Depression - The Danish ECT/MRI Study
Condition: Depressive Disorder; Depression; Depressive Disorder, Major
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Observational

Summary: 
      The main purpose of this study is to determine whether electroconvulsive therapy (ECT) causes
      any structural or functional brain changes and thus indicating its mechanism of action. The
      second aim is to find predictors of an immediate response, sustained remission, relapse and
      side-effects. Thirdly, this study aims to explore whether ECT causes any changes in
      blood-brain barriers permeability and whether these changes correlate to memory problems. The
      fourth objective is to examine whether ECT causes any brain tissue damage.
    

Detailed description: 
      ECT has been the most effective treatment of depression for decades. Despite of this, neither
      the mechanism of action or side-effects are fully elucidated. The reason why some patients
      relapse shortly after remission is still not completely understood. Thus, there is a need to
      find predictors of the favourable clinical effect, relapse and side-effects. ECT is
      considered by professionals to be a safe procedure. However, this view is based on rather old
      and small studies. Additionally, many patients do not consent to this treatment because they
      fear a permanent loss of memory or that they will contract a brain damage after the completed
      ECT series. Therefore, it is very important to examine whether ECT might have negative
      effects on the structure or function of the brain, using state of the art Magnetic Resonance
      Imaging (MRI) techniques on a greater study population.

      The study consists of 60 inpatients, diagnosed with depression, admitted to one of the
      recruiting Mental Health Centres, and scheduled to ECT. The most modern MRI sequences
      examining brain structure and function are used at 3 time points: at baseline (just before
      ECT series), the second examination (just after ECT series) and the third (follow-up)
      examination (6 months after ECT series). Blood samples (measurements of Brain-Derived
      Neurotrophic Factor - BDNF, Vascular Endothelial Growth Factor - VEGF along with the marker
      of brain injury - S100B-protein) and the evaluation of clinical effect and side-effects to
      ECT are performed at the same time points.

      The study has 4 main hypotheses. The first hypothesis assumes that the immediate and
      sustained response to ECT can be predicted by combining neuroimaging findings and
      blood-samples results. The second hypothesis is based on the assumption that ECT modulates
      the microstructure and connectivity in the fronto-limbic pathways (FLPs) and that this
      modulation correlates with the clinical effect. Thus, the altered microstructure of the FLPs
      in depression is normalised by an ECT series. Furthermore, the depression-associated
      increased resting state connectivity in FLPs is normalised by ECT. The third hypothesis is
      that ECT will induce changes in blood-brain barrier (BBB) permeability, which will correlate
      with the severity of memory problems. The last hypothesis assumes that ECT does not cause any
      brain tissue damage (including brain atrophy and white matter lesions - WMLs).
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The study population consists of the inpatients admitted to one of the recruiting Mental
        Health Centres (MHC) in the Capital Region of Denmark (Mental Health Centre Glostrup or
        Amager or Copenhagen or others), diagnosed with either depression according to the 10th
        version of the International Classification of Diseases (ICD-10) or major depression
        according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV) and
        scheduled to ECT series.
      
Biospecimen description: 
      Whole blood samples are kept in the biobank until the last enrolled patient has been
      examined. They will be then analysed for S100B-protein concentration and destroyed. Whole
      blood, serum and plasma samples are kept in the biobank until the last enrolled patient has
      been examined. They will then be analysed for concentrations of BDNF and VEGF and destroyed.
      Extra whole blood samples are stored in the psychiatric biobank for the future research (as
      part of another protocol - PSV-2001-04, I-Suite 00422 - ID nr 2001-54-798)
    
Keywords: Electroconvulsive therapy; Depressive Disorder; Magnetic Resonance Imaging; Hippocampus; Brain-Derived Neurotrophic Factor; Vascular Endothelial Growth Factor; Blood-Brain Barrier