Exploring Effects of Electroconvulsive Therapy on the Human Brain in Depression - The Danish ECT/MRI Study

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).

Inclusion criteria

• age 18-95 years
• admitted at the MHC Glostrup, MHC Amager or MHC Copenhagen (or other Mental Health Centres in the Capital Region)
• fulfilling the criteria for depression according to ICD-10 and major depression according to DSM-IV and where ECT is planned.
• must be able to give informed consent to participate in the study

Exclusion criteria

• Schizophrenia or any other psychotic disorder except for psychotic depression
• Dependency syndrome according to ICD-10.
• Severe somatic or neurological condition (e.g. stroke) confounding results
• Head trauma resulting in unconsciousness for more than 5 minutes
• Severe psychotic symptoms or suicide impulses making transportation hazardous
• Contraindications against MRI or Gadovist infusion
• Pregnancy
• Maintenance ECT or ECT received during the last 6 months
• Any form of compulsory treatment
• Subjects who do not consent to be informed of incidental findings that could have healthcare implications will not be scanned and can thus not be included