Electroconvulsive therapy can increase brain derived neurotrophic factor serum levels to enhance the neurorestorement of the hippocampus (WC2010-049)

Background

Starting date: 01/01/2011
We want to study the potential neurorestorative effect of electroconvulsive therapy (ECT) in depressed patients by measuring BDNF serum levels and medial temporal lobe volumes in severely depressed patients before, during and after ECT. Patients with severe depression have been shown to have decreased metabolic activity and structural changes in the medial temporal lobe, specifically in the hippocampus. Earlier we found in non-demented severely depressed elderly that a mild degree of medial temporal lobe atrophy (MTA), not white matter hyperintensities or global cortical atrophy, contributes to a 30% reduction of responders to ECT (Oudega et al, in press). Hippocampal atrophy is correlated with decreased expression of neurotrophic factors, most notably brain-derived neurotrophic factor (BDNF). BDNF is a nerve growth factor expressed in the central nervous system and is responsible for cell growth and survival. Decreased expression of BDNF correlates with the presence of depression. Serum BDNF levels have been shown to correlate with a BDNF derived effect on the hippocampus. Antidepressants and electroconvulsive therapy (ECT), the most effective treatment, have been shown to induce an increase of BDNF serum levels (Sen et al 2008). ECT in rodents increases brain-derived neurotrophic factor (BDNF) gene expression (Altar et al, 2003) and induces hippocampal mossy fiber sprouting (Chen et al 2001, Vaidya et al, 1999), probably reversing MTA.
This study could identify the correlation between BDNF and hippocampal volume in humans, by using a pre and post treatment design circumventing the problem of interpretation of abnormalities in depression as either primary or secondary. Such a study design allows for measuring a potential neurorestorative effect of ECT in humans. The study is performed in a unique patient cohort. It will include, based on earlier studies, 30% non-demented severely depressed elderly with a mild degree of MTA. MTA in these patients is either caused by depression, an age-related phenomena or a neuroimaging finding suggesting pre-Alzheimer’s disease. A neurorestorative effect on hippocampal volume and function is only to be expected in those MTA caused by depression. The relationship of BDNF and the neurorestorement of the hippocampus can be evaluated by follow up of at least one year. Severely depressed elderly treated with ECT show high remission rates, based on previous studies we expect approximately 48% of patients to remit. The study uses state of the art measurements on BDNF serum levels and medial temporal lobe volume with voxel based morphometry.