Neurorestorative Effects of Electroconvulsive Therapy (ECT) in Patients With Severe Late Life Depression

Structural Brain Plasticity in Elderly Depressed Patients Following Electroconvulsive Therapy

To study the potential neurorestorative effects of electroconvulsive therapy (ECT) in depressed patients by measuring brain derived neurotrophic factor (BDNF) serum levels and hippocampal volumes in severely depressed patients receiving ECT.

The investigators want to study the potential neurorestorative effects of electroconvulsive therapy (ECT) in depressed patients by measuring brain derived neurotrophic factor (BDNF) serum levels and hippocampal volumes in severely depressed patients receiving ECT.

Clinical studies in severely depressed patients have shown that antidepressants and ECT can increase Brain Derived Neurotrophic Factor (BDNF) serum levels. BDNF serum levels will be measured before, during and after ECT. In animal studies this increase in serum BDNF was shown to induce hippocampal mossy fiber sprouting and the investigators want to study this phenomenon in humans. Recently, a volumetric magnetic resonance imaging study showed increased hippocampal volume in patients with depression. Hippocampal volumes will be determined with magnetic resonance imaging scannings including voxel based morphometry. Severe depression is accompanied by a dysfunction of the hypothalamus pituitary adrenal (HPA) axis. Cortisol and several other hormones have psychotropic effects, and their excesses or deficiencies induce states of mania or depression. High levels of cortisol suppress hippocampal neurogenesis. Animal models have shown that this suppressive effect of cortisol on hippocampal neurogenesis could be reversed to normal levels by electroconvulsive stimulation, the animal model for ECT. This animal study is in good accordance with clinical findings.

The investigators hypothesize the following: Increase of brain-derived neurotrophic factor serum levels induced by electroconvulsive therapy are associated with remission and is correlated with a neurorestorative effect, which is an increase of hippocampal volume. Non- response to ECT is explained by either low BDNF serum levels regardless of hippocampus size, or by (more advanced) medial temporal lobe atrophy (beyond a point of no return) despite increased BDNF serum levels.

Additionally, four relevant functional candidate genes will be examined, based on their putative role in neurotrophic processes and/or in treatment response in depression: the brain derived neurotrophic factor gene, the serotonin transporter gene, the vascular endothelial growth factor gene and the apolipoprotein gene.

The investigators will also evaluate cognitive and psychomotor changes following electroconvulsive therapy given their clinical relevance in late life depression.

Inclusion Criteria:

• Patients are considered suitable after they were diagnosed as having severe depression according to Diagnostic and Statistical Manual IV (DSM-IV criteria) and were above 55 years of age.

Exclusion Criteria:

• another major psychiatric illness, (a history of) a major neurological illness (including Parkinson's disease, stroke, and dementia) and metal implants precluding Magnetic Resonance Imaging (MRI).

Subjects were included at the University Psychiatric Center Katholieke Universiteit Leuven (KU Leuven), Belgium and Geestelijke Gezondheidszorg in Geest (GGZinGeest), Amsterdam, the Netherlands. The project is part of the project Mood Disorders in Elderly and Electroconvulsive therapy (MODECT).