Improvement of treatment resistant depression by suppression of lateral habenula activity
Major depression is a common disease, affecting up to 17% of the Western world population. To advance therapeutic options for treatment resistant depression we propose a monoamine-related approach in line with a conceptualized view of depression as a system disorder that is caused by changes in specific neurocircuitry. We hypothesize a) that changes of neurocircuitry are focused in the lateral habenula (LHb) with alterations in LHb network activity and connectivity being the prime cause for depression and b) that deep brain stimulation (DBS) of the LHb is a treatment strategy in an animal model of treatment resistant depression (congenital learned helplessness or cLH). LHb hyperactivity in depression will be tested with highest-field magnetic resonance imaging (MRI) in Magdeburg and Mannheim on depressed patients and in cLH rats, respectively. The effective connections between the LHb and the prefrontal and hippocampal brain regions, as well as MR spectroscopy will be tested in a translational manner. The neuronal connectivity of the LHb in congenital helpless rats will be tested using manganese enhanced MRI to directly trace alterations in neuronal networks by the Israeli group. The effect of lesion and DBS of the LHb on various cognitive and depressive-like behaviors and on monoamine levels will be tested by the French group. Neurochemical experiments will assess levels of monoamines and their metabolites. Finally, lesioned animals will be scanned in Mannheim.
Brain stimulation, Imaging techniques, Animal models, Behavioural, Depression and bipolar disorders
2011 - 2014
Alexander Sartorius (Coordinator)