Deep Brain Stimulation for Treatment Resistant Depression

Major Depression is one of the most common and costly of all psychiatric disorders. While depression can be effectively treated in the majority of patients by either medication or some form of evidence-based psychotherapy, up to 20% of patients fail to respond to standard interventions. For these patients, trial-and-error combinations of multiple medications and electroconvulsive therapy are often required. For patients who remain severely depressed despite these aggressive approaches, new strategies are needed. Converging clinical, biochemical, neuroimaging, and post-mortem data suggest depression is unlikely to be a disease of a single brain region or neurotransmitter system. Rather, it is now generally viewed as a systems-level disorder affecting integrated pathways linking select cortical, subcortical and limbic sites and their related neurotransmitter and molecular mediators. Treatments for depression can be viewed within a limbic-cortical system framework, where different modes of treatment modulate specific regional targets, resulting in a variety of complementary, adaptive chemical and molecular changes that re-establish a normal mood state. Functional neuroimaging studies have played a critical role in characterizing these limbic-cortical pathways. Previous studies have demonstrated consistent involvement of the subgenual cingulate (Cg25) in both acute sadness and antidepressant treatment effects, suggesting a critical role for this region in modulating negative mood states. This study will test whether high frequency deep brain stimulation of the subgenual cingulate white matter (Cg25-DBS) is a safe and efficacious antidepressant treatment in forty patients with treatment resistant depression, and to investigate potential mechanisms of action of this intervention.