[Frontiers in Bioscience 4638-4648, May 1, 2008]

The evolution of deep brain stimulation for neuropsychiatric disorders

Benjamin D. Greenberg1, Kathleen D. Askland1, Linda L. Carpenter1

1 Department of Psychiatry and Human Behavior, Warren Alpert Medical School at Brown University, Butler Hospital Providence, RI, USA


1. Abstract
2. Introduction
2.1. Burden of depression
2.2. Phenomenology
2.3. Pathophysiology
2.4. Pharmacologic treatments
2.5. Treatment resistance
3. Development of DBS for psychiatry
3.1. History
3.2. Affect and mood effects observed during depth electrode stimulation
3.3. DBS for obsessive compulsive disorder
4. Technical aspects of DBS
4.1. Implantation surgery
4.2. Stimulation technique
4.3. Customizing therapy
5. DBS for primary depressive illness
5.1. Defining the antidepressant target in modern DBS
5.2. Inferior thalamic peduncle (ITP)
5.3. Subgenual cingulate (Brodman area 25)
5.4. Ventral capsule/ventral striatum (VC/VS)
5.5. Antidepressant mechanism of action of DBS
6. Adverse effects of DBS
7. Ethical considerations
8. Perspective
8.1. Long-term follow-up
8.2. Research protocols for investigational treatment with DBS
8.3. Summary
9. Acknowledgement
10. References


Deep brain stimulation (DBS) is the most focal method for stimulating the human brain. In contrast to lesions, DBS is nonablative, with the advantages of reversibility and adjustability. Thus, therapeutic effectiveness can be enhanced and stimulation-related side effects minimized during long-term patient management. While DBS is an approved adjunct therapy for severe, medication-refractory movement disorders, it remains investigational in neuropsychiatry. However, experience to date, though limited, suggests that DBS may offer a degree of hope to patients with severe and treatment-resistant neuropsychiatric illness. Thus far, work in obsessive-compulsive disorder (OCD), the first psychiatric condition studied using modern DBS devices, has shown consistently positive results across multiple small-scale studies. Work in treatment-resistant Major Depressive Disorder (MDD) also suggests therapeutic potential in preliminary studies, generating cautious optimism for this indication. With the increase in potential applications, a number of clinical and preclinical research efforts have now focused on understanding the mechanisms of action of DBS. Further development of DBS for these and other illnesses with primarily behavioral symptoms will require thoughtful collaboration among multiple disciplines.