Patients with Major Depressive Disorder who had not responded to drugs, therapy or ECT were given Deep Brain Stimulation and monitored for a year.

“Our research confirmed that 60 per cent of patients have shown a clinically significant response to the surgery and the benefits were sustained for at least one year,” said Dr. Andres Lozano, Neurosurgeon at Krembil Neurosciences Centre - Toronto Western Hospital and Canada Research Chair in Neuroscience. “The underpinnings of depression are poorly understood and this therapy, although not perfect, offers numerous advantages.”

Deep Brain Stimulation involves two thin wire electrodes (one on each side) being inserted into white matter near part of the brain called the subcallosal cingulate region (or Cg25), an area which has been dubbed the "sadness centre" because it is very active when people experience depressed mood. The electrodes are connected to a battery powered device called an Implanted Pulse Generator (IPG), which sends high frequency electrical pulses to the electrodes. The IPG is implanted underneath the skin just below the collar bone. Deep Brain Stimulation equipment is often referred to as a "brain pacemaker".

The researchers regulated the intensity of the current according to the response of the patient. Only patients who were unable to get better with most other types of antidepressant treatment – including medication, psychotherapy and electroconvulsive therapy – were included in the study.

"In previous studies using brain imaging, we found the subcallosal cingulate region was a key region in an emerging emotion regulation circuit implicated in major depression," explains Helen Mayberg, professor in the Department of Psychiatry and Behavioral Sciences and the Department of Neurology at Emory University School of Medicine.

"We postulated that if stimulation worked for the treatment of other neurological disorders where abnormal function of specific circuits was well established, such as Parkinson's disease, then stimulation of the Cg25 region within this apparent depression circuit might provide significant benefit for patients with treatment-resistant depression."

The researchers were able to track the clinical response of the patients over a 12-month period using standard depression rating scales as well as various quantitative measures of behaviour and general functioning, neuropsychological testing and scanning of both regional brain blood flow and glucose metabolism using positron emission tomography (PET).

PET imaging of these patients demonstrated that metabolic activity changed locally at the site of stimulation but also throughout the previously identified depression network, providing evidence that modulating the circuit and not just a single region was likely responsible for the antidepressant effects.

"We see depression as a complex disturbance of the specific circuits in the brain responsible for regulating mood and emotions," Mayberg says.

"We hypothesized that if DBS could locally modulate a critical central location within this mood circuit, such modulation would result in clinical improvement – and it appears it does."

The study began at the University of Toronto in 2002, led by Helen S. Mayberg, MD, and collaborators Andres Lozano, MD, PhD, neurosurgeon, and psychiatrist Sidney Kennedy, MD.

Mayberg is now a professor in the Department of Psychiatry and Behavioural Sciences and the Department of Neurology at Emory University School of Medicine. This clinical trial is the culmination of Mayberg's 20 years of research using brain imaging technology that has worked to characterise functional brain abnormalities in major depression and to identify the mechanisms of various antidepressant treatments.

A report on the first six patients in the study was published in the Journal Neuron in 2005. The new paper reports on an expanded sample of patients and an extended period of clinical follow-up.

While deep brain stimulation may seem to be a promising treatment for treatment resistant depression, research by York et al (2008) has found that deep brain stimulation as a treatment for Parkinson's disease carries a risk of mild cognitive decline, such as verbal memory, verbal fluency, timed transcription, and word naming.


Source: Adapted from press releases provided by EurekAlert and Newswise

Reference

Biological Psychiatry published online July 2008 DOI: 10.1016/jbiopsych.2008.05.034

York MK, Dulay M, Macias A, Levin HS, Grossman R, Simpson R, Jankovic J. (2008). Cognitive declines following bilateral subthalamic nucleus deep brain stimulation for the treatment of Parkinson’s disease. Journal of Neurology, Neurosurgery, and Psychiatry 79:789-795.