Helen S. Mayberg & Andres
M. Lozano talk with ScienceWatch.com and answer a
few questions about this month's Emerging Research Front
Paper in the field of Psychiatry/Psychology. The
authors have also sent along an image of their
work.
Article: Deep brain stimulation for
treatment-resistant depression
Authors: Mayberg,
HS;Lozano, AM;Voon, V;McNeely, HE;Seminowicz,
D;Hamani, C;Schwalb, JM;Kennedy, SH
Journal: NEURON, 45 (5): 651-660 MAR 3 2005
Univ Toronto, Baycrest Ctr, Rotman Res Inst, Toronto, ON
M6A 2E1, Canada.
Univ Toronto, Baycrest Ctr, Rotman Res Inst, Toronto, ON
M6A 2E1, Canada.
(addresses have been truncated.)
Why do you think your paper is highly
cited?
Coauthor:
Andres M. Lozano
This paper describes a first proof-of-principle experiment testing a
potential new treatment for intractable major depression. The work served
to unite the fields of brain imaging of neuropsychiatric disorders with
neurosurgery and specifically deep brain stimulation (DBS) surgery.
Clinical and behavioral effects were robust, the procedure was safe, and
correlative imaging results supported the initial hypotheses.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
The new discovery is that modulating a specific area of the brain involved
in mood regulation with deep brain stimulation could possibly be effective
in patients with treatment-resistant depression.
Would you summarize the significance of your paper in
layman’s terms?
The subcallosal cingulate—Brodmann Area 25 (BA25)—has been
implicated in the pathophysiology of depression and antidepressant response
mechanisms. BA25 is an area in the cerebral cortex of the brain and
delineated based on its cytoarchitectonic characteristics. It is also
called the subgenual area or area subgenualis. It is the 25th "Brodmann
area" defined by Korbinian Brodmann, a German neurologist who became famous
for his definition of the cerebral cortex into 52 distinct regions.
Based on converging evidence, we piloted the use of continuous deep brain
stimulation (DBS) to modulate subcallosal cingulate activity as a novel
treatment strategy for patients resistant to other available treatments.
Chronic stimulation of this region using implantable electrodes was
associated with a striking and sustained remission of depression in four of
six patients. If these encouraging first findings are replicated in
controlled clinical trials, this new treatment strategy may offer a new
treatment option for depression when other available treatments are not
helpful.
How did you become involved in this research and were
any particular problems encountered along the way?
Based on a long series of previous studies of antidepressant treatment
mechanisms studied using functional neuroimaging, we tested the potential
application of deep brain stimulation to modify the activity in these
pathological brain circuits. There were no problems that weren't
anticipated based on past experience with this surgical procedure or in
treating a severely ill and refractory treatment resistant depressed
patient population.
Where do you see your research leading in the
future?
The study has already been expanded from the original six patients reported
in Neuron. A second paper extending this work was just published
reporting on a total of 20 patients followed for one year (Lozano AM,
et al., "Subcallosal cingulate gyrus deep brain stimulation for
treatment resistant depression" Biol Psych 64: 461-67, 2008).
This procedure is now also being tested in an FDA-approved,
industry-sponsored, placebo-controlled, multicenter clinical trial. New
studies of clinical efficacy, mechanisms, and procedural optimization
(patient selection, targeting) are underway at both Emory University and
the University of Toronto. These clinical studies further provide
foundation for complementary translational studies of both depression
pathophysiology and DBS mechanisms in new animal models.
Do you foresee any social or political implications for
your research?
A new treatment option for treatment resistant depressed patients has
considerable social and medical implications, if the safety and efficacy of
the treatment is confirmed in randomized, placebo-controlled clinical
trials.
Helen S. Mayberg, M.D.
Dorothy Fuqua Chair in Psychiatric Imaging and Therapeutics
Professor, Psychiatry and Neurology
Emory University
Atlanta, GA, USA Web
Andres M. Lozano, M.D., Ph.D.
Professor and RR Tasker Chair in Functional Neurosurgery
Canada Research Chair in Neuroscience
Division of Neurosurgery
Toronto Western Hospital
Toronto, Ontario, Canada Web