Millisecond Brain Signals Predict Response
to Fast-Acting Antidepressant
Electromagnetic Biomarker Could Minimize Trial-and-Error
Images of the brainís fastest signals reveal an electromagnetic
marker that predicts a patientís response to a fast-acting antidepressant,
researchers have discovered.
"Such biomarkers that identify who will benefit from a new class
of antidepressants could someday minimize trial-and-error prescribing
and speed delivery of care for what can be a life-threatening illness," said
Carlos Zarate, M.D., of the National Institute of Mental Health
(NIMH), Mood and Anxiety Disorders Program.
In the new study at the National Institutes of Health in Bethesda,
MD, depressed patients showed increasing activity in a mood-regulating
hub near the front of the brain while viewing flashing frightful
faces & the more the increase, the better their response to
an experimental fast-acting medication called ketamine. By contrast,
healthy controls showed decreasing activity in this brain area
under the same conditions.
Zarate, Giacomo Salvadore, M.D., Brian Cornwell, Ph.D., and NIMH
colleagues report on their discovery online in Biological Psychiatry September
Two years ago, Zarate and colleagues reported that ketamine,
which targets the brain chemical glutamate (http://www.nimh.nih.gov/science-news/2008/faster-acting-medications-for-bipolar-disorders-manic-phase-may-be-feasible.shtml),
depressions in just hours (http://www.nimh.nih.gov/science-news/2006/experimental-medication-kicks-depression-in-hours-instead-of-weeks.shtml)
instead of the weeks it takes conventional antidepressants, which
work through the brain chemical serotonin. Evidence suggests that
glutamate likely acts closer to the source of the depression than
serotonin, and is not dependant on slower mechanisms, such as the
synthesis of new
Earlier imaging studies with conventional antidepressants had
hinted that increased activity of the mood-regulating hub, called
the anterior cingulate cortex (ACC), signals a better response.
To find out if ACC activity might also forecast response to glutamate-targeting
medications, the NIMH researchers imaged the brain activity of
11 depressed patients and 11 healthy participants, using magnetoencephalography
(MEG). This imaging technology can non-invasively detect brain
electromagnetic activity lasting only milliseconds & the speed
of communications in neural circuits & whereas other functional
brain imaging techniques can only capture activity that last seconds
or minutes, and some involve radiation exposure. This precise timing
enabled the MEG scanner to capture the brainís split-second responses
to rapidly flashing pictures of fearful faces, a task known to
activate the ACC.
While healthy participantsí ACC activity dropped off as they quickly
habituated to the faces, patientsí ACC activity showed an opposite
trend. The more robust this increase, the more symptoms improved
just four hours after a patient received a single infusion of ketamine.
ďThe ACC may be slow to respond, but not completely impaired,
in patients who respond to ketamine,Ē explained Cornwell.
The lag in ACC activity could be a window into the dysfunctional
workings of the glutamate-related circuitry targeted by the medication,
the researchers suggest. Ketamineís side effects make it a poor
candidate for becoming a practical antidepressant, but the new
findings are helping to focus the search for new treatments that
work through the same mechanism, they say.
|The degree of increased activity
in a mood regulating hub called the anterior cingulate
(arrow) in response to flashing frightful faces predicted
a patientsí response to a fast-acting antidepressant mechanism.
MEG data superimposed on anatomical MRI image of the brain.
Source: NIMH Mood and Anxiety Disorders Program.
|Carlos Zarate, M.D., (left) NIMH
Mood and Anxiety Disorders Program, with MEG scanner. Source:
The National Institute of Mental Health (NIMH) mission is to reduce
the burden of mental and behavioral disorders through research
on mind, brain, and behavior. More information is available at
the NIMH website, http://www.nimh.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and Centers
and is a component of the U.S. Department of Health and Human Services.
It is the primary federal agency for conducting and supporting basic,
clinical and translational medical research, and it investigates
the causes, treatments, and cures for both common and rare diseases.
For more information about NIH and its programs, visit www.nih.gov.
Salvadore G, Cornwell BR, Colon-Rosario
V, Coppola R, Grillon C, Zarate CA, Manji H. Increased anterior cingulate
cortical activity in response to fearful faces: a neurophysiological
biomarker that predicts rapid antidepressant response to ketamine. Biol
Psychiatry. 2008 Sept. 25. [Epub ahead of print]
Tottenham, N., Tanaka, J., Leon, A.C., McCarry, T., Nurse, M., Hare,
T.A., Marcus, D.J., Westerlund, A., Casey, B.J., Nelson, C.A. (in
press). The NimStim set of facial expressions: judgments from untrained
research participants. Psychiatry Research.