People with hyperactive brain responses to fearful faces may be the best candidates for a new class of antidepressants, finds a study in press in Biological Psychiatry by Giacomo Salvadore, MD, and his NIMH colleagues.

While conventional depression medications work through neurotransmitters such as serotonin and norepinephrine and take weeks to take effect, ketamine, a drug commonly used in pediatric anesthesia, targets glutamate and can lift depression in just hours, says Salvadore. Researchers are looking to target the effects of ketamine to figure out who it works best for and to eventually develop a class of antidepressants that share its quick-acting properties without the risk of addiction or psychotic symptoms.

To that end, Salvadore and his colleagues used magnetoencephalography to scan the brain activity of 11 people with depression and 11 healthy participants as they viewed illustrations of scared faces. At the beginning of the experiment, all the participants showed a spike of activation in their anterior cingulate cortex (ACC), an area of the brain that regulates mood. In healthy people, this tapered off over time, while many of the depressed people showed the opposite phenomenon, an increase in ACC activation over time.

Later, the researchers gave all the participants with depression a low dose of ketamine. Those who earlier showed elevated ACC activation were more likely to respond to the drug, says Salvadore.

Currently, physicians and psychologists use a trial-and-error process to find the treatment that works best for individual patients, Salvadore says. Hopefully this line of research will make identifying a treatment more scientific.

"The goal is to use this neural characteristic ... to tell with more certainty who will respond and who will not," Salvadore says.

—S. Dingfelder