Depression's 'Dimmer Switch' Discovered

Scientists have discovered a "dimmer switch" in the brain that can not only help them better understand the brain chemistry behind mood disorders like depression, but how to treat them, too, according to new research published in the journal Science.

"The idea that some people see the world as a glass half empty has a chemical basis in the brain," senior author Roberto Malinow, said in a news release. "What we have found is a process that may dampen the brain's sensitivity to negative life events."

Researchers at University of California, San Diego School of Medicine have identified a control mechanism for an area of the brain that processes sensory and emotive information that humans experience as "disappointment." Specifically, through experiments with rodents, they found that neurons feeding into a small region above the thalamus known as the lateral habenula (LHb) secrete both a common excitatory neurotransmitter, glutamate, and its opposite, the inhibitory neurotransmitter GABA.

Previous studies have only identified two other systems in the brain where neurons had been observed to co-release excitatory and inhibitory neurotransmitters.

"Our study is one of the first to rigorously document that inhibition can co-exist with excitation in a brain pathway," explained lead author Steven Shabel. "In our case, that pathway is believed to signal disappointment."

Proper functioning of the LHb is believed to be important in much more than just disappointment. It has been implicated in regulating pain responses and a variety of motivational behaviors, and has also been linked to psychosis.

Depression, in particular, has been linked to hyperactivity of the LHb, but until this study, researchers had little evidence as to why this overstimulation occurred in some people and not others.

Researchers were also able to show that neurons of rodents with hints of human depression produced less GABA, relative to glutamate. When these animals were given an antidepressant to raise their brain's serotonin levels, their relative GABA levels increased.

"The take-home of this study is that inhibition in this pathway is coming from an unusual co-release of neurotransmitters into the habenula," Shabel said.

"We may now have a precise neurochemical explanation for why antidepressants make some people more resilient to negative experiences."