We might tend to think of depression arising from a lack of stimulation in the brain. But in at least one part of the brain — the lateral habenula — negative emotions might actually be caused by overstimulation.
"This part of the brain seems to be hyperactive in animal models of depression," said UC San Diego postdoctoral researcher Steven Shabel, first author on a study published Thursday in Science.
He and his colleagues in Roberto Malinow's lab have discovered an unusual connection leading to the lateral habenula, which is associated with feelings of disappointment.
This connection seemed strange to the researchers because most brain pathways are dedicated to a single role. They either excite a part of the brain with bursts of glutamate or calm it down with the neurotransmitter GABA; they either press on the gas pedal or hit the brakes.
But this connection was doing double duty.
"It seems like it's both pressing the gas and activating the brakes at the same time," Shabel explained .
A balance between those two signals keeps mood cruising at a safe speed. But when Shabel looked at the brains of rats showing signs of depression, he found the brakes had been cut. The lateral habenula was being overstimulated, which could be what drove depression in the animal models.
Shabel says current antidepressants help restore balance in this pathway, but do so indirectly.
"Perhaps you'd have an antidepressant which is more selective for helping people's motivation, and doesn't have some of the negative side effects that are common with antidepressants," he said.
