Depression Shrinks The Brain, And Now Scientists Have Found The Protein Responsible For It

When people suffer from depression, their brains literally shrink. Now scientists think they've uncovered the reason. Megan Leetz, CC BY-ND 2.0

Science has known for some time that depression, the devastating neurological disorder, has the curious property of shrinking the sufferer’s brain. Less clear was how exactly that happened, but a new study from Yale University reports that scientists may have found an answer.

Inside your brain are hundreds of billions of neurons constantly firing to send signals that cause you to think, feel, move, react, see, taste, and experience the world. Connecting those neurons are spindly structures called dendrites. They act as bridges for each packet of information that gets sent around the neighborhood of your brain and even play a role in releasing certain neurotransmitters. But new research suggests that when a person lacks a specific protein, called REDD1, these dendrites shrink. And the precious feelings of pleasure and happiness that once raced through your brain now get bottlenecked — never to be felt or enjoyed.

"Acute stress is a normal part of life, and you bounce back and that's fine," Colleen Loo, depression researcher of the University of New South Wales, who was not involved with the study, told NewScientist. "But the longer you're depressed the more likely you are to have shrinkage in the brain.”

Depression is the most common mental illness in the United States. It’s estimated that 17 percent of the U.S. population at one time or another will experience a depressive episode, and the grandfather illness, Major Depressive Disorder, arises in roughly three to five percent of all males and eight to 10 percent in females. Though typically mistaken for a mood disorder, depression has legitimate chemical roots and a neurological underpinning that makes overcoming the disease more complicated than “snapping out of it.”

It’s for this reason so many prescription drugs have been developed in the pursuit of treating depression. And the current research helps explain it even further. When scientists bred ordinary lab rats to be without the protein REDD1, which has previously been shown to reduce myelin, the fatty material that protects neurons, the mice that were exposed to extreme stress showed resistance to developing depressive symptoms. Normal mice, however, fell into the usual pattern of behavior — their brain’s shrinking and their eating habits subsiding.

By contrast, the mutant rats that had been engineered to overproduce REDD1 grew depressed without any added stress. And when they were injected with stress hormones, REDD1 levels spiked. When they were then given a drug that blocked the production of stress hormones, they stopped producing the protein even though they were externally stressed.

Together these findings implicate REDD1 as the mediating factor in producing depressive symptoms in rats, whose brains are often studied in scientific research because of their similarities to human brains. In fact, when study leader Ronald Duman looked at postmortem brain tissue of humans, he found REDD1’s overabundance in depression sufferers. But it’s not necessarily REDD1 that’s doing the heavy lifting, but another protein.

This protein, called mTORC1, is produced according to the commands of REDD1. As far as Duman sees it, REDD1 inhibits the production of mTORC1, which itself is used to repair broken brain cells. One of the chief reasons ketamine and other similar antidepressants work so well is that they boost mTORC1 levels. According to the latest theory, this allows the brain cells to heal and the dendrites to return to full strength.

Ultimately, researchers hope to use this protein as the target for future studies and possible pharmacological approaches in treating depression. “This study is teasing out what are the molecular pathways by which stress translates to shrinkage of brain cells,” Loo explained. “But knowing the complexity of humans, it doesn't mean this is the whole story.”


Source: Ota K, Liu R, Voleti B, et al. REDD1 is essential for stress-induced synaptic loss and depressive behavior. Nature Medicine. 2014.