Most of the brain's roughly 100 billion neurons are produced before birth. However, the small number of new neurons that continue to form in the adult hippocampus may play an important role in protecting against depression, according to new research from Columbia University Vagelos College of Physicians and Surgeons. The findings provide the first evidence that neurogenesis, the process of producing new neurons, stalls in the brains of adults with major depressive disorder.
Researchers also identified molecular programs involved in controlling this process, offering potential clues for developing new treatments. "Historically, depression was thought to be a disease of neurotransmitter deficiency, especially serotonin, but we now think that depression stems from multiple issues that affect our neurons' ability to adapt to stress and changing environments," says Maura Dupont, professor of psychiatry, who led the research. "Without the ability to create new neurons, people with depression may not have the resilience to effectively adapt to the environment." How New Neurons May Shape Memory and Emotion The researchers focused on the hippocampus, a brain region that plays a major role in episodic memory and emotional responses to the environment.
It is also one of the few areas of the adult brain that continues to generate new neurons. Although the hippocampus is not the only brain region involved in depression, its influence over both memory and emotion has made it an important area of study. Researchers believe changes there may contribute to the tendency of people with depression to interpret experiences more negatively.
"The hippocampus is important for our ability to distinguish between similar but different memories and separate the emotional connotation of past memories and current events," Dupont says. This ability is known as pattern separation. When it becomes impaired, individual memories and the emotions attached to them may become less distinct, allowing separate experiences to blend together.
"You may be out with a friend for lunch, but she's tired and doesn't talk much. With intact pattern separation, you remember this as a unique event. With impaired pattern separation, it becomes mixed with previous memories of feeling rejected, leading you to think, 'They're upset with me'," Dupont explains.
"And I see this a lot in my patients, where they can only retrieve negative information from their memories." Research in mice has shown that adult neurogenesis is necessary for pattern separation. A recent study involving patients with brain tumors, in whom neurogenesis was eliminated by radiation therapy directed at the hippocampus, suggests that the same relationship may exist in humans. "It's important to emphasize that we do not yet know the complete mechanism, particularly in humans, but the newborn neurons seem to enhance pattern separation because they are especially responsive to new experiences and can be incorporated into new memory circuits more easily, allowing new memories to be stored separately from the old ones," Dupont says.
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