The Brain Makes New Neurons Even in Adulthood — Depression May Stop It

A small stream of new neurons continues to form in the adult hippocampus even though most of the brain's roughly 100 billion neurons are created before birth, and new research from Columbia University Vagelos College of Physicians and Surgeons suggests this limited adult neurogenesis could play an important role in protecting against depression. The researchers report for the first time that neurogenesis stalls in the brains of adults with major depressive disorder, and they identified molecular programs controlling the process that could become targets for future 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," said 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."

The researchers focused on the hippocampus, a brain region central to memory and emotional responses and one of the few parts of the adult brain that produces new neurons. New neurons appear to support what Dupont calls "pattern separation" — the ability to distinguish between similar but different memories, and to separate the emotional weight of past events from present ones. "You may be out with a friend for lunch, but she's tired and doesn't talk much," Dupont said. "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.' 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, and evidence from a recent study of people whose hippocampal neurogenesis was eliminated by radiation treatment for brain tumours suggests the same link may exist in humans. "Turning neurogenesis back on may be a way to treat depression in some people by rewiring their hippocampus circuit," Dupont said.

To map the changes, researchers examined nearly half a million brain cells from the hippocampus of depressed and non-depressed donors, collected soon after death, measuring the activity of every gene in individual cells. They found molecular disruptions across the wider hippocampal circuit, including signs of inflammation and cellular stress in the trisynaptic circuit that forms new emotional memories. Some affected genes carried variants already linked to major depression, while others showed epigenetic changes — modifications that alter gene activity without changing the underlying DNA and can reflect life experiences such as stress.