Depression May Shut Down the Brain's Ability to Grow New Neurons, Study Finds

Most of the brain's roughly 100 billion neurons form before birth, but a small number continue to be produced in the adult hippocampus throughout life. New research led by Maura Dupont, a professor of psychiatry at Columbia University Vagelos College of Physicians and Surgeons, provides the first evidence that this process, called neurogenesis, stalls in the brains of adults with major depressive disorder. The researchers also identified molecular programs that control it, offering possible clues for new treatments.

The study focused on the hippocampus, a brain region central to episodic memory and emotional responses, and one of the few adult brain areas that keeps generating new neurons. Researchers believe changes there may contribute to depression's tendency to skew memories negative, partly through a function called pattern separation — the ability to keep similar memories distinct. Studies in mice show adult neurogenesis is necessary for pattern separation, and a study of brain tumor patients whose neurogenesis was eliminated by radiation suggests the same link may hold in humans.

To trace the changes, researchers examined nearly half a million brain cells collected from people with depression and from control subjects shortly after death, measuring the activity of every gene in individual cells. Beyond neurogenesis, they found molecular disruptions across the wider hippocampal circuit, in genes involved in forming neuron connections, cell communication, energy supply and transport. The trisynaptic circuit, the hippocampus's main pathway for forming emotional memories, showed signs of inflammation and cellular stress.

Some altered genes carried variants already linked to major depression, while others showed epigenetic changes — alterations in how strongly genes are switched on or off, without changing DNA itself — that may reflect factors such as stress, aging or chemical exposure. Researchers say the range of changes found may indicate depression is not a single disease, and hope it could eventually be classified by molecular subtype, as cancer increasingly is.