The research from Columbia University Vagelos College of Physicians and Surgeons provides the first evidence that neurogenesis—the process of producing new neurons—stalls in the brains of adults with major depressive disorder (MDD). The study focused on the hippocampus, a brain region crucial for episodic memory and emotional responses, which is one of the few areas in the adult brain that continues to generate new neurons. The researchers suggest that without the ability to create new neurons, individuals with depression may lack the neural resilience needed to adapt effectively to environmental stressors and changes.
Beyond the observed reduction in neurogenesis, the study identified widespread molecular disruptions throughout the hippocampal circuit involved in storing episodic memories and their emotional significance. These disruptions included altered activity in genes responsible for forming new neuronal connections, cellular communication, energy supply, and intracellular transport. Additionally, evidence of inflammation and cellular stress was found in the trisynaptic circuit, the hippocampus’s primary pathway for establishing new emotional memories. The analysis, conducted on nearly half a million brain cells from both depressed individuals and control subjects, also revealed changes in genes previously associated with MDD and epigenetic modifications potentially influenced by environmental factors, such as stress. These diverse molecular changes may contribute to the heterogeneous presentation of depression across individuals.