Researchers from Columbia University Vagelos College of Physicians and Surgeons found that the production of new neurons, a process known as neurogenesis, appears to stall in the hippocampus of adults with major depressive disorder.

The hippocampus is a region of the brain involved in memory and emotional responses. It is also one of the few areas of the adult brain where new neurons continue to develop.

The findings suggest that reduced production of these neurons could affect the brain’s ability to distinguish new experiences from memories of previous negative experiences.

This process, known as pattern separation, helps people recognize that similar situations are not necessarily the same.

For example, someone may have lunch with a friend who happens to be unusually quiet.

A healthy pattern separation process can help the person understand that the situation is different from previous experiences of rejection.

When pattern separation is impaired, however, the new experience may become mixed with painful memories, potentially leading to a more negative interpretation.

Researchers said newly formed neurons may help the brain create separate circuits for new memories, allowing people to respond to current experiences without automatically connecting them to previous negative events.

However, they stressed that the exact mechanism, particularly in humans, is not yet fully understood.

The study also found that depression affects more than the production of new neurons.

Researchers identified molecular changes across the hippocampal circuit, including genes involved in creating connections between brain cells, communication between neurons, energy production and the movement of materials inside cells.

The researchers also found signs of inflammation and cellular stress in the brain circuits involved in forming new emotional memories.

To investigate these changes, the team examined nearly half a million brain cells collected from people with depression and people without the condition shortly after their deaths.

Using advanced techniques, researchers analyzed gene activity in individual cells and examined changes in cellular proteins.

This allowed them to identify changes occurring in specific cells and locations within the hippocampus.

The researchers also found changes in genes previously associated with major depression, while some other changes appeared to involve epigenetic mechanisms.

Epigenetic changes can influence how strongly genes are switched on or off without changing the underlying DNA sequence. Researchers said these mechanisms can be affected by factors including stress, learning, ageing and environmental exposures.

According to the researchers, the wide range of biological changes observed could help explain why depression can affect people differently.

The findings could eventually contribute to new approaches to treating depression. Researchers are particularly interested in whether restoring neurogenesis could help some people by changing how the hippocampus processes memories.

However, the study does not mean that scientists have found a single cause of depression or that treatments capable of restoring neurogenesis are currently available.

Instead, researchers say the findings could help move the understanding of depression beyond the traditional focus on neurotransmitters such as serotonin and toward a more detailed understanding of the cellular and molecular changes involved.

The team also hopes that depression could eventually be classified according to its biological and molecular characteristics, potentially allowing treatments to be tailored to different forms of the disorder.