Nature Medicine: Depression May Impair the Brain’s Ability to Adapt to New Experiences

Scientists at Columbia University have found that major depressive disorder may halt the formation of new neurons in the hippocampus, one of the few regions of the human brain where neurogenesis continues after birth. The findings, published in Nature Medicine, could shed new light on the biological mechanisms underlying depression and point to potential new treatment strategies.

Most of the roughly 100 billion neurons in the human brain develop before birth. However, a small number of new nerve cells continue to form throughout adulthood, particularly in the hippocampus, a brain region involved in memory formation and the processing of emotional experiences.

The researchers found for the first time that this process appears to be effectively halted in people with major depressive disorder. According to study leader Maura Dupont, a professor of psychiatry at Columbia University, the brain’s ability to generate new neurons may be closely linked to its capacity to adapt to stress and changing circumstances.

The hippocampus plays a particularly important role in distinguishing between similar but different experiences and separating past emotional experiences from what is happening in the present. Scientists refer to this process as pattern separation. When it is impaired, new experiences may become mixed with negative memories.

For example, if a friend looks tired and speaks very little during lunch, a healthy brain can recognize this as a separate situation. When pattern separation is impaired, however, a person may associate the friend’s behavior with a previous experience of rejection and conclude that the friend is angry with them.

Previous animal studies have shown that normal pattern separation depends on neurogenesis in the hippocampus. Newly formed neurons are particularly responsive to novel experiences and may be more readily incorporated into new neural circuits, helping the brain distinguish fresh memories from older ones.

The researchers also found that depression is associated with much broader molecular changes in the hippocampus. These changes affect genes involved in the formation of connections between neurons, energy metabolism and intracellular transport. Signs of inflammation and cellular stress were also observed in neural circuits involved in the formation of emotional memories.

For the study, the scientists analyzed nearly 500,000 brain cells from deceased patients with depression and individuals without the disorder. Advanced techniques allowed them to examine gene activity in individual cells, identify changes in proteins and determine the precise location of cells within hippocampal structures.

The team also identified altered activity in several genes whose variants have previously been associated with the risk of major depressive disorder. Other changes may be linked to epigenetic processes, which can reflect the effects of stress, learning, aging and other environmental factors.

The researchers say the findings support the view that depression is not a single disorder with one underlying cause, but rather a complex condition involving multiple molecular abnormalities.

Follow NEWS.am Medicine on Facebook and Twitter