Depression may interrupt the brain’s ability to make new neurons, human tissue study suggests
Does knowing that researchers can see cellular changes associated with depression alter how you think about the condition?
Depression changes how people feel, sleep, think and remember. New research suggests it may also alter one of the brain’s most intriguing forms of renewal.
Scientists examining human hippocampal tissue found that people with depression had more cells resembling neural stem cells but fewer cells in an intermediate stage of becoming mature neurons. The pattern suggests that the process of making new neurons may stall partway through. The underlying research is available in the NIH research summary.
That does not mean depression permanently stops the brain from renewing itself. The study was small and based on postmortem tissue. But it gives researchers a new place to look for the biology behind depression.
The hippocampus can keep producing neurons in adulthood
The hippocampus plays a major role in memory and emotional processing. Evidence indicates that it is also one of the brain regions where new neurons can continue to develop during adult life, a process known as neurogenesis.
An NIH-funded team analyzed about half a million hippocampal cells from 30 deceased donors: 19 without depression and 11 with depression. None of the donors with depression had taken antidepressants during the three months before death, reducing the chance that recent medication use explained the cellular differences.
The study examined human brain tissue directly, allowing researchers to map stages of neuron development that are difficult to study in living people.
More stem cells did not mean more new neurons
At first glance, finding more neural stem-like cells in depression might sound positive. But researchers also found fewer intermediate cells—the developing cells that would normally sit between a stem cell and a mature neuron.
That combination points to a possible bottleneck. The brain may have a supply of precursor cells but struggle to move them through the next steps of development.
The important finding was not simply the number of stem cells; it was the apparent interruption in the developmental pipeline.
The findings may help explain memory changes in depression
Depression is often associated with difficulties in concentration, memory and a tendency to give greater weight to negative information. Because the hippocampus helps organize memory, scientists have long been interested in how its structure and function change during depression.
Reduced or altered neurogenesis is one possible piece of that puzzle, not a complete explanation. Depression is biologically diverse, and symptoms can arise through multiple interacting systems involving stress hormones, inflammation, neural circuits, genetics and life experience.
No single cellular finding can explain a condition as complex as depression, but this one may help connect mood symptoms with changes in memory-related brain biology.
This research is not a new depression test or treatment
Postmortem studies provide a snapshot at the end of life. They cannot show when the cellular differences began, whether depression caused them or whether they contributed to depression.
The sample was also modest, particularly the group with depression. Researchers will need additional studies to confirm the pattern and determine whether treatments can restore progression from stem cells to developing neurons.
The study identifies a potential treatment target, not a treatment that is ready for patients.
Final word
One of the most interesting things about the adult brain is that it retains more capacity for change than scientists once assumed. The possibility that depression interferes with a renewal process in the hippocampus gives researchers a more specific biological question to pursue.
It also reinforces why depression should not be reduced to a matter of attitude or willpower. It is associated with measurable changes in brain function and, increasingly, with identifiable cellular biology.
The next challenge is to learn whether this apparent neurogenesis bottleneck can be reversed—and whether doing so actually improves depression.
QUESTION FOR READERS: Does knowing that researchers can see cellular changes associated with depression alter how you think about the condition?
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