By Peter M. Vishton, PhD, William & Mary

Edited by Kate Findley and proofread by Angela Shoemaker, The Great Courses Daily

Researchers have found that exercise enhances the production of mood-boosting neurotransmitters. However, a relatively newer theory suggests a wholly different pathway by which both exercise and SSRIs might impact depression symptoms.

Defying Conventional Wisdom

It may be that the key to reducing depression is to make more neurons. This is called neurogenesis.

The conventional wisdom for many decades in neuroscience was that the brain produced neurons only early in development. By later childhood—certainly by the onset of puberty—it was believed that your brain had produced all of the neurons that it ever would. 

It’s long been understood that the brain continues to alter the patterns of connections between existing neurons throughout our lives and the strengths of those existing connections are altered by our experiences. In terms of the production of completely new neurons, that was presumed not to happen in the human brain.

If a peripheral neuron is destroyed—for example, if someone suffers a bad injury to a finger—it will often heal itself. In the central nervous system, though, neurons seem not to regenerate after they are destroyed. 

Studies on Neurogenesis

This is, to a large extent, true, but several teams of researchers in the 1980s and 1990s found evidence for adult neurogenesis—the creation of new neurons. The results were first found not in humans, actually, but in songbirds and, later, rats.

The basic technique for doing this is ingenious. A mildly radioactive label is injected into the bloodstream of the animal; that is, a label that’s designed to adhere to the animal’s DNA. 

In later microscopic imaging of the brain tissue, the labeled DNA can then be seen. When the body makes a new cell—any cells now, not just brain cells—it does so via a process called mitosis. 

The cell makes a copy of its own DNA, along with other critical internal components of the cell, and then divides—splitting in two to create a copy of itself. After a cell has undergone this mitosis, the labeled DNA looks different in very predictable ways. Essentially you can see where the brain has been making new cells during the time between the labeling injections and when the imaging takes place.

Amazingly, the brains of many animals seem to make new neurons on a pretty regular basis. The original work was done with songbirds—birds like canaries—who typically learn new songs every spring. 

As they undergo this seasonal learning process, their brains change in size substantially to support this new learning. The new cells are created, recruited into learning circuits, and then used just like older cells are.

Neuron Creation Process

In humans, it seems that new neurons are actually not produced in most brain regions. They might be, but, if they are, the neurogenesis is very slow and perhaps rare. There is now good evidence, however, that a neuron creation process takes place in at least two parts of the human brain; parts where rapid learning seems to take place.

The first is called the striatum; this is a subcortical part of the brain that’s central to implementing your responses to positive and negative reinforcements. When fighting procrastination, for example, you get that shot of pleasure when you complete something. 

That nucleus accumbens is one subpart of this larger striatum region. Just like songbirds, this is a part of the brain where continual learning and restructuring takes place.

The other region where rapid neurogenesis seems to take place in humans is in the hippocampus. This is a part of the brain that’s critical for many important cognitive functions.

Our internal mental map of the surrounding environment seems to be implemented in this part of the brain—including our sense of where we are on that mental map. Our ability to form new long-term memories is implemented in the hippocampus as well. 

People who suffer damage to the hippocampus can often remember many things that took place in their earlier life, but, after suffering the hippocampus injury, they lack the ability to remember new names, new places, new events—this is a condition called anterograde amnesia.

A particular region of the hippocampus seems to hang on to a stock of undifferentiated neuronal cells—essentially stem cells. When it uses some of them, the stock is replenished. 

Throughout our lives, these stem cells are converted into functioning neurons and incorporated into the regular function of the hippocampus. The precise details of how this takes place is still a bit of a mystery.

What we do know is that neurogenesis takes place. Something else we know is that it doesn’t take place nearly as much in people who suffer from depression symptoms. 

Depression and Neurogenesis

Several studies have found that people who suffer from major depression for several months actually have measurable smaller hippocampus regions. If the hippocampus reduces the rate at which it produces new neurons for an extended period, it will begin to shrink. This directly fits this notion that depression is related to a low rate of neuronal production in the hippocampus and other areas of the brain associated with learning and arousal.

We also know that patients who take antidepressant medications don’t typically experience an immediate recovery—their mood doesn’t immediately improve when they start to take a SSRI drug. Usually, the positive impact of the medication doesn’t kick in for several weeks. 

This is a bit surprising if depression is all about the neurotransmitters. The effects of those on serotonin and other neurotransmitters really shouldn’t take many weeks; it should take place over the course of hours or days at the most.

Interestingly, it also takes a few weeks for the brain to start producing new neurons more rapidly again. The neurogenesis and depressive symptoms seem to follow about the same timeline. Again, it seems that depression might be very much about neuron production.

All of this sounds like the story might be winding down. Depression is strongly associated with reduction in neurogenesis. Increase neurogenesis—maybe with drugs, or maybe with exercise—and depression goes away.

This article was edited by Kate Findley, Writer for The Great Courses Daily, and proofread by Angela Shoemaker, Proofreader and Copy Editor for The Great Courses Daily.