Greg Mattingly, MD, on Can Brain Changes That Occur in Chronic Depression Be Reversed?

In this video, Greg Mattingly, MD, discusses how some of the neurological impacts of chronic depression can possibly be reversed.

Additional Resources:

Unmet Needs in the Treatment of Depression

The Neurological Impacts of Chronic Depression

Dr. Mattingly is Associate Clinical Professor, Washington University, St. Louis, Missouri, principal investigator in clinical trials for Midwest Research Group and founding partner of St. Charles Psychiatric Associates, St. Charles, Missouri.


Chronic depression causes damage within neural networks in the brain. As we've talked about before, chronic depression causes decreased neural connectivity, where one set of neural cells doesn't cross‑talk to another set of nerve cells.

Pioneering work by Yvette Sheline, Wayne Drevets, and others has shown the chronic depression decreases the size of the hippocampus, damages parts of the anterior cingulate and other pathways within the brain.

The good news is, some of this damage can be reversed. We have wonderful new information about the role of neural networks, about the role of neural growth factors.

I'd like to go back in time. One of the reasons that I chose to go into neuroscience, chose to go into psychiatry, was in 1986, the Nobel Prize was awarded for the discovery of neural growth factor. That pioneering work was done by some researchers whose lab was at my university, at Washington University. For the women in the audience, Rita Montalcini was the first woman to win a Nobel Prize in neural science.

Rita Montalcini, Stanley Cohen in 1986, realized there's chemicals in the brain that we can turn on, that make nerve cells resilient under stress, that can make nerve cells grow, and arborize, and increase neural connectivity.

The next Nobel Prize that I'd like to remind us all of was 1999 when 2 researchers at the Rockefeller [University] center won the Nobel Prize for intracellular signal. When we touch glutamate receptors, what's going on inside the nerve cell on an enzymatic level that increases BDNF, that increases synaptogenesis, that increases neural arborization to increase neural connectivity?

The good news is, we have a new group of antidepressants, we tend to call them the fast‑acting antidepressants. They're medicines that tend to modulate the glutamate and GABA interface, that tend to help with neural growth factors, that tend to help with resilience.

Beyond medicines, we know there are other lifestyle interventions we can do within our patients' lives that increase neural connectivity. Number one is exercise. Exercise for all of us increases BDNF levels. What does that mean in the life of a patient with depression?

We’ve shown that exercise on top of an antidepressant and on top of psychotherapy doubles the chance that someone will go into remission when they're treated for depression. That increased improvement in depressive symptoms directly correlates with exercise's ability to turn on neural growth factors.

Another one that I'd like to pitch out to the audience, especially in this day and age of the COVID pandemic, is living life with a sense of purpose. Living life with a sense of purpose, each positive life event, gives us a little puff of BDNF, and each puff of BDNF increases neural connectivity and improves resilience for our patients.

Treating depression into remission, considering these new fast‑acting antidepressants that are on the horizon, exercise, living a life of purpose with social connection, all of those things help to mitigate against the damage in the brain that chronic depression can cause.



Submit Feedback