Dr. Greg Mattingly on the Neurological Impacts of Chronic Depression

In this video, Greg Mattingly, MD, talks about the neurological impacts of chronic depression.

Additional Resource:

Unmet Needs in the Treatment of 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.


We know that chronic depression doesn't just psychologically affect someone, but we know that neurologically, it affects the brain. Chronic depression over time tends to decrease the levels of chemicals in the brain that keep nerve cells resilient, growing, sprouting, and causing new connections.

We know that over time, the brain becomes stressed, we see cortisol levels go up, we see inflammation go up, and we see glutamate levels go down.

Associated with this increased inflammation, associated with decreased neural growth factors, we say that the brain connectivity over time diminishes, so that one part of the brain that used to cross‑talk to another part of the brain, we see that those pathways become less interconnected over time.

If we dive into a molecular or synaptic level, we see the synapses themselves become less arborized. We have decreased arborization on the tips of our nerve cells, which means one nerve cell has a harder time cross‑talking to another nerve cell.

What does that mean in the lives of our patients? When we talk about decreased neuroconnectivity, when we talk about impaired neural networks, what it means is, our patients are not resilient under stress. I'd like to ask each of you as clinicians, talk to your patients and say, "How are you doing on a good day?" but then, ask them the follow‑up question, "How do you do on a tough day?"

What you'll find is, many of your patients function OK under low levels of stress when neuroconnectivity isn't being tested. Under higher stressful days, maybe a stressful day at work, maybe a stressful day emotionally with their family, with their loved ones, in a relationship, what we find is, impaired neural connectivity decreases resilience in the brain and decreases resilience within one's life.