Prevalence and Risk Factors for Major Depressive Disorder (MDD)

Andrew J. Cutler, MD: Hello, and thank you for joining this HCPLive® Peer Exchange program titled Expert Perspectives on Advances in the Management of Major Depressive Disorder. I’m your host, Dr Andrew Cutler and I’m a clinical associate professor of psychiatry at SUNY Upstate Medical University in Syracuse, New York. I’m joined today by 2 experts in the field of depression. Wouldeach of you please introduce yourself? Greg, why don’t you start?

Gregory Mattingly, MD: Sure, I’m Greg Mattingly, an associate clinical professor at the Washington University School of Medicine, and president of the Midwest Research Group in S. Louis, Missouri.

Sagar V. Parikh, MD, FRCPC: Hi everyone, I’m Sagar Parikh. I’m a psychiatrist and professor at the University of Michigan in Ann Arbor, Michigan.

Andrew J. Cutler, MD: Welcome, I’m really looking forward to our discussion, which will focus on treatment options for major depressive disorder or MDD. We will discuss data with newer mechanisms of action, and it’s a very exciting time in our field. We’re going to talk about new and emerging treatment options and management in specific patient populations and how some of these new treatments are aiming to fulfill the unmet needs of MDD. Thank you for joining us and let’s begin. Greg, would you start us off by discussing some of the trends in the prevalence of major depressive disorder in the United States? Tell us a little bit about how the COVID-19 pandemic has affected this, also.

Gregory Mattingly, MD: Certainly, Andy. As our audience knows, even before the COVID-19 pandemic, unfortunately, rates of depression in the United States had been going up, and not just rates of depression, but disability, and overall negative outcomes. Unfortunately, in depression, we’d been losing the battle. The stress of the COVID-19 pandemic only made things worse. Data that’s come out from numerous studies in the CDC across our country has shown that the rates of depression didn’t go up by 10% or 20% or 30% during COVID-19 but most of the studies have shown, Andy, that rates of major depression in the United States have gone up by over 200%. In particular, the most severe patients, the patients that come to our practices, we see those rates have dramatically increased over the last several years.

Andrew J. Cutler, MD: That’s really concerning, Greg. Let’s talk a little bit about our current understanding of the pathophysiology and some risk factors for MDD. Sagar, could you help us with that?

Sagar V. Parikh, MD, FRCPC: I think the pandemic Greg was just talking about was very instructive. When we think of the biopsychosocial model of depression, we had a negative experiment conducted because of what happened. We know that social interaction is an important contributor to mental well-being. And what did we have in the pandemic? We had isolation. As Greg said, we have higher rates of depression. We know that stress can drive depression. The pandemic was extremely stressful in a variety of ways. Finally, what is one of our best treatments for depression? It’s behavioral activation. It’s doing fun things. It’s getting out there. What did we do during the pandemic? We hunkered down. We couldn’t meet our friends, and we couldn’t even do a lot of the things that we like. Gyms were closed and so on. I think that just reinforced our understanding of depression and what makes us vulnerable and what are also avenues for treatment.

Andrew J. Cutler, MD: Sagar, don’t you also think that the uncertainty of this pandemic, is a new variant going to arise, and is someone I know or love going to get this? Don’t you think that added to this as well?

Sagar V. Parikh, MD, FRCPC: Well, we know that the etiology of depression in people is often preceded by heightened anxiety. That‘s often subsyndromal. It‘s not technically a symptom of depression, but obviously, it‘s frequently there and it presages depression in many people. When you talk about the uncertainty and the fear generated by the pandemic, yes, that certainly would be a setup for depression.

Andrew J. Cutler, MD: I agree. I think for vulnerable people that uncertainty is really concerning. Greg, there’s been some interesting advances in our understanding of the pathophysiology going beyond the monoamine theory. Can you talk us through some of the newer thinking here about what’s going on in the brain?

Gregory Mattingly, MD: Certainly. Many of us were trained in the monoamine generation. Talking about those primary monoamines; serotonin, norepinephrine, and dopamine. I know that all 3 of us have been involved in research over the past 20 or 30 years looking at how we touch various aspects of those monoamines to try to improve depression. Unfortunately, what we know is that mechanism, that series of monoamines only get us so far when it comes to the improvement of depression. It helps certain people, but it leaves other people behind that just don’t improve by tinkering with that mechanism. Some of the new research has been looking at the GABA [gamma-amino butyric acid] glutamate junction, and pathways that turn on neural growth, turn on neural membrane formation and release this group of compounds in the brain that we think of neural growth factors. Andy, I know you and I have talked about this a lot and one of the reasons I chose to go into neuroscience years ago was the Nobel Prize in 1986 for the discovery of neural growth factor. The fascinating thing now is we have tools that we’re looking at that are probing that GABA glutamate junction and turning on neural membrane formation, and turning on the release of neural growth factors.

Andrew J. Cutler, MD: It’s really fascinating how we’ve learned about the interplay; this excitatory inhibitory balance, and the interplay of glutamate and GABA. Then of course, as you mentioned, the neuroplasticity and synaptogenesis. How ultimately that may be how a lot of our medicines work. Also, Greg, when you and I trained, we were sort of taught there was a part of the brain that was responsible for depression or wasn’t working. We now know it’s much more about those circuits and the networks and network connectivity. I think it’s been very exciting to see how our understanding has evolved, and that’s leading to new targets for newer medications and other interventions.

Transcript edited for clarity