Mental Illness and Brain Donation: An Interview with Josha A. Gordon

The Brain Donor Project recently had the honor of a one-on-one conversation with Dr. Joshua A. Gordon, Director of the National Institute of Mental Health. Since May is National Mental Health Awareness Month, we wanted to know how the science of severe mental illness is advancing…and we wanted to make sure that brain donation is helping.

BDP:  Is brain donation important?

Dr. Gordon:  It is incredibly important. We have lots of other wonderful tools, such as neuroimaging, which lets us see the activity of the brain. We also have tools where we can create brain cells from stem cells that we get from individuals’ skin and other tissue. So, there are lots of opportunities to teach us more and more about the origins of mental illness. But we also want to better understand the actual effects of lived experience with mental illness – and that’s where we really need the post-mortem brain tissue collections.

BDP:  As you know, severe mental illness is the largest single category of diagnoses reported by pre-registrants to the BDP. And treatment-resistant depression, which shows up more and more seems particularly tragic. Any developments on that front? 

Dr. Gordon:  I would say there are a few developments in treatment-resistant depression that are worth noting. First and foremost, there are a few new treatments out there. One notable FDA-approved treatment is a drug called S-ketamine, which is an intranasal version of ketamine that has been shown to be efficacious for people with treatment-resistant depression and has FDA approval for that indication.

There are a number of efforts to test the role of psychedelics in treatment-resistant depression. Those studies are currently in phase three trials, and the hope is that these drugs will be helpful for some people who have treatment-resistant depression. The other development that we’re working hard on is trying to identify biomarkers that will predict who will respond to first-line treatments versus who will go on to need one of these other therapies, so that we can get the right therapy to the right patient the first time, instead of going through many, many trials.

BDP:  What about devices? I’m hearing some things about implantable devices that may have some promise.

Dr. Gordon:  There are several types of implantable devices in use right now. For example, we have deep brain stimulators, which involve planting an electrode deep into one of two different areas in the brain. And there are vagal nerve stimulators,  which can send electrical pulses to the brain via the vagus nerve to help treat depression. These devices can work for some individuals, but we more research is needed

In addition, we have newer devices that are in the academic study stage. These devices can do things like read out the data from inside someone’s brain, find patterns that might be leading to that individual’s depressive mood, and try to stimulate the brain to disrupt those patterns. There are a few case reports of this working very nicely and  researchers are continuing explore ways to improve the efficacy and applicability of these tools.

BDP:  With the crisis in mental health provider staffing and the increased demand for services, how do you see this playing out? How are we going to make people better faster?

Dr. Gordon:  I think there’s a couple of new developments that are going to help in this regard. First and foremost, there’s the development of digital therapeutic aids that will help reach a broader range of patients. The best evidence indicates that these devices work best when they’re used in the context of a treatment relationship. Second, as I mentioned before, we’re also hoping that biomarkers will enable us to identify those individuals who will respond to specific treatments and get them those treatments as early as possible. A third important area is making sure that we understand how our treatments work in typically underserved populations. So, whether we’re talking about traditional treatments or these digital therapeutics or biomarkers, we have to make sure that we’re meeting the needs of the diverse populations here in the United States and around the globe.

BDP:  What else can we be doing to help you?

In terms of collection of post-mortem tissues,  the ability to link an individual’s samples across studies, while also protecting their identity will be important. In addition, as we do more of this biomarker work, and as we do more in-depth characterization of our patients, it’ll be important to have those data recorded and linked to the other kinds of information you’re able to get. 

But I also want to emphasize the importance of the work that the Brain Donor Project is already doing. Having a large and diverse collection of brains  that have been preserved and managed in a standardized way has greatly increased the power of our scientific investigations and advanced our understanding of the brain and its role in mental illnesses. And, so I want to underscore that what you’re already doing is incredibly important, and we’re really proud and pleased that you’ve been doing it so well.