U of M bipolar study could forge new path in treatment

NINA MOINI: An estimated 7 million adults in the US live with bipolar disorder, a mental health condition that causes dramatic shifts in a person's mood. But we're still learning all the neurological complexities of bipolar disorder.

A University of Minnesota medical research team has been awarded $4.4 million in a first in the world study of severe bipolar disorder. Dr. Ziad Nahas is leading this study. He's the executive vice chair and professor in the Department of Psychiatry and Behavioral Sciences. Thanks so much for your time this afternoon, Dr. Nahas.

ZIAD NAHAS: Thank you for hosting me, Nina.

NINA MOINI: If you could, could start by just explaining some of the symptoms people with bipolar disorder have generally?

ZIAD NAHAS: Bipolar disorder as a name, insinuate has two extreme, and obviously a lot of nuances in between. But the two poles are essentially severe depression and mania.

Depression is not just sadness, but impact your daily life, your ability to attend to your work, your family, your loved one, you're experiencing emotional pain. And it has certainly a lot of ramification on general health in general.

Whereas mania is the flip opposite is when people have delusions of grandeur, when they are very hyperactive and they cannot sleep, and they talk much, and they want to have impulsive behavior and really conquer the world without necessarily having the tools to do that.

NINA MOINI: And so the study is for people with severe bipolar disorder. At what point or how do you that it is considered severe?

ZIAD NAHAS: The technical definition of treatment resistant is having failed two antidepressant treatment and recurrent depressive episode.

But obviously, in the context of what we're studying, which involve a neurosurgical procedure to be able to both investigate the electrophysiological underpinning of the disorder, as well as to stimulate the brain chronically to treat it, we're looking for people that are substantially more severe. These are people that may have failed 5, 10 different psychotropic drugs. They may have even tried electroconvulsive therapy without any success.

And so obviously, in addition to the failed treatment, we're assessing chronicity of the symptom. Typically, the episode need to be at least two years, if not longer. On average, we get people with 10, 15 Sometimes they tell me I've been depressed all my life. And so clearly, the definition for our study involve a substantial disability that goes along with the illness. And in addition to documented failed treatment.

NINA MOINI: So my understanding is that there's two parts to the study. First, studying how the brain switches between mania and depression, which is fascinating because everyone I feel like has a different brain or functions, differently. And it sounds like you're leaning into the nuances there. And then it's also about relieving symptoms, but it does require surgery. Can you explain that surgery portion?

ZIAD NAHAS: Of course. So in the brain, in the same way that we have specific networks that regulate how we speak, the prosody of our speech, the movement, the refinement of our dexterities, et cetera, there are areas in the brain that regulate mood. And over the last couple of decades, we've made substantial improvement and headway in understanding these networks.

Roughly speaking, if you and I are conversing right now and paying attention and planning the next response, this is really engaging lateral aspect of the brain. Whereas, if I'm left to myself thinking about my own state and perhaps attending to my emotional pain and I'm depressed, these are medial network.

And so what we have been able to develop in collaboration with a lot of really smart people, one of my collaborators here at the University of Minnesota is Damian Feher in imaging. And we have essentially figured out a way that if we do functional imaging but acquire data for up to an hour, we can identify the network with a very high level of specificity at the individual level.

And so we take those images, instruct our surgeon, David Darrow and Michael park, to place paddles that are approved for spinal cord stimulation. These are small, a couple of inches long paddles, flexible, that have contact electrodes where we would implant them inside the skull on the surface of the brain, but specifically targeting these networks that I just mentioned.

NINA MOINI: But it's not permanent, right? I understand it's not permanent.

ZIAD NAHAS: These will be permanent in the sense that if-- we're not just doing the study-- as you mentioned it, it has two parts. So we're not just doing the study to investigate the underlying brain activity. What we also want to do is stimulate these mood regulating network and see if over time, we're able to fine tune our stimulation so that it's the most adaptive to what the individual brain requires in the moment, and over time, witness an improvement in their severe depression.

NINA MOINI: So what is the hope-- it sounds like this is a really hopeful discovery or process that you've all made. And I think just at a human level, when people are listening, they're thinking about loved ones and people they who struggle with bipolar or a number of other things.

When you're conducting this type of a study, is there a way that people can participate? And then what's the ultimate hope that it would be used for? Would it be like an everyday thing for people or something that would be really not that accessible to that many people to start?

ZIAD NAHAS: This particular study, and again, because of the severity and the nature of the intervention, which is neurosurgical intervention, which is often not the first thing we think about in treating psychiatric disorders, it's going to obviously has a very strict eligibility criteria. If patient are interested in learning more about the study, they can reach us via email at IPL, Interventional Psychiatry Lab, ipl@umn.edu.

Now, the hope is really not just that we would uncover the underlying mechanism for switching between depression and mania, which is still elusive to the scientific field. But from our invasive stimulation approach, that is way more targeted, way more specific, we expect that information and knowledge will be gathered so that we can turn and generalize this through non-invasive way of stimulating the brain.

So the information that we will get will help us understand how the disorder expresses itself. And then based on our ability to modulate very specific targets, then that particular target could then be accessed via non-invasive stimulation modalities or perhaps pharmacology as well.

NINA MOINI: All right. Very fascinating and important work. Thank you so much for sharing with us, doctor.

ZIAD NAHAS: You're most welcome.

NINA MOINI: Thank you. That's Dr. Ziad Nahas, the executive vice chair and professor in the Department of Psychiatry and Behavioral Sciences at the University of Minnesota Medical School.