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Interviewer: You've already tried mood-balancing medications such as SSRIs and cognitive behavioral therapy to treat obsessive-compulsive disorder or major depressive disorder, and those treatments aren't working. You're not alone. Treatment-resistant OCD and depression isn't uncommon.

Matter of fact, it's estimated 40% to 50% of OCD patients are considered treatment resistant. And when those first-line treatments don't work, many explore surgical options.

Dr. Ben Shofty is a neurosurgeon from the Clinical Neurosciences Center at the University of Utah Health and is an expert in surgical treatments for OCD and MDD.

And today, we're going to learn about common surgical treatment options that are providing hope to those with treatment-resistant OCD and depression.

Dr. Shofty, how long does a patient need to be on standard treatments until they're considered treatment resistant?

Dr. Shofty: For a patient to be even considered for therapy, they have to have availed all other therapeutic options, especially the non-invasive ones, which mainly consist of drug therapies, SSRIs, SNRIs, and tricyclic antidepressants, and behavioral therapies like psychotherapy, exposure and response prevention, and cognitive behavioral therapies.

Interviewer: And how long does somebody have to be on the non-invasive types of treatments before they can be considered nonresponsive? Is that a year or longer than that?

Dr. Shofty: Usually, we are looking at patients that have been suffering from the disease at least five years.

Interviewer: Before we head to some of the specifics about the three different treatments, some common questions that might come to mind when treating OCD and MDD with surgical procedures. First of all, in general, are the treatments effective?

Dr. Shofty: The treatments are super effective. Considering the fact that these patients are usually patients that have failed everything else, I think the treatments are life-changing.

Surgical treatment for OCD has been approved by the FDA for more than 10 years, and recently we had a lot of good high-quality data from around the world, in the United States, Europe, and even Australia, that show about 60% to 70% of patients respond to treatment and their disease improves by roughly 40% to 50%, which is a huge change. I mean, these patients can actually go back to living a relatively normal life.

Interviewer: So, I hear those numbers, and in the real world, that is a significant difference.

Dr. Shofty: That's a huge difference, yeah. That's a life-changing difference. Even some of the patients that we do not classify as responders because they only had 30% improvement in their disease metrics, this is a huge improvement even if they're not officially defined as responders.

Interviewer: And surgery can be kind of scary. Do you find that the patients that come in tend to be a little apprehensive about getting surgery for their condition or are they at a point where not so much because they're just looking for any sort of help?

Dr. Shofty: These patients are usually desperate. I mean, they've exhausted every other therapeutic option out there, including a lot of well-based therapies and some experimental therapies, and this is pretty much their last resort.

I also think over the last 10 to 15 years, there has been such a technological improvement in our ability to perform these surgeries safely. And these are quality-of-life surgeries, right? We're trying to improve these patients' quality of life.

So, these are super safe surgeries. Usually, there's a day of recovery inside the hospital, and then the patients go home the following day and go back to their normal lives pretty soon after the surgery.

Interviewer: Then after the procedures, and I realize that for each one it might differ and for each person it probably differs as well, but how long until patients start kind of seeing results?

Dr. Shofty: These are chronic diseases. Patients have been living with them for many years, usually anywhere between 5 and 30, and it takes time for the effect to sort of fully manifest itself. We don't talk about success of therapy at least until six months have gone by. Usually, the maximal effect is witnessed within a year.

Interviewer: When treating OCD and MDD with surgery, generally how do these surgical treatments work?

Dr. Shofty: Our main advancement and the main reason that these therapies are becoming so efficient these days is that we finally understood that it's not a single area of the brain that's not working well, but it's a network, which means that a few, two or maybe more, different areas of the brain are not talking to each other in the way that they should.

And once we've understood that, we can look into a specific patient's disease and the way his brain networks are sort of modulated or altered or working differently, and we can try and target that specific area and that specific place in the brain which is causing this miscommunication.

Once we do that, once we figure that out, the tool that we use doesn't really matter. I mean, we can choose from our sort of toolbox the perfect or the best treatment and sort of tailor the therapy to that individual patient.

Interviewer: That's incredible that you're able to trigger . . . you're able to pinpoint exactly where you need to go and what you need to do in each area.

Dr. Shofty: Yeah. And I think that's the main reason why these therapies are becoming better and better, because our ability to understand the specific patient and the specific patient's disease is becoming better.

Interviewer: And what are some other of the new developments that have allowed this treatment to be so successful?

Dr. Shofty: So, we have a bunch of tools that have become better and better over the last years. One of them is DBS, Deep Brain Stimulation, in which we have newer electrodes and newer devices that can provide smarter and more sophisticated stimulation to the area of the brain that we want to affect.

Interviewer: And Deep Brain Stimulation, I've heard of that before for other conditions.

Dr. Shofty: Yes, it's been around for almost 30 years. It's been used widely for movement disorders such as Parkinson's disease and essential tremor and others, and it's been FDA approved for OCD for more than 10 years.

Interviewer: So, Deep Brain Stimulation might be a procedure that would work for one particular patient. What are other options that are in your toolbox that might work for somebody else?

Dr. Shofty: One of them is creating a lesion or severing a specific bundle of fibers that sometimes causes severe OCD. We can do that today in a minimally invasive approach using laser fibers and under MRI guidance so we know exactly what we're burning and we are just damaging that specific fiber bundle inside the brain.

Interviewer: And with a tool like that, when you're damaging that specific fiber bundle, are there other side effects that might arise out of that?

Dr. Shofty: The reason that this approach was developed is to minimize the side effects, because you are only hitting the sort of damaged part of the brain that you want to affect. And when people used to do that 20 or 30 years ago, they didn't have all these sophisticated tools and they caused more damage than was probably needed. So, today we actually err on the safer side and do less damage.

And then if we have to enlarge the treatment, we can go back in and do it again. It's minimally invasive. Patients go home the next day. There are barely any incisions, so the recovery is super quick.

Interviewer: The third option is Vagus Nerve Stimulation or VNS. How does that work?

Dr. Shofty: So, VNS is an approved therapy for patients with the treatment-resistant depression. It is a peripheral neurostimulator. It connects to the vagus nerve, which then carries the electrical stimulation to the brain.

Interviewer: What is the biggest barrier or reason why somebody doesn't pursue a surgical treatment for their OCD or MDD?

Dr. Shofty: So, I think that there's a knowledge gap with our sort of community providers and community psychiatrists who are not always aware of the modern sort of surgeries and therapies that we can offer these patients. They're also not always aware of the recent advances and publications that have shown that these treatments are safe and highly effective for these specific patients.

Interviewer: Yeah. Somebody like you, this is all you pay attention to, so of course you would know about it.

Dr. Shofty: Yeah, exactly. I mean, medicine is so subspecialized today that it's hard to keep track with all the recent advances. But I think there are a lot of recent advances that have been published that show and support these approaches for these patients.

Interviewer: How should a patient bring this up with their primary physician that they're working with for their OCD or MDD if they're interested in a surgical option and it hasn't been offered?

Dr. Shofty: I think that if you've exhausted all other treatment options, you should bring it up just like that. "I've heard that there's a new psychiatric neurosurgery center at The U and I wanted to consult with them. Is there a chance you can refer me there?"

And we have a quick screening process that allows us to sort of say if the patient is a possible candidate. And for possible candidates, we have a very fast-track assessment process.

The second barrier is to be insurance. I think over the last four or five years, insurance companies have started understanding it's actually cost-effective to approve these surgeries for these patients. And Anthem has actually made a significant policy change and have added DBS for OCD as a medical necessity in their guidelines. So, I think it's easier today to get insurance approval for these procedures.

Interviewer: Well, I'd imagine that there's somebody listening that is very interested in a surgical option at this point given the success rate and given the change in somebody's life. Tell me a brief story as we wrap this up of somebody who came in, had the procedure, what they were like, and then . . . what their life was like, and then had the procedure, and then what their life was like after.

Dr. Shofty: So, we've had an OCD patient who was basically house-ridden for more than three years. Every time he needed to go out of his house and come back, it used to take anywhere between four and six hours going back from the front door to the living room because he had to do so many rituals and so many compulsions. We've operated on him successfully, and six months later, he's back to work. He still has OCD, but he manages it.

One of the good things about these therapies is that they allow patients to respond to medical treatment and to psychological treatments such as exposure and response prevention, which they did not respond to before surgery. So, it's not only the effect of surgery, but it's the effect that it enables them to respond to other types of therapies.

And a lot of our patients have a similar story. They just went back to living a normal life with the disease and not living just under the disease.

Interviewer: Hollywood has been banking on fascinating taboos in their shows and movies and this is why psychiatric illness have been such a major theme. But what do you really know about them? That's next on The Scope.

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Interviewer: We're talking today with Dr. Jason Hunziker, psychiatrist at the University of Utah about Hollywood and psychiatric illnesses, in movies and TV shows. One that pops into my head is the film Sybil, which was actually a real case taken from a book that was actually based on a real life patient.

Dr. Hunziker: Yes, dissociative identity disorder or at that time known as multiple personality disorder.

Interviewer: Like Sybil had.

Dr. Hunziker: Exactly. It is one of the more common psychiatric illnesses used in movies because so much is not known about that illness. But it also plays on all of our kind of fantasies and fascinations, and our interest about what the brain can do and how fragile it really can be.

Interviewer: So what exactly is Hollywood's definition of dissociative identity disorder?

Dr. Hunziker: The way films look at it is a way that I think it was described early on, which is somebody who has suffered from a very bad trauma, usually some type of sexual trauma, when they were young, that may or may not have been repeated over and over again, that somehow fractures their brain.

Interviewer: What does fracture your brain mean?

Dr. Hunziker: What that means is that the brain is so powerful that it does what it can to protect the human body against some outside source that's so overwhelming that it feels like you might die literally from that exposure. So the brain then separates itself and allows you to protect it by sending your consciousness level off somewhere else while your body just kind of remains there in person dealing with that trauma.

Interviewer: So it's kind of like you have multiple views.

Dr. Hunziker: Exactly, and that's where this came from. While you're gone somebody else is interacting with the people around, and so the thought was that people would form these different personalities to deal with different stressors in their life. And so Hollywood, of course, jumped all over that. What a great story, you have all these different people living inside you and when you go to the grocery store you can be Jill, and when you go to the carwash you're Bobbie, and when you're at home with your Mom you're a three-year-old girl who's scared. So Hollywood loves that stuff. But that's not the reality of what this illness really is.

Interviewer: Reality then; what have you seen in your studies and patients' cases?

Dr. Hunziker: There is so much controversy, even in the mental health industry about dissociative identity disorder. There are those that swear by almost the Hollywood version of what this looks like. And then there are others who say people clearly use dissociation to help protect themselves, and that's kind of where I fall in line. I think that people use that mechanism to get out of a stressful situation, and they then have a different personality style that interacts with you during those moments that they are real self is not present.
So when patients that I've seen, and that's generally what I've seen, is that when they get under stress they fall back onto disassociation to protect themselves, and they literally are not the same person. I talk to them, and they don't respond as quickly. They respond differently. But they are not Bobbie or Johnny, or Cindy; they don't have a name to it. It's just a part of their personality that remains to get the job done while the other part is protected and away from the stress.

Interviewer: This sounds to me, and correct me if I'm wrong, but kind of like a PTSD.

Dr. Hunziker: Exactly like PTSD. I think we see that a lot more now and I think dissociation is becoming more prominent because of our soldiers who are coming home and they struggle with flashbacks and paranoia, and depression and anger. All of these things, and when they get into a experience that's similar to what they experienced in the Middle East, they shut down and disappear, and they try to alleviate the stress by letting their brain wander somewhere else.

Interviewer: But it's not exactly like having multiple personalities, and that's what the illness was called back then.

Dr. Hunziker: That's correct. And again, it's hard, because there are two different camps on this, and there will be arguments that there are distinct personalities, and those distinct personalities need to all be reintegrated into one person, so the person can be whole again. But that's just not been my experience clinically when I have somebody who has that diagnosis or come to me with that diagnosis. That's not what I have seen.

Interviewer: When someone comes to you and they tell you, I have multiple personalities, as you mentioned before that some of your patients come and they tell you that they have multiple personalities, are they aware then that they have multiple personalities?

Dr. Hunziker: Again, that's where the controversy is, too. If they really are not present with the other personalities, it's hard to know why they know that they have multiple people and who they are and what their names are and what they are doing.

Interviewer: Right.

Dr. Hunziker: But they will, and I do have patients who tell me they have multiple personalities, and they'll have four or five or ten, and they have names for all of them. And some patients have been through the reintegration process and so they feel like it's mainly under control and all their personalities are meshed together. Others say they're still struggling with that. But the importance is when they tell me that, what I understand is they are extremely distressed, and whatever that stress is is causing their brain to not function in a way that's healthy for them. And so we focus more on that, and not so much on each individual personality.

Interviewer: Because you really don't know how many personalities they might have.

Dr. Hunziker: That's correct, and it's easier to say, we want to keep you, the real you, here with us dealing with everyday life, and we don't want you to keep using that crutch or that defense mechanism of dissociation to leave and then not deal with the issue that we really need to deal with.

Interviewer: How do you develop something like this? It's so fascinating, and like you said, controversial in so many areas of film and life?

Dr. Hunziker: It's hard to know how this really develops and we do see patterns in people who have dissociation as a major feature of their illness. And that pattern generally is the trauma. Some type of extreme trauma where you think your life is being threatened will then promote this type of defense.

Interviewer: It's almost like you're protecting yourself.

Dr. Hunziker: Yes, from experiencing what's going on, because it's too overwhelming. Because when you're young, we use these types of defense mechanisms all the time. I mean, we all use dissociation...

Interviewer: We play house or doctor.

Dr. Hunziker: Exactly, and we disappear into, and you'll hear your mom say, well you used to disappear into this different world. Well you did, and that works for us when we're kids. But when we're adults disappearing doesn't work as well. But when you get a trauma, particularly at that age, you get stuck and then that defense mechanism can become the prominent defense mechanism that you use later in life when it doesn't work anymore to disappear and go to your...

Interviewer: Happy place.

Dr. Hunziker: Your happy place, exactly. And instead you are not present with the people around you and then when you interact with them it's different, it's odd.

Interviewer: Any final thoughts on this?

Dr. Hunziker: Again, I'm glad that Hollywood brings awareness to mental illness, but I think we have to remember that Hollywood tends to over generalize and/or overly extreme put mental illness in the forefront that some of the symptoms that they describe are not accurate. But if you do have family members that struggle from zoning out or not being present all the time, or forgetful and don't remember doing certain things, that's probably time to get them into the doctor and be evaluated to make sure that dissociation is not something that they are experiencing.

Dr. Miller: We're your daily dose of science, conversation, medicine. This is The Scope; University of Utah Health Sciences Radio.

Interviewer: Examining the latest research and telling you about the latest breakthroughs, The Science and Research Show is on The Scope. Who your parents are matter. Dr. Christopher Gregg, a professor in neurobiology and anatomy, is researching patterns of inheritance that long-term effects on behavior and the development of mental health disorders. Dr. Gregg, what motivates your work?

Dr. Christopher Gregg: The cost of mental health in society, mental health issues, are unbelievable. Unbelievable. Most of the people in prisons, most of the people that are homeless, most of the people that are struggling to get by in life are suffering from some mental health issue.

Addiction, all of these problems are brain related and behavior related. At the moment, most of the pharmaceutical companies are pulling money out because the brain is so hard to figure out. It's so hard to find targets and it's so hard to find effective ways to influence behaviors in a predicable manner.

So in my mind, I think because we think we are able to decode these pathways in the brain, I think we have a very unique place in the field. I think we have a real opportunity to make a difference.

Interviewer: You're interested in how behavior is inherited?

Dr. Christopher Gregg: When people think about behavior I think they think a lot about the factors in their environment. So you might think about what role your parents played in your upbringing, what are your socioeconomic circumstances, what sorts of stresses and pressures do you have in your life, and so you think about the behaviors that you have or maybe why a particular disorder or addiction or some stress or anxiety disorder might emerge and you might think about those issues.

But, in fact, it looks like most psychiatric disorders are strongly influenced by your genes. So as a consequence, we have focused an enormous amount of effort in our research program in trying to define the genes that influence specific behaviors.

Interviewer: So why is that interesting to you?

Dr. Christopher Gregg: We had known before that there were these rare examples of genes called imprinted genes that exclusively express the copy you get from your father or exclusively express the copy you get from your mother, but people didn't have any way to study them in a kind of unbiased manner. So we set about to find all of these imprinting effects in the genome.

The bigger vision continues to be a general interest in finding antagonistic pathways in the brain. So when you think about many behaviors or different physiological states, they're opposing. You can be hungry or you can be satiated. You can be anxious or you can be calm. You can be social or you can be antisocial.

Naively, we thought maybe we could kind of decode the genome into the genes that push you down one path versus the genes that push you down the other path.

Interviewer: Why did you look into that in the first place?

Dr. Christopher Gregg: There was a theory proposed several years ago by an evolutionary biologist named David Higg. David proposed that there would be a conflict between mothers and fathers in placental mammals. The reason was that mothers are the only ones that make a metabolic investment by supplying nutrients through the placenta or through the nursing through lactation and fathers don't make any investment.
David predicted that mothers would evolve mechanisms that make the offspring less demanding and fathers would evolve mechanisms that make the offspring more demanding so they grow bigger, consume more resources, and outcompete the offspring for mother and father.

Interviewer: So how do you think how genes are expressed in the brain might fit Higg's hypothesis?

Dr. Christopher Gregg: We think the weaning period is sort of a major point of conflict because this is the period when offspring develop behavioral traits that are required for them to be independent from the mother. They become independent in terms of being able to find their own food. They have changes to anxiety and exploratory behaviors, changes to learning and cognition. Those changes have a major impact on the mother. The faster and more effectively that the offspring transition to being independent the less the demand on the mother's resources.

Interviewer: A lot of your work focuses on genes that regulate brain function or behavior and whether they're inherited from your mother or your father.

Dr. Christopher Gregg: The researchers in my lab have spent time developing technologies that allow us to study the expression of genes you get from your mother and compare them to the expressions of genes you get from your father. We find there are a lot of really interesting differences.

What's particularly compelling about some of those differences is that they seem to be particularly enriched in the brain. So we looked at differences in the expression of genes from maternally and paternally inherited chromosomes in the liver, in the muscle, and now in two brain regions, and in the developing brain and we find there are a lot of differences in the developing brain and in the adult brain but not very many differences in the liver and in the muscle. The chromosomes you get from your mother and the chromosomes you get from your father are used differently in the brain.

Interviewer: Were you surprised to find that? Did you actually think it would turn out that way?

Dr. Christopher Gregg: We were very surprised. We continue to be surprise as we discover more and more things as we're doing this work. Now what I think is important to recognize is the implications of our study for human disease are that if you inherit mutations from your mother versus your father in these genes, it will have different effects on you.

Imagine you did a mutation in a particular gene that's imprinted and you inherent that mutation from your father. If you don't express the copy that you get from your father because there's a bias to express to copy that you get from your mother because it's a maternally expressed imprinting, then that mutation is not going to have such a deleterious effect on you. On the other hand, if you inherited that same mutation from your mother for that gene, then the effect is expected to be much stronger because there's no other healthy copy to buffer the effect.

Interviewer: So the idea is that one day, if you find that a susceptibility to being autistic is more likely to come from your mother, then the healthcare system can come up with a way to test for that?

Dr. Christopher Gregg: We already are able to analyze the genome sequence of a patient and we're able to analyze a genome sequence of that patient's parents. We can determine whether a mutation has been inherited from a mother or a father and by looking at that mutation, as well as many other mutations in an individual's genome, we think that we'll be able to infer whether that person is at risk for developing psychiatric disorders at later stages in life.

Interviewer: Are there some genes that you found that might suggest this antagonistic control, where one side has the opposite function of the other and that might be connected to a behavior?

Dr. Christopher Gregg: In very preliminary work we think we have defined antagonistic gene pathways that regulate anxiety and maybe risk for panic disorders.

Interviewer: So what's the next step to take that work?

Dr. Christopher Gregg: I think we have a very clear path ahead of use. We're going to define these pathways that are antagonistic and make you less or more anxious, for example. Then we have developed software in the lab that builds on those insights to find how those pathways intersect with known drugged pathways and our goal is to develop novel therapeutics and novel therapeutic strategies by leveraging that insight.

Then on the diagnostic side, by finding novel pathways that influence anxiety we can more accurately identify individuals that are at risk for developing an anxiety disorder.

The greater vision of the work in the lab is to define all of the sort of these functionally antagonistic pathways in the brain that drive different aspects of behavior and to develop a panel of markers that will help diagnose susceptibility for aberrant motivated behaviors and to develop novel therapeutics that modulate these pathways so that you can treat people that have problems with addiction, anxiety, social behaviors, eating disorders, these types of things.

Interviewer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.