NP Notes: Research and Future Directions (SCZ Episode 7)

Craig Chepke, MD, DFAPA: Hello, and welcome to the Great Exchanges and Schizophrenia podcast. I'm your host, Craig Chepke. I'm the medical director of Excel Psychiatric Associates in Huntersville, North Carolina and the scientific director of Psych Congress. And I'm here today with my friend and colleague of Dr Julie Carbray. Julie, tell us about yourself.  

Julie Carbray, PhD, APRN: Craig, I'm excited to do this podcast with you. I'm Julie Carbray. I'm at the University of Illinois, Chicago, Department of Psychiatry and Institute for Juvenile Research, where I'm the Director of our Pediatric Mood Disorder Clinic. It's great to be here, Craig, as a fellow steering committee member for Psych Congress and to talk about schizophrenia.  

Craig Chepke, MD, DFAPA: Yeah, I always really enjoy our conversations, Julie, and you bring just such a wealth of knowledge about an area that a lot of our colleagues are really begging for more information, and that's the developmental aspect, the translational aspect, and how people go from a child to an adult with an illness. Today, obviously, we're talking about schizophrenia, but in order to understand better, we've got—schizophrenia—we've got to understand the neurobiology better, and it's eluded us for decades, but we're starting to make some advances. Are we—what kind of research have you seen in the schizophrenia space lately for development?  

Julie Carbray, PhD, APRN: Well, we know it's a highly heritable disorder. We still don't, we haven't isolated this specific gene, genetic variance, but there's a lot of enthusiasm about understanding more what might be some of those neural developmental genetic sequences that might be correlated with this disorder. We view it more now as a neurodevelopmental disorder. We know that some of the environmental challenges that embrace early development in persons who move on to have schizophrenia, maybe things like even their birth experience, older fathers, early adverse childhood experiences, exposure to cannabis across those teenage years. And we also know that the brains of persons with schizophrenia look different. We know that gray matter volume seems to be less. We see increasing cortical thinning, and we see connectivity across different parts of the brain as looking very different, which makes sense, and which might explain a little bit why our psychopharmacologic agents may have some action. And more recently, I know you and I were talking about changes across the brain, different aspects of the brain, looking more at the ventral striatum being more involved as opposed to other areas of the brain initially.  

Craig Chepke, MD, DFAPA: Yeah, gosh, that is a lot to unpack. One thing that really lit up for me though, or recalled interaction with a family that I had, gosh, about a month ago or so, you mentioned the brain looks different, and the family had done a little bit of research and they really wanted me to order an MRI of the brain for this young first-episode individual. What are your thoughts on that?  

Julie Carbray, PhD, APRN: Yeah, we get that a lot. And we were very fortunate in our earlier days doing some of the research we were doing where we had some capacity to do it across our clinical trials. Often it's hard to get that done, but I do have to say we're getting MRIs done more these days than we probably were about 10 years ago. But it's typically across some different elements of psychosis that cause concern where we might have several areas of, say we're having tactile experiences, the patient is explaining bugs crawling. Or there might be periods of time where they might sort of look like they're having absence seizures or there's elements where we want to rule out is there anything apart from that. But we're still in the place where it's difficult to get an MRI and to justify it for symptoms of psychosis generally.  

Craig Chepke, MD, DFAPA: Exactly. And also you're at a large university center, you have the highest resolution scanners out in the community. We wouldn't be able to see much of anything, and it's not something that every single person with schizophrenia needs or it would even benefit from—  

Julie Carbray, PhD, APRN: And it's not diagnostic.  

Craig Chepke, MD, DFAPA: Yeah, exactly.  

Julie Carbray, PhD, APRN: So, unfortunately, sometimes families just really want a diagnostic picture of the brain, and that's really not where our science is yet. Although we may have some—

Craig Chepke, MD, DFAPA: Exactly.  

Julie Carbray, PhD, APRN: —indications that this looks similar to what we see in schizophrenia, it's not diagnosing anything. So you're really ruling out other issues.  

Craig Chepke, MD, DFAPA: Yeah, I think I said something like, I know that you wish you had something that could really confirm if what I'm making as this diagnosis is right. I wish that too. We're just not there yet and it's still in more of the research phase. And if there's so many false positive and false negatives, we'd be more likely to find something incidental that has nothing to do with it and would lead us down a rabbit hole than to really have anything useful, nothing that would change what we're doing with the treatment, things like that. And so I think that probably comes up a lot. It does in my practice at least.  

Julie Carbray, PhD, APRN: Absolutely. And Craig, for this disease specifically, you see problems with cognition. You see problems that look like depression or suddenly a decline in motivation and overall functioning becomes so impaired. So, it looks like a brain disease, doesn't it?  

Craig Chepke, MD, DFAPA: Absolutely.  

Julie Carbray, PhD, APRN: It looks like—and so the family, of course, has a great reason to want to rule out isn't there something else going on here? And so, being very delicate about what are these symptoms of concern? Where in the brain may this particular patient be having impaired functioning so that we can understand where we can guide our treatments. One area that schizophrenia has really moved forward to is looking at schizophrenia, not as a homogenous group, but more heterogeneous. So we know about the positive and negative symptoms, but how they play out in each individual looks so different. And especially in my world where we're seeing a neurodevelopmental prodrome that, emerging into psychosis. Sometimes these kids look like they have a motivation, anhedonia depression along with some unusual reverberations of psychosis. And so learning the signature of that person's illness becomes very important in guiding care.  

Craig Chepke, MD, DFAPA: And I love how you brought up how it's being viewed as a neurodevelopmental disorder. I've actually seen a lot of individuals with schizophrenia that also have on their chart a diagnosis of autism. But I think it's just that they got the autism diagnosis because of some of the prodromal symptoms and early-phase symptoms. And then that just once something gets on your electronic medical record, it never leaves. And so how many of these individuals, I think, actually have true comorbid autism and schizophrenia? Very few. But I think it speaks to the fact that we see things clinically that very much look like that, but that is part of that, for many individuals with schizophrenia, that's part of their symptom cluster. And we can call it heterogeneous or I call it that we're just not smart enough to understand that these are more than one illness. Go back to Eugen Bleuler who called it ‘the schizophrenias’ for a reason. There's so much heterogeneity, and we've just had treatments that are pretty one note, that historically they block the dopamine receptor either fully or completely.  

Julie Carbray, PhD, APRN: Partially or fully. Yes, yes. There was a great paper that came out just this past week on first-episode psychosis and advice for clinicians. And it's exactly getting at what you're talking about, Craig actually looking at differential diagnosis with autism, with mood disorders, and what are some of the challenges in the field around diagnostic tools and the lack of quick, I don't want to say quick tools, but tools that are at the fingertips for clinicians to be able to make some of those diagnostic differentials. There's some great case presentations, and so I think that's what's going to help us to move forward with guiding better care so that hopefully 10 years from now we're able to help these young persons with this prodrome to really get at what they need in terms of treatment and not get lost in some of the diagnostic mess that we can find from the neurodevelopmental perspective.  

Craig Chepke, MD, DFAPA: Yeah, and you probably should say quick, because for clinicians out in the trenches, it's got to be quick. We have limited time to see too many patients and do too much documentation, too many for  us, and we can't do a screening tool for everything that's incredibly comprehensive. But I do think it's important that we do improve the time to diagnosis. And what are some tips that you have for clinicians about some earlier interventions before the full-blown onset of schizophrenia? What do you think clinicians can do reasonably in their practice?  

Julie Carbray, PhD, APRN: Yeah, I think what really instills wellness across our patients, generally helps persons with schizophrenia. If they are still within a family structure, you also want to connect with those care-giving for the person who is experiencing psychosis and tracking symptoms, getting to understand what those symptoms look like, looking at functional impairment, what are they no longer doing that they were doing previously? Are we seeing more of those negative symptoms and what do they look like? Does it appear to be affiliated with mood or not? And really having a timeline where you're looking at what this person always looked like and what families will say is he's not himself. He is not the kid we knew, or he's not the young adult we knew, or he went off to college and we don't know what happened. Something started with this. And then you're reconstructing that timeline together. You're tracking symptoms, you're establishing healthy routines of sleep, of having a sense of purpose, of connecting with others, and really challenging that patient with what they can do and what they can't do. And then of course, beginning to educate about what they're feeling, what they need in the moment, what's happening in their brain. There's some discussion about being more internally connected versus externally connected, what's happening across their relationships, so that you can then develop that signature: For you, I'm concerned about these areas, and this will help us move forward into treatment.

Craig Chepke, MD, DFAPA: Such great advice about the wellness. I think that's incredibly important for so many reasons. One, we know that there are tremendous comorbidities in persons with schizophrenia of obesity, diabetes, cardiovascular disease, the number one killer of people with schizophrenia, just like it is the number one killer of all Americans, cardiovascular disease. But then also, on top of that, exercise is a great way to improve your neuroplasticity. And what do people with neurodevelopmental disorders need? Probably some neuroplasticity would be a good thing. And so, there's bringing in body benefits to exercise and other wellness techniques as well. So, I think that's fantastic.  

Julie Carbray, PhD, APRN: Absolutely. And if you think about negative symptoms, what we see is we see patients really beginning to retreat into their room, stopping engaging in things, maybe engaging in internet or very interactive ways of soothing themselves or trying to establish some control. So really identifying what might help them to not sort of go into that abyss of loneliness and internal preoccupation, but still finding points of connection across their day and exercise. You and I both know how challenging that can be to even getting folks moving around their house. I'm in Chicago where it's five degrees today, so, helping our patients to identify what are they doing within their home even to move.

Craig Chepke, MD, DFAPA: Right? And so exercise will stimulate neuroplasticity, but glutamate can too. What about pharmacological techniques and research leading into the neurobiology of non dopamine neurotransmitters? What can you tell us about that?  

Julie Carbray, PhD, APRN: Yeah, there was a lot of hope with maybe taking a look at glutamate, but we've had a couple of failed trials more recently, and so I think—but we've also had a great scientific discovery that launched this past year that was not acting in traditional ways on those DT receptors that also gives us some hope that we might be able to look across pharmacologic agents and possibly repurposing and looking at how do we better get at connectivity across the brain. What other receptors might be involved? And if glutamate is not one, where do we go next?  

Craig Chepke, MD, DFAPA: Well, I mean, glutamate has to be one. The cortex runs on glutamate. I mean, nothing happens in the human cerebral cortex without glutamate. So, anything in the CNS, glutamate’s involved. We just are too dumb to figure out as a field how, and how to harness that and leverage it in a way that can give us some therapeutics. But definitely, glutamate’s involved. But the point being that it's more than just dopamine. Dopamine is obviously incredibly important. We'll never move beyond including dopamine in our model of schizophrenia, but we've got to move beyond having it be ninety-nine percent of our thoughts on schizophrenia, and we need to figure out other ways to harness it because many treatments that—we have so many treatments that do directly interface with the D2 receptor, and so many individuals with schizophrenia still struggle, and we need to move beyond that.  

Julie Carbray, PhD, APRN: Right? I mean, for so long, that's all we've had for schizophrenia. And so there continues to be enthusiasm about new agents, but getting that right agent….

Craig Chepke, MD, DFAPA: Well, we've got one agent so far and then many more in the pipeline, so hopefully we'll continue to get many more.

Julie Carbray, PhD, APRN: It gives us some hope.  

Craig Chepke, MD, DFAPA: Exactly. We need hope and we need new treatments. What about non-pharmacological techniques, though?  

Julie Carbray, PhD, APRN: I was just going to say--that's one area where I think we're seeing more hope. For a long time, CBT was unimaginable with this population, and now we're getting some great studies that demonstrate its efficacy. We know that psychoeducation resonates. We know that cognitive remediation, really helping to retool the brain and enhance that neuroplasticity as well, from a cognitive perspective, demonstrates hope. We know that family support is critical, and we also know that a sense of purpose and ongoing psychotherapy has great benefit to patients with schizophrenia. I know when I was trained, oh, so long ago, that was not emphasized as much. We really only born to psychopharmacology, but we see that group therapy online support groups, connecting with other persons that are struggling with similar challenges in managing their illness is also critical. So yeah, there are some great psychosocial treatments that are imperative to employ as well, along with our psychopharmacologic treatments.

Craig Chepke, MD, DFAPA: Right. And the problem is that a lot of the therapists trained in these modalities for schizophrenia specifically, are not available to many of our colleagues. Do you have just one or two tips of things that our listeners can do in their practice from just a grassroots psychotherapeutic perspective of how do you connect and engage with someone with schizophrenia in this regard?  

Julie Carbray, PhD, APRN: Yeah, I think what's very important is relationship and developing that connection with somebody who seems to really understand what your experiences are, not challenging the experiences, but partnering and trying to understand what navigating those experiences is like for them. So that's like a basic psychotherapeutic intervention, right?  

Just being available. I'm thinking about a patient who is sharing his own visions of seeing a demon at times, and we would just sort of talk about it, what his experience was like, and that was everything to him. He was very concerned that if he was to share it elsewhere, that people would think he was crazy, that it would push people away. And so beginning there, and then having an understanding of incorporating some ways for him to manage this across his days. I don't want to say normalizing it, but in some respects, being able to use cognitive behavioral strategies to do something with this event that was happening with some frequency, causing some distress and helping him in the real moment to be able to walk through his day and keep hitting at his goals. So that would be an approach that any of us can do as psych nurse practitioners: Partnering, giving empathy, understanding a couple of approaches together that are understandable for him to accomplish and easily incorporate it across his day to be able to then release some of the distress and move forward with his recovery goals.  

Craig Chepke, MD, DFAPA: Absolutely. Great stuff as always, Julie. Unfortunately, we're out of time, but I do want to thank you for being here today and thank everyone for tuning in to the Great Exchanges in Schizophrenia podcast.