Talk recorded by CureTalks on June 28, 2022
Schizophrenia is one of the top 15 leading causes of disability throughout the world. It is a mental illness characterized by alterations to people's thought and behavior which can include psychosis – a condition which makes it difficult for them to recognise what is real and what isn't.
These symptoms often begin in late teens to mid-twenties and early treatment means better recovery. Early intervention, before psychosis develops in schizophrenia patients is thought to delay or even prevent the transition to psychosis and improve outcomes.
We are talking to Dr. Monica E. Calkins, Associate Professor of Psychology in Psychiatry at the University of Pennsylvania, to explore early indicators and discuss advances in early identification, prevention and finding more effective treatment of schizophrenia.
Transcript
Shweta Mishra: Hello and welcome to CureTalks. This is Shweta Mishra your host and today we are exploring Early Diagnosis and Treatment Options for Schizophrenia. We have with us Dr. Monica Calkins from the University of Pennsylvania. Dr. Calkins is Associate Professor of Psychology and Psychiatry and Director of Clinical Research Assessment in the Neuropsychiatry section at the University of Pennsylvania. Joining Dr. Calkins on the panel is patient advocate, Emeka Chima who was diagnosed with schizophrenia at the age of 15 and serves on the executive board as secretary for the non-profit organization- students with psychosis. Welcome to CureTalks everyone. Dr. Calkins we are talking about a condition here, which is one of the top 15 leading causes of disability throughout the world and it is recognized that Schizophrenia is not a single entity, but a large level of heterogeneity is present in the illness, and it can have multiple causes. So, could you please begin with what lies in the etiology of Schizophrenia? Is it genetic, is it environmental or a combination of both and what are other factors that are at play here that puts a person at high risk for schizophrenia or other psychosis spectrum disorders?
Dr. Monica E. Calkins: Yes, thank you. And thanks for having me here today. So, yes, as you said, it's a serious mental health disorder and really, no two people with schizophrenia have the exact same experience. There are just to kind of talk a little bit about what schizophrenia is first before we talk about the causes. There are six primary categories of symptoms that people with schizophrenia can experience and, in some combination, or another, so those include hallucinations which is perceiving things that other people don't that can be hearing or seeing or tasting or smelling or touching things, other people don't. So, for example in schizophrenia, audits where hallucinations, like hearing voices are common but people with schizophrenia can have other types of hallucinations as well. There are also delusions. These are very firmly held beliefs that things are happening to the person around the world that other people don't believe are happening and it's very real to the individual. So, person may believe that others are trying to hurt them or follow them, to that person that is their reality in the moment. Some people might believe that other people can hear their thoughts or that others are controlling your thoughts, or actions against their will, and those can be very distressing and scary feelings for people. Then they're also a third category is negative symptoms. And that's where a person might have some difficulties in experiencing emotions, like feeling a loss of Interest or pleasure of motivation, finding it really hard to get motivated to do things. And then they also experience some difficulties in expressing emotions like emotions on their face or through their bodily gestures. Some people with schizophrenia experience, disorganized speech, meaning that the person's speech can be difficult for other people to follow and in some cases can be very challenging for the person to communicate to other people what they're experiencing. And the fifth category is disorganized behaviour and that includes range of different behaviors in that including sometimes poor hygiene or dressing in a highly unusual manner and then finally, some people experience catatonic behavior, which is where the person has a really significant decrease in responding to the environment. So that's where a person for example, may be mute or immobile. So, for these symptoms, as you can imagine, they can really be significantly impacting for the individual and can lead to a really significant decline in the person's ability to function, to interact with peers, to do jobs for the family and when it happens to very younger people, young people that can lead to challenges and achieving the typical functioning.
So, important to note that the psychosis symptoms that I mentioned so it's hallucinations and delusions. They can and do occur in other mental health disorders, not just in schizophrenia. So, for example, people with severe mood episodes, can sometimes experience those types of symptoms as well. So those symptoms are not themselves diagnostics as schizophrenia. And then in schizophrenia, which does affect about 1 percent of the population, that's about one out of every 100 people, the onset usually occurs between the ages of 16 and 30. And that means that often the symptoms begin during the critical developmental period of adolescence or early adulthood and could really impact people's abilities to achieve their life goals. So as far as what causes schizophrenia, then, a good deal of research has shown that schizophrenia is the result of both of the things that you mentioned. So, the interactions between genes and environments during the development of the brain both before and after birth, so they're both genetic and environmental risk factors. For genetic risk factors, we know that schizophrenia is highly heritable, which means that having a genetic family history of schizophrenia increases a person's risk and there are recent large genetic studies, which show that there are multiple risk genes. So, it's not just like a single gene that contributes to risk, but multiple risk genes and these are likely genes that have what we call small effect and is called polygenic. So, meaning that there are many genes of small effect. And in recent years investigators have developed what they call polygenic risk scores, which estimate the overall genetic risk that a person has/might be carrying. Then there are also important environmental risk factors. And those are several factors, many of which we can think of, as sort of biological environmental risk factors mean that they likely impact the brain as its developing. And those include things like infections, migration, nutrition, discrimination and traumatic life events. And so, as the brain develops through childhood and early adolescence, these initial risks and exposures appear to contribute to a typical brain development for that individual. And this can interact with further environmental exposures such as cannabis use and social stress as the person is continuing to develop and grow and those transitions to psychosis, the ultimate transition to psychosis is then what we call neuro developmental process where those genetic vulnerabilities, interact with various adverse environmental influences, at anytime during brain development and continuing on through the onset of illness.
Shweta Mishra: Thank you. Thank you for all that comprehensive, explanation Doctor. Thank you so much. So, what does clinical high-risk mean when we are talking about schizophrenia? And what is the significance of this stage in the disease progression?
Dr. Monica E. Calkins: Yeah. So, critical high risk is symptoms that a person experiences that research has shown increased the person's risk of developing a threshold psychosis disorder like schizophrenia. And so those symptoms include what we call sub threshold for attenuated versions of the symptoms that I talked about. So, for example, a person might start to think or wonder whether other people are following them. So, they're not convinced as they would be if they had a delusion, but it can be really troubling and become quite distressing or interfere with the person's school or work or social relationships. And in the sub-threshold form of hallucinations, for example, a person might hear unusual sounds or whispers, but they know that it's not real and the person doesn't really have the full experience of a true perception as they would for a hallucination. So, it's more of an attenuated version of that symptom that we might see later on in a threshold psychosis state. So, there are two reasons that this clinical high-risk stage is really important. First clinically speaking those symptoms can be very early warning signs that person may be developing psychotic disorders. They present a real opportunity to see clinical care before the symptoms have progressed to a much more severe level. And then, one important thing to note here is this some people do have those kinds of symptoms and symptoms go away on their own or some people can experience them at this low level without ever transitioning to a psychosis Disorder. So, the challenges we can't currently predict for any given individual what's going to happen. And if those symptoms don't progress, they still can be associated with other things, like depression, or anxiety, or substance use. And so, they're still important to recognize and potentially address through clinical care. Since we can't tell what the course of those symptoms might be, or how they might impact the individual. It's important that young people are supported and encouraged to talk about their mental health experiences with trusted people. So, the parents or teachers, primary care providers, faith leaders and seek professional help early on. And this leads me to the second reason that the clinical high-risk stage is important, those early symptoms are also a window into the changes in the brain that are happening very early in the course of illness. So as researchers, this gives us the opportunity to investigate those changes and hopefully ultimately develop better medications or other interventions that we hope one day can be able to improve the course of a person's symptoms or maybe even prevent schizophrenia and other psychotic disorders all together.
Shweta Mishra: Right. Thank you so much. And you just made a very important point here, right. Highlighting the importance of sharing and reaching out for medical care sooner rather than later. So, thank you for that doctor. I'd like to talk a bit about diagnosis of schizophrenia, Doctor. So how is it currently diagnosed and for definitive diagnosis do you rely more on the neuro imaging scans or blood neurotransmitter levels, more on how the patients present themselves?
Dr. Monica E. Calkins: Yeah, so currently the diagnosis is based primarily on those mental health symptoms that I described. So, we would gather a description and history of symptoms. We try to incorporate as many sources of information as we can. So medical records, interviews with the individual about their experiences and the family member or someone close to the person who can provide observations and help inform the timeline of the symptoms. A medical professional often a psychiatrist will also usually order blood work and may order neuroimaging to know the medical causes of the psychosis symptoms such as a brain tumor, other brains pathology, but at this point neuroimaging is not diagnostic. So, there's no signature saying this person has schizophrenia from neuroimaging scan. Our hope is that one day a neuroimaging can contribute more to the diagnostic process, especially in the early phases of illness.
Shweta Mishra: Right, thank you for sharing that doctor. That's very helpful. So, talking about advances in diagnosis of mental health conditions, I know doctor you are involved with accelerated medicines program for schizophrenia, the AMP SCZ initiative for patients who are at high risk of developing schizophrenia. Could you talk a little bit about the aim of this program and the interventions that are ongoing or being developed to fill this gap in early diagnosis and perhaps treatment?
Dr. Monica E. Calkins: Absolutely, I'd be happy to. This is a really exciting, unprecedented commitment on the part of a number of different stakeholders to really gain some traction and try to make a difference, in terms of our understanding, be able to predict schizophrenia and other outcomes. So, the accelerated medicines partnership program is a public-private partnership between the National Institutes of Health, the US Food and Drug Administration, European Medicines Agency, and a number of different public, and Private organizations. So, it's managed through the foundation of the National Institutes of Health, and they've invested in 99.4 million dollars globally into this project, which is a massive endeavor, huge commitment on their part. It's a five-year effort and our aims are really to include developing tools that identify the early stages of risk for schizophrenia and predicting a likelihood of progression to psychosis and other outcomes. Another aim is to develop tools that can really help us to identify new targets for drug-based treatments that can be tested later on in clinical trials. So, currently it's not itself an interventional trial but it is something that we hope stands a very good chance better than many things that have come before in terms of developing new medications. So, a core component is to establish a research network focused on individuals with those clinical high-risk symptoms that I was telling you about and at AMP Schizophrenia there is a coordination center and then two research networks of 42 study sites across the globe were part of ProNET which is the Psychosis Risk Outcomes Network, the lead site is at Yale and there are 26 International sites of which Penn is one of those. The other research network is Prescient that centered in Melbourne, Australia, that has 16 sites. So there'll be a number of different assessments of 2,500 participants across North America, Australia, Asia and Europe, followed for two years, and will include a number of different measures including biomarkers, imaging, electroencephalography, fluid based markers, saliva and blood cognitive assessments, speech sampling and from this big data set we hope to be able to derive algorithms that predict clinical outcomes, including the transition to psychosis, persistent cognitive and functional impairment without psychosis. And also, hopefully remission of the clinical high risk state, so, being able to better to understand what the predictors of all of those are.
Shweta Mishra: That sounds very promising, Doctor and I would now like to bring some patient perspective to this discussion, Doctor and we have Emeka on the panel who is an undergrad and studying Information Systems Management and advocates for neurodivergent communities through his speeches and presentations. Emeka, welcome once again, and I know you have experienced living with two Chronic illnesses, schizophrenia and depression at the age of 15. So, before you begin with your questions for Dr. Calkins, would you like to tell us a bit about your story and how you overcame these illnesses and what you feel was the most important aspect of your care and what was your driving force?
Emeka Chima: Yes, so, my name is Emeka Chima. I am coming from Coopersburg, Maryland. So, my story starts, well I have ongoing history of mental illness. I was diagnosed with autism at age, 10. And later on, with mild schizophrenia and mild depression. At age 15, I was hospitalized once in 2014, twice in 2015. And I've been attending many outpatient programs as well. Those were really helpful for me. I met a lot of good people. Now be able to build a robust support system. I will always say the driving force for me has been self advocacy as well as the people around me, like community empowerment has been a driving force in my life. It has propelled me to new heights and my recovery journey. My mom, my dad they are my best allies. Currently I am with Students with Psychosis – non-profit group presenting virtually and in person. Upcoming from June 9, 2011, will be presenting at the MHA National Conference. I'm excited and happy to be able to be included in that project.
Shweta Mishra: I'm happy for you, Emeka.