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More data point to potency of genes in development of psychosis
Early findings suggest that positive environment is not protective
ORLANDO – A genetic profile that’s considered risky for psychosis matters more for patients who come from an environmental background that is considered good, while it doesn’t seem to make much of a difference among those whose environmental background is more adverse, according to research presented at the annual congress of the Schizophrenia International Research Society.
Researchers at the University of Pennsylvania, Philadelphia, are examining a wide variety of data – from socioeconomic factors to neuroimaging – to assess how these data all feed into the psychosis picture, asking whether some factors matter more than others and which factors can be used to predict the development of psychosis in the future.
“The goal of all of the research ... is to try and capture people earlier in the course of development where we can try and tweak the developmental trajectory,” said Raquel Gur, MD, PhD, professor of psychiatry, neurology, and radiology at the university.
The findings come from the Philadelphia Neurodevelopmental Cohort, a community sample of about 9,500 children and young adults aged 8-21 years, with an average age of 15 years, collected through pediatricians. About 1,600 had neuroimaging. Researchers followed 961 participants who had baseline measurements recorded and were seen at follow-up visits after 2 years and 4 years, or longer.
Participants had clinical testing done to determine traumatic stressful events and to look for symptoms seen as precursors to psychosis. They also had neurocognitive battery tests performed. Neuroimaging, genomics testing, and information from their electronic medical record were also examined.
One of the most salient findings so far in their ongoing analysis involved the relationship between polygenic risk score (PRS) and their environmental risk score (ERS), which factored in items such as household income from their geographic area, percentage of married adults in their area, crime rates in their area, and traumatic stressful events experienced personally. The ERS scores were grouped into “good” scores and “bad” scores.
Researchers saw a trend in which, among those with good ERS scores, the average PRS was higher for those with psychotic spectrum symptoms than for those with normal development, with very little overlapping of 95% confidence intervals. But among those with bad ERS scores, the average PRS was about the same for those with psychotic spectrum symptoms and those with normal development.
“If you have genetic vulnerability, a good environment is not going to protect you. You’re going to manifest it,” Dr. Gur said. “However, in a negative environment that has adversity that includes both a poor environment and traumatic events, the polygenic risk score matters less.”
They are continuing to explore and assess these findings.
The researchers also found differences in cognitive functioning among those with poor environmental scores, which dovetail with defects seen in schizophrenia, such as executive functioning.
“Neurocognitive functioning can be established with brief computerized testing,” Dr. Gur said, “and shows deficit in the psychosis spectrum group in domains that have been implicated in schizophrenia.”
Dr. Gur reported no relevant financial disclosures.
Early findings suggest that positive environment is not protective
Early findings suggest that positive environment is not protective
ORLANDO – A genetic profile that’s considered risky for psychosis matters more for patients who come from an environmental background that is considered good, while it doesn’t seem to make much of a difference among those whose environmental background is more adverse, according to research presented at the annual congress of the Schizophrenia International Research Society.
Researchers at the University of Pennsylvania, Philadelphia, are examining a wide variety of data – from socioeconomic factors to neuroimaging – to assess how these data all feed into the psychosis picture, asking whether some factors matter more than others and which factors can be used to predict the development of psychosis in the future.
“The goal of all of the research ... is to try and capture people earlier in the course of development where we can try and tweak the developmental trajectory,” said Raquel Gur, MD, PhD, professor of psychiatry, neurology, and radiology at the university.
The findings come from the Philadelphia Neurodevelopmental Cohort, a community sample of about 9,500 children and young adults aged 8-21 years, with an average age of 15 years, collected through pediatricians. About 1,600 had neuroimaging. Researchers followed 961 participants who had baseline measurements recorded and were seen at follow-up visits after 2 years and 4 years, or longer.
Participants had clinical testing done to determine traumatic stressful events and to look for symptoms seen as precursors to psychosis. They also had neurocognitive battery tests performed. Neuroimaging, genomics testing, and information from their electronic medical record were also examined.
One of the most salient findings so far in their ongoing analysis involved the relationship between polygenic risk score (PRS) and their environmental risk score (ERS), which factored in items such as household income from their geographic area, percentage of married adults in their area, crime rates in their area, and traumatic stressful events experienced personally. The ERS scores were grouped into “good” scores and “bad” scores.
Researchers saw a trend in which, among those with good ERS scores, the average PRS was higher for those with psychotic spectrum symptoms than for those with normal development, with very little overlapping of 95% confidence intervals. But among those with bad ERS scores, the average PRS was about the same for those with psychotic spectrum symptoms and those with normal development.
“If you have genetic vulnerability, a good environment is not going to protect you. You’re going to manifest it,” Dr. Gur said. “However, in a negative environment that has adversity that includes both a poor environment and traumatic events, the polygenic risk score matters less.”
They are continuing to explore and assess these findings.
The researchers also found differences in cognitive functioning among those with poor environmental scores, which dovetail with defects seen in schizophrenia, such as executive functioning.
“Neurocognitive functioning can be established with brief computerized testing,” Dr. Gur said, “and shows deficit in the psychosis spectrum group in domains that have been implicated in schizophrenia.”
Dr. Gur reported no relevant financial disclosures.
ORLANDO – A genetic profile that’s considered risky for psychosis matters more for patients who come from an environmental background that is considered good, while it doesn’t seem to make much of a difference among those whose environmental background is more adverse, according to research presented at the annual congress of the Schizophrenia International Research Society.
Researchers at the University of Pennsylvania, Philadelphia, are examining a wide variety of data – from socioeconomic factors to neuroimaging – to assess how these data all feed into the psychosis picture, asking whether some factors matter more than others and which factors can be used to predict the development of psychosis in the future.
“The goal of all of the research ... is to try and capture people earlier in the course of development where we can try and tweak the developmental trajectory,” said Raquel Gur, MD, PhD, professor of psychiatry, neurology, and radiology at the university.
The findings come from the Philadelphia Neurodevelopmental Cohort, a community sample of about 9,500 children and young adults aged 8-21 years, with an average age of 15 years, collected through pediatricians. About 1,600 had neuroimaging. Researchers followed 961 participants who had baseline measurements recorded and were seen at follow-up visits after 2 years and 4 years, or longer.
Participants had clinical testing done to determine traumatic stressful events and to look for symptoms seen as precursors to psychosis. They also had neurocognitive battery tests performed. Neuroimaging, genomics testing, and information from their electronic medical record were also examined.
One of the most salient findings so far in their ongoing analysis involved the relationship between polygenic risk score (PRS) and their environmental risk score (ERS), which factored in items such as household income from their geographic area, percentage of married adults in their area, crime rates in their area, and traumatic stressful events experienced personally. The ERS scores were grouped into “good” scores and “bad” scores.
Researchers saw a trend in which, among those with good ERS scores, the average PRS was higher for those with psychotic spectrum symptoms than for those with normal development, with very little overlapping of 95% confidence intervals. But among those with bad ERS scores, the average PRS was about the same for those with psychotic spectrum symptoms and those with normal development.
“If you have genetic vulnerability, a good environment is not going to protect you. You’re going to manifest it,” Dr. Gur said. “However, in a negative environment that has adversity that includes both a poor environment and traumatic events, the polygenic risk score matters less.”
They are continuing to explore and assess these findings.
The researchers also found differences in cognitive functioning among those with poor environmental scores, which dovetail with defects seen in schizophrenia, such as executive functioning.
“Neurocognitive functioning can be established with brief computerized testing,” Dr. Gur said, “and shows deficit in the psychosis spectrum group in domains that have been implicated in schizophrenia.”
Dr. Gur reported no relevant financial disclosures.
REPORTING FROM SIRS 2019
Early childhood infections tied to psychosis risk
ORLANDO – Infections before the age of 4 are linked to the risk of nonaffective psychosis (NAP) in adulthood, according to a study presented at the annual congress of the Schizophrenia International Research Society. Researchers also found that a lower IQ seems to make the psychosis risk more likely.
It’s well-established in the literature that infections are tied to schizophrenia and that a premorbid IQ deficit is linked as well. Researchers looked to a huge data pool from the Swedish population to try to better define these risks.
“We know that there is an association between infection and schizophrenia,” said Golam Khandaker, MRCPsych, PhD, head of the inflammation and psychiatry research group at the University of Cambridge (England). “We know that there is premorbid IQ deficit in schizophrenia. So, we wanted to know, is there a sensitive period during childhood when exposure to infection is more harmful?”
Researchers analyzed data for 647,000 people in the Swedish population who were born between 1973 and 1997, and conscripted for military service through 2010. Exposure to infection was considered to be any hospitalization with any serious infection between birth and age 13. IQ measurements were taken during military conscription at the age of 18. And researchers looked for risk of nonaffective psychosis from the age of 18 on.
There was a significant increase in risk of nonaffective psychosis in adulthood among those who’d had an infection, with a hazard ratio of 1.16 (95% confidence interval, 1.08-1.24). But when researchers broke down this risk into smaller age spans, they found that only infection between birth and 1 year old (HR, 1.19; 95% CI, 1.06-1.33) and between age 2 and 4 (HR, 1.11; 95% CI, 1.02-1.22) was linked with a significantly elevated risk of NAP. Researchers also saw a link between infection and IQ.
Researchers assessed whether familial factors could be confounding this link. They looked at rates of NAP among those with an early infection and no early infection in the general population and found that it was no different statistically than among full siblings with an early infection, compared with those with no early infection. In other words, the infection-psychosis risk was the same – whether someone was a close family member or not.
Dr. Khandaker said the findings more definitively establish a link between infection and psychosis risk and suggest that the early years are when children are at their most vulnerable.
“The association between adult nonaffective psychosis with premorbid IQ and childhood infection are not explained by shared familial confounding,” he said. “So these associations could be causal.”
When they looked at the role of IQ and the link between infection and psychosis risk, researchers found an interaction: With every 1-point decrease in IQ score, there was a corresponding increased risk of NAP among those with childhood infections (odds ratio, 1.006; P = .02).
“Childhood infections,” Dr. Khandaker said, “increase psychosis risk partly by interfering with neurodevelopment, and partly by exaggerating the effects of cognitive vulnerability to psychosis.”
Dr. Khandaker disclosed no relevant financial relationships.
ORLANDO – Infections before the age of 4 are linked to the risk of nonaffective psychosis (NAP) in adulthood, according to a study presented at the annual congress of the Schizophrenia International Research Society. Researchers also found that a lower IQ seems to make the psychosis risk more likely.
It’s well-established in the literature that infections are tied to schizophrenia and that a premorbid IQ deficit is linked as well. Researchers looked to a huge data pool from the Swedish population to try to better define these risks.
“We know that there is an association between infection and schizophrenia,” said Golam Khandaker, MRCPsych, PhD, head of the inflammation and psychiatry research group at the University of Cambridge (England). “We know that there is premorbid IQ deficit in schizophrenia. So, we wanted to know, is there a sensitive period during childhood when exposure to infection is more harmful?”
Researchers analyzed data for 647,000 people in the Swedish population who were born between 1973 and 1997, and conscripted for military service through 2010. Exposure to infection was considered to be any hospitalization with any serious infection between birth and age 13. IQ measurements were taken during military conscription at the age of 18. And researchers looked for risk of nonaffective psychosis from the age of 18 on.
There was a significant increase in risk of nonaffective psychosis in adulthood among those who’d had an infection, with a hazard ratio of 1.16 (95% confidence interval, 1.08-1.24). But when researchers broke down this risk into smaller age spans, they found that only infection between birth and 1 year old (HR, 1.19; 95% CI, 1.06-1.33) and between age 2 and 4 (HR, 1.11; 95% CI, 1.02-1.22) was linked with a significantly elevated risk of NAP. Researchers also saw a link between infection and IQ.
Researchers assessed whether familial factors could be confounding this link. They looked at rates of NAP among those with an early infection and no early infection in the general population and found that it was no different statistically than among full siblings with an early infection, compared with those with no early infection. In other words, the infection-psychosis risk was the same – whether someone was a close family member or not.
Dr. Khandaker said the findings more definitively establish a link between infection and psychosis risk and suggest that the early years are when children are at their most vulnerable.
“The association between adult nonaffective psychosis with premorbid IQ and childhood infection are not explained by shared familial confounding,” he said. “So these associations could be causal.”
When they looked at the role of IQ and the link between infection and psychosis risk, researchers found an interaction: With every 1-point decrease in IQ score, there was a corresponding increased risk of NAP among those with childhood infections (odds ratio, 1.006; P = .02).
“Childhood infections,” Dr. Khandaker said, “increase psychosis risk partly by interfering with neurodevelopment, and partly by exaggerating the effects of cognitive vulnerability to psychosis.”
Dr. Khandaker disclosed no relevant financial relationships.
ORLANDO – Infections before the age of 4 are linked to the risk of nonaffective psychosis (NAP) in adulthood, according to a study presented at the annual congress of the Schizophrenia International Research Society. Researchers also found that a lower IQ seems to make the psychosis risk more likely.
It’s well-established in the literature that infections are tied to schizophrenia and that a premorbid IQ deficit is linked as well. Researchers looked to a huge data pool from the Swedish population to try to better define these risks.
“We know that there is an association between infection and schizophrenia,” said Golam Khandaker, MRCPsych, PhD, head of the inflammation and psychiatry research group at the University of Cambridge (England). “We know that there is premorbid IQ deficit in schizophrenia. So, we wanted to know, is there a sensitive period during childhood when exposure to infection is more harmful?”
Researchers analyzed data for 647,000 people in the Swedish population who were born between 1973 and 1997, and conscripted for military service through 2010. Exposure to infection was considered to be any hospitalization with any serious infection between birth and age 13. IQ measurements were taken during military conscription at the age of 18. And researchers looked for risk of nonaffective psychosis from the age of 18 on.
There was a significant increase in risk of nonaffective psychosis in adulthood among those who’d had an infection, with a hazard ratio of 1.16 (95% confidence interval, 1.08-1.24). But when researchers broke down this risk into smaller age spans, they found that only infection between birth and 1 year old (HR, 1.19; 95% CI, 1.06-1.33) and between age 2 and 4 (HR, 1.11; 95% CI, 1.02-1.22) was linked with a significantly elevated risk of NAP. Researchers also saw a link between infection and IQ.
Researchers assessed whether familial factors could be confounding this link. They looked at rates of NAP among those with an early infection and no early infection in the general population and found that it was no different statistically than among full siblings with an early infection, compared with those with no early infection. In other words, the infection-psychosis risk was the same – whether someone was a close family member or not.
Dr. Khandaker said the findings more definitively establish a link between infection and psychosis risk and suggest that the early years are when children are at their most vulnerable.
“The association between adult nonaffective psychosis with premorbid IQ and childhood infection are not explained by shared familial confounding,” he said. “So these associations could be causal.”
When they looked at the role of IQ and the link between infection and psychosis risk, researchers found an interaction: With every 1-point decrease in IQ score, there was a corresponding increased risk of NAP among those with childhood infections (odds ratio, 1.006; P = .02).
“Childhood infections,” Dr. Khandaker said, “increase psychosis risk partly by interfering with neurodevelopment, and partly by exaggerating the effects of cognitive vulnerability to psychosis.”
Dr. Khandaker disclosed no relevant financial relationships.
REPORTING FROM SIRS 2019
‘Exergaming’ boosts motivation in schizophrenia patients
Attrition rates encouraging in community program
ORLANDO – Using games to promote exercise – or “exergaming” – is proving to boost the motivation of schizophrenia patients to engage in physical activity and help with symptoms, researchers said at the annual congress of the Schizophrenia International Research Society.
Physical fitness has been shown to boost cognitive function in people with schizophrenia – a particularly attractive option because it does not create stigma in the way that engaging in in-person therapy or taking medications might – and it is essentially free of side effects, said Jimmy Choi, PsyD, a senior scientist at the Olin Neuropsychiatry Research Center and staff neuropsychologist at the Institute of Living’s Schizophrenia Rehabilitation Program in Hartford, Conn.
The problem, Dr. Choi said, is that many studies have shown that compliance – or completion of half of an exercise program by participants – is fairly low, at 65%-68%. Among those who are not compliant, the benefits of exercise programs on cognition, psychosis symptoms, and mental status are conspicuously lower.
Effect sizes in laboratory trials on the efficacy of physical fitness are much higher than effectiveness seen in studies of community programs, Dr. Choi said, likely because laboratory trials offer participants a monetary reward for participation, while community studies might offer less attractive incentives, such as tickets for weekly or monthly raffles.
At Olin, a more true-to-life community program of exergaming – which included the use of virtual reality – was created by recreational therapists, exercise physiologists, psychologists, and technology experts to optimize the experience and outcomes, each with a distinct role – either developing the overall experience to promote enjoyment, achieving exhaustion but without an injury risk, incorporating patients’ baseline cognitive profile to make the programs suitable, or tailoring virtual experiences for each participant.
With 35 participants, researchers saw encouraging effects on working memory, processing speed, as well as positive and negative schizophrenia symptoms – with effect sizes ranging from 0.54 for working memory scores to 0.19 for positive schizophrenia symptoms, such as hallucinations.
The attrition rate of 14% was the same for those assessed as having low motivation as it was for those assessed as having high motivation, suggesting that exergaming helped boost and sustain motivation among patients for whom it is usually difficult, said Dr. Choi, who added that he and his colleagues have a paper in press outlining these results in Schizophrenia Research: Cognition.
“Exergaming shows promise in improving adherence to physical exercise and reducing attrition,” he said. “Highly motivated participants benefited more in terms of cognition and symptoms, but even those with low motivation saw improvements in working memory and negative symptoms.”
Dr. Choi added that his center is continuing to evaluate exergaming.
“A nice bike exercise or treadmill, that’s still more portable and cheaper for community clinics to do,” he said. “That’s one of the reasons ... we’re currently doing a randomized, controlled trial looking to see if exergaming could stand up to doing a singular exercise aerobic program.”
The study and Exergame equipment were funded by a Hartford Hospital auxiliary special projects grant. Dr. Choi reported having no financial conflicts.
Attrition rates encouraging in community program
Attrition rates encouraging in community program
ORLANDO – Using games to promote exercise – or “exergaming” – is proving to boost the motivation of schizophrenia patients to engage in physical activity and help with symptoms, researchers said at the annual congress of the Schizophrenia International Research Society.
Physical fitness has been shown to boost cognitive function in people with schizophrenia – a particularly attractive option because it does not create stigma in the way that engaging in in-person therapy or taking medications might – and it is essentially free of side effects, said Jimmy Choi, PsyD, a senior scientist at the Olin Neuropsychiatry Research Center and staff neuropsychologist at the Institute of Living’s Schizophrenia Rehabilitation Program in Hartford, Conn.
The problem, Dr. Choi said, is that many studies have shown that compliance – or completion of half of an exercise program by participants – is fairly low, at 65%-68%. Among those who are not compliant, the benefits of exercise programs on cognition, psychosis symptoms, and mental status are conspicuously lower.
Effect sizes in laboratory trials on the efficacy of physical fitness are much higher than effectiveness seen in studies of community programs, Dr. Choi said, likely because laboratory trials offer participants a monetary reward for participation, while community studies might offer less attractive incentives, such as tickets for weekly or monthly raffles.
At Olin, a more true-to-life community program of exergaming – which included the use of virtual reality – was created by recreational therapists, exercise physiologists, psychologists, and technology experts to optimize the experience and outcomes, each with a distinct role – either developing the overall experience to promote enjoyment, achieving exhaustion but without an injury risk, incorporating patients’ baseline cognitive profile to make the programs suitable, or tailoring virtual experiences for each participant.
With 35 participants, researchers saw encouraging effects on working memory, processing speed, as well as positive and negative schizophrenia symptoms – with effect sizes ranging from 0.54 for working memory scores to 0.19 for positive schizophrenia symptoms, such as hallucinations.
The attrition rate of 14% was the same for those assessed as having low motivation as it was for those assessed as having high motivation, suggesting that exergaming helped boost and sustain motivation among patients for whom it is usually difficult, said Dr. Choi, who added that he and his colleagues have a paper in press outlining these results in Schizophrenia Research: Cognition.
“Exergaming shows promise in improving adherence to physical exercise and reducing attrition,” he said. “Highly motivated participants benefited more in terms of cognition and symptoms, but even those with low motivation saw improvements in working memory and negative symptoms.”
Dr. Choi added that his center is continuing to evaluate exergaming.
“A nice bike exercise or treadmill, that’s still more portable and cheaper for community clinics to do,” he said. “That’s one of the reasons ... we’re currently doing a randomized, controlled trial looking to see if exergaming could stand up to doing a singular exercise aerobic program.”
The study and Exergame equipment were funded by a Hartford Hospital auxiliary special projects grant. Dr. Choi reported having no financial conflicts.
ORLANDO – Using games to promote exercise – or “exergaming” – is proving to boost the motivation of schizophrenia patients to engage in physical activity and help with symptoms, researchers said at the annual congress of the Schizophrenia International Research Society.
Physical fitness has been shown to boost cognitive function in people with schizophrenia – a particularly attractive option because it does not create stigma in the way that engaging in in-person therapy or taking medications might – and it is essentially free of side effects, said Jimmy Choi, PsyD, a senior scientist at the Olin Neuropsychiatry Research Center and staff neuropsychologist at the Institute of Living’s Schizophrenia Rehabilitation Program in Hartford, Conn.
The problem, Dr. Choi said, is that many studies have shown that compliance – or completion of half of an exercise program by participants – is fairly low, at 65%-68%. Among those who are not compliant, the benefits of exercise programs on cognition, psychosis symptoms, and mental status are conspicuously lower.
Effect sizes in laboratory trials on the efficacy of physical fitness are much higher than effectiveness seen in studies of community programs, Dr. Choi said, likely because laboratory trials offer participants a monetary reward for participation, while community studies might offer less attractive incentives, such as tickets for weekly or monthly raffles.
At Olin, a more true-to-life community program of exergaming – which included the use of virtual reality – was created by recreational therapists, exercise physiologists, psychologists, and technology experts to optimize the experience and outcomes, each with a distinct role – either developing the overall experience to promote enjoyment, achieving exhaustion but without an injury risk, incorporating patients’ baseline cognitive profile to make the programs suitable, or tailoring virtual experiences for each participant.
With 35 participants, researchers saw encouraging effects on working memory, processing speed, as well as positive and negative schizophrenia symptoms – with effect sizes ranging from 0.54 for working memory scores to 0.19 for positive schizophrenia symptoms, such as hallucinations.
The attrition rate of 14% was the same for those assessed as having low motivation as it was for those assessed as having high motivation, suggesting that exergaming helped boost and sustain motivation among patients for whom it is usually difficult, said Dr. Choi, who added that he and his colleagues have a paper in press outlining these results in Schizophrenia Research: Cognition.
“Exergaming shows promise in improving adherence to physical exercise and reducing attrition,” he said. “Highly motivated participants benefited more in terms of cognition and symptoms, but even those with low motivation saw improvements in working memory and negative symptoms.”
Dr. Choi added that his center is continuing to evaluate exergaming.
“A nice bike exercise or treadmill, that’s still more portable and cheaper for community clinics to do,” he said. “That’s one of the reasons ... we’re currently doing a randomized, controlled trial looking to see if exergaming could stand up to doing a singular exercise aerobic program.”
The study and Exergame equipment were funded by a Hartford Hospital auxiliary special projects grant. Dr. Choi reported having no financial conflicts.
REPORTING FROM SIRS 2019
Smartphone interventions benefit schizophrenia patients
Mobile devices viewed as a unique opportunity
ORLANDO – Smartphones offer a way to give people with schizophrenia access to immediate medical guidance in times of need and clinicians a convenient way to check in with patients, an expert said at the annual congress of the Schizophrenia International Research Society.
Dror Ben-Zeev, PhD, professor of psychiatry and behavioral sciences at the University of Washington, Seattle, said that, despite the many differences in the habits and experiences of people with schizophrenia, there do not appear to be many differences in the way they use mobile technology, compared with the general population.
Even as far back as 2012, when smartphone technology was much less widely adopted, and he and his colleagues conducted a survey of patients in the Chicago area, 63% of schizophrenia patients said they had a mobile device. Ninety percent of them said they used the device to talk, one-third used it for text messaging, and 13% used it to browse the Internet.
More recently, a meta-analysis of 15 studies, published in 2016, found that, among those with psychotic disorders who were surveyed since 2014, 81% owned a mobile device. A majority said they favored using mobile technology for contact with medical services and for supporting self-management (Schizophr Bull. 2016 Mar;42[2]:448-55).
“Do they own phones? Do they use phones? Absolutely, they do,” Dr. Ben-Zeev said. “And in a surprising way, it might be one of the areas where the gap between psychotic illness and the general population is close to nonexistent.”
FOCUS, a smartphone app designed for easy use by patients to allow them to quickly cope with symptoms and to allow clinicians to ask how they’re doing, has helped to improve patient symptoms, Dr. Ben-Zeev said. Patients receive three daily prompts to check in with the app, which offers a chance to report symptoms. It also offers “on-demand” resources 24 hours a day for help with handling voices, social challenges, medications, sleep issues, and mood difficulties.
When patients report hearing voices, for instance, they are asked to describe them in multiple choice fashion, including an option to supply their own description. If a patient reports that, for example, the voices “know everything,” the app asks them to think of a time when the voices were sure something would happen, but it didn’t. The app also offers videos in which therapists give advice to help patients with symptoms.
In a 30-day trial, participants used the FOCUS app an average of five times a day in the previous week, and 63% of the uses were participant initiated rather than app initiated. Positive and Negative Syndrome Scale scores (77.6 vs. 71.5; P less than .001) and depression scores (19.7 vs. 13.9; P less than .01) were both significantly improved after the trial, compared with before (Schizophr Bull. 2014 Nov;40[6]:1244-53).
Meanwhile, a 3-month randomized, controlled trial comparing the FOCUS intervention with Wellness Recovery Action Plan (WRAP), a clinic-based group intervention, had what Dr. Ben-Zeev referred in an interview as “very compelling findings” (Psychiatr Serv. 2018 Sep 1;69[9]:978-85). That study, lead by Dr. Ben-Zeev and his colleagues, found that participants with serious mental illness who were assigned to FOCUS were more likely than those assigned to WRAP to begin treatment (90% vs. 58%) and to remain fully engaged in care over an 8-week period.
Researchers are also exploring the benefits of a program called CrossCheck, in which patients’ use of smartphones relays information that could predict a psychosis relapse (Psychiatr Rehab J. 2017 Sep;40[3]:266-75). For instance, use in the middle of the night indicates sleeping difficulties, and location data could indicate a change in residence. Both are warning signs of a possible impending relapse.
“There is a unique opportunity,” Dr. Ben-Zeev said, “to leverage this status to try to improve what we do.”
Dr. Ben-Zeev also is codirector of the university’s Behavioral Research in Technology and Engineering Center and director of the mHealth for Mental Health Program, a research collaborative that focuses on developing, evaluating, and implementing mobile technologies. Dr. Ben-Zeev has a licensing and consulting agreement with Pear Therapeutics and a consulting agreement with eQuility.
Mobile devices viewed as a unique opportunity
Mobile devices viewed as a unique opportunity
ORLANDO – Smartphones offer a way to give people with schizophrenia access to immediate medical guidance in times of need and clinicians a convenient way to check in with patients, an expert said at the annual congress of the Schizophrenia International Research Society.
Dror Ben-Zeev, PhD, professor of psychiatry and behavioral sciences at the University of Washington, Seattle, said that, despite the many differences in the habits and experiences of people with schizophrenia, there do not appear to be many differences in the way they use mobile technology, compared with the general population.
Even as far back as 2012, when smartphone technology was much less widely adopted, and he and his colleagues conducted a survey of patients in the Chicago area, 63% of schizophrenia patients said they had a mobile device. Ninety percent of them said they used the device to talk, one-third used it for text messaging, and 13% used it to browse the Internet.
More recently, a meta-analysis of 15 studies, published in 2016, found that, among those with psychotic disorders who were surveyed since 2014, 81% owned a mobile device. A majority said they favored using mobile technology for contact with medical services and for supporting self-management (Schizophr Bull. 2016 Mar;42[2]:448-55).
“Do they own phones? Do they use phones? Absolutely, they do,” Dr. Ben-Zeev said. “And in a surprising way, it might be one of the areas where the gap between psychotic illness and the general population is close to nonexistent.”
FOCUS, a smartphone app designed for easy use by patients to allow them to quickly cope with symptoms and to allow clinicians to ask how they’re doing, has helped to improve patient symptoms, Dr. Ben-Zeev said. Patients receive three daily prompts to check in with the app, which offers a chance to report symptoms. It also offers “on-demand” resources 24 hours a day for help with handling voices, social challenges, medications, sleep issues, and mood difficulties.
When patients report hearing voices, for instance, they are asked to describe them in multiple choice fashion, including an option to supply their own description. If a patient reports that, for example, the voices “know everything,” the app asks them to think of a time when the voices were sure something would happen, but it didn’t. The app also offers videos in which therapists give advice to help patients with symptoms.
In a 30-day trial, participants used the FOCUS app an average of five times a day in the previous week, and 63% of the uses were participant initiated rather than app initiated. Positive and Negative Syndrome Scale scores (77.6 vs. 71.5; P less than .001) and depression scores (19.7 vs. 13.9; P less than .01) were both significantly improved after the trial, compared with before (Schizophr Bull. 2014 Nov;40[6]:1244-53).
Meanwhile, a 3-month randomized, controlled trial comparing the FOCUS intervention with Wellness Recovery Action Plan (WRAP), a clinic-based group intervention, had what Dr. Ben-Zeev referred in an interview as “very compelling findings” (Psychiatr Serv. 2018 Sep 1;69[9]:978-85). That study, lead by Dr. Ben-Zeev and his colleagues, found that participants with serious mental illness who were assigned to FOCUS were more likely than those assigned to WRAP to begin treatment (90% vs. 58%) and to remain fully engaged in care over an 8-week period.
Researchers are also exploring the benefits of a program called CrossCheck, in which patients’ use of smartphones relays information that could predict a psychosis relapse (Psychiatr Rehab J. 2017 Sep;40[3]:266-75). For instance, use in the middle of the night indicates sleeping difficulties, and location data could indicate a change in residence. Both are warning signs of a possible impending relapse.
“There is a unique opportunity,” Dr. Ben-Zeev said, “to leverage this status to try to improve what we do.”
Dr. Ben-Zeev also is codirector of the university’s Behavioral Research in Technology and Engineering Center and director of the mHealth for Mental Health Program, a research collaborative that focuses on developing, evaluating, and implementing mobile technologies. Dr. Ben-Zeev has a licensing and consulting agreement with Pear Therapeutics and a consulting agreement with eQuility.
ORLANDO – Smartphones offer a way to give people with schizophrenia access to immediate medical guidance in times of need and clinicians a convenient way to check in with patients, an expert said at the annual congress of the Schizophrenia International Research Society.
Dror Ben-Zeev, PhD, professor of psychiatry and behavioral sciences at the University of Washington, Seattle, said that, despite the many differences in the habits and experiences of people with schizophrenia, there do not appear to be many differences in the way they use mobile technology, compared with the general population.
Even as far back as 2012, when smartphone technology was much less widely adopted, and he and his colleagues conducted a survey of patients in the Chicago area, 63% of schizophrenia patients said they had a mobile device. Ninety percent of them said they used the device to talk, one-third used it for text messaging, and 13% used it to browse the Internet.
More recently, a meta-analysis of 15 studies, published in 2016, found that, among those with psychotic disorders who were surveyed since 2014, 81% owned a mobile device. A majority said they favored using mobile technology for contact with medical services and for supporting self-management (Schizophr Bull. 2016 Mar;42[2]:448-55).
“Do they own phones? Do they use phones? Absolutely, they do,” Dr. Ben-Zeev said. “And in a surprising way, it might be one of the areas where the gap between psychotic illness and the general population is close to nonexistent.”
FOCUS, a smartphone app designed for easy use by patients to allow them to quickly cope with symptoms and to allow clinicians to ask how they’re doing, has helped to improve patient symptoms, Dr. Ben-Zeev said. Patients receive three daily prompts to check in with the app, which offers a chance to report symptoms. It also offers “on-demand” resources 24 hours a day for help with handling voices, social challenges, medications, sleep issues, and mood difficulties.
When patients report hearing voices, for instance, they are asked to describe them in multiple choice fashion, including an option to supply their own description. If a patient reports that, for example, the voices “know everything,” the app asks them to think of a time when the voices were sure something would happen, but it didn’t. The app also offers videos in which therapists give advice to help patients with symptoms.
In a 30-day trial, participants used the FOCUS app an average of five times a day in the previous week, and 63% of the uses were participant initiated rather than app initiated. Positive and Negative Syndrome Scale scores (77.6 vs. 71.5; P less than .001) and depression scores (19.7 vs. 13.9; P less than .01) were both significantly improved after the trial, compared with before (Schizophr Bull. 2014 Nov;40[6]:1244-53).
Meanwhile, a 3-month randomized, controlled trial comparing the FOCUS intervention with Wellness Recovery Action Plan (WRAP), a clinic-based group intervention, had what Dr. Ben-Zeev referred in an interview as “very compelling findings” (Psychiatr Serv. 2018 Sep 1;69[9]:978-85). That study, lead by Dr. Ben-Zeev and his colleagues, found that participants with serious mental illness who were assigned to FOCUS were more likely than those assigned to WRAP to begin treatment (90% vs. 58%) and to remain fully engaged in care over an 8-week period.
Researchers are also exploring the benefits of a program called CrossCheck, in which patients’ use of smartphones relays information that could predict a psychosis relapse (Psychiatr Rehab J. 2017 Sep;40[3]:266-75). For instance, use in the middle of the night indicates sleeping difficulties, and location data could indicate a change in residence. Both are warning signs of a possible impending relapse.
“There is a unique opportunity,” Dr. Ben-Zeev said, “to leverage this status to try to improve what we do.”
Dr. Ben-Zeev also is codirector of the university’s Behavioral Research in Technology and Engineering Center and director of the mHealth for Mental Health Program, a research collaborative that focuses on developing, evaluating, and implementing mobile technologies. Dr. Ben-Zeev has a licensing and consulting agreement with Pear Therapeutics and a consulting agreement with eQuility.
EXPERT ANALYSIS FROM SIRS 2019
Stem cells enabling key insights into schizophrenia
ORLANDO – Stem cell models could boost schizophrenia treatment to a new level, helping to gauge the importance of both rare and common genetic variants that are difficult to study in traditional-style trials, an expert said at the annual congress of the Schizophrenia International Research Society.
The promise of the approach is particularly crucial at this point in the course of schizophrenia research, when the heritability of the disease is being repeatedly underscored in the literature, said Kristen Brennand, PhD, associate professor of neuroscience, genetics and genomics, and psychiatry at the Icahn School of Medicine at Mount Sinai, New York.
“It seems that each new paper that comes out raises that estimate of heritability and the numbers I’ve seen recently are as high as 85%,” she said. “Schizophrenia is as heritable as autism and bipolar, more heritable than BRCA1 breast cancer, it’s more heritable than alcoholism. But that heritability is highly complex.”
Highly penetrant variants that are more easily studied account for only a small sliver of this heritability. Rare variants that are harder to study account for more. And common variants – the count is up to 145 and will almost certainly grow – also play a big role.
“These are variants that all of us carry,” Dr. Brennand said. “We all carry dozens of these variants. Patients just either carry more of them or they’re hitting pathways in a different way than they’re hitting the rest of us.”
Using human-induced pluripotent stem cells (HiPSC) – grown out of skin biopsy samples from schizophrenia patients and then grown into neural progenitor cells and ultimately neurons – are much more practical for studying the genetics of these variants than case-control studies that require tens of thousands of subjects.
Researchers have found that cohorts using HiPSCs concord with the genetic findings from postmortem datasets of schizophrenia patients.
More recently, in work not yet published, she said her lab has focused on rare 2p16.3 deletions of the NRXN1 gene, finding that neuronal branching is reduced and that there is decreased neuronal activity in schizophrenia patients with these deletions.
Her lab is also using HiPSCs and clustered regularly interspaced short palindromic repeats editing to validate the function of common variants and genes linked with schizophrenia. A key finding has been that there could be important relationships between risk genes that are more distant from schizophrenia single-nucleotide polymorphisms (SNPs).
“We’re expanding the list of potential schizophrenia risk genes by considering not just immediately proximal but also distal interactions between schizophrenia SNPs,” Dr. Brennand said. “If there are 224 genes that are next to risk SNPs, you can add a few hundred more potential genes that might be coregulated by these risk SNPs.”
Harnessing the power of HiPSCs could be the gateway to precision medicine in schizophrenia, she said. A drug that might benefit, say, two out of a dozen patients would likely fail in a clinical trial, unless patient selection is improved.
“Perhaps genotype might predict clinical response, perhaps stem cell drug responsiveness might predict clinical response,” she said. “What I envision is this dream where we have patients and we genotype them, and we better understand how their DNA impacts their gene expression, and how their gene expression impacts their synaptic function, and that this might help us better understand their prognosis.”
Dr. Brennand reported a financial relationship with Alkermes.
ORLANDO – Stem cell models could boost schizophrenia treatment to a new level, helping to gauge the importance of both rare and common genetic variants that are difficult to study in traditional-style trials, an expert said at the annual congress of the Schizophrenia International Research Society.
The promise of the approach is particularly crucial at this point in the course of schizophrenia research, when the heritability of the disease is being repeatedly underscored in the literature, said Kristen Brennand, PhD, associate professor of neuroscience, genetics and genomics, and psychiatry at the Icahn School of Medicine at Mount Sinai, New York.
“It seems that each new paper that comes out raises that estimate of heritability and the numbers I’ve seen recently are as high as 85%,” she said. “Schizophrenia is as heritable as autism and bipolar, more heritable than BRCA1 breast cancer, it’s more heritable than alcoholism. But that heritability is highly complex.”
Highly penetrant variants that are more easily studied account for only a small sliver of this heritability. Rare variants that are harder to study account for more. And common variants – the count is up to 145 and will almost certainly grow – also play a big role.
“These are variants that all of us carry,” Dr. Brennand said. “We all carry dozens of these variants. Patients just either carry more of them or they’re hitting pathways in a different way than they’re hitting the rest of us.”
Using human-induced pluripotent stem cells (HiPSC) – grown out of skin biopsy samples from schizophrenia patients and then grown into neural progenitor cells and ultimately neurons – are much more practical for studying the genetics of these variants than case-control studies that require tens of thousands of subjects.
Researchers have found that cohorts using HiPSCs concord with the genetic findings from postmortem datasets of schizophrenia patients.
More recently, in work not yet published, she said her lab has focused on rare 2p16.3 deletions of the NRXN1 gene, finding that neuronal branching is reduced and that there is decreased neuronal activity in schizophrenia patients with these deletions.
Her lab is also using HiPSCs and clustered regularly interspaced short palindromic repeats editing to validate the function of common variants and genes linked with schizophrenia. A key finding has been that there could be important relationships between risk genes that are more distant from schizophrenia single-nucleotide polymorphisms (SNPs).
“We’re expanding the list of potential schizophrenia risk genes by considering not just immediately proximal but also distal interactions between schizophrenia SNPs,” Dr. Brennand said. “If there are 224 genes that are next to risk SNPs, you can add a few hundred more potential genes that might be coregulated by these risk SNPs.”
Harnessing the power of HiPSCs could be the gateway to precision medicine in schizophrenia, she said. A drug that might benefit, say, two out of a dozen patients would likely fail in a clinical trial, unless patient selection is improved.
“Perhaps genotype might predict clinical response, perhaps stem cell drug responsiveness might predict clinical response,” she said. “What I envision is this dream where we have patients and we genotype them, and we better understand how their DNA impacts their gene expression, and how their gene expression impacts their synaptic function, and that this might help us better understand their prognosis.”
Dr. Brennand reported a financial relationship with Alkermes.
ORLANDO – Stem cell models could boost schizophrenia treatment to a new level, helping to gauge the importance of both rare and common genetic variants that are difficult to study in traditional-style trials, an expert said at the annual congress of the Schizophrenia International Research Society.
The promise of the approach is particularly crucial at this point in the course of schizophrenia research, when the heritability of the disease is being repeatedly underscored in the literature, said Kristen Brennand, PhD, associate professor of neuroscience, genetics and genomics, and psychiatry at the Icahn School of Medicine at Mount Sinai, New York.
“It seems that each new paper that comes out raises that estimate of heritability and the numbers I’ve seen recently are as high as 85%,” she said. “Schizophrenia is as heritable as autism and bipolar, more heritable than BRCA1 breast cancer, it’s more heritable than alcoholism. But that heritability is highly complex.”
Highly penetrant variants that are more easily studied account for only a small sliver of this heritability. Rare variants that are harder to study account for more. And common variants – the count is up to 145 and will almost certainly grow – also play a big role.
“These are variants that all of us carry,” Dr. Brennand said. “We all carry dozens of these variants. Patients just either carry more of them or they’re hitting pathways in a different way than they’re hitting the rest of us.”
Using human-induced pluripotent stem cells (HiPSC) – grown out of skin biopsy samples from schizophrenia patients and then grown into neural progenitor cells and ultimately neurons – are much more practical for studying the genetics of these variants than case-control studies that require tens of thousands of subjects.
Researchers have found that cohorts using HiPSCs concord with the genetic findings from postmortem datasets of schizophrenia patients.
More recently, in work not yet published, she said her lab has focused on rare 2p16.3 deletions of the NRXN1 gene, finding that neuronal branching is reduced and that there is decreased neuronal activity in schizophrenia patients with these deletions.
Her lab is also using HiPSCs and clustered regularly interspaced short palindromic repeats editing to validate the function of common variants and genes linked with schizophrenia. A key finding has been that there could be important relationships between risk genes that are more distant from schizophrenia single-nucleotide polymorphisms (SNPs).
“We’re expanding the list of potential schizophrenia risk genes by considering not just immediately proximal but also distal interactions between schizophrenia SNPs,” Dr. Brennand said. “If there are 224 genes that are next to risk SNPs, you can add a few hundred more potential genes that might be coregulated by these risk SNPs.”
Harnessing the power of HiPSCs could be the gateway to precision medicine in schizophrenia, she said. A drug that might benefit, say, two out of a dozen patients would likely fail in a clinical trial, unless patient selection is improved.
“Perhaps genotype might predict clinical response, perhaps stem cell drug responsiveness might predict clinical response,” she said. “What I envision is this dream where we have patients and we genotype them, and we better understand how their DNA impacts their gene expression, and how their gene expression impacts their synaptic function, and that this might help us better understand their prognosis.”
Dr. Brennand reported a financial relationship with Alkermes.
EXPERT ANALYSIS FROM SIRS 2019
Criminalization of mental illness must stop, judge says
ORLANDO – Judge Steve Leifman, who presides over 11th judicial circuit court in Miami-Dade County, Fla., was about to take the bench several years ago when he agreed to see a couple, who then begged him to help their son, who had mental illness. Judge Leifman was about to hear his case.
The man was a Harvard-educated former psychiatrist and at first appeared healthy, but then took on a look of terror and began screaming when the judge asked him a question. Although the man was clearly psychotic, Judge Leifman had no choice but to release him to the streets – he had no authority under the law to involuntarily commit anyone to psychiatric treatment.
There was little doubt that the man would end up committing a crime and being put behind bars.
Judge Leifman, who gave the keynote address at the annual congress of the Schizophrenia International Research Society, now has made it his life’s work to reform a system in which jails are the de facto hospitals for people with mental illness.
he said. “And I don’t know why people aren’t angrier about it.”
[embed:render:related:node:172161]
He quoted figures that are staggering in their illustration of how mental illness has become criminalized. People with mental illnesses in the United States are 9 times more likely to be incarcerated than hospitalized, and 18 times more likely to find a bed in jail than at a state civil hospital, he said. On any given day, about 400,000 people with mental illness are in jail and 800,000 are under correctional supervision. He said that 40% of all people with mental illness in the United States will at some point come into contact with the criminal justice system.
Together, U.S. counties spend $80 billion a year on correctional costs. States spend an additional $71 billion, he said.
Judge Leifman has helped start an initiative called Stepping Up to lead reform. It’s an effort by the National Association of Counties, American Psychiatric Association Foundation, and the Council of State Government. More than 400 counties over the past few years have passed resolutions saying they’re committed to change.
Judge Leifman organized a summit, with criminal justice and health groups coming together to assess the issue, only to diagnose a system that’s “designed to fail.” Local officials have crafted a new system with links to comprehensive care for people with mental illness that make jail a last resort rather than a first stop. A key component is “crisis intervention team policing,” in which law enforcement officers are trained to identify people with mental illness, deescalate situations, and get them to proper care rather than arrest them. All 36 Miami-Dade County police departments are trained in this program, and it has eased the incarceration and recidivism rates.
“It has been a huge cultural shift,” Judge Leifman said.
“We’ve improved public safety, we’ve reduced police injuries, we’ve helped police officers get back to patrol much quicker, we’ve saved critical tax dollars, we’ve saved lives, and we’ve decriminalized mental illness,” he said. “But we still have plenty to do. Because as good as all this has been, it’s limited. ... Our state’s mental health systems are still too fragmented, they’re still antiquated, and they’re painfully underresourced. And the laws are old and they don’t reflect the science today.”
Judge Leifman reported no relevant disclosures.
ORLANDO – Judge Steve Leifman, who presides over 11th judicial circuit court in Miami-Dade County, Fla., was about to take the bench several years ago when he agreed to see a couple, who then begged him to help their son, who had mental illness. Judge Leifman was about to hear his case.
The man was a Harvard-educated former psychiatrist and at first appeared healthy, but then took on a look of terror and began screaming when the judge asked him a question. Although the man was clearly psychotic, Judge Leifman had no choice but to release him to the streets – he had no authority under the law to involuntarily commit anyone to psychiatric treatment.
There was little doubt that the man would end up committing a crime and being put behind bars.
Judge Leifman, who gave the keynote address at the annual congress of the Schizophrenia International Research Society, now has made it his life’s work to reform a system in which jails are the de facto hospitals for people with mental illness.
he said. “And I don’t know why people aren’t angrier about it.”
[embed:render:related:node:172161]
He quoted figures that are staggering in their illustration of how mental illness has become criminalized. People with mental illnesses in the United States are 9 times more likely to be incarcerated than hospitalized, and 18 times more likely to find a bed in jail than at a state civil hospital, he said. On any given day, about 400,000 people with mental illness are in jail and 800,000 are under correctional supervision. He said that 40% of all people with mental illness in the United States will at some point come into contact with the criminal justice system.
Together, U.S. counties spend $80 billion a year on correctional costs. States spend an additional $71 billion, he said.
Judge Leifman has helped start an initiative called Stepping Up to lead reform. It’s an effort by the National Association of Counties, American Psychiatric Association Foundation, and the Council of State Government. More than 400 counties over the past few years have passed resolutions saying they’re committed to change.
Judge Leifman organized a summit, with criminal justice and health groups coming together to assess the issue, only to diagnose a system that’s “designed to fail.” Local officials have crafted a new system with links to comprehensive care for people with mental illness that make jail a last resort rather than a first stop. A key component is “crisis intervention team policing,” in which law enforcement officers are trained to identify people with mental illness, deescalate situations, and get them to proper care rather than arrest them. All 36 Miami-Dade County police departments are trained in this program, and it has eased the incarceration and recidivism rates.
“It has been a huge cultural shift,” Judge Leifman said.
“We’ve improved public safety, we’ve reduced police injuries, we’ve helped police officers get back to patrol much quicker, we’ve saved critical tax dollars, we’ve saved lives, and we’ve decriminalized mental illness,” he said. “But we still have plenty to do. Because as good as all this has been, it’s limited. ... Our state’s mental health systems are still too fragmented, they’re still antiquated, and they’re painfully underresourced. And the laws are old and they don’t reflect the science today.”
Judge Leifman reported no relevant disclosures.
ORLANDO – Judge Steve Leifman, who presides over 11th judicial circuit court in Miami-Dade County, Fla., was about to take the bench several years ago when he agreed to see a couple, who then begged him to help their son, who had mental illness. Judge Leifman was about to hear his case.
The man was a Harvard-educated former psychiatrist and at first appeared healthy, but then took on a look of terror and began screaming when the judge asked him a question. Although the man was clearly psychotic, Judge Leifman had no choice but to release him to the streets – he had no authority under the law to involuntarily commit anyone to psychiatric treatment.
There was little doubt that the man would end up committing a crime and being put behind bars.
Judge Leifman, who gave the keynote address at the annual congress of the Schizophrenia International Research Society, now has made it his life’s work to reform a system in which jails are the de facto hospitals for people with mental illness.
he said. “And I don’t know why people aren’t angrier about it.”
[embed:render:related:node:172161]
He quoted figures that are staggering in their illustration of how mental illness has become criminalized. People with mental illnesses in the United States are 9 times more likely to be incarcerated than hospitalized, and 18 times more likely to find a bed in jail than at a state civil hospital, he said. On any given day, about 400,000 people with mental illness are in jail and 800,000 are under correctional supervision. He said that 40% of all people with mental illness in the United States will at some point come into contact with the criminal justice system.
Together, U.S. counties spend $80 billion a year on correctional costs. States spend an additional $71 billion, he said.
Judge Leifman has helped start an initiative called Stepping Up to lead reform. It’s an effort by the National Association of Counties, American Psychiatric Association Foundation, and the Council of State Government. More than 400 counties over the past few years have passed resolutions saying they’re committed to change.
Judge Leifman organized a summit, with criminal justice and health groups coming together to assess the issue, only to diagnose a system that’s “designed to fail.” Local officials have crafted a new system with links to comprehensive care for people with mental illness that make jail a last resort rather than a first stop. A key component is “crisis intervention team policing,” in which law enforcement officers are trained to identify people with mental illness, deescalate situations, and get them to proper care rather than arrest them. All 36 Miami-Dade County police departments are trained in this program, and it has eased the incarceration and recidivism rates.
“It has been a huge cultural shift,” Judge Leifman said.
“We’ve improved public safety, we’ve reduced police injuries, we’ve helped police officers get back to patrol much quicker, we’ve saved critical tax dollars, we’ve saved lives, and we’ve decriminalized mental illness,” he said. “But we still have plenty to do. Because as good as all this has been, it’s limited. ... Our state’s mental health systems are still too fragmented, they’re still antiquated, and they’re painfully underresourced. And the laws are old and they don’t reflect the science today.”
Judge Leifman reported no relevant disclosures.
REPORTING FROM SIRS 2019
Metabolite levels might help differentiate schizophrenia, bipolar
ORLANDO – Profiling metabolites found in the plasma could be a way to get an earlier handle on how a person’s mental illness will progress, researchers said the annual congress of the Schizophrenia International Research Society.
Investigators at the University of São Paulo found that certain substances – such as phospholipids and sphingolipids – were found in differing levels at the time of a first episode of psychosis, allowing them to accurately identify bipolar disorder or schizophrenia or healthy controls 87% of the time.
The findings suggest a way to help get patients more targeted treatment earlier in their disease course, said Helena Joaquim, MD, PhD, a postdoctoral fellow in the university’s psychiatry department.
“The levels of these metabolites can be a biomarker for psychosis, as well as a diagnostic marker for schizophrenia and bipolar disorder, aiding clinical practice,” the researchers wrote in a poster presentation.
At the time of a first episode of psychosis, the actual diagnosis can be difficult to pinpoint, making the illness more difficult to treat. Since lipid metabolism is altered in neuropsychiatric diseases, the researchers turned to the metabolite levels of patients to pin down a specific diagnosis sooner.
They collected plasma from 28 schizophrenia patients, 27 bipolar patients, and 30 healthy controls. They looked specifically at acylcarnitines, phospholipids, lysophospholipids and sphingolipids. They found that phospholipids were elevated in schizophrenia patients, compared with controls, and even more elevated in patients with bipolar disorder. A similar pattern was seen with lysophospholipids. Sphingolipids were found at lower levels in schizophrenia and elevated in bipolar disorder, compared with controls.
Levels of those three metabolites allowed researchers 87.1% of the time to correctly identify patients as a healthy control or as having schizophrenia or bipolar disorder. Acylcarnitines were not found to be differentiated between schizophrenia and bipolar disorder, the researchers found.
The most interesting part of their efforts so far, Dr. Joaquim said, was a shotgun analysis, an untargeted approach in which about 186 metabolites were measured and plotted on a graph. The compounds have not yet all been identified, but researchers found that levels of these substances were clustered in conspicuous ways.
“It seems like the negative schizophrenia patients are more like the depressive bipolar, and the positive symptoms are more like manic bipolar,” Dr. Joaquim said.
. For example, looking at metabolite levels might help determine whether schizophrenia patients are more likely to be troubled by positive symptoms, such as hallucinations.
“We have to look back,” Dr. Joaquim said, “and try to identify those metabolites that are the most different between the groups.”
Dr. Joaquim reported no relevant disclosures.
ORLANDO – Profiling metabolites found in the plasma could be a way to get an earlier handle on how a person’s mental illness will progress, researchers said the annual congress of the Schizophrenia International Research Society.
Investigators at the University of São Paulo found that certain substances – such as phospholipids and sphingolipids – were found in differing levels at the time of a first episode of psychosis, allowing them to accurately identify bipolar disorder or schizophrenia or healthy controls 87% of the time.
The findings suggest a way to help get patients more targeted treatment earlier in their disease course, said Helena Joaquim, MD, PhD, a postdoctoral fellow in the university’s psychiatry department.
“The levels of these metabolites can be a biomarker for psychosis, as well as a diagnostic marker for schizophrenia and bipolar disorder, aiding clinical practice,” the researchers wrote in a poster presentation.
At the time of a first episode of psychosis, the actual diagnosis can be difficult to pinpoint, making the illness more difficult to treat. Since lipid metabolism is altered in neuropsychiatric diseases, the researchers turned to the metabolite levels of patients to pin down a specific diagnosis sooner.
They collected plasma from 28 schizophrenia patients, 27 bipolar patients, and 30 healthy controls. They looked specifically at acylcarnitines, phospholipids, lysophospholipids and sphingolipids. They found that phospholipids were elevated in schizophrenia patients, compared with controls, and even more elevated in patients with bipolar disorder. A similar pattern was seen with lysophospholipids. Sphingolipids were found at lower levels in schizophrenia and elevated in bipolar disorder, compared with controls.
Levels of those three metabolites allowed researchers 87.1% of the time to correctly identify patients as a healthy control or as having schizophrenia or bipolar disorder. Acylcarnitines were not found to be differentiated between schizophrenia and bipolar disorder, the researchers found.
The most interesting part of their efforts so far, Dr. Joaquim said, was a shotgun analysis, an untargeted approach in which about 186 metabolites were measured and plotted on a graph. The compounds have not yet all been identified, but researchers found that levels of these substances were clustered in conspicuous ways.
“It seems like the negative schizophrenia patients are more like the depressive bipolar, and the positive symptoms are more like manic bipolar,” Dr. Joaquim said.
. For example, looking at metabolite levels might help determine whether schizophrenia patients are more likely to be troubled by positive symptoms, such as hallucinations.
“We have to look back,” Dr. Joaquim said, “and try to identify those metabolites that are the most different between the groups.”
Dr. Joaquim reported no relevant disclosures.
ORLANDO – Profiling metabolites found in the plasma could be a way to get an earlier handle on how a person’s mental illness will progress, researchers said the annual congress of the Schizophrenia International Research Society.
Investigators at the University of São Paulo found that certain substances – such as phospholipids and sphingolipids – were found in differing levels at the time of a first episode of psychosis, allowing them to accurately identify bipolar disorder or schizophrenia or healthy controls 87% of the time.
The findings suggest a way to help get patients more targeted treatment earlier in their disease course, said Helena Joaquim, MD, PhD, a postdoctoral fellow in the university’s psychiatry department.
“The levels of these metabolites can be a biomarker for psychosis, as well as a diagnostic marker for schizophrenia and bipolar disorder, aiding clinical practice,” the researchers wrote in a poster presentation.
At the time of a first episode of psychosis, the actual diagnosis can be difficult to pinpoint, making the illness more difficult to treat. Since lipid metabolism is altered in neuropsychiatric diseases, the researchers turned to the metabolite levels of patients to pin down a specific diagnosis sooner.
They collected plasma from 28 schizophrenia patients, 27 bipolar patients, and 30 healthy controls. They looked specifically at acylcarnitines, phospholipids, lysophospholipids and sphingolipids. They found that phospholipids were elevated in schizophrenia patients, compared with controls, and even more elevated in patients with bipolar disorder. A similar pattern was seen with lysophospholipids. Sphingolipids were found at lower levels in schizophrenia and elevated in bipolar disorder, compared with controls.
Levels of those three metabolites allowed researchers 87.1% of the time to correctly identify patients as a healthy control or as having schizophrenia or bipolar disorder. Acylcarnitines were not found to be differentiated between schizophrenia and bipolar disorder, the researchers found.
The most interesting part of their efforts so far, Dr. Joaquim said, was a shotgun analysis, an untargeted approach in which about 186 metabolites were measured and plotted on a graph. The compounds have not yet all been identified, but researchers found that levels of these substances were clustered in conspicuous ways.
“It seems like the negative schizophrenia patients are more like the depressive bipolar, and the positive symptoms are more like manic bipolar,” Dr. Joaquim said.
. For example, looking at metabolite levels might help determine whether schizophrenia patients are more likely to be troubled by positive symptoms, such as hallucinations.
“We have to look back,” Dr. Joaquim said, “and try to identify those metabolites that are the most different between the groups.”
Dr. Joaquim reported no relevant disclosures.
REPORTING FROM SIRS 2019
Sense of self targeted by schizophrenia research
ORLANDO – New ways of assessing and measuring the way the sense of self becomes distorted in patients with schizophrenia patients and those at risk of developing the disease are deepening understanding of the disorder, an expert said at annual congress of the Schizophrenia International Research Society.
Sohee Park, PhD, Gertrude Conaway Vanderbilt Professor of Psychology at Vanderbilt University, Nashville, Tenn., said a unified and continuous sense of self is essential to leading a functional life. But this sense of self is a complex assemblage, made up of explicit experiences and actions, a more internal awareness of our own body, as well as a “social, narrative self” involving our social identity and history. This coherent and continuous sense of self is formulated and tied together by working memory and by our ability to form expectations or predictions about what might happen next, Dr. Park said.
In schizophrenia, the sense of self becomes fragmented as these predictions – on issues such as how sensory input is perceived – break down.
Dr. Park said a more comprehensive approach is needed in understanding this breakdown if clinicians can be expected to help people with schizophrenia.
“Connection between biological disorder and personal illness experience is not really well articulated in our field,” she said. “But it’s a connection we must make if we are to understand this condition and to develop treatments and interventions that make sense and are meaningful to the person who experiences psychosis.”
With her colleagues, Dr. Park has developed a way to better measure these bodily “self-disturbances” that patients with schizophrenia experience, and how they persist over time. B-BODI – the Benson et al. Body Disturbances Inventory – is a kind of catalog of pictures representing experiences of self-disturbance, such as someone having an out-of-body experience or a person who feels her body parts changing. The pictures come with written statements, and are designed to elicit more information from the patients about their experiences, such as how vivid, disturbing, and frequent they are.
Researchers have found that these experiences of body and self-disturbances are correlated with the positive symptoms of schizophrenia – such as hallucinations and confused thoughts – as well as with loneliness. But those experiences are not correlated with negative symptoms, such as loss of ability to feel pleasure.
, and the use of pictures could help patients better convey what they’re experiencing, Dr. Park said.
“Self-disturbances are difficult to verbalize,” she said. B-BODI can help verbalize these strange experiences that are hard to describe – especially in those who have difficulty communicating.
She and her colleagues have found that those at risk of schizophrenia have a more “flexible body boundary” than do those not at risk. They performed an assessment of the degree to which subjects experienced the “Pinocchio illusion,” in which subjects are blindfolded, touch their noses, and have their biceps stimulated to create the sensation that their arm is moving away from the nose – which is interpreted as the nose growing longer. They found that subjects who scored higher on the Prodromal Questionnaire Brief – an assessment of schizophrenia risk – had higher Pinocchio illusion scores.
These abnormalities in self-perception all feed into the difficulty with which people with schizophrenia have in interacting with others. To address this difficulty, her group has developed a virtual reality training program to help patients with these interactions.
In the program, the user is asked to choose an avatar to interact with by looking at the face of the avatar for a few seconds. Once chosen, the face of the avatar is fully revealed and a conversation takes place. Then the participant receives feedback. Negative symptoms of schizophrenia were significantly reduced after participation after just 10 sessions, Dr. Park said. The program has received favorable reviews from patients – one described the avatars as “very friendly” – and holds promise for helping schizophrenia patients with social situations.
“Virtual reality,” she said, “offers the ideal rehearsal space.”
This work was supported by the National Institute of Mental Health and NARSAD, formerly known as the National Alliance for Research on Schizophrenia and Depression. Dr. Park reported no financial disclosures.
ORLANDO – New ways of assessing and measuring the way the sense of self becomes distorted in patients with schizophrenia patients and those at risk of developing the disease are deepening understanding of the disorder, an expert said at annual congress of the Schizophrenia International Research Society.
Sohee Park, PhD, Gertrude Conaway Vanderbilt Professor of Psychology at Vanderbilt University, Nashville, Tenn., said a unified and continuous sense of self is essential to leading a functional life. But this sense of self is a complex assemblage, made up of explicit experiences and actions, a more internal awareness of our own body, as well as a “social, narrative self” involving our social identity and history. This coherent and continuous sense of self is formulated and tied together by working memory and by our ability to form expectations or predictions about what might happen next, Dr. Park said.
In schizophrenia, the sense of self becomes fragmented as these predictions – on issues such as how sensory input is perceived – break down.
Dr. Park said a more comprehensive approach is needed in understanding this breakdown if clinicians can be expected to help people with schizophrenia.
“Connection between biological disorder and personal illness experience is not really well articulated in our field,” she said. “But it’s a connection we must make if we are to understand this condition and to develop treatments and interventions that make sense and are meaningful to the person who experiences psychosis.”
With her colleagues, Dr. Park has developed a way to better measure these bodily “self-disturbances” that patients with schizophrenia experience, and how they persist over time. B-BODI – the Benson et al. Body Disturbances Inventory – is a kind of catalog of pictures representing experiences of self-disturbance, such as someone having an out-of-body experience or a person who feels her body parts changing. The pictures come with written statements, and are designed to elicit more information from the patients about their experiences, such as how vivid, disturbing, and frequent they are.
Researchers have found that these experiences of body and self-disturbances are correlated with the positive symptoms of schizophrenia – such as hallucinations and confused thoughts – as well as with loneliness. But those experiences are not correlated with negative symptoms, such as loss of ability to feel pleasure.
, and the use of pictures could help patients better convey what they’re experiencing, Dr. Park said.
“Self-disturbances are difficult to verbalize,” she said. B-BODI can help verbalize these strange experiences that are hard to describe – especially in those who have difficulty communicating.
She and her colleagues have found that those at risk of schizophrenia have a more “flexible body boundary” than do those not at risk. They performed an assessment of the degree to which subjects experienced the “Pinocchio illusion,” in which subjects are blindfolded, touch their noses, and have their biceps stimulated to create the sensation that their arm is moving away from the nose – which is interpreted as the nose growing longer. They found that subjects who scored higher on the Prodromal Questionnaire Brief – an assessment of schizophrenia risk – had higher Pinocchio illusion scores.
These abnormalities in self-perception all feed into the difficulty with which people with schizophrenia have in interacting with others. To address this difficulty, her group has developed a virtual reality training program to help patients with these interactions.
In the program, the user is asked to choose an avatar to interact with by looking at the face of the avatar for a few seconds. Once chosen, the face of the avatar is fully revealed and a conversation takes place. Then the participant receives feedback. Negative symptoms of schizophrenia were significantly reduced after participation after just 10 sessions, Dr. Park said. The program has received favorable reviews from patients – one described the avatars as “very friendly” – and holds promise for helping schizophrenia patients with social situations.
“Virtual reality,” she said, “offers the ideal rehearsal space.”
This work was supported by the National Institute of Mental Health and NARSAD, formerly known as the National Alliance for Research on Schizophrenia and Depression. Dr. Park reported no financial disclosures.
ORLANDO – New ways of assessing and measuring the way the sense of self becomes distorted in patients with schizophrenia patients and those at risk of developing the disease are deepening understanding of the disorder, an expert said at annual congress of the Schizophrenia International Research Society.
Sohee Park, PhD, Gertrude Conaway Vanderbilt Professor of Psychology at Vanderbilt University, Nashville, Tenn., said a unified and continuous sense of self is essential to leading a functional life. But this sense of self is a complex assemblage, made up of explicit experiences and actions, a more internal awareness of our own body, as well as a “social, narrative self” involving our social identity and history. This coherent and continuous sense of self is formulated and tied together by working memory and by our ability to form expectations or predictions about what might happen next, Dr. Park said.
In schizophrenia, the sense of self becomes fragmented as these predictions – on issues such as how sensory input is perceived – break down.
Dr. Park said a more comprehensive approach is needed in understanding this breakdown if clinicians can be expected to help people with schizophrenia.
“Connection between biological disorder and personal illness experience is not really well articulated in our field,” she said. “But it’s a connection we must make if we are to understand this condition and to develop treatments and interventions that make sense and are meaningful to the person who experiences psychosis.”
With her colleagues, Dr. Park has developed a way to better measure these bodily “self-disturbances” that patients with schizophrenia experience, and how they persist over time. B-BODI – the Benson et al. Body Disturbances Inventory – is a kind of catalog of pictures representing experiences of self-disturbance, such as someone having an out-of-body experience or a person who feels her body parts changing. The pictures come with written statements, and are designed to elicit more information from the patients about their experiences, such as how vivid, disturbing, and frequent they are.
Researchers have found that these experiences of body and self-disturbances are correlated with the positive symptoms of schizophrenia – such as hallucinations and confused thoughts – as well as with loneliness. But those experiences are not correlated with negative symptoms, such as loss of ability to feel pleasure.
, and the use of pictures could help patients better convey what they’re experiencing, Dr. Park said.
“Self-disturbances are difficult to verbalize,” she said. B-BODI can help verbalize these strange experiences that are hard to describe – especially in those who have difficulty communicating.
She and her colleagues have found that those at risk of schizophrenia have a more “flexible body boundary” than do those not at risk. They performed an assessment of the degree to which subjects experienced the “Pinocchio illusion,” in which subjects are blindfolded, touch their noses, and have their biceps stimulated to create the sensation that their arm is moving away from the nose – which is interpreted as the nose growing longer. They found that subjects who scored higher on the Prodromal Questionnaire Brief – an assessment of schizophrenia risk – had higher Pinocchio illusion scores.
These abnormalities in self-perception all feed into the difficulty with which people with schizophrenia have in interacting with others. To address this difficulty, her group has developed a virtual reality training program to help patients with these interactions.
In the program, the user is asked to choose an avatar to interact with by looking at the face of the avatar for a few seconds. Once chosen, the face of the avatar is fully revealed and a conversation takes place. Then the participant receives feedback. Negative symptoms of schizophrenia were significantly reduced after participation after just 10 sessions, Dr. Park said. The program has received favorable reviews from patients – one described the avatars as “very friendly” – and holds promise for helping schizophrenia patients with social situations.
“Virtual reality,” she said, “offers the ideal rehearsal space.”
This work was supported by the National Institute of Mental Health and NARSAD, formerly known as the National Alliance for Research on Schizophrenia and Depression. Dr. Park reported no financial disclosures.
REPORTING FROM SIRS 2019
Psychosis drug development persists amid snags
ORLANDO – The landscape for drug development in schizophrenia includes several new promising targets as the field tries to regain its footing after a series of disappointments in recent years, a group of experts said in a session preceding the annual congress of the Schizophrenia International Research Society.
However, the experts also expressed a sense of urgency that trial design and better patient selection have to be improved. Some recent trial failures are likely because of faulty design rather than choosing the wrong target, they said in a satellite session that was funded and organized by Sunovion Pharmaceuticals.
“The question is really critical, because we’ve seen too many major pharma [companies] completely withdraw from this field because of their costly failures,” said Herbert Y. Meltzer, MD, director of the translational neuropharmacology program at Northwestern University, Chicago. “We’ve got to get it right.”
Some of the more prominent, recent trials that were embarked on with hope only to end with unfavorable results include pomaglumetad, a metabotropic glutamate receptor agonist that tried but failed to reduce residual positive and negative schizophrenia symptoms; bitopertin, a glycine transporter 1 inhibitor, for similar symptoms; several phosphodiesterase-10 inhibitors targeting acutely exacerbated schizophrenia symptoms; encenicline, a nicotinic receptor agonist for cognition; and Lu AF35700, a dopamine-and serotonin-receptor agonist, which the manufacturer recently announced failed to reduce positive and negative symptom scores.
Chrisoph U. Correll, MD, professor of psychiatry and molecular medicine at Hofstra University, Hempstead, N.Y., said it’s possible that the phosphodiesterase-10 inhibitors could be looked at again.
“Maybe there is an approach to treat negative symptoms,” he said, adding that some trials might not have chosen patients effectively. “They may have had the wrong patients. They might have had also the wrong prior treatment and not having washed out patients enough.”
Dr. Meltzer said it’s clear to him that the encenicline trial, in particular, involved a problem of design. “There’s no way increasing cholinergic activity through the nicotinic receptor agonist is not going to improve cognition.”
He said embracing genetics is the best way forward, saying that the “shotgun approach” of the past has siphoned money and time away from more important work. “The future of the field is in the genetics – we’re going to have to get the right people into the right trials for the right drug and design them accordingly. 
Oliver Howes, MD, PhD, professor of psychiatry at King’s College London, described new areas of interest in the disease pathway, ahead of the dopamine receptor, which has long been a dominant focus of research and treatment efforts.
“How might we target these upstream factors that might regulate dopamine synthesis and release capacity?” is a key research question at the moment, he said.
A drug – called SEP-363856 – that targets the trace amine-associated receptor 1, which has a role in neurotransmission, significantly improved Positive and Negative Syndrome Scale scores in phase 2 trials. Researchers are also making progress in employing parvalbumin interneurons to dampen dopamine synthesis, Dr. Howes said.
Drugmakers halted development of a drug that targeted dopamine firing regulated by the muscarinic receptors M4 and M1 because of gastrointestinal side effects. But there is renewed hope of a more refined approach that targets only M4, rather than M1, which was thought to be responsible for the effects. Some preclinical efforts have been encouraging in this regard, Dr. Howes said.
“This more selective M4 agonist,” he said, “could manipulate the dopamine system in the way that we want.”
Dr. Meltzer, Dr. Correll, and Dr. Howes reported financial relationships with Sunovion, Alkermes, Bristol-Myers Squibb, Lundbeck, Takeda, and other companies.
ORLANDO – The landscape for drug development in schizophrenia includes several new promising targets as the field tries to regain its footing after a series of disappointments in recent years, a group of experts said in a session preceding the annual congress of the Schizophrenia International Research Society.
However, the experts also expressed a sense of urgency that trial design and better patient selection have to be improved. Some recent trial failures are likely because of faulty design rather than choosing the wrong target, they said in a satellite session that was funded and organized by Sunovion Pharmaceuticals.
“The question is really critical, because we’ve seen too many major pharma [companies] completely withdraw from this field because of their costly failures,” said Herbert Y. Meltzer, MD, director of the translational neuropharmacology program at Northwestern University, Chicago. “We’ve got to get it right.”
Some of the more prominent, recent trials that were embarked on with hope only to end with unfavorable results include pomaglumetad, a metabotropic glutamate receptor agonist that tried but failed to reduce residual positive and negative schizophrenia symptoms; bitopertin, a glycine transporter 1 inhibitor, for similar symptoms; several phosphodiesterase-10 inhibitors targeting acutely exacerbated schizophrenia symptoms; encenicline, a nicotinic receptor agonist for cognition; and Lu AF35700, a dopamine-and serotonin-receptor agonist, which the manufacturer recently announced failed to reduce positive and negative symptom scores.
Chrisoph U. Correll, MD, professor of psychiatry and molecular medicine at Hofstra University, Hempstead, N.Y., said it’s possible that the phosphodiesterase-10 inhibitors could be looked at again.
“Maybe there is an approach to treat negative symptoms,” he said, adding that some trials might not have chosen patients effectively. “They may have had the wrong patients. They might have had also the wrong prior treatment and not having washed out patients enough.”
Dr. Meltzer said it’s clear to him that the encenicline trial, in particular, involved a problem of design. “There’s no way increasing cholinergic activity through the nicotinic receptor agonist is not going to improve cognition.”
He said embracing genetics is the best way forward, saying that the “shotgun approach” of the past has siphoned money and time away from more important work. “The future of the field is in the genetics – we’re going to have to get the right people into the right trials for the right drug and design them accordingly.
Oliver Howes, MD, PhD, professor of psychiatry at King’s College London, described new areas of interest in the disease pathway, ahead of the dopamine receptor, which has long been a dominant focus of research and treatment efforts.
“How might we target these upstream factors that might regulate dopamine synthesis and release capacity?” is a key research question at the moment, he said.
A drug – called SEP-363856 – that targets the trace amine-associated receptor 1, which has a role in neurotransmission, significantly improved Positive and Negative Syndrome Scale scores in phase 2 trials. Researchers are also making progress in employing parvalbumin interneurons to dampen dopamine synthesis, Dr. Howes said.
Drugmakers halted development of a drug that targeted dopamine firing regulated by the muscarinic receptors M4 and M1 because of gastrointestinal side effects. But there is renewed hope of a more refined approach that targets only M4, rather than M1, which was thought to be responsible for the effects. Some preclinical efforts have been encouraging in this regard, Dr. Howes said.
“This more selective M4 agonist,” he said, “could manipulate the dopamine system in the way that we want.”
Dr. Meltzer, Dr. Correll, and Dr. Howes reported financial relationships with Sunovion, Alkermes, Bristol-Myers Squibb, Lundbeck, Takeda, and other companies.
ORLANDO – The landscape for drug development in schizophrenia includes several new promising targets as the field tries to regain its footing after a series of disappointments in recent years, a group of experts said in a session preceding the annual congress of the Schizophrenia International Research Society.
However, the experts also expressed a sense of urgency that trial design and better patient selection have to be improved. Some recent trial failures are likely because of faulty design rather than choosing the wrong target, they said in a satellite session that was funded and organized by Sunovion Pharmaceuticals.
“The question is really critical, because we’ve seen too many major pharma [companies] completely withdraw from this field because of their costly failures,” said Herbert Y. Meltzer, MD, director of the translational neuropharmacology program at Northwestern University, Chicago. “We’ve got to get it right.”
Some of the more prominent, recent trials that were embarked on with hope only to end with unfavorable results include pomaglumetad, a metabotropic glutamate receptor agonist that tried but failed to reduce residual positive and negative schizophrenia symptoms; bitopertin, a glycine transporter 1 inhibitor, for similar symptoms; several phosphodiesterase-10 inhibitors targeting acutely exacerbated schizophrenia symptoms; encenicline, a nicotinic receptor agonist for cognition; and Lu AF35700, a dopamine-and serotonin-receptor agonist, which the manufacturer recently announced failed to reduce positive and negative symptom scores.
Chrisoph U. Correll, MD, professor of psychiatry and molecular medicine at Hofstra University, Hempstead, N.Y., said it’s possible that the phosphodiesterase-10 inhibitors could be looked at again.
“Maybe there is an approach to treat negative symptoms,” he said, adding that some trials might not have chosen patients effectively. “They may have had the wrong patients. They might have had also the wrong prior treatment and not having washed out patients enough.”
Dr. Meltzer said it’s clear to him that the encenicline trial, in particular, involved a problem of design. “There’s no way increasing cholinergic activity through the nicotinic receptor agonist is not going to improve cognition.”
He said embracing genetics is the best way forward, saying that the “shotgun approach” of the past has siphoned money and time away from more important work. “The future of the field is in the genetics – we’re going to have to get the right people into the right trials for the right drug and design them accordingly.
Oliver Howes, MD, PhD, professor of psychiatry at King’s College London, described new areas of interest in the disease pathway, ahead of the dopamine receptor, which has long been a dominant focus of research and treatment efforts.
“How might we target these upstream factors that might regulate dopamine synthesis and release capacity?” is a key research question at the moment, he said.
A drug – called SEP-363856 – that targets the trace amine-associated receptor 1, which has a role in neurotransmission, significantly improved Positive and Negative Syndrome Scale scores in phase 2 trials. Researchers are also making progress in employing parvalbumin interneurons to dampen dopamine synthesis, Dr. Howes said.
Drugmakers halted development of a drug that targeted dopamine firing regulated by the muscarinic receptors M4 and M1 because of gastrointestinal side effects. But there is renewed hope of a more refined approach that targets only M4, rather than M1, which was thought to be responsible for the effects. Some preclinical efforts have been encouraging in this regard, Dr. Howes said.
“This more selective M4 agonist,” he said, “could manipulate the dopamine system in the way that we want.”
Dr. Meltzer, Dr. Correll, and Dr. Howes reported financial relationships with Sunovion, Alkermes, Bristol-Myers Squibb, Lundbeck, Takeda, and other companies.
EXPERT ANALYSIS FROM SIRS 2019
Interest renewed in targeting gluten in schizophrenia
ORLANDO – Going gluten free shows a benefit for a subset of schizophrenia patients, and it offers a new array of potential intervention – suggesting that knowing what some patients consume or interrupting newly identified mechanisms could make real differences in symptom severity, an expert said at the annual congress of the Schizophrenia International Research Society.
Deanna L. Kelly, PharmD, director of the Treatment Research Program at the University of Maryland, Baltimore, said that if she’d been told 10 years ago that she’d be studying links between diet and schizophrenia, “I would have probably not believed you.”
Interest in the link between wheat, which contains gluten, and schizophrenia is not brand new. Research published in the 1960s found that, as wheat consumption fell in Scandinavia during World War II, so did hospital admissions for schizophrenia. In the United States, schizophrenia admissions rose as wheat consumption rose. But interest in the topic died off in the 1980s, when links between a gluten-free diet and schizophrenia symptoms were found to be weak or nonexistent.
Dr. Kelly said that’s because that research looked at all comers without a finely tuned schizophrenia population.
a protein that helps bread rise during baking and is hard to digest. Researchers have found that antibodies to other gluten proteins – such as anti–tissue transglutaminase antibodies, used to diagnose celiac disease – are not elevated in schizophrenia patients, compared with healthy controls (Schizophr Res. 2018 May;195:585-6). But native gliadin antibodies (AGA IgG) are significantly elevated – this is seen in about 30% of patients, compared with about 10% in controls, Dr. Kelly said.
Elevated AGA IgG is also correlated to higher levels of peripheral inflammation and higher levels of peripheral kynurenine, a metabolite of tryptophan linked to schizophrenia.
In a feasibility study with 16 patients published this year, researchers randomized patients with elevated AGA IgG to a gluten-free diet – they were fed with certified gluten-free shakes – or a diet that wasn’t gluten free over 5 weeks. Patients stayed at a hospital to ensure adherence to the diet and for close monitoring. They found that those who were gluten free showed significant improvement in negative symptoms, measured by the Scale for the Assessment of Negative Symptoms, compared with those who continued eating gluten. These symptoms included the inability to experience pleasure, inability to speak, lack of initiative, and inability to express emotion (J Psychiatry Neurosci. 2019 Mar 27;44[3]:1-9).
“Removing gliadin may improve negative symptoms in schizophrenia,” Dr. Kelly said.
Those on the gluten-free diet also showed improvement in gastrointestinal symptoms and improvement in certain cognitive traits, such as attention and verbal learning.
Her research team is now conducting on a larger trial comparing the two diets, this time with the gluten-containing diet involving a higher amount of gluten, which researchers think better reflects real-life diets.
Researchers are still not sure how gliadin intake affects schizophrenia symptoms, but it could involve problems with the blood brain barrier, the permeability of the gut, or the effects on the microbiome, she said. But the importance of gliadin and gluten to this group of schizophrenia patients raises the possibility of treatment with ongoing dietary changes, anti-inflammatory treatments, blocking absorption of gluten, improving how it’s digested or by blocking gliadin antibodies.
“We’re trying to learn about disease states themselves, but each person should find their best lives,” Dr. Kelly said. “Everyone deserves optimized and personalized treatment.”
Dr. Kelly reported financial relationships with Lundbeck and HLS Therapeutics.
ORLANDO – Going gluten free shows a benefit for a subset of schizophrenia patients, and it offers a new array of potential intervention – suggesting that knowing what some patients consume or interrupting newly identified mechanisms could make real differences in symptom severity, an expert said at the annual congress of the Schizophrenia International Research Society.
Deanna L. Kelly, PharmD, director of the Treatment Research Program at the University of Maryland, Baltimore, said that if she’d been told 10 years ago that she’d be studying links between diet and schizophrenia, “I would have probably not believed you.”
Interest in the link between wheat, which contains gluten, and schizophrenia is not brand new. Research published in the 1960s found that, as wheat consumption fell in Scandinavia during World War II, so did hospital admissions for schizophrenia. In the United States, schizophrenia admissions rose as wheat consumption rose. But interest in the topic died off in the 1980s, when links between a gluten-free diet and schizophrenia symptoms were found to be weak or nonexistent.
Dr. Kelly said that’s because that research looked at all comers without a finely tuned schizophrenia population.
a protein that helps bread rise during baking and is hard to digest. Researchers have found that antibodies to other gluten proteins – such as anti–tissue transglutaminase antibodies, used to diagnose celiac disease – are not elevated in schizophrenia patients, compared with healthy controls (Schizophr Res. 2018 May;195:585-6). But native gliadin antibodies (AGA IgG) are significantly elevated – this is seen in about 30% of patients, compared with about 10% in controls, Dr. Kelly said.
Elevated AGA IgG is also correlated to higher levels of peripheral inflammation and higher levels of peripheral kynurenine, a metabolite of tryptophan linked to schizophrenia.
In a feasibility study with 16 patients published this year, researchers randomized patients with elevated AGA IgG to a gluten-free diet – they were fed with certified gluten-free shakes – or a diet that wasn’t gluten free over 5 weeks. Patients stayed at a hospital to ensure adherence to the diet and for close monitoring. They found that those who were gluten free showed significant improvement in negative symptoms, measured by the Scale for the Assessment of Negative Symptoms, compared with those who continued eating gluten. These symptoms included the inability to experience pleasure, inability to speak, lack of initiative, and inability to express emotion (J Psychiatry Neurosci. 2019 Mar 27;44[3]:1-9).
“Removing gliadin may improve negative symptoms in schizophrenia,” Dr. Kelly said.
Those on the gluten-free diet also showed improvement in gastrointestinal symptoms and improvement in certain cognitive traits, such as attention and verbal learning.
Her research team is now conducting on a larger trial comparing the two diets, this time with the gluten-containing diet involving a higher amount of gluten, which researchers think better reflects real-life diets.
Researchers are still not sure how gliadin intake affects schizophrenia symptoms, but it could involve problems with the blood brain barrier, the permeability of the gut, or the effects on the microbiome, she said. But the importance of gliadin and gluten to this group of schizophrenia patients raises the possibility of treatment with ongoing dietary changes, anti-inflammatory treatments, blocking absorption of gluten, improving how it’s digested or by blocking gliadin antibodies.
“We’re trying to learn about disease states themselves, but each person should find their best lives,” Dr. Kelly said. “Everyone deserves optimized and personalized treatment.”
Dr. Kelly reported financial relationships with Lundbeck and HLS Therapeutics.
ORLANDO – Going gluten free shows a benefit for a subset of schizophrenia patients, and it offers a new array of potential intervention – suggesting that knowing what some patients consume or interrupting newly identified mechanisms could make real differences in symptom severity, an expert said at the annual congress of the Schizophrenia International Research Society.
Deanna L. Kelly, PharmD, director of the Treatment Research Program at the University of Maryland, Baltimore, said that if she’d been told 10 years ago that she’d be studying links between diet and schizophrenia, “I would have probably not believed you.”
Interest in the link between wheat, which contains gluten, and schizophrenia is not brand new. Research published in the 1960s found that, as wheat consumption fell in Scandinavia during World War II, so did hospital admissions for schizophrenia. In the United States, schizophrenia admissions rose as wheat consumption rose. But interest in the topic died off in the 1980s, when links between a gluten-free diet and schizophrenia symptoms were found to be weak or nonexistent.
Dr. Kelly said that’s because that research looked at all comers without a finely tuned schizophrenia population.
a protein that helps bread rise during baking and is hard to digest. Researchers have found that antibodies to other gluten proteins – such as anti–tissue transglutaminase antibodies, used to diagnose celiac disease – are not elevated in schizophrenia patients, compared with healthy controls (Schizophr Res. 2018 May;195:585-6). But native gliadin antibodies (AGA IgG) are significantly elevated – this is seen in about 30% of patients, compared with about 10% in controls, Dr. Kelly said.
Elevated AGA IgG is also correlated to higher levels of peripheral inflammation and higher levels of peripheral kynurenine, a metabolite of tryptophan linked to schizophrenia.
In a feasibility study with 16 patients published this year, researchers randomized patients with elevated AGA IgG to a gluten-free diet – they were fed with certified gluten-free shakes – or a diet that wasn’t gluten free over 5 weeks. Patients stayed at a hospital to ensure adherence to the diet and for close monitoring. They found that those who were gluten free showed significant improvement in negative symptoms, measured by the Scale for the Assessment of Negative Symptoms, compared with those who continued eating gluten. These symptoms included the inability to experience pleasure, inability to speak, lack of initiative, and inability to express emotion (J Psychiatry Neurosci. 2019 Mar 27;44[3]:1-9).
“Removing gliadin may improve negative symptoms in schizophrenia,” Dr. Kelly said.
Those on the gluten-free diet also showed improvement in gastrointestinal symptoms and improvement in certain cognitive traits, such as attention and verbal learning.
Her research team is now conducting on a larger trial comparing the two diets, this time with the gluten-containing diet involving a higher amount of gluten, which researchers think better reflects real-life diets.
Researchers are still not sure how gliadin intake affects schizophrenia symptoms, but it could involve problems with the blood brain barrier, the permeability of the gut, or the effects on the microbiome, she said. But the importance of gliadin and gluten to this group of schizophrenia patients raises the possibility of treatment with ongoing dietary changes, anti-inflammatory treatments, blocking absorption of gluten, improving how it’s digested or by blocking gliadin antibodies.
“We’re trying to learn about disease states themselves, but each person should find their best lives,” Dr. Kelly said. “Everyone deserves optimized and personalized treatment.”
Dr. Kelly reported financial relationships with Lundbeck and HLS Therapeutics.
EXPERT ANALYSIS FROM SIRS 2019
