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Tom Collins is a freelance writer in South Florida who has written about medical topics from nasty infections to ethical dilemmas, runaway tumors to tornado-chasing doctors. He travels the globe gathering conference health news and lives in West Palm Beach.
Best of RIV highlights practical, innovative projects
Delirium, alcohol detox, and med rec
A project to improve how hospitalists address inpatient delirium, which has led to reductions in length of stay and cost, took center stage in the Best of RIV plenary session at HM19 in March.
The project, conducted at the University of California, San Francisco (UCSF), was presented alongside projects on alcohol detox at the Cleveland Veterans Affairs Medical Center and on medication reconciliation at Brigham and Women’s Hospital in Boston.
“The plenary is the top three of the 1,000 that are out there – so, impressive work,” said Benji Mathews, MD, SFHM, the chair of the Research, Innovations and Vignettes competition.
At UCSF, the project was meant to tackle the huge problem of delirium in the hospital, said Catherine Lau, MD, SFHM, associate professor of medicine there. Each year delirium affects more than 7 million people who are hospitalized, and hospital-acquired delirium is linked with prolonged stays and more emergency department visits and hospital readmissions. But research has found that as many as a third of these hospital-acquired cases can be prevented, Dr. Lau said.
New admissions and transfers – a total of more than 2,800 patients – were assessed for delirium risk, and those deemed high risk were entered into a delirium care plan, aimed at prevention with nonpharmacologic steps such as maximizing their mobility and helping them sleep at night.
All patients also were screened on every nursing shift for delirium, and those diagnosed with the disorder were placed in the delirium care plan, with notification of the patient’s team for treatment.
The average length of stay decreased by 0.8 days (P less than .001), with a decrease of 1.9 days in patients with delirium, compared with outcomes for nearly 2,600 patients before the intervention was implemented, Dr. Lau said. Researchers also found a decrease in $850 spent per patient (P less than .001), with a direct savings to the hospital of a total of $997,000, she said. The 30-day readmission rate also fell significantly, from 18.9% to 15.9% (P = .03).
The screening itself seemed to be the most important factor in the project, Dr. Lau said.
“Just the recognition that their patient was at risk for delirium or actually had delirium really raised awareness,” she said.
The project on alcohol detox used careful risk assessments at emergency department discharge, e-consults, protocols to limit benzodiazepine prescribing, and telephone follow-up to reduce hospital admissions and 30-day readmissions, as well as length of stay.
Researchers used scores on CIWA – a 10-question measurement of the severity of someone’s alcohol withdrawal – and history of complicated alcohol-use withdrawal to determine whether ED patients should be admitted to the floor or sent home with or without prescriptions for gabapentin and lorazepam, said Robert Patrick, MD, a hospitalist at the Cleveland VA.
Perhaps the most innovative feature of the program was using systolic blood pressure and heart rate in addition to CIWA to determine whether someone should receive a benzodiazepine, he said. Someone with a CIWA of 9-12, for instance, would be prescribed one of these drugs only if their vitals were elevated, Dr. Patrick said.
He encouraged other hospitalists to try a similar program at their centers.
“You don’t have to be at a VA to do this,” he said. “And most importantly, you don’t have to have a cooperative ED to do this. You can do this just within your hospitalist group.”
In another presentation, Jeffrey Schnipper MD, MPH, FHM, associate professor of medicine at Harvard Medical School, Boston, described the results from a project in which SHM’s MARQUIS program – an evidence-based “toolkit” on medication reconciliation – was implemented at 18 hospitals. The kit offers a plan to get the best possible medication history, give medication counseling on discharge, and identify patients at risk for medication discrepancies. The 18 sites were coached, with areas of improvement identified.
By months 13-18 of the study period, the number of medication discrepancies had fallen to 0.93 per patient for those who’d received at least one form of intervention, compared with 2.69 per patient among those who’d received none.
“The MARQUIS interventions, including the toolkit and mentored implementation,” Dr. Schnipper said, “are associated with a marked reduction in medication discrepancies.”
Delirium, alcohol detox, and med rec
Delirium, alcohol detox, and med rec
A project to improve how hospitalists address inpatient delirium, which has led to reductions in length of stay and cost, took center stage in the Best of RIV plenary session at HM19 in March.
The project, conducted at the University of California, San Francisco (UCSF), was presented alongside projects on alcohol detox at the Cleveland Veterans Affairs Medical Center and on medication reconciliation at Brigham and Women’s Hospital in Boston.
“The plenary is the top three of the 1,000 that are out there – so, impressive work,” said Benji Mathews, MD, SFHM, the chair of the Research, Innovations and Vignettes competition.
At UCSF, the project was meant to tackle the huge problem of delirium in the hospital, said Catherine Lau, MD, SFHM, associate professor of medicine there. Each year delirium affects more than 7 million people who are hospitalized, and hospital-acquired delirium is linked with prolonged stays and more emergency department visits and hospital readmissions. But research has found that as many as a third of these hospital-acquired cases can be prevented, Dr. Lau said.
New admissions and transfers – a total of more than 2,800 patients – were assessed for delirium risk, and those deemed high risk were entered into a delirium care plan, aimed at prevention with nonpharmacologic steps such as maximizing their mobility and helping them sleep at night.
All patients also were screened on every nursing shift for delirium, and those diagnosed with the disorder were placed in the delirium care plan, with notification of the patient’s team for treatment.
The average length of stay decreased by 0.8 days (P less than .001), with a decrease of 1.9 days in patients with delirium, compared with outcomes for nearly 2,600 patients before the intervention was implemented, Dr. Lau said. Researchers also found a decrease in $850 spent per patient (P less than .001), with a direct savings to the hospital of a total of $997,000, she said. The 30-day readmission rate also fell significantly, from 18.9% to 15.9% (P = .03).
The screening itself seemed to be the most important factor in the project, Dr. Lau said.
“Just the recognition that their patient was at risk for delirium or actually had delirium really raised awareness,” she said.
The project on alcohol detox used careful risk assessments at emergency department discharge, e-consults, protocols to limit benzodiazepine prescribing, and telephone follow-up to reduce hospital admissions and 30-day readmissions, as well as length of stay.
Researchers used scores on CIWA – a 10-question measurement of the severity of someone’s alcohol withdrawal – and history of complicated alcohol-use withdrawal to determine whether ED patients should be admitted to the floor or sent home with or without prescriptions for gabapentin and lorazepam, said Robert Patrick, MD, a hospitalist at the Cleveland VA.
Perhaps the most innovative feature of the program was using systolic blood pressure and heart rate in addition to CIWA to determine whether someone should receive a benzodiazepine, he said. Someone with a CIWA of 9-12, for instance, would be prescribed one of these drugs only if their vitals were elevated, Dr. Patrick said.
He encouraged other hospitalists to try a similar program at their centers.
“You don’t have to be at a VA to do this,” he said. “And most importantly, you don’t have to have a cooperative ED to do this. You can do this just within your hospitalist group.”
In another presentation, Jeffrey Schnipper MD, MPH, FHM, associate professor of medicine at Harvard Medical School, Boston, described the results from a project in which SHM’s MARQUIS program – an evidence-based “toolkit” on medication reconciliation – was implemented at 18 hospitals. The kit offers a plan to get the best possible medication history, give medication counseling on discharge, and identify patients at risk for medication discrepancies. The 18 sites were coached, with areas of improvement identified.
By months 13-18 of the study period, the number of medication discrepancies had fallen to 0.93 per patient for those who’d received at least one form of intervention, compared with 2.69 per patient among those who’d received none.
“The MARQUIS interventions, including the toolkit and mentored implementation,” Dr. Schnipper said, “are associated with a marked reduction in medication discrepancies.”
A project to improve how hospitalists address inpatient delirium, which has led to reductions in length of stay and cost, took center stage in the Best of RIV plenary session at HM19 in March.
The project, conducted at the University of California, San Francisco (UCSF), was presented alongside projects on alcohol detox at the Cleveland Veterans Affairs Medical Center and on medication reconciliation at Brigham and Women’s Hospital in Boston.
“The plenary is the top three of the 1,000 that are out there – so, impressive work,” said Benji Mathews, MD, SFHM, the chair of the Research, Innovations and Vignettes competition.
At UCSF, the project was meant to tackle the huge problem of delirium in the hospital, said Catherine Lau, MD, SFHM, associate professor of medicine there. Each year delirium affects more than 7 million people who are hospitalized, and hospital-acquired delirium is linked with prolonged stays and more emergency department visits and hospital readmissions. But research has found that as many as a third of these hospital-acquired cases can be prevented, Dr. Lau said.
New admissions and transfers – a total of more than 2,800 patients – were assessed for delirium risk, and those deemed high risk were entered into a delirium care plan, aimed at prevention with nonpharmacologic steps such as maximizing their mobility and helping them sleep at night.
All patients also were screened on every nursing shift for delirium, and those diagnosed with the disorder were placed in the delirium care plan, with notification of the patient’s team for treatment.
The average length of stay decreased by 0.8 days (P less than .001), with a decrease of 1.9 days in patients with delirium, compared with outcomes for nearly 2,600 patients before the intervention was implemented, Dr. Lau said. Researchers also found a decrease in $850 spent per patient (P less than .001), with a direct savings to the hospital of a total of $997,000, she said. The 30-day readmission rate also fell significantly, from 18.9% to 15.9% (P = .03).
The screening itself seemed to be the most important factor in the project, Dr. Lau said.
“Just the recognition that their patient was at risk for delirium or actually had delirium really raised awareness,” she said.
The project on alcohol detox used careful risk assessments at emergency department discharge, e-consults, protocols to limit benzodiazepine prescribing, and telephone follow-up to reduce hospital admissions and 30-day readmissions, as well as length of stay.
Researchers used scores on CIWA – a 10-question measurement of the severity of someone’s alcohol withdrawal – and history of complicated alcohol-use withdrawal to determine whether ED patients should be admitted to the floor or sent home with or without prescriptions for gabapentin and lorazepam, said Robert Patrick, MD, a hospitalist at the Cleveland VA.
Perhaps the most innovative feature of the program was using systolic blood pressure and heart rate in addition to CIWA to determine whether someone should receive a benzodiazepine, he said. Someone with a CIWA of 9-12, for instance, would be prescribed one of these drugs only if their vitals were elevated, Dr. Patrick said.
He encouraged other hospitalists to try a similar program at their centers.
“You don’t have to be at a VA to do this,” he said. “And most importantly, you don’t have to have a cooperative ED to do this. You can do this just within your hospitalist group.”
In another presentation, Jeffrey Schnipper MD, MPH, FHM, associate professor of medicine at Harvard Medical School, Boston, described the results from a project in which SHM’s MARQUIS program – an evidence-based “toolkit” on medication reconciliation – was implemented at 18 hospitals. The kit offers a plan to get the best possible medication history, give medication counseling on discharge, and identify patients at risk for medication discrepancies. The 18 sites were coached, with areas of improvement identified.
By months 13-18 of the study period, the number of medication discrepancies had fallen to 0.93 per patient for those who’d received at least one form of intervention, compared with 2.69 per patient among those who’d received none.
“The MARQUIS interventions, including the toolkit and mentored implementation,” Dr. Schnipper said, “are associated with a marked reduction in medication discrepancies.”
‘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.”
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.”
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.”
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
More evidence shows value of CBT for schizophrenia
ORLANDO – Cognitive-behavioral therapy (CBT) should be more widely offered to patients with psychosis, and a growing body of evidence is demonstrating why, an expert said at the annual congress of the Schizophrenia International Research Society.
Tony Morrison, ClinPsyD, said that, while antipsychotic medications are appropriate for many patients with disorders such as schizophrenia, they are not offered cognitive therapy nearly often enough.
“What I am against is the sole reliance on antipsychotics,” said Dr. Morrison, professor of clinical psychology at the University of Manchester (England). “Putting all of our eggs in that basket is not particularly sensible.” That’s because so many patients who are started on antipsychotic medications discontinue them, either because they are ineffective or because they conclude that the risk of side effects – weight gain, cardiovascular problems, and sexual dysfunction among them – are not worth it.
In a trial published last year, 75 patients with psychosis who were not taking antipsychotic medication were randomized to receive up to 26 sessions of CBT over 6 months, antipsychotic medication, or both. After a year, no difference was found in Positive and Negative Symptom Scale (PANSS) scores between the three groups, researchers found, although the combination group saw an improvement in PANSS scores at 24 weeks before later falling in line with the other groups (Lancet Psychiatry. 2018 May;5[5]:411-23).
Patients in the medical treatment arm mostly received aripiprazole, olanzapine, or quetiapine. Patients received an average of 14 sessions of CBT, with 80% attending at least 6 sessions. Researchers did not see any significant level adverse events in the CBT group.
The findings show that this is fertile ground to explore further, Dr. Morrison said. “It is safe to conduct trials in which people with psychosis are not taking antipsychotics,” he said.
A larger, more definitive trial is needed in this area.
Treatment of patients for whom antipsychotic medication has already been shown not to work is a bigger challenge, but a recent study Dr. Morrison led shows that CBT could work in these patients as well (Health Technol Assess. 2019 Feb;23[7]:1-144).
In that study, 487 patients with schizophrenia who were resistant to treatment with clozapine were randomized to CBT – up to 30 sessions over 9 months – or treatment as usual, without CBT. Researchers saw a slight benefit in PANSS scores for CBT at 9 months (P = .049). But this benefit was not maintained after patients stopped their cognitive therapy, and no difference in PANSS scores was seen at 21 months, the study’s primary endpoint.
Nonetheless, the findings were encouraging, Dr. Morrison said, showing that CBT “compares favorably with augmenting treatment with a second antipsychotic.” Researchers, however, were not able to determine which patients were likely to benefit most from CBT, despite “lots of subanalyses” in an effort to do so.
Patients resistant to initial medical therapy will need their illness tackled from a variety of fronts – subsequent antipsychotic therapy, psychological therapy, social-activity based therapy, and peer support.
“I think we probably need lots of things in combination – a much more rich package of care,” Dr. Morrison said.
Dr. Morrison reported no disclosures.
ORLANDO – Cognitive-behavioral therapy (CBT) should be more widely offered to patients with psychosis, and a growing body of evidence is demonstrating why, an expert said at the annual congress of the Schizophrenia International Research Society.
Tony Morrison, ClinPsyD, said that, while antipsychotic medications are appropriate for many patients with disorders such as schizophrenia, they are not offered cognitive therapy nearly often enough.
“What I am against is the sole reliance on antipsychotics,” said Dr. Morrison, professor of clinical psychology at the University of Manchester (England). “Putting all of our eggs in that basket is not particularly sensible.” That’s because so many patients who are started on antipsychotic medications discontinue them, either because they are ineffective or because they conclude that the risk of side effects – weight gain, cardiovascular problems, and sexual dysfunction among them – are not worth it.
In a trial published last year, 75 patients with psychosis who were not taking antipsychotic medication were randomized to receive up to 26 sessions of CBT over 6 months, antipsychotic medication, or both. After a year, no difference was found in Positive and Negative Symptom Scale (PANSS) scores between the three groups, researchers found, although the combination group saw an improvement in PANSS scores at 24 weeks before later falling in line with the other groups (Lancet Psychiatry. 2018 May;5[5]:411-23).
Patients in the medical treatment arm mostly received aripiprazole, olanzapine, or quetiapine. Patients received an average of 14 sessions of CBT, with 80% attending at least 6 sessions. Researchers did not see any significant level adverse events in the CBT group.
The findings show that this is fertile ground to explore further, Dr. Morrison said. “It is safe to conduct trials in which people with psychosis are not taking antipsychotics,” he said.
A larger, more definitive trial is needed in this area.
Treatment of patients for whom antipsychotic medication has already been shown not to work is a bigger challenge, but a recent study Dr. Morrison led shows that CBT could work in these patients as well (Health Technol Assess. 2019 Feb;23[7]:1-144).
In that study, 487 patients with schizophrenia who were resistant to treatment with clozapine were randomized to CBT – up to 30 sessions over 9 months – or treatment as usual, without CBT. Researchers saw a slight benefit in PANSS scores for CBT at 9 months (P = .049). But this benefit was not maintained after patients stopped their cognitive therapy, and no difference in PANSS scores was seen at 21 months, the study’s primary endpoint.
Nonetheless, the findings were encouraging, Dr. Morrison said, showing that CBT “compares favorably with augmenting treatment with a second antipsychotic.” Researchers, however, were not able to determine which patients were likely to benefit most from CBT, despite “lots of subanalyses” in an effort to do so.
Patients resistant to initial medical therapy will need their illness tackled from a variety of fronts – subsequent antipsychotic therapy, psychological therapy, social-activity based therapy, and peer support.
“I think we probably need lots of things in combination – a much more rich package of care,” Dr. Morrison said.
Dr. Morrison reported no disclosures.
ORLANDO – Cognitive-behavioral therapy (CBT) should be more widely offered to patients with psychosis, and a growing body of evidence is demonstrating why, an expert said at the annual congress of the Schizophrenia International Research Society.
Tony Morrison, ClinPsyD, said that, while antipsychotic medications are appropriate for many patients with disorders such as schizophrenia, they are not offered cognitive therapy nearly often enough.
“What I am against is the sole reliance on antipsychotics,” said Dr. Morrison, professor of clinical psychology at the University of Manchester (England). “Putting all of our eggs in that basket is not particularly sensible.” That’s because so many patients who are started on antipsychotic medications discontinue them, either because they are ineffective or because they conclude that the risk of side effects – weight gain, cardiovascular problems, and sexual dysfunction among them – are not worth it.
In a trial published last year, 75 patients with psychosis who were not taking antipsychotic medication were randomized to receive up to 26 sessions of CBT over 6 months, antipsychotic medication, or both. After a year, no difference was found in Positive and Negative Symptom Scale (PANSS) scores between the three groups, researchers found, although the combination group saw an improvement in PANSS scores at 24 weeks before later falling in line with the other groups (Lancet Psychiatry. 2018 May;5[5]:411-23).
Patients in the medical treatment arm mostly received aripiprazole, olanzapine, or quetiapine. Patients received an average of 14 sessions of CBT, with 80% attending at least 6 sessions. Researchers did not see any significant level adverse events in the CBT group.
The findings show that this is fertile ground to explore further, Dr. Morrison said. “It is safe to conduct trials in which people with psychosis are not taking antipsychotics,” he said.
A larger, more definitive trial is needed in this area.
Treatment of patients for whom antipsychotic medication has already been shown not to work is a bigger challenge, but a recent study Dr. Morrison led shows that CBT could work in these patients as well (Health Technol Assess. 2019 Feb;23[7]:1-144).
In that study, 487 patients with schizophrenia who were resistant to treatment with clozapine were randomized to CBT – up to 30 sessions over 9 months – or treatment as usual, without CBT. Researchers saw a slight benefit in PANSS scores for CBT at 9 months (P = .049). But this benefit was not maintained after patients stopped their cognitive therapy, and no difference in PANSS scores was seen at 21 months, the study’s primary endpoint.
Nonetheless, the findings were encouraging, Dr. Morrison said, showing that CBT “compares favorably with augmenting treatment with a second antipsychotic.” Researchers, however, were not able to determine which patients were likely to benefit most from CBT, despite “lots of subanalyses” in an effort to do so.
Patients resistant to initial medical therapy will need their illness tackled from a variety of fronts – subsequent antipsychotic therapy, psychological therapy, social-activity based therapy, and peer support.
“I think we probably need lots of things in combination – a much more rich package of care,” Dr. Morrison said.
Dr. Morrison reported no disclosures.
REPORTING FROM SIRS 2019