Kari Oakes

A coordinated approach to infection control and antibiotic stewardship would dramatically reduce the number of people affected by antibiotic-resistant pathogens and health care–associated infections (HAIs), saving tens of thousands of lives and billions of dollars over the next 5 years, according to a federal report.

With a nationwide prevention and antibiotic stewardship program, the total number of HAIs could be reduced by 619,000 over the next 5 years, saving 37,000 lives and reducing direct medical costs by $7.7 billion, Dr. Thomas Frieden, director of the Centers for Disease Control and Prevention (CDC), said in a telebriefing sponsored by the agency.

The coordinated approach requires both a public health tracking and alerting system and robust interfacility infection control practices. “Facilities that go it alone can’t effectively protect their own patients,” he said.

A CDC Vital Signs report projected outcomes for institution-based versus coordinated responses to antibiotic-resistant infections, predicting infections and deaths from 2014-2019 in a series of three scenarios.

Rachel Slayton, Ph.D., of the Center for Emerging and Zoonotic Infectious Diseases, used carbapenem-resistant Enterobacteriaceae (CRE) as the test case to determine the effect size of coordinated compared with institution-based infection control and alerting practices.*

She and her coauthors projected that the number of health care-associated CRE infections would rise about 10% over the next 5 years, from 310,000 to 340,000, under current practices. Using these prevalence figures, a coordinated approach would result in CRE prevalence within a health care network of just 2% after 5 years, compared with a 12% baseline prevalence and an 8.6% prevalence with augmented individual efforts.

“Two percent is still two percent too much, but it’s still a whole lot better than 12%,” said Dr. Frieden.

Infection control practices that are enhanced by interfacility coordination may include maintaining regional databases that permit alerts when an individual with an HAI transfers from one facility to the other; having inter-institution agreement about best practices for gowning, gloving, and isolation; and commencing enhanced screening for HAIs when public health officials identify a potential outbreak. Antibiotic stewardship is also enhanced when institutions explicitly agree to follow best prescribing practices.

Implementation of the coordinated approach would be supported by the CDC’s Antibiotic Resistance Solutions Initiative, with $264 million requested in the federal fiscal year 2016 budget for a broad set of programs. Part of this amount would provide for funding of a coordinated prevention approach in all 50 states, with support for state and local health departments, and a network of laboratory facilities for improved surveillance for resistant pathogens.

*CORRECTION 8/9/2015: The original version of this story misidentified the test case organism.

A coordinated approach to infection control and antibiotic stewardship would dramatically reduce the number of people affected by antibiotic-resistant pathogens and health care–associated infections (HAIs), saving tens of thousands of lives and billions of dollars over the next 5 years, according to a federal report.

With a nationwide prevention and antibiotic stewardship program, the total number of HAIs could be reduced by 619,000 over the next 5 years, saving 37,000 lives and reducing direct medical costs by $7.7 billion, Dr. Thomas Frieden, director of the Centers for Disease Control and Prevention (CDC), said in a telebriefing sponsored by the agency.

The coordinated approach requires both a public health tracking and alerting system and robust interfacility infection control practices. “Facilities that go it alone can’t effectively protect their own patients,” he said.

A CDC Vital Signs report projected outcomes for institution-based versus coordinated responses to antibiotic-resistant infections, predicting infections and deaths from 2014-2019 in a series of three scenarios.

Rachel Slayton, Ph.D., of the Center for Emerging and Zoonotic Infectious Diseases, used carbapenem-resistant Enterobacteriaceae (CRE) as the test case to determine the effect size of coordinated compared with institution-based infection control and alerting practices.*

She and her coauthors projected that the number of health care-associated CRE infections would rise about 10% over the next 5 years, from 310,000 to 340,000, under current practices. Using these prevalence figures, a coordinated approach would result in CRE prevalence within a health care network of just 2% after 5 years, compared with a 12% baseline prevalence and an 8.6% prevalence with augmented individual efforts.

“Two percent is still two percent too much, but it’s still a whole lot better than 12%,” said Dr. Frieden.

Infection control practices that are enhanced by interfacility coordination may include maintaining regional databases that permit alerts when an individual with an HAI transfers from one facility to the other; having inter-institution agreement about best practices for gowning, gloving, and isolation; and commencing enhanced screening for HAIs when public health officials identify a potential outbreak. Antibiotic stewardship is also enhanced when institutions explicitly agree to follow best prescribing practices.

Implementation of the coordinated approach would be supported by the CDC’s Antibiotic Resistance Solutions Initiative, with $264 million requested in the federal fiscal year 2016 budget for a broad set of programs. Part of this amount would provide for funding of a coordinated prevention approach in all 50 states, with support for state and local health departments, and a network of laboratory facilities for improved surveillance for resistant pathogens.

*CORRECTION 8/9/2015: The original version of this story misidentified the test case organism.

A coordinated approach to infection control and antibiotic stewardship would dramatically reduce the number of people affected by antibiotic-resistant pathogens and health care–associated infections (HAIs), saving tens of thousands of lives and billions of dollars over the next 5 years, according to a federal report.

With a nationwide prevention and antibiotic stewardship program, the total number of HAIs could be reduced by 619,000 over the next 5 years, saving 37,000 lives and reducing direct medical costs by $7.7 billion, Dr. Thomas Frieden, director of the Centers for Disease Control and Prevention (CDC), said in a telebriefing sponsored by the agency.

The coordinated approach requires both a public health tracking and alerting system and robust interfacility infection control practices. “Facilities that go it alone can’t effectively protect their own patients,” he said.

A CDC Vital Signs report projected outcomes for institution-based versus coordinated responses to antibiotic-resistant infections, predicting infections and deaths from 2014-2019 in a series of three scenarios.

Rachel Slayton, Ph.D., of the Center for Emerging and Zoonotic Infectious Diseases, used carbapenem-resistant Enterobacteriaceae (CRE) as the test case to determine the effect size of coordinated compared with institution-based infection control and alerting practices.*

She and her coauthors projected that the number of health care-associated CRE infections would rise about 10% over the next 5 years, from 310,000 to 340,000, under current practices. Using these prevalence figures, a coordinated approach would result in CRE prevalence within a health care network of just 2% after 5 years, compared with a 12% baseline prevalence and an 8.6% prevalence with augmented individual efforts.

“Two percent is still two percent too much, but it’s still a whole lot better than 12%,” said Dr. Frieden.

Infection control practices that are enhanced by interfacility coordination may include maintaining regional databases that permit alerts when an individual with an HAI transfers from one facility to the other; having inter-institution agreement about best practices for gowning, gloving, and isolation; and commencing enhanced screening for HAIs when public health officials identify a potential outbreak. Antibiotic stewardship is also enhanced when institutions explicitly agree to follow best prescribing practices.

Implementation of the coordinated approach would be supported by the CDC’s Antibiotic Resistance Solutions Initiative, with $264 million requested in the federal fiscal year 2016 budget for a broad set of programs. Part of this amount would provide for funding of a coordinated prevention approach in all 50 states, with support for state and local health departments, and a network of laboratory facilities for improved surveillance for resistant pathogens.

*CORRECTION 8/9/2015: The original version of this story misidentified the test case organism.

A coordinated approach to infection control and antibiotic stewardship would dramatically reduce the number of people affected by antibiotic-resistant pathogens and health care–associated infections (HAIs), saving tens of thousands of lives and billions of dollars over the next 5 years, according to a federal report.

With a nationwide prevention and antibiotic stewardship program, the total number of HAIs could be reduced by 619,000 over the next 5 years, saving 37,000 lives and reducing direct medical costs by $7.7 billion, Dr. Thomas Frieden, director of the Centers for Disease Control and Prevention (CDC), said in a telebriefing sponsored by the agency.

The coordinated approach requires both a public health tracking and alerting system and robust interfacility infection control practices. “Facilities that go it alone can’t effectively protect their own patients,” he said.

A CDC Vital Signs report projected outcomes for institution-based versus coordinated responses to antibiotic-resistant infections, predicting infections and deaths from 2014-2019 in a series of three scenarios.

Rachel Slayton, Ph.D., of the Center for Emerging and Zoonotic Infectious Diseases, used carbapenem-resistant Enterobacteriaceae (CRE) as the test case to determine the effect size of coordinated compared with institution-based infection control and alerting practices.*

She and her coauthors projected that the number of health care-associated CRE infections would rise about 10% over the next 5 years, from 310,000 to 340,000, under current practices. Using these prevalence figures, a coordinated approach would result in CRE prevalence within a health care network of just 2% after 5 years, compared with a 12% baseline prevalence and an 8.6% prevalence with augmented individual efforts.

“Two percent is still two percent too much, but it’s still a whole lot better than 12%,” said Dr. Frieden.

Infection control practices that are enhanced by interfacility coordination may include maintaining regional databases that permit alerts when an individual with an HAI transfers from one facility to the other; having inter-institution agreement about best practices for gowning, gloving, and isolation; and commencing enhanced screening for HAIs when public health officials identify a potential outbreak. Antibiotic stewardship is also enhanced when institutions explicitly agree to follow best prescribing practices.

Implementation of the coordinated approach would be supported by the CDC’s Antibiotic Resistance Solutions Initiative, with $264 million requested in the federal fiscal year 2016 budget for a broad set of programs. Part of this amount would provide for funding of a coordinated prevention approach in all 50 states, with support for state and local health departments, and a network of laboratory facilities for improved surveillance for resistant pathogens.

[email protected]

On Twitter: @karioakes

*CORRECTION 8/9/2015: The original version of this story misidentified the test case organism.

A coordinated approach to infection control and antibiotic stewardship would dramatically reduce the number of people affected by antibiotic-resistant pathogens and health care–associated infections (HAIs), saving tens of thousands of lives and billions of dollars over the next 5 years, according to a federal report.

With a nationwide prevention and antibiotic stewardship program, the total number of HAIs could be reduced by 619,000 over the next 5 years, saving 37,000 lives and reducing direct medical costs by $7.7 billion, Dr. Thomas Frieden, director of the Centers for Disease Control and Prevention (CDC), said in a telebriefing sponsored by the agency.

The coordinated approach requires both a public health tracking and alerting system and robust interfacility infection control practices. “Facilities that go it alone can’t effectively protect their own patients,” he said.

A CDC Vital Signs report projected outcomes for institution-based versus coordinated responses to antibiotic-resistant infections, predicting infections and deaths from 2014-2019 in a series of three scenarios.

Rachel Slayton, Ph.D., of the Center for Emerging and Zoonotic Infectious Diseases, used carbapenem-resistant Enterobacteriaceae (CRE) as the test case to determine the effect size of coordinated compared with institution-based infection control and alerting practices.*

She and her coauthors projected that the number of health care-associated CRE infections would rise about 10% over the next 5 years, from 310,000 to 340,000, under current practices. Using these prevalence figures, a coordinated approach would result in CRE prevalence within a health care network of just 2% after 5 years, compared with a 12% baseline prevalence and an 8.6% prevalence with augmented individual efforts.

“Two percent is still two percent too much, but it’s still a whole lot better than 12%,” said Dr. Frieden.

Infection control practices that are enhanced by interfacility coordination may include maintaining regional databases that permit alerts when an individual with an HAI transfers from one facility to the other; having inter-institution agreement about best practices for gowning, gloving, and isolation; and commencing enhanced screening for HAIs when public health officials identify a potential outbreak. Antibiotic stewardship is also enhanced when institutions explicitly agree to follow best prescribing practices.

Implementation of the coordinated approach would be supported by the CDC’s Antibiotic Resistance Solutions Initiative, with $264 million requested in the federal fiscal year 2016 budget for a broad set of programs. Part of this amount would provide for funding of a coordinated prevention approach in all 50 states, with support for state and local health departments, and a network of laboratory facilities for improved surveillance for resistant pathogens.

[email protected]

On Twitter: @karioakes

*CORRECTION 8/9/2015: The original version of this story misidentified the test case organism.

A coordinated approach to infection control and antibiotic stewardship would dramatically reduce the number of people affected by antibiotic-resistant pathogens and health care–associated infections (HAIs), saving tens of thousands of lives and billions of dollars over the next 5 years, according to a federal report.

With a nationwide prevention and antibiotic stewardship program, the total number of HAIs could be reduced by 619,000 over the next 5 years, saving 37,000 lives and reducing direct medical costs by $7.7 billion, Dr. Thomas Frieden, director of the Centers for Disease Control and Prevention (CDC), said in a telebriefing sponsored by the agency.

The coordinated approach requires both a public health tracking and alerting system and robust interfacility infection control practices. “Facilities that go it alone can’t effectively protect their own patients,” he said.

A CDC Vital Signs report projected outcomes for institution-based versus coordinated responses to antibiotic-resistant infections, predicting infections and deaths from 2014-2019 in a series of three scenarios.

Rachel Slayton, Ph.D., of the Center for Emerging and Zoonotic Infectious Diseases, used carbapenem-resistant Enterobacteriaceae (CRE) as the test case to determine the effect size of coordinated compared with institution-based infection control and alerting practices.*

She and her coauthors projected that the number of health care-associated CRE infections would rise about 10% over the next 5 years, from 310,000 to 340,000, under current practices. Using these prevalence figures, a coordinated approach would result in CRE prevalence within a health care network of just 2% after 5 years, compared with a 12% baseline prevalence and an 8.6% prevalence with augmented individual efforts.

“Two percent is still two percent too much, but it’s still a whole lot better than 12%,” said Dr. Frieden.

Infection control practices that are enhanced by interfacility coordination may include maintaining regional databases that permit alerts when an individual with an HAI transfers from one facility to the other; having inter-institution agreement about best practices for gowning, gloving, and isolation; and commencing enhanced screening for HAIs when public health officials identify a potential outbreak. Antibiotic stewardship is also enhanced when institutions explicitly agree to follow best prescribing practices.

Implementation of the coordinated approach would be supported by the CDC’s Antibiotic Resistance Solutions Initiative, with $264 million requested in the federal fiscal year 2016 budget for a broad set of programs. Part of this amount would provide for funding of a coordinated prevention approach in all 50 states, with support for state and local health departments, and a network of laboratory facilities for improved surveillance for resistant pathogens.

[email protected]

On Twitter: @karioakes

*CORRECTION 8/9/2015: The original version of this story misidentified the test case organism.

MIAMI BEACH – Patients with active bipolar disorder significantly underestimated the quality of their sleep, despite having sleep quality comparable to that of healthy controls.

Sleep complaints are common among individuals with bipolar disorder, and addressing disruptive and troubling sleep problems can be an important component of treating bipolar disorder, noted Dr. Venkatesh Krishnamurthy and his collaborators at Penn State University (Hershey, Pa.).

“Mood state may affect perception of sleep, and the impact of mood state on subjective-objective differences of sleep parameters needs to be further explored,” the researchers noted.

They reported their comparison of subjective and objective measures of sleep for symptomatic patients with bipolar disorder in a poster presentation at a meeting of the American Society for Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

The study researchers evaluated 30 individuals with symptomatic bipolar disorder, compared with 31 healthy controls, reported Dr. Krishnamurthy, assistant professor at the department of psychiatry’s Sleep Research and Treatment Center at Penn State’s Milton S. Hershey Medical Center. Patients with bipolar disorder were inpatients or in a partial hospitalization program; 11 patients had bipolar depression, 18 had mixed-state bipolar disorder, and 1 had bipolar disorder with a manic episode, Dr. Krishnamurthy said in an interview.

To compare subjective and objective measures of sleep in the two groups, the researchers administered a sleep-quality questionnaire and used actigraphy to document sleep objectively.

The Pittsburgh Sleep Quality Index (PSQI), the instrument used for subjective assessment, is a self-reporting tool that asks patients to report on aspects of sleep quality, usual sleep duration, daytime sleepiness, and sleep medication use over the past month.

The actigraphs used in the study used accelerometers to measure patient movement at a per-second level, and were worn around the clock for the week of the study. These devices, said Dr. Krishnamurthy, give sleep data that correlate well with polysomnography, the gold standard for sleep assessment.

For both patient groups, Dr. Krishnamurthy and his colleagues reported sleep latency, sleep duration, sleep dysfunction, sleep efficiency in percentage, sleep quality, and medication need as assessed by the PSQI, as well as the overall PSQI score.

The group with bipolar disorder reported a mean time to falling asleep of 61 minutes, compared with 14 minutes for the control group (P = 0.00064). Total sleep duration from the PSQI was 6.2 hours in the bipolar disorder patients, compared with 7.4 hours in the control group (P = 0.017). All other subjective measures of sleep quality were significantly worse for the patients with bipolar disorder, and the overall score on the PSQI was also much higher (worse), compared with the control group (11.7 vs 3.3, P = 1 x 10^-11).

Actigraphy was used for a 1-week period to measure sleep latency, total sleep time, sleep efficiency, and number and length of awakenings for both groups. When measured objectively, there was no significant difference in the time it took to fall asleep between the patients with bipolar disorder and the healthy controls (14.64 minutes vs. 13.15 minutes), nor was there a significant difference in total sleep time (400.7 minutes vs. 413 minutes). Overall sleep efficiency was similar between groups.

The absolute difference in sleep duration, latency, and efficiency between subjective and objective measures was compared between groups. There was significantly less difference between objective and subjective ratings of all three sleep measures in the healthy subjects than in those with bipolar disorder.

Overall, the patients with bipolar disorder exhibited a strong perception of poor sleep quality, daytime impairment, and insufficient sleep, as shown by the PSQI scores for this group in comparison with the healthy controls. However, these perceptions did not correlate with objective sleep measures for sleep latency, total sleep duration, or sleep efficiency.

Patients with bipolar disorder were significantly more likely to lack employment and to be smokers or use illicit substances; their body mass index was also significantly higher on average than their healthy counterparts.

The bipolar disorder patients may have altered circadian rhythms, cognitive dysfunction because of the illness, and dysfunctional sleep beliefs, which may have independent effects on subjective perceptions of sleep that were not accounted for in the study, said Dr. Krishnamurthy.

The study’s findings mean that clinicians may wish to consider incorporating objective assessments of sleep, such as actigraphy, into care of individuals with bipolar disorder and sleep disturbances, Dr. Krishnamurthy said in an interview. In addition, “behavioral methods to address sleep misperception may be helpful in bipolar subjects.”

The Penn State Hershey College of Medicine funded the study. The authors reported no relevant disclosures.

[email protected]

On Twitter @karioakes

MIAMI BEACH – Patients with active bipolar disorder significantly underestimated the quality of their sleep, despite having sleep quality comparable to that of healthy controls.

Sleep complaints are common among individuals with bipolar disorder, and addressing disruptive and troubling sleep problems can be an important component of treating bipolar disorder, noted Dr. Venkatesh Krishnamurthy and his collaborators at Penn State University (Hershey, Pa.).

“Mood state may affect perception of sleep, and the impact of mood state on subjective-objective differences of sleep parameters needs to be further explored,” the researchers noted.

They reported their comparison of subjective and objective measures of sleep for symptomatic patients with bipolar disorder in a poster presentation at a meeting of the American Society for Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

The study researchers evaluated 30 individuals with symptomatic bipolar disorder, compared with 31 healthy controls, reported Dr. Krishnamurthy, assistant professor at the department of psychiatry’s Sleep Research and Treatment Center at Penn State’s Milton S. Hershey Medical Center. Patients with bipolar disorder were inpatients or in a partial hospitalization program; 11 patients had bipolar depression, 18 had mixed-state bipolar disorder, and 1 had bipolar disorder with a manic episode, Dr. Krishnamurthy said in an interview.

To compare subjective and objective measures of sleep in the two groups, the researchers administered a sleep-quality questionnaire and used actigraphy to document sleep objectively.

The Pittsburgh Sleep Quality Index (PSQI), the instrument used for subjective assessment, is a self-reporting tool that asks patients to report on aspects of sleep quality, usual sleep duration, daytime sleepiness, and sleep medication use over the past month.

The actigraphs used in the study used accelerometers to measure patient movement at a per-second level, and were worn around the clock for the week of the study. These devices, said Dr. Krishnamurthy, give sleep data that correlate well with polysomnography, the gold standard for sleep assessment.

For both patient groups, Dr. Krishnamurthy and his colleagues reported sleep latency, sleep duration, sleep dysfunction, sleep efficiency in percentage, sleep quality, and medication need as assessed by the PSQI, as well as the overall PSQI score.

The group with bipolar disorder reported a mean time to falling asleep of 61 minutes, compared with 14 minutes for the control group (P = 0.00064). Total sleep duration from the PSQI was 6.2 hours in the bipolar disorder patients, compared with 7.4 hours in the control group (P = 0.017). All other subjective measures of sleep quality were significantly worse for the patients with bipolar disorder, and the overall score on the PSQI was also much higher (worse), compared with the control group (11.7 vs 3.3, P = 1 x 10^-11).

Actigraphy was used for a 1-week period to measure sleep latency, total sleep time, sleep efficiency, and number and length of awakenings for both groups. When measured objectively, there was no significant difference in the time it took to fall asleep between the patients with bipolar disorder and the healthy controls (14.64 minutes vs. 13.15 minutes), nor was there a significant difference in total sleep time (400.7 minutes vs. 413 minutes). Overall sleep efficiency was similar between groups.

The absolute difference in sleep duration, latency, and efficiency between subjective and objective measures was compared between groups. There was significantly less difference between objective and subjective ratings of all three sleep measures in the healthy subjects than in those with bipolar disorder.

Overall, the patients with bipolar disorder exhibited a strong perception of poor sleep quality, daytime impairment, and insufficient sleep, as shown by the PSQI scores for this group in comparison with the healthy controls. However, these perceptions did not correlate with objective sleep measures for sleep latency, total sleep duration, or sleep efficiency.

Patients with bipolar disorder were significantly more likely to lack employment and to be smokers or use illicit substances; their body mass index was also significantly higher on average than their healthy counterparts.

The bipolar disorder patients may have altered circadian rhythms, cognitive dysfunction because of the illness, and dysfunctional sleep beliefs, which may have independent effects on subjective perceptions of sleep that were not accounted for in the study, said Dr. Krishnamurthy.

The study’s findings mean that clinicians may wish to consider incorporating objective assessments of sleep, such as actigraphy, into care of individuals with bipolar disorder and sleep disturbances, Dr. Krishnamurthy said in an interview. In addition, “behavioral methods to address sleep misperception may be helpful in bipolar subjects.”

The Penn State Hershey College of Medicine funded the study. The authors reported no relevant disclosures.

[email protected]

On Twitter @karioakes

MIAMI BEACH – Patients with active bipolar disorder significantly underestimated the quality of their sleep, despite having sleep quality comparable to that of healthy controls.

Sleep complaints are common among individuals with bipolar disorder, and addressing disruptive and troubling sleep problems can be an important component of treating bipolar disorder, noted Dr. Venkatesh Krishnamurthy and his collaborators at Penn State University (Hershey, Pa.).

“Mood state may affect perception of sleep, and the impact of mood state on subjective-objective differences of sleep parameters needs to be further explored,” the researchers noted.

They reported their comparison of subjective and objective measures of sleep for symptomatic patients with bipolar disorder in a poster presentation at a meeting of the American Society for Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

The study researchers evaluated 30 individuals with symptomatic bipolar disorder, compared with 31 healthy controls, reported Dr. Krishnamurthy, assistant professor at the department of psychiatry’s Sleep Research and Treatment Center at Penn State’s Milton S. Hershey Medical Center. Patients with bipolar disorder were inpatients or in a partial hospitalization program; 11 patients had bipolar depression, 18 had mixed-state bipolar disorder, and 1 had bipolar disorder with a manic episode, Dr. Krishnamurthy said in an interview.

To compare subjective and objective measures of sleep in the two groups, the researchers administered a sleep-quality questionnaire and used actigraphy to document sleep objectively.

The Pittsburgh Sleep Quality Index (PSQI), the instrument used for subjective assessment, is a self-reporting tool that asks patients to report on aspects of sleep quality, usual sleep duration, daytime sleepiness, and sleep medication use over the past month.

The actigraphs used in the study used accelerometers to measure patient movement at a per-second level, and were worn around the clock for the week of the study. These devices, said Dr. Krishnamurthy, give sleep data that correlate well with polysomnography, the gold standard for sleep assessment.

For both patient groups, Dr. Krishnamurthy and his colleagues reported sleep latency, sleep duration, sleep dysfunction, sleep efficiency in percentage, sleep quality, and medication need as assessed by the PSQI, as well as the overall PSQI score.

The group with bipolar disorder reported a mean time to falling asleep of 61 minutes, compared with 14 minutes for the control group (P = 0.00064). Total sleep duration from the PSQI was 6.2 hours in the bipolar disorder patients, compared with 7.4 hours in the control group (P = 0.017). All other subjective measures of sleep quality were significantly worse for the patients with bipolar disorder, and the overall score on the PSQI was also much higher (worse), compared with the control group (11.7 vs 3.3, P = 1 x 10^-11).

Actigraphy was used for a 1-week period to measure sleep latency, total sleep time, sleep efficiency, and number and length of awakenings for both groups. When measured objectively, there was no significant difference in the time it took to fall asleep between the patients with bipolar disorder and the healthy controls (14.64 minutes vs. 13.15 minutes), nor was there a significant difference in total sleep time (400.7 minutes vs. 413 minutes). Overall sleep efficiency was similar between groups.

The absolute difference in sleep duration, latency, and efficiency between subjective and objective measures was compared between groups. There was significantly less difference between objective and subjective ratings of all three sleep measures in the healthy subjects than in those with bipolar disorder.

Overall, the patients with bipolar disorder exhibited a strong perception of poor sleep quality, daytime impairment, and insufficient sleep, as shown by the PSQI scores for this group in comparison with the healthy controls. However, these perceptions did not correlate with objective sleep measures for sleep latency, total sleep duration, or sleep efficiency.

Patients with bipolar disorder were significantly more likely to lack employment and to be smokers or use illicit substances; their body mass index was also significantly higher on average than their healthy counterparts.

The bipolar disorder patients may have altered circadian rhythms, cognitive dysfunction because of the illness, and dysfunctional sleep beliefs, which may have independent effects on subjective perceptions of sleep that were not accounted for in the study, said Dr. Krishnamurthy.

The study’s findings mean that clinicians may wish to consider incorporating objective assessments of sleep, such as actigraphy, into care of individuals with bipolar disorder and sleep disturbances, Dr. Krishnamurthy said in an interview. In addition, “behavioral methods to address sleep misperception may be helpful in bipolar subjects.”

The Penn State Hershey College of Medicine funded the study. The authors reported no relevant disclosures.

[email protected]

On Twitter @karioakes

MIAMI BEACH – Elevated levels of the same cytokine* were seen in three serious mental illnesses, but each illness had separate and distinct patterns of inflammatory markers, according to a study of immune function and mental illness.

Dr. David R. Goldsmith and colleagues conducted a meta-analysis that pooled results of three dozen studies of outpatients with bipolar disorder, schizophrenia, and major depression, to search for commonalities and differences in immune system activation.

The results were presented in a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Dr. Goldsmith, chief resident for the research track at Emory University’s department of psychiatry and behavioral sciences, Atlanta, and his collaborators looked at 36 studies examining individuals with major depressive disorder (MDD) (12 studies), euthymic bipolar disorder (14 studies), and chronic schizophrenia (10 studies). It is the first meta-analysis to pool results from studies of blood cytokine levels in outpatients with three serious mental illnesses, he said.

Serious mental illness is associated with immune activation, and previous studies have found activation of various cytokines in many mental illnesses. In the acute phase of mental illness, elevations have been found in both interleukin-6 (IL-6) and the cytokine receptor SIL-2R; for MDD and schizophrenia, cytokine levels are acutely increased, tend to decrease with treatment, and eventually rise again, he said.

However, Dr. Goldsmith and his collaborators found that only the cytokine* IL-6 was significantly elevated, compared with healthy controls, for all three illnesses included in the meta-analysis (P < .01 for all). IL-6 is associated with acute and chronic inflammation. For MDD and schizophrenia, two other cytokines were significantly elevated in the meta-analysis: the soluble IL-2 receptor (SIL–2R), a cytokine receptor associated with T-cell activation; and IL-1 beta, a cytokine produced by activated macrophages (P < .01 for all interactions, except P = .01 for IL-1 beta in bipolar disorder.)

For all three disorders, several inflammatory cytokines were significantly elevated, compared with healthy subjects.

Dr. Goldsmith noted some limitations of the meta-analysis. For example, there was a high degree of variability across studies in collection and storage techniques. In addition, no consistent set of tests exists to assess inflammation in mental illness, so the measures obtained varied from study to study. Potential confounders such as smoking and substance abuse were difficult to account for as well. The study limitations highlight the need for “a common set of inflammatory markers that must carefully be studied in order to understand the role of the cytokines in chronic psychiatric disorders and inform novel treatment decisions that may only be relevant to a subset of patients,” he noted.

Going forward, more uniform data collection and larger datasets should help delineate the association between inflammation and serious mental illness. “Despite the heterogeneity of the data, we do see some signal for the role of persistent immune activation, which we think will be important for some people with mental illness,” Dr. Goldsmith said in an interview.Dr. Goldsmith received the Janssen Pharmaceuticals Academic Research Mentoring Award in 2014. He reported no other conflicts of interest.

*Correction, 7/10/2015: An earlier version of this story mischaracterized an inflammatory marker. IL-6 is a cytokine.

[email protected]

On Twitter @karioakes

MIAMI BEACH – Elevated levels of the same cytokine* were seen in three serious mental illnesses, but each illness had separate and distinct patterns of inflammatory markers, according to a study of immune function and mental illness.

Dr. David R. Goldsmith and colleagues conducted a meta-analysis that pooled results of three dozen studies of outpatients with bipolar disorder, schizophrenia, and major depression, to search for commonalities and differences in immune system activation.

The results were presented in a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Dr. Goldsmith, chief resident for the research track at Emory University’s department of psychiatry and behavioral sciences, Atlanta, and his collaborators looked at 36 studies examining individuals with major depressive disorder (MDD) (12 studies), euthymic bipolar disorder (14 studies), and chronic schizophrenia (10 studies). It is the first meta-analysis to pool results from studies of blood cytokine levels in outpatients with three serious mental illnesses, he said.

Serious mental illness is associated with immune activation, and previous studies have found activation of various cytokines in many mental illnesses. In the acute phase of mental illness, elevations have been found in both interleukin-6 (IL-6) and the cytokine receptor SIL-2R; for MDD and schizophrenia, cytokine levels are acutely increased, tend to decrease with treatment, and eventually rise again, he said.

However, Dr. Goldsmith and his collaborators found that only the cytokine* IL-6 was significantly elevated, compared with healthy controls, for all three illnesses included in the meta-analysis (P < .01 for all). IL-6 is associated with acute and chronic inflammation. For MDD and schizophrenia, two other cytokines were significantly elevated in the meta-analysis: the soluble IL-2 receptor (SIL–2R), a cytokine receptor associated with T-cell activation; and IL-1 beta, a cytokine produced by activated macrophages (P < .01 for all interactions, except P = .01 for IL-1 beta in bipolar disorder.)

For all three disorders, several inflammatory cytokines were significantly elevated, compared with healthy subjects.

Dr. Goldsmith noted some limitations of the meta-analysis. For example, there was a high degree of variability across studies in collection and storage techniques. In addition, no consistent set of tests exists to assess inflammation in mental illness, so the measures obtained varied from study to study. Potential confounders such as smoking and substance abuse were difficult to account for as well. The study limitations highlight the need for “a common set of inflammatory markers that must carefully be studied in order to understand the role of the cytokines in chronic psychiatric disorders and inform novel treatment decisions that may only be relevant to a subset of patients,” he noted.

Going forward, more uniform data collection and larger datasets should help delineate the association between inflammation and serious mental illness. “Despite the heterogeneity of the data, we do see some signal for the role of persistent immune activation, which we think will be important for some people with mental illness,” Dr. Goldsmith said in an interview.Dr. Goldsmith received the Janssen Pharmaceuticals Academic Research Mentoring Award in 2014. He reported no other conflicts of interest.

*Correction, 7/10/2015: An earlier version of this story mischaracterized an inflammatory marker. IL-6 is a cytokine.

[email protected]

On Twitter @karioakes

MIAMI BEACH – Elevated levels of the same cytokine* were seen in three serious mental illnesses, but each illness had separate and distinct patterns of inflammatory markers, according to a study of immune function and mental illness.

Dr. David R. Goldsmith and colleagues conducted a meta-analysis that pooled results of three dozen studies of outpatients with bipolar disorder, schizophrenia, and major depression, to search for commonalities and differences in immune system activation.

The results were presented in a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Dr. Goldsmith, chief resident for the research track at Emory University’s department of psychiatry and behavioral sciences, Atlanta, and his collaborators looked at 36 studies examining individuals with major depressive disorder (MDD) (12 studies), euthymic bipolar disorder (14 studies), and chronic schizophrenia (10 studies). It is the first meta-analysis to pool results from studies of blood cytokine levels in outpatients with three serious mental illnesses, he said.

Serious mental illness is associated with immune activation, and previous studies have found activation of various cytokines in many mental illnesses. In the acute phase of mental illness, elevations have been found in both interleukin-6 (IL-6) and the cytokine receptor SIL-2R; for MDD and schizophrenia, cytokine levels are acutely increased, tend to decrease with treatment, and eventually rise again, he said.

However, Dr. Goldsmith and his collaborators found that only the cytokine* IL-6 was significantly elevated, compared with healthy controls, for all three illnesses included in the meta-analysis (P < .01 for all). IL-6 is associated with acute and chronic inflammation. For MDD and schizophrenia, two other cytokines were significantly elevated in the meta-analysis: the soluble IL-2 receptor (SIL–2R), a cytokine receptor associated with T-cell activation; and IL-1 beta, a cytokine produced by activated macrophages (P < .01 for all interactions, except P = .01 for IL-1 beta in bipolar disorder.)

For all three disorders, several inflammatory cytokines were significantly elevated, compared with healthy subjects.

Dr. Goldsmith noted some limitations of the meta-analysis. For example, there was a high degree of variability across studies in collection and storage techniques. In addition, no consistent set of tests exists to assess inflammation in mental illness, so the measures obtained varied from study to study. Potential confounders such as smoking and substance abuse were difficult to account for as well. The study limitations highlight the need for “a common set of inflammatory markers that must carefully be studied in order to understand the role of the cytokines in chronic psychiatric disorders and inform novel treatment decisions that may only be relevant to a subset of patients,” he noted.

Going forward, more uniform data collection and larger datasets should help delineate the association between inflammation and serious mental illness. “Despite the heterogeneity of the data, we do see some signal for the role of persistent immune activation, which we think will be important for some people with mental illness,” Dr. Goldsmith said in an interview.Dr. Goldsmith received the Janssen Pharmaceuticals Academic Research Mentoring Award in 2014. He reported no other conflicts of interest.

*Correction, 7/10/2015: An earlier version of this story mischaracterized an inflammatory marker. IL-6 is a cytokine.

[email protected]

On Twitter @karioakes

MIAMI BEACH – The rich microbial diversity we all carry within our guts “talks” to our brains, and our brains talk back. The state of the very new field of “psychobiotics” was reviewed in a panel session at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

The National Institutes of Health’s National Center for Complementary and Integrative Health, formerly known as the National Center for Complementary and Alternative Medicine, or NCCAM, convened the workshop to bring together panelists from the bench to the bedside to discuss the state of research on the brain-gut-microbiome axis.

Daniel McDonald of the University of Colorado Boulder spoke about the American Gut Project. This crowd-funded project aggregates a very large number of gut microbiota samples and, using a standardized biosequencing protocol, compiles deidentified data for analysis. Using an ordination technique called principal coordinates analysis, researchers are able to use data processing and visualization techniques that show clustering of microbiota types and can show effect sizes for participant characteristics and lifestyles, such as alcohol use, basic diet type, age, and geographic location.

To date, 4,200 participants have had their gut microbiota sequenced. Several sub-projects focus on analysis with broad implications for neurologic and psychological research; these include a project focusing on the microbiomes of intensive care unit patients, a longitudinal study of the infant fecal microbiome, and a large autism spectrum project that is collecting microbiome samples from individuals with autism spectrum disorder and as many of their family members as possible. Though some associations with gut microbiota profiles are emerging, “We are still very young in understanding these communities,” said Mr. McDonald, a PhD candidate at the university.

Future goals include setting up the participant portal to enable better outreach to other countries. Currently, Mr. McDonald said, “a huge amount of diversity is being missed” by the project’s focus on samples from North America.”

Melanie Gareau, Ph.D., a physiologist with the College of Biological Sciences at the University of California, Davis, discussed her use of a mouse model to investigate the microbiota-gut-brain axis. The brain-gut relationship is bidirectional, but,Dr. Gareau said, microbiota clearly have an influence. Some gut variables, she said, include permeability, diet, and bacterial-host interactions. Variables within the brain and nervous system include the influence of such mediators as serotonin and other signaling molecules, such as brain-derived neurotrophic factor and the proto-oncogene c-Fos.

A central concept of gut physiology, said Dr. Gareau, is that the gut is bounded by a semipermeable membrane containing hundreds of millions of microbes. In humans, Dr. Gareau said, “Intestinal dysbiosis is increasingly recognized as a risk factor for disease development.” Emphasizing the bidirectional nature of the relationship, however, Dr. Gareau noted that stress is an external force that affects homeostasis; just as the hypothalamic-pituitary-adrenal axis can be regulated by the balance of microbiota, chronic stress can lead to changes in gut microbiota.

Dr. Gareau uses specialized breeds of mice, and also mice that have been bred and raised to be germ free, to observe the effect of manipulation of the gut microbiome on behavior. Mice that are infected with a murine-specific pathogen, she said, show impaired recognition and memory. When infected mice are exposed to stress, the negative impact on memory is intensified, and the effect persists after the infection has cleared. Related work shows that probiotic administration can improve behavior in wild-type mice.

Dr. Kirsten Tillisch, a gastroenterologist who is chief of integrative medicine at the University of California, Los Angeles, reminded attendees: “I am made up of more bug genes than I am human genes.” Further, she said, “Our microbiota signatures are very different between individuals. So it’s hard for us to get at ‘normal’ when studying humans.”

She noted that the interactions between the brain and the gut – and its resident microbiota – are made more complex in humans by our more advanced brains. Although animal models are incredibly useful because of the relative ease with which variables can be manipulated, she said, human research is still essential.

Calling for higher-quality research implementation and design in the field, Dr. Tillisch said neuroimaging shows potential to demonstrate anatomic and physiologic characteristics associated with particular gut microbial signatures; these can then be correlated with behavior and mood assessments.

In sum, “We carry around several pounds of organisms, Dr. Tillisch said. “It’s important not to neglect them and to treat them well.”

[email protected]

On Twitter @karioakes

MIAMI BEACH – The rich microbial diversity we all carry within our guts “talks” to our brains, and our brains talk back. The state of the very new field of “psychobiotics” was reviewed in a panel session at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

The National Institutes of Health’s National Center for Complementary and Integrative Health, formerly known as the National Center for Complementary and Alternative Medicine, or NCCAM, convened the workshop to bring together panelists from the bench to the bedside to discuss the state of research on the brain-gut-microbiome axis.

Daniel McDonald of the University of Colorado Boulder spoke about the American Gut Project. This crowd-funded project aggregates a very large number of gut microbiota samples and, using a standardized biosequencing protocol, compiles deidentified data for analysis. Using an ordination technique called principal coordinates analysis, researchers are able to use data processing and visualization techniques that show clustering of microbiota types and can show effect sizes for participant characteristics and lifestyles, such as alcohol use, basic diet type, age, and geographic location.

To date, 4,200 participants have had their gut microbiota sequenced. Several sub-projects focus on analysis with broad implications for neurologic and psychological research; these include a project focusing on the microbiomes of intensive care unit patients, a longitudinal study of the infant fecal microbiome, and a large autism spectrum project that is collecting microbiome samples from individuals with autism spectrum disorder and as many of their family members as possible. Though some associations with gut microbiota profiles are emerging, “We are still very young in understanding these communities,” said Mr. McDonald, a PhD candidate at the university.

Future goals include setting up the participant portal to enable better outreach to other countries. Currently, Mr. McDonald said, “a huge amount of diversity is being missed” by the project’s focus on samples from North America.”

Melanie Gareau, Ph.D., a physiologist with the College of Biological Sciences at the University of California, Davis, discussed her use of a mouse model to investigate the microbiota-gut-brain axis. The brain-gut relationship is bidirectional, but,Dr. Gareau said, microbiota clearly have an influence. Some gut variables, she said, include permeability, diet, and bacterial-host interactions. Variables within the brain and nervous system include the influence of such mediators as serotonin and other signaling molecules, such as brain-derived neurotrophic factor and the proto-oncogene c-Fos.

A central concept of gut physiology, said Dr. Gareau, is that the gut is bounded by a semipermeable membrane containing hundreds of millions of microbes. In humans, Dr. Gareau said, “Intestinal dysbiosis is increasingly recognized as a risk factor for disease development.” Emphasizing the bidirectional nature of the relationship, however, Dr. Gareau noted that stress is an external force that affects homeostasis; just as the hypothalamic-pituitary-adrenal axis can be regulated by the balance of microbiota, chronic stress can lead to changes in gut microbiota.

Dr. Gareau uses specialized breeds of mice, and also mice that have been bred and raised to be germ free, to observe the effect of manipulation of the gut microbiome on behavior. Mice that are infected with a murine-specific pathogen, she said, show impaired recognition and memory. When infected mice are exposed to stress, the negative impact on memory is intensified, and the effect persists after the infection has cleared. Related work shows that probiotic administration can improve behavior in wild-type mice.

Dr. Kirsten Tillisch, a gastroenterologist who is chief of integrative medicine at the University of California, Los Angeles, reminded attendees: “I am made up of more bug genes than I am human genes.” Further, she said, “Our microbiota signatures are very different between individuals. So it’s hard for us to get at ‘normal’ when studying humans.”

She noted that the interactions between the brain and the gut – and its resident microbiota – are made more complex in humans by our more advanced brains. Although animal models are incredibly useful because of the relative ease with which variables can be manipulated, she said, human research is still essential.

Calling for higher-quality research implementation and design in the field, Dr. Tillisch said neuroimaging shows potential to demonstrate anatomic and physiologic characteristics associated with particular gut microbial signatures; these can then be correlated with behavior and mood assessments.

In sum, “We carry around several pounds of organisms, Dr. Tillisch said. “It’s important not to neglect them and to treat them well.”

[email protected]

On Twitter @karioakes

MIAMI BEACH – The rich microbial diversity we all carry within our guts “talks” to our brains, and our brains talk back. The state of the very new field of “psychobiotics” was reviewed in a panel session at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

The National Institutes of Health’s National Center for Complementary and Integrative Health, formerly known as the National Center for Complementary and Alternative Medicine, or NCCAM, convened the workshop to bring together panelists from the bench to the bedside to discuss the state of research on the brain-gut-microbiome axis.

Daniel McDonald of the University of Colorado Boulder spoke about the American Gut Project. This crowd-funded project aggregates a very large number of gut microbiota samples and, using a standardized biosequencing protocol, compiles deidentified data for analysis. Using an ordination technique called principal coordinates analysis, researchers are able to use data processing and visualization techniques that show clustering of microbiota types and can show effect sizes for participant characteristics and lifestyles, such as alcohol use, basic diet type, age, and geographic location.

To date, 4,200 participants have had their gut microbiota sequenced. Several sub-projects focus on analysis with broad implications for neurologic and psychological research; these include a project focusing on the microbiomes of intensive care unit patients, a longitudinal study of the infant fecal microbiome, and a large autism spectrum project that is collecting microbiome samples from individuals with autism spectrum disorder and as many of their family members as possible. Though some associations with gut microbiota profiles are emerging, “We are still very young in understanding these communities,” said Mr. McDonald, a PhD candidate at the university.

Future goals include setting up the participant portal to enable better outreach to other countries. Currently, Mr. McDonald said, “a huge amount of diversity is being missed” by the project’s focus on samples from North America.”

Melanie Gareau, Ph.D., a physiologist with the College of Biological Sciences at the University of California, Davis, discussed her use of a mouse model to investigate the microbiota-gut-brain axis. The brain-gut relationship is bidirectional, but,Dr. Gareau said, microbiota clearly have an influence. Some gut variables, she said, include permeability, diet, and bacterial-host interactions. Variables within the brain and nervous system include the influence of such mediators as serotonin and other signaling molecules, such as brain-derived neurotrophic factor and the proto-oncogene c-Fos.

A central concept of gut physiology, said Dr. Gareau, is that the gut is bounded by a semipermeable membrane containing hundreds of millions of microbes. In humans, Dr. Gareau said, “Intestinal dysbiosis is increasingly recognized as a risk factor for disease development.” Emphasizing the bidirectional nature of the relationship, however, Dr. Gareau noted that stress is an external force that affects homeostasis; just as the hypothalamic-pituitary-adrenal axis can be regulated by the balance of microbiota, chronic stress can lead to changes in gut microbiota.

Dr. Gareau uses specialized breeds of mice, and also mice that have been bred and raised to be germ free, to observe the effect of manipulation of the gut microbiome on behavior. Mice that are infected with a murine-specific pathogen, she said, show impaired recognition and memory. When infected mice are exposed to stress, the negative impact on memory is intensified, and the effect persists after the infection has cleared. Related work shows that probiotic administration can improve behavior in wild-type mice.

Dr. Kirsten Tillisch, a gastroenterologist who is chief of integrative medicine at the University of California, Los Angeles, reminded attendees: “I am made up of more bug genes than I am human genes.” Further, she said, “Our microbiota signatures are very different between individuals. So it’s hard for us to get at ‘normal’ when studying humans.”

She noted that the interactions between the brain and the gut – and its resident microbiota – are made more complex in humans by our more advanced brains. Although animal models are incredibly useful because of the relative ease with which variables can be manipulated, she said, human research is still essential.

Calling for higher-quality research implementation and design in the field, Dr. Tillisch said neuroimaging shows potential to demonstrate anatomic and physiologic characteristics associated with particular gut microbial signatures; these can then be correlated with behavior and mood assessments.

In sum, “We carry around several pounds of organisms, Dr. Tillisch said. “It’s important not to neglect them and to treat them well.”

[email protected]

On Twitter @karioakes

MIAMI BEACH – External trigeminal nerve stimulation resulted in a significant improvement in depressive symptoms when used as an adjunct to medication for treatment-resistant depression in a dose-finding study. The noninvasive, home-administered procedure was effective at a wide range of electrical frequencies, and improvement was seen as early as 2 weeks after beginning treatment, according to one measure used in the study.

Results of the double-blind, placebo-controlled study comparing eTNS to sham therapy for 43 adult patients with treatment-resistant major depressive disorder were reported by Dr. Ian A. Cook during a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Dr. Cook is professor-in-residence in the departments of psychiatry and biobehavioral sciences, and bioengineering at the University of California, Los Angeles. Dr. Cook, also research scientist at UCLA’s Semel Institute for Neuroscience and Human Behavior, is on a leave of absence from the university to serve as the chief medical officer of NeuroSigma. The company has a license agreement with UCLA for the eTNS technology used in the study.

Interest in electrical stimulation of cranial nerves began in epileptology, Dr. Cook said in an interview. Scientists found that stimulating the vagus nerve via implanted devices reduced seizures. Dr. Christopher M. DeGiorgio, an epileptologist at UCLA, began experimenting with stimulation of a different cranial nerve, the trigeminal nerve, to treat his patients with intractable epilepsy and began receiving surprising feedback. Many reported that they had felt their mood lighten over the course of their participation in the experiment. This was true, said Dr. Cook, even for those whose epilepsy was not improved by trigeminal nerve stimulation, so it wasn’t simply a reduction in disease burden that had alleviated their depression symptoms. Those findings previously were published in 2013.

The path of the vagus nerve leads to brain areas thought to be involved in regulating mood – as does the path of the trigeminal nerve. However, unlike the vagus nerve, which can only be stimulated by an implanted device, the three branches of the trigeminal nerve lie just beneath the skin as they course across the face. In order to test the effect of external stimulation of the trigeminal nerve, investigators used a patch applied across the forehead to deliver mild electrical pulses to the supraorbital fibers of the V1 tract of the trigeminal nerve bilaterally.

The new dose-ranging study examined 43 adults with unipolar major depressive disorder whose symptoms had not improved after 6 weeks of at least one antidepressant medication. Patients were assigned to receive a sham regimen with no electrical stimulation (n = 8), or to active stimulation with 2 Hz (n = 9), 20 Hz (n = 12), and 120 Hz (n = 14). The electrical stimulation was self-administered at home by patients overnight for an 8-hour period nightly for the 6 weeks of the study period. After the 6-week dose-ranging period, patients were then crossed over to active stimulation at 120 Hz for an additional 6 weeks. Medication use continued unchanged for all patients during the course of the trial; blinding was confirmed by patient questionnaire.

No significant differences were seen in treatment outcomes among any of the intervention arms, so their results were pooled and compared to the sham arm for comparison. Noted Dr. Cook and coinvestigators in their poster: “Symptom improvement did not differ across the three active stimulation frequencies (“doses”), suggesting that low doses of stimulation may lead to meaningful symptom improvement in major depressive disorder (MDD) and that the cumulative integration of stimulation events may be an important determinant of clinical effects.”

Though both the sham and the intervention arms had initial improvement on the Beck Depression Inventory (BDI), only the intervention arm continued to improve, showing a 41.7% reduction in score, compared with a 10.9% reduction for the placebo arm (2-tailed P = .013). Improvement on the Inventory of Depressive Symptomatology (IDS-SR) was 30.3% for the intervention vs. 2.5% for the sham arm but did not reach significance (P = .060), and no significant difference was seen on the Hamilton Depression Rating Scale (HDRS-17).

“The mechanism of action of eTNS is incompletely understood – as it is for many medications,” Dr. Cook said. However, foundational work using PET with O-15 did capture changes in cerebral blood flow occurring while subjects received eTNS, showing increased blood flow in limbic and frontal regions. “We believe that the rapid and significant increases in cerebral blood flow are important to the mechanism of action for psychiatric conditions, because the areas where that was observed have been implicated in the control of mood, anxiety, cognition, and behavior in the neuroimaging literature,” said Dr. Cook.

Though eTNS is an investigational device in the United States, it is approved for use in Europe. U.S. randomized, double-blind, sham-controlled studies are currently testing eTNS as monotherapy in children with attention-deficit/hyperactivity disorder and as adjunctive treatment for posttraumatic stress disorder in combat veterans.

The study was funded by NeuroSigma. In addition to his management role, Dr. Cook holds stock options in the company.

[email protected]

On Twitter @karioakes

MIAMI BEACH – External trigeminal nerve stimulation resulted in a significant improvement in depressive symptoms when used as an adjunct to medication for treatment-resistant depression in a dose-finding study. The noninvasive, home-administered procedure was effective at a wide range of electrical frequencies, and improvement was seen as early as 2 weeks after beginning treatment, according to one measure used in the study.

Results of the double-blind, placebo-controlled study comparing eTNS to sham therapy for 43 adult patients with treatment-resistant major depressive disorder were reported by Dr. Ian A. Cook during a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Dr. Cook is professor-in-residence in the departments of psychiatry and biobehavioral sciences, and bioengineering at the University of California, Los Angeles. Dr. Cook, also research scientist at UCLA’s Semel Institute for Neuroscience and Human Behavior, is on a leave of absence from the university to serve as the chief medical officer of NeuroSigma. The company has a license agreement with UCLA for the eTNS technology used in the study.

Interest in electrical stimulation of cranial nerves began in epileptology, Dr. Cook said in an interview. Scientists found that stimulating the vagus nerve via implanted devices reduced seizures. Dr. Christopher M. DeGiorgio, an epileptologist at UCLA, began experimenting with stimulation of a different cranial nerve, the trigeminal nerve, to treat his patients with intractable epilepsy and began receiving surprising feedback. Many reported that they had felt their mood lighten over the course of their participation in the experiment. This was true, said Dr. Cook, even for those whose epilepsy was not improved by trigeminal nerve stimulation, so it wasn’t simply a reduction in disease burden that had alleviated their depression symptoms. Those findings previously were published in 2013.

The path of the vagus nerve leads to brain areas thought to be involved in regulating mood – as does the path of the trigeminal nerve. However, unlike the vagus nerve, which can only be stimulated by an implanted device, the three branches of the trigeminal nerve lie just beneath the skin as they course across the face. In order to test the effect of external stimulation of the trigeminal nerve, investigators used a patch applied across the forehead to deliver mild electrical pulses to the supraorbital fibers of the V1 tract of the trigeminal nerve bilaterally.

The new dose-ranging study examined 43 adults with unipolar major depressive disorder whose symptoms had not improved after 6 weeks of at least one antidepressant medication. Patients were assigned to receive a sham regimen with no electrical stimulation (n = 8), or to active stimulation with 2 Hz (n = 9), 20 Hz (n = 12), and 120 Hz (n = 14). The electrical stimulation was self-administered at home by patients overnight for an 8-hour period nightly for the 6 weeks of the study period. After the 6-week dose-ranging period, patients were then crossed over to active stimulation at 120 Hz for an additional 6 weeks. Medication use continued unchanged for all patients during the course of the trial; blinding was confirmed by patient questionnaire.

No significant differences were seen in treatment outcomes among any of the intervention arms, so their results were pooled and compared to the sham arm for comparison. Noted Dr. Cook and coinvestigators in their poster: “Symptom improvement did not differ across the three active stimulation frequencies (“doses”), suggesting that low doses of stimulation may lead to meaningful symptom improvement in major depressive disorder (MDD) and that the cumulative integration of stimulation events may be an important determinant of clinical effects.”

Though both the sham and the intervention arms had initial improvement on the Beck Depression Inventory (BDI), only the intervention arm continued to improve, showing a 41.7% reduction in score, compared with a 10.9% reduction for the placebo arm (2-tailed P = .013). Improvement on the Inventory of Depressive Symptomatology (IDS-SR) was 30.3% for the intervention vs. 2.5% for the sham arm but did not reach significance (P = .060), and no significant difference was seen on the Hamilton Depression Rating Scale (HDRS-17).

“The mechanism of action of eTNS is incompletely understood – as it is for many medications,” Dr. Cook said. However, foundational work using PET with O-15 did capture changes in cerebral blood flow occurring while subjects received eTNS, showing increased blood flow in limbic and frontal regions. “We believe that the rapid and significant increases in cerebral blood flow are important to the mechanism of action for psychiatric conditions, because the areas where that was observed have been implicated in the control of mood, anxiety, cognition, and behavior in the neuroimaging literature,” said Dr. Cook.

Though eTNS is an investigational device in the United States, it is approved for use in Europe. U.S. randomized, double-blind, sham-controlled studies are currently testing eTNS as monotherapy in children with attention-deficit/hyperactivity disorder and as adjunctive treatment for posttraumatic stress disorder in combat veterans.

The study was funded by NeuroSigma. In addition to his management role, Dr. Cook holds stock options in the company.

[email protected]

On Twitter @karioakes

MIAMI BEACH – External trigeminal nerve stimulation resulted in a significant improvement in depressive symptoms when used as an adjunct to medication for treatment-resistant depression in a dose-finding study. The noninvasive, home-administered procedure was effective at a wide range of electrical frequencies, and improvement was seen as early as 2 weeks after beginning treatment, according to one measure used in the study.

Results of the double-blind, placebo-controlled study comparing eTNS to sham therapy for 43 adult patients with treatment-resistant major depressive disorder were reported by Dr. Ian A. Cook during a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Dr. Cook is professor-in-residence in the departments of psychiatry and biobehavioral sciences, and bioengineering at the University of California, Los Angeles. Dr. Cook, also research scientist at UCLA’s Semel Institute for Neuroscience and Human Behavior, is on a leave of absence from the university to serve as the chief medical officer of NeuroSigma. The company has a license agreement with UCLA for the eTNS technology used in the study.

Interest in electrical stimulation of cranial nerves began in epileptology, Dr. Cook said in an interview. Scientists found that stimulating the vagus nerve via implanted devices reduced seizures. Dr. Christopher M. DeGiorgio, an epileptologist at UCLA, began experimenting with stimulation of a different cranial nerve, the trigeminal nerve, to treat his patients with intractable epilepsy and began receiving surprising feedback. Many reported that they had felt their mood lighten over the course of their participation in the experiment. This was true, said Dr. Cook, even for those whose epilepsy was not improved by trigeminal nerve stimulation, so it wasn’t simply a reduction in disease burden that had alleviated their depression symptoms. Those findings previously were published in 2013.

The path of the vagus nerve leads to brain areas thought to be involved in regulating mood – as does the path of the trigeminal nerve. However, unlike the vagus nerve, which can only be stimulated by an implanted device, the three branches of the trigeminal nerve lie just beneath the skin as they course across the face. In order to test the effect of external stimulation of the trigeminal nerve, investigators used a patch applied across the forehead to deliver mild electrical pulses to the supraorbital fibers of the V1 tract of the trigeminal nerve bilaterally.

The new dose-ranging study examined 43 adults with unipolar major depressive disorder whose symptoms had not improved after 6 weeks of at least one antidepressant medication. Patients were assigned to receive a sham regimen with no electrical stimulation (n = 8), or to active stimulation with 2 Hz (n = 9), 20 Hz (n = 12), and 120 Hz (n = 14). The electrical stimulation was self-administered at home by patients overnight for an 8-hour period nightly for the 6 weeks of the study period. After the 6-week dose-ranging period, patients were then crossed over to active stimulation at 120 Hz for an additional 6 weeks. Medication use continued unchanged for all patients during the course of the trial; blinding was confirmed by patient questionnaire.

No significant differences were seen in treatment outcomes among any of the intervention arms, so their results were pooled and compared to the sham arm for comparison. Noted Dr. Cook and coinvestigators in their poster: “Symptom improvement did not differ across the three active stimulation frequencies (“doses”), suggesting that low doses of stimulation may lead to meaningful symptom improvement in major depressive disorder (MDD) and that the cumulative integration of stimulation events may be an important determinant of clinical effects.”

Though both the sham and the intervention arms had initial improvement on the Beck Depression Inventory (BDI), only the intervention arm continued to improve, showing a 41.7% reduction in score, compared with a 10.9% reduction for the placebo arm (2-tailed P = .013). Improvement on the Inventory of Depressive Symptomatology (IDS-SR) was 30.3% for the intervention vs. 2.5% for the sham arm but did not reach significance (P = .060), and no significant difference was seen on the Hamilton Depression Rating Scale (HDRS-17).

“The mechanism of action of eTNS is incompletely understood – as it is for many medications,” Dr. Cook said. However, foundational work using PET with O-15 did capture changes in cerebral blood flow occurring while subjects received eTNS, showing increased blood flow in limbic and frontal regions. “We believe that the rapid and significant increases in cerebral blood flow are important to the mechanism of action for psychiatric conditions, because the areas where that was observed have been implicated in the control of mood, anxiety, cognition, and behavior in the neuroimaging literature,” said Dr. Cook.

Though eTNS is an investigational device in the United States, it is approved for use in Europe. U.S. randomized, double-blind, sham-controlled studies are currently testing eTNS as monotherapy in children with attention-deficit/hyperactivity disorder and as adjunctive treatment for posttraumatic stress disorder in combat veterans.

The study was funded by NeuroSigma. In addition to his management role, Dr. Cook holds stock options in the company.

[email protected]

On Twitter @karioakes

MIAMI BEACH – A molecular variation of an old anesthetic showed promise for treatment-resistant depression in a small placebo-controlled study. Patients with treatment-resistant depression who received any dose of intranasal ketamine improved more than those receiving placebo, according to Dr. Jaskaran Singh, senior director at Janssen Pharmaceutica.

In results of a double-blind, placebo-controlled multicenter study of 67 patients with treatment-resistant depression (TRD) presented during a poster session, Dr. Singh and his collaborators noted that higher doses of esketamine were associated with greater improvement on the Montgomery-Åsberg Depression Rating Scale (MADRS). Additionally, dissociative symptoms abated with repeated dosing.

Esketamine, currently in phase II clinical trials for TRD, is the S-enantiomer of ketamine, an anesthetic in use for five decades. The trial sought to identify the antidepressant effectiveness of esketamine, compared with placebo, at various doses for those who inhaled the drug in low doses via intranasal spray. The study also tracked undesirable side effects, including the dissociative effect that can result from both esketamine and ketamine, Dr. Singh said at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Esketamine is thought to relieve depression by its N-methyl D-aspartate receptor antagonist properties. Ongoing basic science, rodent, and human studies are underway to elucidate the proposed multiple mechanisms that cause ketamine and esketamine’s very rapid and somewhat durable antidepressant effects.

Dr. Singh reported the results from one of two panels of the multicenter study. Enrollees, aged 20-64 years, were eligible if they had a diagnosis of major depressive disorder and had not shown adequate response to at least two antidepressants and showed at least moderate depression on the 30-item Inventory of Depressive Symptomatology-Clinician rated (IDS-C30). Key exclusion criteria included significant other psychiatric diagnoses, suicidal ideation with intent to act, and history of nonresponsiveness to either ketamine/esketamine or electroconvulsive therapy.

The initial screening period for all participants was up to 4 weeks; patients were then randomized 3:1:1:1 to receive a placebo nasal spray (n = 33) or intranasal esketamine in 28-mg, 56-mg, or 84-mg doses on days 1 and 4 of the study period. Individuals who had been randomized to receive any dose of esketamine received that dose two additional times, at days 8 and 11.

Individuals on the placebo arm who showed mild to no symptoms according to the 15-item Quick Inventory of Depressive Sympomatology (IDS-QR) continued on placebo; those who continued with moderate to severe depressive symptoms (n = 33) on the IDS-QR were rerandomized 1:1:1:1 to receive placebo or one of the three doses of esketamine on study days 8 and 11. Sixty of 67 patients completed the initial 2-week study period, Dr. Singh said.

An optional open-label period allowed all participants to receive intranasal ketamine, with dose titration starting at 54 mg and dosing frequency tapering from twice weekly to every 2 weeks by study day 74. All individuals received 8 weeks of follow-up. Results from the open-label phase were not reported in this poster presentation.

Results of the intention-to-treat group of those who received the same treatment for the initial 2-week study period showed that those receiving any dose of esketamine had significant improvement in MADRS score, compared with placebo. Additional benefit was seen for higher esketamine dosing, with mean MADRS score differences from placebo of –4.2 points for 28-mg esketamine (P = .021), –6.3 points for 56 mg (P = .001), and –9.0 points for 84 mg (P <.001). Significant improvements, compared with placebo, were seen almost immediately after the first esketamine dose was administered, he said.

All individuals receiving ketamine during the double-blind period were included in safety analysis. Overall, 42 of 56 participants (75%) receiving any dose of esketamine experienced treatment-emergent adverse events, compared with 18 of 33 from the placebo arm (55%). Dizziness, headache, dissociation, dysgeusia, nausea, dissociative disorder, and hypoesthesia oral all occurred in more than 10% of the esketamine-receiving group. Addressing a side effect that is of particular concern, Dr. Singh noted: “The magnitude of dissociative symptoms is dose dependent and attenuates with repeated dosing.”

Analysis of the open-label phase of this arm of the study is underway; study of a second panel is ongoing in Japan. Dr. Singh and his collaborators recommended further study of the effects of intranasal esketamine over longer periods.

The study was funded by Janssen Research and Development. Dr. Singh is an employee of Janssen Pharmaceutica.

[email protected]

On Twitter @karioakes

MIAMI BEACH – A molecular variation of an old anesthetic showed promise for treatment-resistant depression in a small placebo-controlled study. Patients with treatment-resistant depression who received any dose of intranasal ketamine improved more than those receiving placebo, according to Dr. Jaskaran Singh, senior director at Janssen Pharmaceutica.

In results of a double-blind, placebo-controlled multicenter study of 67 patients with treatment-resistant depression (TRD) presented during a poster session, Dr. Singh and his collaborators noted that higher doses of esketamine were associated with greater improvement on the Montgomery-Åsberg Depression Rating Scale (MADRS). Additionally, dissociative symptoms abated with repeated dosing.

Esketamine, currently in phase II clinical trials for TRD, is the S-enantiomer of ketamine, an anesthetic in use for five decades. The trial sought to identify the antidepressant effectiveness of esketamine, compared with placebo, at various doses for those who inhaled the drug in low doses via intranasal spray. The study also tracked undesirable side effects, including the dissociative effect that can result from both esketamine and ketamine, Dr. Singh said at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Esketamine is thought to relieve depression by its N-methyl D-aspartate receptor antagonist properties. Ongoing basic science, rodent, and human studies are underway to elucidate the proposed multiple mechanisms that cause ketamine and esketamine’s very rapid and somewhat durable antidepressant effects.

Dr. Singh reported the results from one of two panels of the multicenter study. Enrollees, aged 20-64 years, were eligible if they had a diagnosis of major depressive disorder and had not shown adequate response to at least two antidepressants and showed at least moderate depression on the 30-item Inventory of Depressive Symptomatology-Clinician rated (IDS-C30). Key exclusion criteria included significant other psychiatric diagnoses, suicidal ideation with intent to act, and history of nonresponsiveness to either ketamine/esketamine or electroconvulsive therapy.

The initial screening period for all participants was up to 4 weeks; patients were then randomized 3:1:1:1 to receive a placebo nasal spray (n = 33) or intranasal esketamine in 28-mg, 56-mg, or 84-mg doses on days 1 and 4 of the study period. Individuals who had been randomized to receive any dose of esketamine received that dose two additional times, at days 8 and 11.

Individuals on the placebo arm who showed mild to no symptoms according to the 15-item Quick Inventory of Depressive Sympomatology (IDS-QR) continued on placebo; those who continued with moderate to severe depressive symptoms (n = 33) on the IDS-QR were rerandomized 1:1:1:1 to receive placebo or one of the three doses of esketamine on study days 8 and 11. Sixty of 67 patients completed the initial 2-week study period, Dr. Singh said.

An optional open-label period allowed all participants to receive intranasal ketamine, with dose titration starting at 54 mg and dosing frequency tapering from twice weekly to every 2 weeks by study day 74. All individuals received 8 weeks of follow-up. Results from the open-label phase were not reported in this poster presentation.

Results of the intention-to-treat group of those who received the same treatment for the initial 2-week study period showed that those receiving any dose of esketamine had significant improvement in MADRS score, compared with placebo. Additional benefit was seen for higher esketamine dosing, with mean MADRS score differences from placebo of –4.2 points for 28-mg esketamine (P = .021), –6.3 points for 56 mg (P = .001), and –9.0 points for 84 mg (P <.001). Significant improvements, compared with placebo, were seen almost immediately after the first esketamine dose was administered, he said.

All individuals receiving ketamine during the double-blind period were included in safety analysis. Overall, 42 of 56 participants (75%) receiving any dose of esketamine experienced treatment-emergent adverse events, compared with 18 of 33 from the placebo arm (55%). Dizziness, headache, dissociation, dysgeusia, nausea, dissociative disorder, and hypoesthesia oral all occurred in more than 10% of the esketamine-receiving group. Addressing a side effect that is of particular concern, Dr. Singh noted: “The magnitude of dissociative symptoms is dose dependent and attenuates with repeated dosing.”

Analysis of the open-label phase of this arm of the study is underway; study of a second panel is ongoing in Japan. Dr. Singh and his collaborators recommended further study of the effects of intranasal esketamine over longer periods.

The study was funded by Janssen Research and Development. Dr. Singh is an employee of Janssen Pharmaceutica.

[email protected]

On Twitter @karioakes

MIAMI BEACH – A molecular variation of an old anesthetic showed promise for treatment-resistant depression in a small placebo-controlled study. Patients with treatment-resistant depression who received any dose of intranasal ketamine improved more than those receiving placebo, according to Dr. Jaskaran Singh, senior director at Janssen Pharmaceutica.

In results of a double-blind, placebo-controlled multicenter study of 67 patients with treatment-resistant depression (TRD) presented during a poster session, Dr. Singh and his collaborators noted that higher doses of esketamine were associated with greater improvement on the Montgomery-Åsberg Depression Rating Scale (MADRS). Additionally, dissociative symptoms abated with repeated dosing.

Esketamine, currently in phase II clinical trials for TRD, is the S-enantiomer of ketamine, an anesthetic in use for five decades. The trial sought to identify the antidepressant effectiveness of esketamine, compared with placebo, at various doses for those who inhaled the drug in low doses via intranasal spray. The study also tracked undesirable side effects, including the dissociative effect that can result from both esketamine and ketamine, Dr. Singh said at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.

Esketamine is thought to relieve depression by its N-methyl D-aspartate receptor antagonist properties. Ongoing basic science, rodent, and human studies are underway to elucidate the proposed multiple mechanisms that cause ketamine and esketamine’s very rapid and somewhat durable antidepressant effects.

Dr. Singh reported the results from one of two panels of the multicenter study. Enrollees, aged 20-64 years, were eligible if they had a diagnosis of major depressive disorder and had not shown adequate response to at least two antidepressants and showed at least moderate depression on the 30-item Inventory of Depressive Symptomatology-Clinician rated (IDS-C30). Key exclusion criteria included significant other psychiatric diagnoses, suicidal ideation with intent to act, and history of nonresponsiveness to either ketamine/esketamine or electroconvulsive therapy.

The initial screening period for all participants was up to 4 weeks; patients were then randomized 3:1:1:1 to receive a placebo nasal spray (n = 33) or intranasal esketamine in 28-mg, 56-mg, or 84-mg doses on days 1 and 4 of the study period. Individuals who had been randomized to receive any dose of esketamine received that dose two additional times, at days 8 and 11.

Individuals on the placebo arm who showed mild to no symptoms according to the 15-item Quick Inventory of Depressive Sympomatology (IDS-QR) continued on placebo; those who continued with moderate to severe depressive symptoms (n = 33) on the IDS-QR were rerandomized 1:1:1:1 to receive placebo or one of the three doses of esketamine on study days 8 and 11. Sixty of 67 patients completed the initial 2-week study period, Dr. Singh said.

An optional open-label period allowed all participants to receive intranasal ketamine, with dose titration starting at 54 mg and dosing frequency tapering from twice weekly to every 2 weeks by study day 74. All individuals received 8 weeks of follow-up. Results from the open-label phase were not reported in this poster presentation.

Results of the intention-to-treat group of those who received the same treatment for the initial 2-week study period showed that those receiving any dose of esketamine had significant improvement in MADRS score, compared with placebo. Additional benefit was seen for higher esketamine dosing, with mean MADRS score differences from placebo of –4.2 points for 28-mg esketamine (P = .021), –6.3 points for 56 mg (P = .001), and –9.0 points for 84 mg (P <.001). Significant improvements, compared with placebo, were seen almost immediately after the first esketamine dose was administered, he said.

All individuals receiving ketamine during the double-blind period were included in safety analysis. Overall, 42 of 56 participants (75%) receiving any dose of esketamine experienced treatment-emergent adverse events, compared with 18 of 33 from the placebo arm (55%). Dizziness, headache, dissociation, dysgeusia, nausea, dissociative disorder, and hypoesthesia oral all occurred in more than 10% of the esketamine-receiving group. Addressing a side effect that is of particular concern, Dr. Singh noted: “The magnitude of dissociative symptoms is dose dependent and attenuates with repeated dosing.”

Analysis of the open-label phase of this arm of the study is underway; study of a second panel is ongoing in Japan. Dr. Singh and his collaborators recommended further study of the effects of intranasal esketamine over longer periods.

The study was funded by Janssen Research and Development. Dr. Singh is an employee of Janssen Pharmaceutica.

[email protected]

On Twitter @karioakes

MIAMI BEACH – Different brain regions appear to be responsible for processing emotional and cognitive stimuli during a common cognitive task used in psychiatric research, a new medical imaging study shows. Further, the activation of subcortical structures changed over time with repeated exposure to the task. The work has implications for researchers and clinicians involved with identifying new targets to treat mood disorders.

Functional magnetic resonance imaging (fMRI) gives detailed anatomic and physiologic data about the brain and has increasing importance for neural outcomes research, according to David Fleck, Ph.D., research associate professor with the Center for Imaging Research at the University of Cincinnati. His work, presented in a poster session, built on previous imaging research that showed differential activation of brain structures when emotional distraction interrupts a cognitive task.

Imaging offers investigators a “completely objective” measure of changes in brain function, and thus is an important tool in clinical trials for medications and treatments for mood disorders, Dr. Fleck said at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. He noted that there can be variability in clinician assessments, and patients can both under- and overreport symptoms. Neuroimaging provides a means to measure absolute change in brain activity or structure, or both, over time.

Forty-one healthy subjects were recruited for the study, which obtained baseline, 1 week, and 8 week fMRI brain scans. During the scans, participants completed the Continuous Performance Task with Emotional and Neutral Distractor (CPT-END). This is a “visual oddball” task where participants are asked to differentiate a target – an image of a circle – from images of a square, and also from distracting images. Seventy percent of the time, subjects were shown a square. They saw the target circle 10% of the time and were presented either a neutral or an emotionally laden image, at a 10% rate for each image type, the remainder of the time.

Dr. Fleck and his colleagues at the University of Cincinnati identified the amygdala and the interior prefrontal gyrus as areas that showed more activation with both the neutral and the emotional distractors at baseline than with either the target circle or the square. However, at weeks 1 and 8, the emotional distractors elicited significantly more activation, particularly in the inferior frontal gyrus.

Deeper brain structures also showed differences between attentional and emotional stimuli, and activation changed over time: “Finally, targets elicited more caudate activation at baseline but not week 8 relative to both distractor types, while emotional distractors elicited more thalamic activation at week 8 but not baseline relative to neutrals and targets,” said Dr. Fleck and coinvestigators.

The study partly replicated and extended a study done more than a decade ago that looked at differential brain activation in cognitive attention versus emotional processes. This is important in mood disorder research, Dr. Fleck said in an interview. Bipolar disorder, for example, has significant cognitive and emotional components that contribute to the disease process. “It is hoped that this work will form the basis for a cognitive/emotional fMRI probe of pharmacological targets in mood disorders,” said Dr. Fleck and coinvestigators.

Dr. Fleck noted that advances in imaging technology since 2002 mean that the image analysis in this study could be much more fine-tuned in its identification of regions of interest, saying, “These findings will form the basis for further work characterizing the neurofunctional signature of mood-disordered patients over time.”

Dr. Fleck reported no conflicts of interest.

[email protected]

On Twitter @karioakes

MIAMI BEACH – Different brain regions appear to be responsible for processing emotional and cognitive stimuli during a common cognitive task used in psychiatric research, a new medical imaging study shows. Further, the activation of subcortical structures changed over time with repeated exposure to the task. The work has implications for researchers and clinicians involved with identifying new targets to treat mood disorders.

Functional magnetic resonance imaging (fMRI) gives detailed anatomic and physiologic data about the brain and has increasing importance for neural outcomes research, according to David Fleck, Ph.D., research associate professor with the Center for Imaging Research at the University of Cincinnati. His work, presented in a poster session, built on previous imaging research that showed differential activation of brain structures when emotional distraction interrupts a cognitive task.

Imaging offers investigators a “completely objective” measure of changes in brain function, and thus is an important tool in clinical trials for medications and treatments for mood disorders, Dr. Fleck said at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. He noted that there can be variability in clinician assessments, and patients can both under- and overreport symptoms. Neuroimaging provides a means to measure absolute change in brain activity or structure, or both, over time.

Forty-one healthy subjects were recruited for the study, which obtained baseline, 1 week, and 8 week fMRI brain scans. During the scans, participants completed the Continuous Performance Task with Emotional and Neutral Distractor (CPT-END). This is a “visual oddball” task where participants are asked to differentiate a target – an image of a circle – from images of a square, and also from distracting images. Seventy percent of the time, subjects were shown a square. They saw the target circle 10% of the time and were presented either a neutral or an emotionally laden image, at a 10% rate for each image type, the remainder of the time.

Dr. Fleck and his colleagues at the University of Cincinnati identified the amygdala and the interior prefrontal gyrus as areas that showed more activation with both the neutral and the emotional distractors at baseline than with either the target circle or the square. However, at weeks 1 and 8, the emotional distractors elicited significantly more activation, particularly in the inferior frontal gyrus.

Deeper brain structures also showed differences between attentional and emotional stimuli, and activation changed over time: “Finally, targets elicited more caudate activation at baseline but not week 8 relative to both distractor types, while emotional distractors elicited more thalamic activation at week 8 but not baseline relative to neutrals and targets,” said Dr. Fleck and coinvestigators.

The study partly replicated and extended a study done more than a decade ago that looked at differential brain activation in cognitive attention versus emotional processes. This is important in mood disorder research, Dr. Fleck said in an interview. Bipolar disorder, for example, has significant cognitive and emotional components that contribute to the disease process. “It is hoped that this work will form the basis for a cognitive/emotional fMRI probe of pharmacological targets in mood disorders,” said Dr. Fleck and coinvestigators.

Dr. Fleck noted that advances in imaging technology since 2002 mean that the image analysis in this study could be much more fine-tuned in its identification of regions of interest, saying, “These findings will form the basis for further work characterizing the neurofunctional signature of mood-disordered patients over time.”

Dr. Fleck reported no conflicts of interest.

[email protected]

On Twitter @karioakes

MIAMI BEACH – Different brain regions appear to be responsible for processing emotional and cognitive stimuli during a common cognitive task used in psychiatric research, a new medical imaging study shows. Further, the activation of subcortical structures changed over time with repeated exposure to the task. The work has implications for researchers and clinicians involved with identifying new targets to treat mood disorders.

Functional magnetic resonance imaging (fMRI) gives detailed anatomic and physiologic data about the brain and has increasing importance for neural outcomes research, according to David Fleck, Ph.D., research associate professor with the Center for Imaging Research at the University of Cincinnati. His work, presented in a poster session, built on previous imaging research that showed differential activation of brain structures when emotional distraction interrupts a cognitive task.

Imaging offers investigators a “completely objective” measure of changes in brain function, and thus is an important tool in clinical trials for medications and treatments for mood disorders, Dr. Fleck said at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting. He noted that there can be variability in clinician assessments, and patients can both under- and overreport symptoms. Neuroimaging provides a means to measure absolute change in brain activity or structure, or both, over time.

Forty-one healthy subjects were recruited for the study, which obtained baseline, 1 week, and 8 week fMRI brain scans. During the scans, participants completed the Continuous Performance Task with Emotional and Neutral Distractor (CPT-END). This is a “visual oddball” task where participants are asked to differentiate a target – an image of a circle – from images of a square, and also from distracting images. Seventy percent of the time, subjects were shown a square. They saw the target circle 10% of the time and were presented either a neutral or an emotionally laden image, at a 10% rate for each image type, the remainder of the time.

Dr. Fleck and his colleagues at the University of Cincinnati identified the amygdala and the interior prefrontal gyrus as areas that showed more activation with both the neutral and the emotional distractors at baseline than with either the target circle or the square. However, at weeks 1 and 8, the emotional distractors elicited significantly more activation, particularly in the inferior frontal gyrus.

Deeper brain structures also showed differences between attentional and emotional stimuli, and activation changed over time: “Finally, targets elicited more caudate activation at baseline but not week 8 relative to both distractor types, while emotional distractors elicited more thalamic activation at week 8 but not baseline relative to neutrals and targets,” said Dr. Fleck and coinvestigators.

The study partly replicated and extended a study done more than a decade ago that looked at differential brain activation in cognitive attention versus emotional processes. This is important in mood disorder research, Dr. Fleck said in an interview. Bipolar disorder, for example, has significant cognitive and emotional components that contribute to the disease process. “It is hoped that this work will form the basis for a cognitive/emotional fMRI probe of pharmacological targets in mood disorders,” said Dr. Fleck and coinvestigators.

Dr. Fleck noted that advances in imaging technology since 2002 mean that the image analysis in this study could be much more fine-tuned in its identification of regions of interest, saying, “These findings will form the basis for further work characterizing the neurofunctional signature of mood-disordered patients over time.”

Dr. Fleck reported no conflicts of interest.

[email protected]

On Twitter @karioakes