This is Part 1 of a two-part series. See also Part 2.
July 9, 2013. The University of Miami Cognition Satellite Meeting was held on Sunday, April 21, the day before the International Congress on Schizophrenia Research officially kicked off. Many scientists arrived early, as evidenced by the crowded room where meeting chair Philip Harvey welcomed everyone to the cognition meeting’s 20th Anniversary. Attendees heard from a whirlwind 23 presenters, who covered topics ranging from the measurement of functional outcome to the genetic underpinnings and brain regions implicated in cognition.
Tweaking the tools
The development of effective remediation strategies to improve cognition and functional outcome in schizophrenia depends on the ability to accurately measure patients' performance. Existing assessments of functional outcome have several limitations, including difficulty capturing the complexity of routine tasks and a reliance on patients' reports of their own real-world functioning that may be skewed by a lack of insight into their illness (Harvey et al., 2013). Consequently, many presentations highlighted new ways to measure functional outcome in schizophrenia.
Richard Keefe of Duke University, Durham, North Carolina (who, Harvey noted, was the only attendee to have spoken at every Cognition Satellite Meeting since it was started), presented the computer-based Virtual Reality Functional Capacity Assessment Tool (VRCAT). The VRCAT relies on a realistic simulated environment to recreate routine activities of daily living, such as checking a pantry for ingredients to a recipe and shopping for the missing components. In an initial validation study, many differences between healthy controls and schizophrenia subjects were observed on the VRCAT, including a longer completion time and more errors in patients. VRCAT performance was also significantly correlated with performance on other measures of functional outcome such as the Brief UCSD Performance-Based Skills Assessment. A larger validation study is in process.
Eric Granholm of the University of California, San Diego, described his work on ecological momentary assessment (EMA), a technique that uses electronic devices to collect responses to brief questionnaires at numerous times throughout the day. Advantages of this approach, he explained, include real-time, real-world sampling of behaviors; identification of immediate predictors of behaviors or symptoms; and the potential for real-time interventions. In an EMA trial of schizophrenia and schizoaffective disorder subjects, Granholm found that positively rated social interactions were associated with a greater positive affect, which then predicted future social interactions (Granholm et al., 2013).
The University of Miami’s Sara Czaja also discussed the use of technology to assess functional outcome in schizophrenia—specifically, a suite of computerized tools that simulate tasks of daily living. In an ongoing study that is assessing efficacy and feasibility, subjects complete tasks such as using an ATM to manage money, navigation of a telephone-menu system for prescription medication refills, and a simulated doctor’s visit with medication management and follow-up appointment instructions. Technology-based tools have a lot to offer, she noted, including flexibility, a high degree of ecological validity, remote delivery, and remedial task performance training.
Intermediate measures of functional outcome are necessary in clinical studies of schizophrenia, said Dawn Velligan of the University of Texas, San Antonio, because more direct measures such as marital status are unlikely to change during the short duration of clinical trials. After appropriate intermediate measures were identified in an initial study, Velligan examined which would be most adaptable for use across cultures (Gonzalez et al., 2013). Adaptation was most challenging in India, China, and Mexico. An ongoing study is comparing the psychometric properties of various intermediate measures in India.
Amy Pinkham of the Southern Methodist University in Dallas, Texas, described the Social Cognition Psychometric Evaluation (SCOPE) project that aims to improve the identification of social cognition impairments in schizophrenia (Pinkham et al., 2013). In the first phase of the study, Pinkham and colleagues surveyed experts to identify four core domains—attributional style/bias, emotion processing, social perception, and theory of mind—and 21 measures of social cognition. A second phase used a RAND panel to whittle down the final measures. A total of eight are currently being evaluated in a two-site initial psychometric study.
Describing the deficits
Several other presentations focused on using existing measures to characterize the deficits in cognition and impairments in functional outcome in schizophrenia and related psychoses. Mark Weiser of Tel Aviv University in Israel discussed work outcome in non-affective psychosis using tax information. Using nearly 80,000 admissions from the Israeli National Psychiatric Hospitalization Case Registry that were linked to Social Security income data, he found that a very low percentage of subjects were earning minimum wage. Those with two or more hospitalizations were associated with an especially poor outcome. He also found that very few people were working before their first episode, providing evidence of a premorbid deficit.
Matthew Kurtz of Wesleyan University in Middletown, Connecticut, examined the interplay between self-efficacy—one’s confidence in his or her ability to perform a task—and illness insight in functional outcome in schizophrenia (Kurtz et al., 2013). The researchers found that, consistent with prior studies, self-efficacy was only associated with social and everyday living skills when patients had explicit insight into their illness. In addition, when self-efficacy was controlled for, the relationship between negative symptoms and functional outcome disappeared, but only in patients with insight. Thus, illness insight is an important mediator in the relationship between self-efficacy and functional outcome.
Anthony David of Kings College London, U.K., described his work examining a different form of insight—the implicit (or unconscious) kind—in psychosis. He found no evidence of implicit awareness, as measured by interference to psychosis-related words on a Stroop-like test or attribution of an illness to a third person rather than oneself. He also presented new functional imaging data suggesting that medial frontal areas may be involved in self-appraisal relevant to insight and that reduced activation during self-appraisal is associated with poorer insight.
It’s important to use longitudinal studies to assess real-world functioning in schizophrenia, said Avi Reichenberg of New York City’s Mount Sinai School of Medicine. He discussed a recent study examining scores on the Specific Levels of Functioning Scale across time in an outpatient schizophrenia population, finding that real-world functioning is characterized by a continuous, progressive, slow decline that accelerates around age 60. An assessment of the predictors of decline is ongoing.
Neeltje van Haren of the Netherlands’ University Medical Centre Utrecht discussed her work examining intelligence quotient (IQ) change over time in schizophrenia. She reported data from the Genetic Risk and Outcome of Psychosis (GROUP) project, a longitudinal study that contains double the number of participants of all other psychosis IQ studies combined. Van Haren and colleagues found that subjects with schizophrenia had a significantly lower IQ at baseline than controls, but no difference in IQ change over time. In addition, baseline IQ was lower in subjects with schizophrenia compared to those with affective psychosis, and no difference was found between the groups’ change in IQ across time.
Judith Jaeger of CogState in New Haven, Connecticut, reviewed the company’s data on the Groton Maze Learning Task, a hidden pathway learning paradigm that measures executive function. Subjects with schizophrenia are impaired on the task (Pietrzak et al., 2009) but improve after cognitive remediation training (Murthy et al., 2012). The task has also been used to demonstrate that better executive function is associated with better performance on activities of daily living.
Only two satellite meeting speakers discussed therapeutic approaches to improving cognition. Volker Roder of the University Hospital of Psychiatry in Bern, Switzerland, described two cognitive behavioral group therapy approaches for an integrative treatment of psychosis: Integrated Psychological Therapy (IPT) and Integrative Neurocognitive Therapy (INT). IPT combines cognitive remediation with behavioral therapy that targets social competence (Mueller et al., 2013). INT is a newer iteration of neurocognitive and social cognitive enhancement, based on cognitive domains identified by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) project. Roder reported that both approaches are well accepted by patients and therapists, though patients need time to show improvements.
Larry Siever of New York City’s Mount Sinai Hospital described the clinical testing of dihydrexidine (DAR-0100), a dopamine D1 receptor agonist for cognitive enhancement in subjects with schizotypal personality disorder. The drug is the first D1 agonist to cross the blood-brain barrier, and its potential benefits to cognition are backed by strong preclinical evidence over the past 20 years, said Siever. In a preliminary study, intravenous administration of DAR-0100 was well tolerated and improved measures of working memory, including the paced auditory serial addition and N-back tasks.
Although studies assessing cognitive improvement in schizophrenia were not a major focus of the satellite meeting, they were certainly a hot topic at ICOSR (see SRF related conference story). In his Tuesday morning plenary talk titled “Assessment and Treatment of Cognitive and Functional Impairments in Schizophrenia: The State of the Art of Cognitive Remediation Interventions,” cognition meeting organizer Phil Harvey devoted a substantial amount of time to discussing cognitive remediation strategies. He said that recent remediation results have been promising, with persistent functional gains reported (Wykes et al., 2011). He cited two example programs—one by Posit Science and the other by Marker Software—though he noted that several others have been developed (Fisher et al., 2009).
The evidence suggests that if patients make gains, they tend to sustain them, said Harvey, and these behavioral improvements are consistent with neurobiological changes (Eack et al., 2010). He also noted that the pharmacological cognitive enhancement studies to date have been somewhat disappointing, although the studies have generally been underpowered (Keefe et al., 2013).—Allison A. Curley.