28 Apr 2017
by Lesley McCollum
Wrapping up the International Congress on Schizophrenia Research in San Diego, an oral session on Tuesday afternoon, March 28, centered around targeting cognitive deficits in the disorder, which don’t respond to available medications.
Cognitive training and CBT
Kristen Haut of Rush University Medical Center in Chicago presented research on cognitive training (CT) in clinical high-risk patients, demonstrating efforts to correct brain function that underlies social cognition deficits in the disorder that are associated with quicker illness progression and increased functional impairment. CT targeting a wide range of cognitive domains for eight weeks improved emotion recognition and appeared to restore functional activity and connectivity in emotion-processing brain regions. The work is currently being followed up with a randomized controlled trial in which the researchers are looking for predictors of response to targeted CT.
In the next talk, Keith Nuechterlein of the University of California, Los Angeles, made a case for combining CT with exercise. In a randomized controlled trial of 42 first-episode psychosis patients, all patients receiving six months of CT improved in their global cognitive score, but those also receiving exercise four days per week improved three times more in role functioning, specifically in measures of attention, reasoning, and problem solving.
Heather Adams of the University of Maryland School of Medicine presented research on cognitive behavioral therapy (CBT) in treatment-resistant schizophrenia patients, which is underused despite being recommended as a routine therapy. Most studies assess the efficacy of CBT based on changes in psychosis, but this outcome does not line up with the theory behind CBT, according to Adams. She framed the approach with the goal of learning how to feel and function better, and targeted intervention education at this outcome. Patients had reduced distress secondary to symptoms and improved in overall functioning.
To support the use of cognitive remediation as a valid treatment approach, Joanna Fiszdon of Yale University presented research in schizophrenia patients comparing cognitive remediation intervention with standard treatment approaches. Two months of cognitive remediation improved verbal learning and memory, visuospatial processing, and verbal working memory in patients, and the gains in cognitive improvement were predicted by how well the patients thought they would do at baseline. Fiszdon hopes that the findings will add to the burgeoning support for cognitive remediation that still is not considered evidence-based treatment.
Though studies of cognitive remediation produce moderate effect sizes, there is a tremendous range in patient response. In the next talk, Alice Medalia of Columbia University in New York presented research with the goal of personalizing cognitive remediation by identifying a baseline variable to tailor the type of cognitive remediation patients received. In a randomized controlled trial, schizophrenia and schizoaffective patients were stratified by whether they had impaired auditory processing ability (APA). Initial results of the ongoing study suggest that APA-impaired patients show far greater improvement when cognitive remediation includes sensory processing training, and APA improvement was associated with overall cognitive gains. Patients with normal baseline APA showed no benefit from sensory processing training. Medalia concluded that it matters what kind of cognitive remediation patients receive—if the treatment doesn’t match the impairment, it won’t do them any good.
Cognitive remediation therapy is lumped into one type of intervention, but actually comprises two types of computerized approaches, top-down or bottom-up, based on different theoretical models of cognitive impairments. Most interventions use top-down models, but Jean-Pierre Lindenmayer of Manhattan Psychiatric Center in New York wanted to determine what type works best for patients. The researchers showed that after 12 weeks of training, patients with chronic schizophrenia all improved without much difference between the two types of intervention, though only patients receiving the bottom-up approach showed improvement in visual learning.
In another attempt to boost the positive effects of cognitive remediation, Christopher Bowie of Queen’s University in Ontario, Canada, presented new findings on whether incorporating other skills training with cognitive remediation could improve patient outcome. All 29 patients with schizophrenia received cognitive remediation, but about half also engaged with a therapist to discuss strategies for achieving goals. Those also receiving the therapist intervention showed larger improvements in everyday functioning scores, reduced job stress, better and retention rates, and a larger percentage returned to work compared with patients receiving only cognitive remediation.
And now for something completely different
Two of the talks shifted from the focus on cognitive interventions. Jordan Hamm of Columbia University presented new data of circuit activity in ketamine and 22q11.2 genetic animal models of schizophrenia. Circuit-level activity of cortical neurons was unstable in both models, indicating disorganization of activity. The common finding between the two very different models supports the attractor hypothesis of schizophrenia, suggesting that preferred patterns of activity are disrupted in the disorder.
Insulin has been considered as a treatment for cognitive improvement in schizophrenia, but studies of the approach have failed. Chantel Kowalchuk of the Center for Addiction and Mental Health and University of Toronto, Canada, presented research suggesting why this might be. An infusion of insulin into the third ventricle of rats increased their insulin sensitivity and glucose uptake, and suppressed their hepatic glucose production as expected. However, olanzapine administration impaired the ability of an insulin infusion to suppress hepatic glucose production, suggesting that olanzapine induces central insulin resistance.