Relationship of Cognition to Clinical Response in First-Episode Schizophrenia Spectrum Disorders

Abstract

First-episode schizophrenia (FES) spectrum disorders are associated with pronounced cognitive dysfunction across all domains. However, less is known about the course of cognitive functioning, following the first presentation of psychosis, and the relationship of cognition to clinical course during initial treatment. The present longitudinal study examined the magnitude of neurocognitive impairment, using the MATRICS Consensus Cognitive Battery, in patients experiencing their first episode of psychosis at baseline and after 12 weeks of randomized antipsychotic treatment with either aripiprazole or risperidone. At baseline, FES patients evidenced marked impairments in cognitive functioning. Notably, performance on the mazes task of planning and reasoning significantly predicted the likelihood of meeting stringent criteria for positive symptom remission during the first 12 weeks of the trial. Performance on indices of general cognitive function, working memory, and verbal learning improved over time, but these improvements were mediated by improvements in both positive and negative symptoms. We did not detect any differential effects of antipsychotic medication assignment (aripiprazole vs risperidone) on cognitive functioning. Our results suggest that a brief paper-and-pencil measure reflecting planning/reasoning abilities may index responsivity to antipsychotic medication. However, improvements in cognitive functioning over time were related to clinical symptom improvement, reflecting "pseudospecificity."

Keywords: aripiprazole; cognition; general cognitive function; planning; psychosis; risperidone.

Fig. 1.

Result of Cox regression analysis of MATRICS Consensus Cognitive Battery reasoning/problem solving performance at baseline in relation to 12-week treatment response rates. As can be seen, ~50% of the patients who performed relatively well on the task at baseline (defined as those scoring at or above the >75th percentile within the sample) successfully responded to antipsychotic treatment after 6 weeks, whereas only ~20% of poor performers (ie, those who performed at or below the 25th percentile) met criteria after the same period of time.

Fig. 2.

Results of mediation analysis of clinical symptoms on cognitive change. Improvements in clinical symptoms partially and/or fully mediated improvements in (a) general cognition, (b) working memory, and (c) verbal learning.