Testing the overlap between symptoms and cognition in schizophrenia: A multi-site study

Background and Hypothesis. Cognitive impairment is a core feature of schizophrenia spectrum disorders (SSD). While the relationship between cognition and symptoms in SSD has been extensively studied, there is a lack of research focusing on individual item-level analysis rather than relying on summary score methodology. Our previous study on a first-episode psychosis cohort showed that symptoms related to impoverished and disorganized communication and motor impoverishment were associated with impairments in verbal and working memory. This study aimed to explore those associations in people with chronic schizophrenia.Study Design. We employed iterative Constrained Principal Component Analysis (iCPCA) to investigate the relationship between 15 cognitive measures, including processing speed, attention, working, verbal memory, reasoning, problem-solving and 26 PANSS items in 198 chronic schizophrenia outpatients from two sites in Australia and one in Canada. The iCPCA method was used to determine item combinations optimized to describe associations between symptoms and cognition while controlling Type I errors.Results. Our analysis revealed that a verbal memory component was associated with the PANSS item Lack of Spontaneity and Flow of Conversation, indicating impairments in communication, language, and thought. Additionally, a working memory and attention component was linked to the PANSS item Motor Retardation, reflecting motor system impoverishment.Conclusions. These results confirm our previous findings, showing that negative symptoms of diminished expression are key predictors of cognitive impairments in schizophrenia. These data underscore the value of optimized item combinations in identifying precise symptom-cognition relationships, which can potentially inform more effective treatment strategies.Keywords: schizophrenia, cognition, psychotic symptoms, verbal and working memory, motor impoverishment, disorganized and impoverished communication.