Association between treatment resistance and cognitive function in schizophrenia

Treatment-resistant schizophrenia (TRS) affects around 30% of individuals with schizophrenia. About half of the patients with TRS who are treated with clozapine do not show a meaningful clinical response, that is, clozapine resistance. To date, the relationship between cognitive function and treatment response categories is not entirely clear. This study evaluated the cognitive performance across subgroups stratified by treatment response, and we hypothesised that cognitive impairment increases with increased treatment resistance.

This study was conducted at the Institute of Mental Health, Singapore, and included healthy controls and people with schizophrenia categorised into these groups: antipsychotic-responsive schizophrenia (ARS), clozapine-responsive TRS (TRS-CR) and clozapine-resistant TRS (ultra-treatment-resistant schizophrenia [UTRS]). Cognitive function was assessed using the Brief Assessment of Cognition-Short Form. Symptoms were measured with the Positive and Negative Syndrome Scale (PANSS). The planned statistical analyses included adjustments for covariates such as age, sex, PANSS scores and antipsychotic dose, which might affect cognitive function.

There were significant differences in overall cognitive performance between the groups: ARS had the least impairment, followed by TRS-CR and UTRS. Antipsychotic dose, and PANSS negative and disorganisation/cognitive factors were significant predictors of overall cognitive function in all patient groups.

Our study found differences in cognitive function that aligned with levels of treatment resistance: the greater the degree of treatment resistance, the poorer the cognitive function. Interventions to improve negative and disorganisation symptoms might be effective to enhance the cognitive function and treatment outcomes in schizophrenia.