A systematic review comparing sex differences in cognitive function in schizophrenia and in rodent models for schizophrenia, implications for improved therapeutic strategies

Abstract : Sex is often overlooked in animal and human research. Cognitive impairment associated with schizophrenia (CIAS) remains an unmet clinical need, as current antipsychotic medication does not provide clinically meaningful improvements. One explanation could be lack of appreciation of gender differences in CIAS. Animal models play a critical role in drug development and improved translation to the clinic is an on-going process. Our systematic review aims to evaluate how well the animal studies translate into clinical findings. Supporting clinical results, our review highlights a male working memory advantage and a female advantage for visual memory and social cognition in rodent models for schizophrenia. Not investigated in animals, a female advantage for attention and speed of processing has been found in schizophrenia patients. Sex differences in reasoning and problem solving are poorly investigated in both human and animal studies. Overall, our review provides evidence of good translation from the animal models into the clinic when sexual dimorphism is assessed. Enhanced understanding of these sex differences will improve the management of CIAS.