Developing predictive animal models and establishing a preclinical trials network for assessing treatment effects on cognition in schizophrenia.

Animal models are an essential initial phase in the discovery of novel drugs to treat psychiatric disorders. At the sixth Measurement and Treatment Research to Improve Cognition in Schizophrenia conference, "New Approaches to Assessing and Improving Cognition in Schizophrenia," a discussion group was formed to address issues related to the development of predictive animal models of cognition that may be used as preclinical assays for putative cognitive enhancers. We identified 2 complementary approaches used to model cognitive impairments in animals. First, basic lesion/pharmacological models provide information about the particular neural substrates that may underlie different types of cognitive deficits found in schizophrenia. Findings from these studies can be mapped onto the second, more elaborate and etiologically relevant neurodevelopmental models of the disorder to ascertain which cognitive systems may be altered by early developmental insults. Particular attention must be given to the types of animal tasks used, in order to relate directly to the cognitive domains that are affected in schizophrenia patients. Importantly, the validation and standardization of the methodologies used in these preclinical assays would require the establishment of a preclinical trials network, serving as a counterpart to the recently established Treatment Units for Research on Neurocognition and Schizophrenia. The need to validate specific approaches to assess cognitive functions relevant to schizophrenia could be satisfied by a concerted effort enabled by a new funding directive from the National Institute of Mental Health with the explicit purpose of facilitating research on these models and assessing novel drug therapies that may be used to ameliorate the cognitive deficits in schizophrenia.