Translating the basic and clinical cognitive neuroscience of schizophrenia to drug development and clinical trials of antipsychotic medications

Neurocognitive deficits have become increasingly important defining features of schizophrenia and its treatment. Multiple domains of neurocognitive functions are impaired in schizophrenia patients, and these impairments are considered to be core features of the disorder. Many recent reports support the importance of the relationship of these neurocognitive deficits to measures of “functional outcome” such as social skills acquisition, social problem solving, and community outcome. Neurocognitive deficits appear to be improved with newer (atypical) antipsychotic medications across a broad range of domains in schizophrenia patients. Together with clinical neuroscience advances, basic research in cognitive neuroscience ranging from animal models of gating functions to early gene expression induced by antipsychotic medications has illuminated the specific neural basis of neurocognitive deficits in schizophrenia and the neurobiology of antipsychotic actions. These translational basic and clinical studies provide powerful screening tools and strategies for drug development and the subsequent assessment of the clinical efficacy of new antipsychotic medications. These interlocking clinical and basic research findings have substantial implications for improving both drug development and improving clinical trials methodology for antipsychotic medications. Thus, there is an informed translation and cross-fertilization between basic and clinical research focused on the development and assessment of putative new antipsychotic compounds.