title: Effect of second-generation antipsychotics on cognition: current issues and future challenges.
abstract: Generalized cognitive impairments are stable deficits linked to schizophrenia and key factors associated with functional disability in the disorder. Preclinical data suggest that second-generation antipsychotics could potentially reduce cognitive impairments; however, recent large clinical trials indicate only modest cognitive benefits relative to first-generation antipsychotics. This might reflect a limited drug effect in humans, a differential drug effect due to brain alterations associated with schizophrenia, or limited sensitivity of the neuropsychological tests for evaluating cognitive outcomes. New adjunctive procognitive drugs may be needed to achieve robust cognitive and functional improvement. Drug discovery may benefit from greater utilization of translational neurocognitive biomarkers to bridge preclinical and clinical proof-of-concept studies, to optimize assay sensitivity, enhance cost efficiency, and speed progress in drug development.
authors.affiliation: Center for Cognitive Medicine (M/C 913), University of Illinois at Chicago, 912 South Wood Street, Suite 235, Chicago, IL 60612, USA. shill@psych.uic.edu
authors.forename: S Kristian
authors.initials: SK
authors.lastname: Hill
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bishop
authors.forename: Donna
authors.initials: D
authors.lastname: Palumbo
authors.forename: John A
authors.initials: JA
authors.lastname: Sweeney
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000145:classification* / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D009483:Neuropsychological Tests; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000150:complications
chemical_list: D014150:Antipsychotic Agents