title: Cognitive and oculomotor performance in subjects with low and high schizotypy: implications for translational drug development studies.
abstract: The development of drugs to improve cognition in patients with schizophrenia is a major unmet clinical need. A number of promising compounds failed in recent clinical trials, a pattern linked to poor translation between preclinical and clinical stages of drug development. Seeking proof of efficacy in early Phase 1 studies in surrogate patient populations (for example, high schizotypy individuals where subtle cognitive impairment is present) has been suggested as a strategy to reduce attrition in the later stages of drug development. However, there is little agreement regarding the pattern of distribution of schizotypal features in the general population, creating uncertainty regarding the optimal control group that should be included in prospective trials. We aimed to address this question by comparing the performance of groups derived from the general population with low, average and high schizotypy scores over a range of cognitive and oculomotor tasks. We found that tasks dependent on frontal inhibitory mechanisms (N-Back working memory and anti-saccade oculomotor tasks), as well as a smooth-pursuit oculomotor task were sensitive to differences in the schizotypy phenotype. In these tasks the cognitive performance of 'low schizotypes' was significantly different from 'high schizotypes' with 'average schizotypes' having an intermediate performance. These results indicate that for evaluating putative cognition enhancers for treating schizophrenia in early-drug development studies the maximum schizotypy effect would be achieved using a design that compares low and high schizotypes.
authors.affiliation: Department of Community-Based Psychiatry, Neuroscience and Psychiatry Unit, The University of Manchester, School of Community-Based Medicine, Manchester, UK.|Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: I
authors.initials: I
authors.lastname: Koychev
authors.affiliation: Cognition, Schizophrenia and Imaging Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, Denmark Hill, London.
authors.forename: D
authors.initials: D
authors.lastname: Joyce
authors.affiliation: Department of Psychology, University of Wollongong, Wollongong, NSW, Australia.|Department of Psychiatry, School of Community-Based Medicine, The University of Manchester, Manchester, UK.
authors.forename: E
authors.initials: E
authors.lastname: Barkus
authors.affiliation: Department of Psychology, University of Bonn, Bonn, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Ettinger
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Schmechtig
authors.affiliation: P1vital, Wallingford, UK.
authors.forename: C T
authors.initials: CT
authors.lastname: Dourish
authors.affiliation: P1vital, Wallingford, UK.
authors.forename: G R
authors.initials: GR
authors.lastname: Dawson
authors.affiliation: P1vital, Wallingford, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Craig
authors.affiliation: Department of Community-Based Psychiatry, Neuroscience and Psychiatry Unit, The University of Manchester, School of Community-Based Medicine, Manchester, UK.
authors.forename: J F W
authors.initials: JF
authors.lastname: Deakin
mesh_terms: D060825:Cognitive Dysfunction / Q000145:classification / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D055808:Drug Discovery; D053483:Eye Movement Measurements; D005260:Female; D006801:Humans; D008297:Male; D018697:Nootropic Agents / Q000627:therapeutic use*; D012559:Schizophrenia / Q000145:classification / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D057170:Translational Research, Biomedical
chemical_list: D018697:Nootropic Agents