Pharmacological Studies of Smooth Pursuit and Antisaccade Eye Movements in Schizophrenia: Current Status and Directions for Future Research

Abstract

Smooth pursuit (SPEM) and antisaccade eye movements have been studied to elucidate the genetics and the pathophysiology of schizophrenia. In recent years, a rapidly growing literature has emerged on pharmacological influences on eye movements. This review focuses on pharmacological studies of the SPEM and antisaccade tasks with relevance to schizophrenia and aims to answer the particular questions: (1) whether pharmacological compounds with relevance to the treatment or pathophysiology of schizophrenia affect performance, and (2) whether SPEM or antisaccade measures may be useful in the development of novel therapeutic targets for this illness. We conclude that (i) short- or medium-term typical antipsychotic treatment of schizophrenia patients has no or little effect on either measure, (ii) treatment with clozapine appears to impair SPEM, (iii) treatment with risperidone and 5-HT2 antagonists improves schizophrenia patients antisaccade error rate deficit, (iv) anticholiner gics, ofte n use d to contr ol extr apyra midal symptoms induc ed by typical a ntipsychotics, may w orsen pe rf ormance, ( v) be nzodiaze pines impa ir SPEM and antisacc ade per for ma nce in hea lthy individuals, (vi) nicotine, selfadministered via cigarette smoking or given via experimental procedures, improves SPEM and antisaccade performance, and (vii) SPEM has the potential to be a useful phenotype for the ketamine model of psychosis, with implications for antipsychotic drug development. Finally, we discuss methodological issues pertaining to the study of eye movements in pharmacological and genetic schizophrenia research and suggest that the SPEM and antisaccade tasks may be profitably used in the development of antipsychotic drugs. Keywords: smooth pursuit eye movements, antisaccade, schizophrenia, neuroleptic, antipsychotic, treatment, endophenotype, drug development