S19.04 - Genetic and neuroimaging studies of antisaccade eye movements in schizophrenia

Abstract

An antisaccade is a rapid eye movement (saccade) made away from a visual stimulus. The task is a good measure of the conflict between an unwanted reflexive response (which must be inhibited) and a volitional response (which must instead be generated). Deficits on the antisaccade task constitute a promising schizophrenia endophenotype. In this talk I will review studies that have demonstrated antisaccade deficits in sibling and twin pairs discordant for schizophrenia. I will then data from present recent investigations of association between antisaccade performance and candidate polymorphisms for schizophrenia and cognition. Finally, I will discuss results from an investigation of the relationship between brain function during eye movements and a single nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene, a candidate gene for schizophrenia and brain function. The COMT val158met SNP (rs4680) was genotyped and the brain response during antisaccades was measured using fMRI in 36 healthy humans. Val158 carriers (N=24) showed reduced BOLD response in ventromedial and dorsomedial frontal areas during antisaccades compared val158 non-carriers (N=12). These findings suggest that COMT val158met genotype may affect the brain response during antisaccades; the results may be compatible with a hypothesis on the role of COMT val158met genotype in tonic and phasic dopamine levels in cortex and measures of cognitive plasticity (e.g. antisaccades).