Smooth pursuit and antisaccade eye movements as endophenotypes in schizophrenia spectrum research

• Main Author: Ettinger, Ulrich
• Published: Goldsmiths College (University of London) 2003
• Subjects: 616.898
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404565

Smooth pursuit eye movement (SPEM) and antisaccade deficits have been proposed as schizophrenia spectrum endophenotypes. An endophenotype is a behavioural or biological deficit thought to represent, more closely than the disease phenotype, the effects of an underlying disease gene. Oculomotor endophenotypes possess phenotypic homogeneity, well-understood neural correlates and objective assessment and may thus be used as phenotypes in linkage studies. This thesis investigated a number of issues concerning the reliability and validity of the SPEM and antisaccade tasks as schizophrenia spectrum endophenotypes (and two tasks thought to be unimpaired in the schizophrenia spectrum, visual fixation and prosaccades). The schizophrenia spectrum encompasses not only people with schizophrenia but any population with an increased frequency of schizophrenia-related phenotypes or genotypes, such as schizotypal individuals or first-degree relatives of schizophrenia patients. A valid endophenotype should thus be detected in these populations. Study I investigated reliability, namely internal consistency and temporal stability, of eye movements in healthy individuals. Study II utilised first-episode psychosis patients and healthy controls, aiming to detect behavioural oculomotor deficits in the absence of secondary confounds that may be encountered in chronic schizophrenia. Study III assessed performance in siblings discordant for schizophrenia. Study IV explored the relationship between p.sychometric schizotypy and oculomotor performance. Study V examined possible state effects of procyclidine, an anticholinergic compound often administered to schizophrenia patients, on performance in a patient group. The results generally confirmed the validity of the SPEM and antisaccade deficits as schizophrenia spectrum endophenotypes: Oculomotor performance was mostly stable both within and between assessments. SPEM and antisaccade impairments were observed in firstepisode psychosis patients and schizophrenia patients and their healthy siblings. Antisaccade, but not SPEM, impairments were associated with high levels of schizotypy. State effects of procyclidine on SPEM and antisaccade performance were observed, suggesting the need to consider the influence of pharmacological treatment in future patient studies. These findings suggest that SPEM and antisaccade deficits may be studied profitably as endophenotypes in schizophrenia spectrum research.