Early expression of a pathophysiological. feature of schizophrenia: Saccadic intrusions into smooth-pursuit eye movements in school-age children vulnerable to schizophrenia

Objective: Neurodevelopmental hypotheses of schizophrenia propose that the responsible pathology occurs much earlier than the usual onset of illness in late adolescence. Nonspecific neurocognitive and behavioral deficits found in children vulnerable to schizophrenia support this hypothesis. This report describes early deficits in a putative genetic endophenotype, saccadic intrusions into smooth-pursuit eye movements (SPEM). Method: SPEM were recorded in 189 children aged 6-15 years: 49 children with schizophrenia, 60 nonpsychotic first-degree relatives, and 80 typically developing children. Results: Children with schizophrenia demonstrated poorer gain and a significantly increased frequency of leading saccades and large anticipatory saccades; however, only leading saccades differentiated first-degree relatives from typical children. Admixture analysis indicates that 94% of children with schizophrenia, 50% of first-degree relatives, and 19% of typically developing children have abnormally increased frequencies of leading saccades. Conclusions: Typically developing young school-age children have a leading saccade phenotype similar to that of adults, suggesting this brain function is fully developed by early school-age years. The abnormal leading saccade phenotype, a schizophrenia-associated familial brain dysfunction, is present by 6 years of age, more than a decade before the highest risk for onset of psychosis. Treatment and prevention strategies will need to consider the early neurodevelopmental nature of schizophrenia.