We will investigate familial eye tracking dysfunction (ETD) in schizophrenia. We will characterize the familial transmission of ETD and study correlates of its transmission. Sample will consist of 100 families of schizophrenics and 100 screened normal controls. Probands will be in- and outpatients screened for exclusionary medical and substance- abuse/dependence conditions. Schizophrenics will first be rapidly screened for smooth pursuit ETD in the lab. Fifty schizophrenics with, and 50 without, quantitatively defined ETD will be recruited. Schizophrenics will get a lab assessment battery, as will their first-degree relatives and the controls. The assessment battery covers phenomenology, eye tracking, and neuropsychology. Phenomenological assessments consist of an Axis I diagnostic interview (Structured Clinical Interview for DSM-III-R) and a spectrum disorder interview (Schedule for Schizotypal Symptoms). Eye tracking tasks include smooth pursuit, saccadic tracking, and an antisaccade task. Smooth pursuit tasks use sinusoidal waveform targets, constant velocity targets, predictable velocity ramp targets, and unpredictable direction and speed ramp waveforms (Rashbass task). The saccadic task is one schizophrenics can do well and is used as a check on subject effort. The antisaccade task assesses deficits in saccade inhibition. Eye tracking performance will be quantified by root-mean- square error, single- and dual-mode pursuit gain, and measures of saccadic events (counts, saccade dynamics). Neuropsychological tests include the Continuous Performance Test, frontal lobe tests (a dorsolateral prefrontal cortex [DLPFC] sensitive delayed spatial localization task and a number of other frontal lobe sensitive tests), and more posteriorly sensitive tests involving visuospatial functions (to test the specificity of frontal lobe dysfunction's relation to eye tracking). Major hypotheses are: ETD in schizophrenics' families is transmitted consistent with a single gene mechanism; frontal lobe test deficits (particularly in DLPFC), disturbed vigilance performance, and schizotypal symptoms are all correlated with smooth-pursuit ETD (within probands and in relatives); these other-abnormalities are also transmitted in families.
Calkins, Monica E; Iacono, William G; Ones, Deniz S (2008) Eye movement dysfunction in first-degree relatives of patients with schizophrenia: a meta-analytic evaluation of candidate endophenotypes. Brain Cogn 68:436-61 |