Neural correlates of eye tracking deficits in first-degree relatives of schizophrenic patients - A positron emission tomography study

Background: Schizophrenia is thought to arise from the interaction of genet ically mediated and environmentally triggered abnormalities in brain functi on. Reduced frontal activation, reported in schizophrenic patients, may be one expression of genetic risk. The present study investigated whether fron tal activation in relatives of schizophrenic patients would be related to e ye tracking deficits (ETD), which are considered a behavioral marker of ris k for schizophrenia. Methods: Subjects were first-degree relatives of schizophrenic patients (n = 17) and controls (n = 11). Relatives were divided into those with normal and abnormal pursuit based on qualitative ratings. Subjects were scanned us ing positron emission tomography and the (H2O)-O-15 bolus subtraction techn ique while performing smooth pursuit and fixation. Brain areas more active in pursuit than fixation were identified in the 3 groups. Correlations were used to investigate the relationship between activation of pursuit regions and pursuit gain in the relatives. Results: Controls significantly activated frontal eye fields (FEFs) and pos terior areas, including the motion processing area, V5, and cuneus. The 2 g roups of relatives activated the same posterior regions as controls, but di ffered from each other in activation of FEFs. Relatives with normal trackin g activated right dorsal FEFs while relatives with ETD did not. Individual subtractions re vealed that 90% of controls and 100% of the relatives with normal tracking activated FEFs during pursuit compared with 42% of relative s with ETD (P = .009). Pursuit gain was significantly and selectively assoc iated with percent activation of right dorsal FEFs (r = 0.74). Conclusions: Subtle frontal dysfunction seems to be a pathophysiological su bstrate of ETD in relatives of schizophrenic patients, and may be one aspec t of genetically mediated differences in brain function relevant to schizop hrenia.