P300 subcomponent abnormalities in schizophrenia: III. Deficits In unaffected siblings of schizophrenic probands.
BACKGROUND
Reduced P300 amplitude is a robust finding in patients with schizophrenia. In previous investigations, we reported reductions of specific subcomponents of the auditory oddball P300 that were independent of acute symptomatology and persistent over time, consistent with a trait abnormality. To clarify whether these stable deficits represented genetic markers of vulnerability to schizophrenia, event-related brain potentials (ERPs) from patients were compared to those from their own healthy siblings and unrelated control subjects.


METHODS
Auditory P300 ERPs were acquired from 11 schizophrenic patients, 12 healthy siblings and 23 matched control subjects. Five P300 subcomponents were identified using current source density measures: frontal, bilateral parietal, and bilateral temporal.


RESULTS
Consistent with previous reports, patients had reduced parietal and frontal P300 amplitudes. The healthy siblings of the schizophrenic probands had an isolated reduction of the frontal P300.


CONCLUSIONS
Frontal P300 amplitude is a potential endophenotypic marker of genetic vulnerability to schizophrenia in individuals who otherwise show no evidence of clinical symptomatology. Given the functional interpretation of the frontal P300 as a physiological correlate of cognitive orienting, this supports the hypothesis that impairments of the neural substrate underlying attentional mechanisms are selective indicators of genetic susceptibility to schizophrenia in high-risk individuals.
Turetsky
B I
BI
Department of Psychiatry, University of Pennsylvania, Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Cannon
T D
TD
Gur
R E
RE
D000328:Adult; D001288:Attention; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000503:physiopathology*; D003071:Cognition; D018913:Event-Related Potentials, P300 / Q000235:genetics*; D005072:Evoked Potentials, Auditory / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000523:psychology*; D006801:Humans; D008297:Male; D009679:Nuclear Family / Q000523:psychology; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology*; D012680:Sensitivity and Specificity; D012737:Sex Factors
D005819:Genetic Markers