Neurophysiological endophenotypes of schizophrenia: the viability of selected candidate measures.
In an effort to reveal susceptibility genes, schizophrenia research has turned to the endophenotype strategy. Endophenotypes are characteristics that reflect the actions of genes predisposing an individual to a disorder, even in the absence of diagnosable pathology. Individual endophenotypes are presumably determined by fewer genes than the more complex phenotype of schizophrenia and would, therefore, reduce the complexity of genetic analyses. Unfortunately, despite there being rational criteria to define a viable endophenotype, the term is sometimes applied indiscriminately to characteristics that are deviant in affected individuals. Schizophrenia patients exhibit deficits in several neurophysiological measures of information processing that have been proposed as candidate endophenotypes. Successful processing of sensory inputs requires the ability to inhibit intrinsic responses to redundant stimuli and, reciprocally, to facilitate responses to less frequent salient stimuli. There is evidence to suggest that both these processes are "impaired" in schizophrenia. Measures of inhibitory failure include prepulse inhibition of the startle reflex, P50 auditory evoked potential suppression, and antisaccade eye movements. Measures of impaired deviance detection include mismatch negativity and the P300 event-related potential. The purpose of this review is to systematically evaluate the endophenotype candidacy of these key neurophysiological abilities. For each candidate, we describe typical experimental procedures, the current understanding of the underlying neurobiology, the nature of the abnormality in schizophrenia, the reliability, stability and heritability of the measure, and any reported gene associations. We conclude with a discussion of the few studies thus far that have employed a multivariate approach with these candidates.
Turetsky
Bruce I
BI
Department of Psychiatry, 10th floor, Gates Building, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA. turetsky@bbl.med.upenn.edu
Calkins
Monica E
ME
Light
Gregory A
GA
Olincy
Ann
A
Radant
Allen D
AD
Swerdlow
Neal R
NR
D001143:Arousal / Q000235:genetics / Q000502:physiology; D001288:Attention / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D003265:Contingent Negative Variation / Q000502:physiology; D004193:Discrimination Learning / Q000502:physiology; D018913:Event-Related Potentials, P300 / Q000502:physiology; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D009433:Neural Inhibition / Q000502:physiology*; D010641:Phenotype; D013216:Reflex, Startle / Q000502:physiology*; D012438:Saccades / Q000502:physiology*; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D018433:Twin Studies as Topic