Attention and sensory gating deficits in relatives of schizophrenic patients

Schizophrenia is a complex, multi-determined illness, the pathophysiology of which likely represents the interaction of a number of genetic and environmental factors. Studies of schizophrenic patients themselves cannot readily characterize specific factors, because all of the factors act in concert to produce the illness. Relatives of schizophrenics generally do not have schizophrenia themselves, but many of them would be expected to carry at least a portion of the genetic risk. The phenotypic expression of these unknown genes in the relatives might then be characterized as particular elements within the pathophysiology of schizophrenia. Several attentional and sensory gating deficits that are common in the relatives of schizophrenic patients include deficits in the gating of the P50 auditory evoked response to repeated stimuli and deficits in smooth pursuit eye movements (SPEM). Both deficits are specifically found in relatives in parents of schizophrenic offspring who have other schizophrenic relatives. These putative obligate carrier of a portion of the genetic risk for schizophrenia also have neuropsychological evidence for attentional dysfunction, similar to that found in their schizophrenic offspring. The P50 gating deficit and the SPEM deficit share a common neurobiological feature, i.e., their normalization by administration of high doses of nicotine. Deficits in the activation of inhibitory interneurons by nicotinic cholinergic receptors may be a common underlying mechanism for these psychophysiological abnormalities. Attempts to identify the neurobiological basis of schizophrenia may thus benefit from the study of subclinical dysfunctions in their relatives.