LINKAGE OF A NEUROPHYSIOLOGICAL DEFICIT IN SCHIZOPHRENIA TO A CHROMOSOME-15 LOCUS

Inheritance of a defect in a neuronal mechanism that regulates respons e to auditory stimuli was studied in nine families with multiple cases of schizophrenia. The defect, a decrease in the normal inhibition of the P50 auditory evoked response to the second of paired stimuli, is a ssociated with attentional disturbances in schizophrenia, Decreased P5 0 inhibition occurs not only in most schizophrenics, but also in many of their nonschizophrenic relatives, in a distribution consistent with inherited vulnerability for the illness, Neurobiological investigatio ns in both humans and animal models indicated that decreased function of the alpha 7-nicotinic cholinergic receptor could underlie the physi ological defect. In the present study, a genome-wide linkage analysis, assuming autosomal dominant transmission, showed that the defect is l inked [maximum logarithm of the odds (lod) score = 5.3 with zero recom bination] to a dinucleotide polymorphism at chromosome 15q13-14, the s ite of the alpha 7-nicotinic receptor. Despite many schizophrenics' ex tremely heavy nicotine use, nicotinic receptors were not previously th ought to be involved in schizophrenia. The linkage data thus provide u nique new evidence that the alpha 7-nicotinic receptor gene may be res ponsible for the inheritance of a pathophysiological aspect of the ill ness.