Gating deficit heritability and correlation with increased clinical severity in schizophrenia patients with positive family history

Objective: The Consortium on the Genetics of Schizophrenia Family Study evaluated 12 primary and other supplementary neurocognitive and neurophysiological endophenotypes in schizophrenia probands and their families. Previous analyses of prepulse inhibition (PPI) and P50 gatingmeasures in this sample revealed heritability estimates that were lower than expected based on earlier family studies. Here the authors investigated whether gating measures were more heritable in multiply affected families with a positive family history compared with families with only a single affected proband (singleton). Method: A total of 296 nuclear families consisting of a schizophrenia proband, at least one unaffected sibling, and both parents underwent a comprehensive endophenotype andclinical characterization.TheFamily Interview for Genetic Studieswasadministered to all participantsandusedto obtain convergent psychiatric symptom information for additional first-degree relatives. Among the families, 97 were multiply affected, and 96 were singletons. Results: Both PPI and P50 gating displayed substantially increased heritability in the 97 multiply affected families (47% and 36%, respectively) compared with estimates derived from the entire sample of 296 families (29% and 20%, respectively). However, no evidence for heritability was observed for either measure in the 96 singleton families. Schizophrenia probands derived fromthe multiply affected families also displayed a significantly increased severity of clinical symptoms compared with those from singleton families. Conclusions: PPI and P50 gating measures demonstrate substantially increased heritability in schizophrenia families with a higher genetic vulnerability for illness, providing further support for the commonality of genes underlying both schizophrenia and gating measures.