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Am J Psychiatry. 2016 Apr 1;173(4):385-91. doi: 10.1176/appi.ajp.2015.15050605. Epub 2015 Oct 6.

Gating Deficit Heritability and Correlation With Increased Clinical Severity in Schizophrenia Patients With Positive Family History.

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From the Department of Psychiatry, the Center for Behavioral Genomics, and the Institute for Genomic Medicine, UC San Diego, La Jolla, Calif.; VISN 22 Mental Illness Research, Education and Clinical Center, VA San Diego Healthcare System, San Diego; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Biobehavioral Sciences, UCLA, the Department of Biostatistics, School of Public Health, UCLA, and the VA Greater Los Angeles Healthcare System, Los Angeles; the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry and Behavioral Sciences, University of Washington, and VA Puget Sound Health Care System, Seattle; the Department of Psychiatry, Harvard Medical School, the Harvard Institute of Psychiatric Epidemiology and Genetics, and the Division of Public Psychiatry, Massachusetts Mental Health Center, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, and the James J. Peters VA Medical Center, New York.



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 gating measures 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).


A total of 296 nuclear families consisting of a schizophrenia proband, at least one unaffected sibling, and both parents underwent a comprehensive endophenotype and clinical characterization. The Family Interview for Genetic Studies was administered to all participants and used to obtain convergent psychiatric symptom information for additional first-degree relatives. Among the families, 97 were multiply affected, and 96 were singletons.


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 from the multiply affected families also displayed a significantly increased severity of clinical symptoms compared with those from singleton families.


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.

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