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Study provides evidence for commonality of genes underlying schizophrenia, gating deficits

Measures of gating deficits had significantly increased heritability among families multiply affected by schizophrenia compared with families singly affected by the disease, suggesting commonality of genes underlying schizophrenia and gating deficits.

“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,” Tiffany A. Greenwood, PhD, of University of California, San Diego, and colleagues wrote.

To determine if gating measures were more heritable in multiply affected families with positive family history vs. families with a single affected proband, researchers assessed 296 nuclear families with a schizophrenia proband and at least one unaffected sibling. Comprehensive endophenotype and clinical characterization were conducted among parents and offspring. The Family Interview for Genetic Studies was administered.

Overall, 97 families were multiply affected and 96 were singly affected.

Both PPI and P50 gating exhibited significantly increased heritability among multiply affected families (47% and 36%, respectively), compared with estimates for the entire cohort (29% and 20%, respectively).

However, researchers found no evidence for heritability among singly affected families.

Schizophrenia probands from multiply affected families exhibited significantly increased clinical symptom severity compared with singly affected families.

“Substantial heritability of both PPI and P50 gating was observed for multiply affected families with a positive family history. Conversely, neither PPI nor P50 gating displayed any evidence of heritability in the subset of singleton families, in which the probands likely represent sporadic cases of schizophrenia,” Greenwood and colleagues wrote. “Pulse-alone startle magnitude showed consistent heritability estimates across all families. While P50 S1 also demonstrated significant heritability across all families, a dramatic increase in S1 heritability was observed for the positive family history subset. This may suggest that both sensory reactivity and gating are more heritable in schizophrenia families with a positive family history.” – by Amanda Oldt

Disclosure: Freedman reports having a patent through the VA on DNA sequences in CHRNA7. Please see the full study for a list of all authors’ relevant financial disclosures.