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Quednow BB, Ettinger U, Mössner R, Rujescu D, Giegling I, Collier DA, Schmechtig A, Kühn KU, Möller HJ, Maier W, Wagner M, Kumari V. The schizophrenia risk allele C of the TCF4 rs9960767 polymorphism disrupts sensorimotor gating in schizophrenia spectrum and healthy volunteers. J Neurosci . 2011 May 4 ; 31(18):6684-91. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Arpi Minassian
Submitted 19 May 2011 Posted 19 May 2011

Studying the genetic underpinnings of sensorimotor gating, which is a function critical to adaptive everyday living, is an important endeavor. Quednow and colleagues’ work joins several others linking PPI to particular genotypes and will ultimately help us understand which genes, or more likely what interactions among genes, influence cognitive abilities such as inhibition. The findings’ specific implications for schizophrenia may be a more complex issue. First, as with some other genes (e.g., COMT; Roussos et al., 2008), the association between the “risk” genotype and decreased PPI is present in healthy subjects. Other neuropsychiatric populations are known to have PPI deficits, and they may also demonstrate this genotype-phenotype relationship. Furthermore, although PPI impairment in schizophrenia fits most of the criteria for an intermediate or endophenotype (see Goldberg and Weinberger, 2004) in that it is heritable and its underlying neurobiology is consistent with what we know...  Read more

View all comments by Arpi Minassian

Comment by:  Neal R. Swerdlow
Submitted 24 May 2011 Posted 24 May 2011

Genes and phenes: what do they mean?
In this very impressive and important study, the authors report reduced prepulse inhibition of acoustic startle (PPI) among individuals carrying the schizophrenia susceptibility gene, TCF4 (rs9960767), in two cohorts: healthy individuals from London (12 carriers), and schizophrenia-spectrum individuals from Bonn (11 carriers). TCF4 becomes another schizophrenia risk gene (along with COMT, DRD3, NRG1, CHRNA7, CHRNA3, among others) that appears to be associated with, or perhaps influence, PPI levels in healthy or schizophrenia subjects. Thus, PPI, along with a number of other endophenotypes, appears to be regulated by many of the same genes that confer an increased risk for developing schizophrenia (Greenwood et al., 2011).

PPI is a useful measure for translational studies. As has already been demonstrated with many other "risk genes," rodents carrying a mutant TCF4 gene appear to exhibit PPI deficits (Brzózka et...  Read more

View all comments by Neal R. Swerdlow
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