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Schizophrenia Bulletin Advance Access published online on November 13, 2006
Schizophrenia Bulletin, doi:10.1093/schbul/sbl055
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© The Author 2006. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Gene/Phene Relationship

The Consortium on the Genetics of Schizophrenia: Neurocognitive Endophenotypes

Raquel E. Gur 1 *, Monica E. Calkins 1, Ruben C. Gur 1, William P. Horan 2, Keith H. Nuechterlein 2, Larry J. Seidman 3, and William S. Stone 3
1 Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania, 10 Gates, 3400 Spruce St., Philadelphia, PA 19104
2 Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at University of California Los Angeles
3 Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Harvard Medical School Department of Psychiatry; Harvard Institute of Psychiatric Epidemiology and Genetics

* To whom correspondence should be addressed.
Raquel E. Gur, E-mail: raquel{at}bbl.med.upenn.edu


  Abstract

The Consortium on the Genetics of Schizophrenia (COGS) is a 7-site collaboration that examines the genetic architecture of quantitative endophenotypes in families with schizophrenia. Here we review the background and rationale for selecting neurocognitive tasks as endophenotypic measures in genetic studies. Criteria are outlined for the potential of measures as endophenotypic vulnerability markers. These include association with illness, state independence (ie, adequate test-retest stability, adequate between-site reliability, impairments in patients not due to medications, impairments observed regardless of illness state), heritability, findings of higher rates in relatives of probands than in the general population, and cosegregation within families. The COGS required that, in addition, the measures be "neurocognitive" and thus linked to neurobiology and that they be feasible in multisite studies. The COGS neurocognitive assessment includes measures of attention, verbal memory, working memory, and a computerized neurocognitive battery that also includes facial processing tasks. Here we describe data demonstrating that these neurobehavioral measures meet criteria for endophenotypic candidacy. We conclude that quantitative neurocognitive endophenotypes need further evidence for efficacy in identifying genetic effects but have the potential of providing unprecedented insight into gene-environment interaction related to dimensions of brain and behavior in health and disease.

Keywords: neurogenetics; attention; memory; emotion.
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