Cognitive markers as potential endophenotypes for schizophrenia

Schizophrenia is a heterogeneous disease strongly influenced by genetic predisposition. A large variety of candidate genes has been identified of which each gene, however, explains only a small proportion of the genetic risk. For this reason, stable markers, so called endophenotypes, have become of primary interest. An endophenotype is a measurable component along the pathway between disease and distal genotype. Therefore it has emerged as an important concept in the study of complex neuropsychiatric diseases. Apart from structural and functional brain measures, several cognitive candidates have been proposed to be endophenotypes for schizophrenia. The Consortium on the Genetics of Schizophrenia (COGS) (http://www.schizophreniaresearch.net/Overview.asp) that examines the genetic architecture of quantitative endophenotypes in families with schizophrenia proposed several neurocognitive tasks as endophenotypic measures in genetic studies, including: Continuous Performance Tests (CPT), Wisconsin Card Sorting Test (WCST), verbal (CVLT) and working memory tasks and a computerized neurocognitive battery that also includes facial processing tasks. Other promising candidates rely on visual backward masking, which is of particular interest because masking deficit may be caused by deficient sensory processing. In our study we investigated cognitive and perceptual functions of 355 patients with schizophrenia, 134 their first degree healthy relatives and 150 healthy controls. We used neurocognitive (CPT, WCST, CVLT) and perceptual tasks (shine-through masking paradigm) and show that the shine-through paradigm distinguishes with high sensitivity and specificity between schizophrenic patients, first-order relatives and healthy controls and could be suggested as a potential endophenotype of the disorder.