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Intelligence and working memory may be the key to identifying the genes for schizophrenia

DECEMBER 17, 2007

Dr Timothea  Toulopoulou and colleagues from the Institute of Psychiatry at King's have published in the Archives  of General Psychiatry this month the first study to use statistical twin modelling to quantify the genetic overlap between schizophrenia and neuropsychological function.

Endophenotypes,  biological traits that increase the liability to a disorder, represent one strategy supporting gene detection efforts for  complex disorders such as schizophrenia. Establishing that a  trait is both heritable  and linked genetically to schizophrenia is key to its validity as an endophenotype. Neuropsychological deficits are among the most  promising indicators of increased genetic risk for schizophrenia; however, it is not clear to what extent these deficits are genetically linked to the disorder.

In the largest  UK study of twins with schizophrenia two hundred sixty seven twins were invited to complete a comprehensive series of intelligence and memory tests.  Both identical and  non-identical twins  took part, in some pairs both twins were affected by the illness and in others only one twin. Sophisticated genetic modelling statistical analyses were  then used to determine to what extent the intelligence deficits were related to the genetic risk for the illness.

The researchers found a significant correlation between intelligence and schizophrenia with 92%  of the covariance between the two accounted for by shared genetic variance. Genetic influences also explained most of the covariance between working memory and schizophrenia. Environmental effects, though separately linked to neurocognition and schizophrenia did not in general contribute to their correlation. These results imply that to some extent the genes that influence schizophrenia are the same as those  responsible for intelligence and working memory. Identifying those genes would effectively allow us to identify some of the genes contributing to schizophrenia. 

Substantial Genetic Overlap between Neurocognition and Schizophrenia: Genetic Modelling in Twin Samples authored by Timothea Toulopoulou; Marco Picchioni; Fruhling Rijsdijk; Mei Hua-Hall; Ulrich  Ettinger; Pak Sham; Robin Murray    Arch Gen Psychiatry  2007;64 1348-1355
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