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