Neuroimaging, pharmacological and genetic studies of the oculomotor system in healthy and schizophrenic individuals

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Deficits in oculomotor control are well validated endophenotypes of schizophrenia. In a project currently funded by a DFG Emmy Noether Programme I am investigating associations of genetic polymorphisms with smooth pursuit and antisaccade eye movements as well as their underlying neural mechanisms. This work will contribute towards our understanding of the mechanistic pathways of schizophrenia risk polymorphisms. In the original application (submitted March 2007) I proposed to study 120 patients with a diagnosis of schizophrenia and 120 healthy controls. However, recent evidence from our group as well as others has shown that much larger discovery samples in combination with independent replication samples are needed to reliably show gene effects at the neurocognitive and oculomotor level. Therefore, I would like to apply to obtain funding for (1) recruiting and testing a further 400 healthy volunteers to perform oculomotor (as well as neuropsychological) tasks and (2) extracting DNA and genotyping schizophrenia risk polymorphisms. The proposed extension of this discovery sample in combination with neuroimaging data on a subset of participants as well as large replication samples drawn from international collaborations would allow me to build up a substantial database of oculomotor endophenotypes and molecular genetics. This database would allow, for the first time, reliably assessing associations between risk polymorphisms and these well validated schizophrenia endophenotypes.