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Genome-wide supported risk variant for schizophrenia impacts on hippocampus activation during contextual fear conditioning

S. Pohlack, V. Nieratschker, F. Nees, M. Ruttorf, S. Witt, M. Rietschel and H. Flor

4th Annual Meeting of NGFN-Plus and NGFN-Transfer in the Program of Medical Genome Research,, p.157

Key features of schizophrenia are declarative memory and contextual processing deficits. Recently, the neurogranin gene has been linked to schizophrenia in a genome-wide association study. Neurogranin is abundantly expressed in key regions of contextual learning and discrimination, such as the hippocampus. Further, abnormal functioning of the hippocampal formation as a major site for cognitive and contextual processing has been found in schizophrenia. Contextual fear conditioning is heritable (35 - 45%) and constitutes a paradigm that is well suited to examine the impact of the genome-wide supported variant rs12807809 on cognitive and contextual processing. Hence, we employed an imaging genetics approach in healthy volunteers to investigate the influence of rs12807809 on the hippocampus during a contextual fear conditioning paradigm using structural as well as functional magnetic resonance imaging (fMRI). Carriers of the schizophrenia risk-allele variant showed significantly decreased activations in the left hippocampus during acquisition, indicating impaired hippocampal activity during contextual learning. The present results suggest that contextual fear conditioning might constitute a valuable endophenotype for schizophrenia research. However, independent replication of our results is necessary.

Contact: Prof. Dr. Frank Zöllner last modified: 19.08.2019
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