Impact of TCF4 on the genetics of schizophrenia
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Mutations of the transcription factor 4 (TCF4) gene cause mental retardation with or without associated facial dysmorphisms and intermittent hyperventilation. Subsequently, a polymorphism of TCF4 was shown in a genome-wide association study to slightly increase the risk of schizophrenia. We have further analysed the impact of this TCF4 variant rs9960767 on early information processing and cognitive functions in schizophrenia patients. We have shown in a sample of 401 schizophrenia patients that TCF4 influences verbal memory in the Rey Auditory Verbal Learning Test. Contrary to expectations, carriers of the schizophrenia-associated allele showed better recognition, thus indicating that while TCF4 influences verbal memory, the TCF4-mediated schizophrenia risk is not determined by the influence of TCF4 on verbal memory. TCF4 does not impact on various other cognitive functions belonging to the domains of attention and executive functions. Moreover, in a pharmacogenetic approach, TCF4 does not modulate the improvement of positive or negative schizophrenia symptoms during treatment with antipsychotics. Finally, we have assessed a key electrophysiological endophenotype of schizophrenia, sensorimotor gating. As measured by prepulse inhibition, the schizophrenia risk allele C of TCF4 rs9960767 reduces sensorimotor gating. This indicates that TCF4 influences key mechanisms of information processing, which may contribute to the pathogenesis of schizophrenia.
KeywordsSchizophrenia TCF4 PPI Verbal memory Sensorimotor Gating Pharmacogenetics
This work was supported by the European Union (Grant FP7-Health-F4-2009-242257-ADAMS), by the German Federal Ministry for Education and Research (BMBF) (Grants POSITIVE 01GV0907, NGFN MooDs PNM-01GS08146-3), and by the DFG (Grant WA 737/7). Dr. Quednow is supported by the Swiss National Science Foundation (Grant No. PP00P1 123516). We thank V. Guttenthaler and A. Petruschke for excellent technical assistance.
Conflict of interest
The authors declare that they have no conflict of interest.
This supplement was not sponsored by outside commercial interests. It was funded by the German Association for Psychiatry and Psychotherapy (DGPPN).
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