Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-48043
Quednow, B B; Ettinger, U; Mössner, R; Rujescu, D; Giegling, I; Collier, D A; Schmechtig, A; Kühn, K U; Möller, H J; Maier, W; Wagner, M; Kumari, V (2011). The schizophrenia risk allele C of the TCF4 rs9960767 polymorphism disrupts sensorimotor gating in schizophrenia spectrum and healthy volunteers. Journal of Neuroscience, 31(18):6684-6691.
In a large-scale meta-analysis, it has been recently shown that the transcription factor 4 (TCF4) gene is among the most prominent susceptibility genes for schizophrenia. Moreover, transgenic mice overexpressing TCF4 in the brain display a reduction of sensorimotor gating measured by prepulse inhibition (PPI) of the acoustic startle response (ASR). PPI is heritable and has been established as an important translational endophenotype of schizophrenia. We therefore investigated the impact of the schizophrenia susceptibility gene TCF4 (rs9960767) on sensorimotor gating of the ASR in healthy humans and in patients with a schizophrenia spectrum disorder. We assessed PPI, startle reactivity, and habituation of the ASR in two independent samples. The first sample consisted of 107 healthy volunteers from London, UK. The second sample was a schizophrenia spectrum group (n = 113) of 73 schizophrenia patients and 40 individuals at high risk for schizophrenia from Bonn, Germany (total sample n = 220). In both samples, PPI was strongly decreased in carriers of the schizophrenia risk allele C of the TCF4 gene (meta-analysis across both samples: p = 0.00002), whereas startle reactivity and habituation were unaffected by TCF4 genotype. Sensorimotor gating is modulated by TCF4 genotype, indicating an influential role of TCF4 gene variations in the development of early information-processing deficits in schizophrenia.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics|
04 Faculty of Medicine > Center for Integrative Human Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||12 May 2011 14:22|
|Last Modified:||27 Nov 2013 21:07|
|Publisher:||Society for Neuroscience|
|Free access at:||Publisher DOI. An embargo period may apply.|
|Citations:||Web of Science®. Times cited: 21|
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