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European Archives of Psychiatry and Clinical Neuroscience

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01.03.2012 | Original Paper

A promoter variant of SHANK1 affects auditory working memory in schizophrenia patients and in subjects clinically at risk for psychosis

verfasst von: Leonhard Lennertz, Michael Wagner, Wolfgang Wölwer, Anna Schuhmacher, Ingo Frommann, Julia Berning, Svenja Schulze-Rauschenbach, Martin W. Landsberg, Anja Steinbrecher, Michael Alexander, Petra E. Franke, Ralf Pukrop, Stephan Ruhrmann, Andreas Bechdolf, Wolfgang Gaebel, Joachim Klosterkötter, Heinz Häfner, Wolfgang Maier, Rainald Mössner

Erschienen in: European Archives of Psychiatry and Clinical Neuroscience | Ausgabe 2/2012

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Abstract

Mutations in postsynaptic scaffolding genes contribute to autism, thus suggesting a role in pathological processes in neurodevelopment. Recently, two de novo mutations in SHANK3 were described in schizophrenia patients. In most cases, abnormal SHANK3 genotype was also accompanied by cognitive disruptions. The present study queries whether common SHANK variants may also contribute to neuropsychological dysfunctions in schizophrenia. We genotyped five common coding or promoter variants located in SHANK1, SHANK2 and SHANK3. A comprehensive test battery was used to assess neuropsychological functions in 199 schizophrenia patients and 206 healthy control subjects. In addition, an independent sample of 77 subjects at risk for psychosis was analyzed for replication of significant findings. We found the T allele of the SHANK1 promoter variant rs3810280 to lead to significantly impaired auditory working memory as assessed with digit span (12.5 ± 3.6 vs. 14.8 ± 4.1, P < .001) in schizophrenia cases, applying strict Bonferroni correction for multiple testing. This finding was replicated for forward digit span in the at-risk sample (7.1 ± 2.0 vs. 8.3 ± 2.0, P = .044). Previously, altered memory functions and reduced dendritic spines and postsynaptic density of excitatory synapses were reported in SHANK1 knock-out mice. Moreover, the atypical neuroleptic clozapine was found to increase SHANK1 density in rats. Our findings suggest a role of SHANK1 in working memory deficits in schizophrenia, which may arise from neurodevelopmental changes to prefrontal cortical areas.

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Titel: A promoter variant of SHANK1 affects auditory working memory in schizophrenia patients and in subjects clinically at risk for psychosis
verfasst von: Leonhard Lennertz
Michael Wagner
Wolfgang Wölwer
Anna Schuhmacher
Ingo Frommann
Julia Berning
Svenja Schulze-Rauschenbach
Martin W. Landsberg
Anja Steinbrecher
Michael Alexander
Petra E. Franke
Ralf Pukrop
Stephan Ruhrmann
Andreas Bechdolf
Wolfgang Gaebel
Joachim Klosterkötter
Heinz Häfner
Wolfgang Maier
Rainald Mössner
Publikationsdatum: 01.03.2012
Verlag: Springer-Verlag
Erschienen in: European Archives of Psychiatry and Clinical Neuroscience / Ausgabe 2/2012
Print ISSN: 0940-1334
Elektronische ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-011-0233-3

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A promoter variant of SHANK1 affects auditory working memory in schizophrenia patients and in subjects clinically at risk for psychosis

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