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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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Title: A promoter variant of SHANK1 affects auditory working memory in schizophrenia patients and in subjects clinically at risk for psychosis.
Authors: Lennertz, Leonhard, Wagner, Michael, Wölwer, Wolfgang, Schuhmacher, Anna, Frommann, Ingo, Berning, Julia, Schulze-Rauschenbach, Svenja, Landsberg, Martin, Steinbrecher, Anja, Alexander, Michael, Franke, Petra, Pukrop, Ralf, Ruhrmann, Stephan, Bechdolf, Andreas, Gaebel, Wolfgang, Klosterkötter, Joachim, Häfner, Heinz, Maier, Wolfgang, Mössner, Rainald
Source: European Archives of Psychiatry & Clinical Neuroscience. Mar2012, Vol. 262 Issue 2, p117-124. 8p. 3 Charts, 1 Graph.
Subjects: People with schizophrenia, Short-term memory, Promoters (Genetics), Pathological physiology, Genetic mutation, Psychoses risk factors, Neuropsychology, Neurodevelopmental treatment, Postsynaptic density protein, Laboratory mice
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. [ABSTRACT FROM AUTHOR]
Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: A promoter variant of SHANK1 affects auditory working memory in schizophrenia patients and in subjects clinically at risk for psychosis.
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  Data: 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 &#177; 3.6 vs. 14.8 &#177; 4.1, P &lt; .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 &#177; 2.0 vs. 8.3 &#177; 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. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of European Archives of Psychiatry &amp; Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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