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CAMK2A polymorphisms predict working memory performance in humans

Molecular Psychiatry volume 18, pages 850–852 (2013)Cite this article

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A Corrigendum to this article was published on 25 September 2012

Working memory is impaired in a number of psychiatric conditions.1, 2 An important role of alpha Ca2+/calmodulin dependent protein kinase II in learning and memory has been shown in rodent models. However, these findings have not been confirmed in humans yet. Here, we report genetic associations between the human CAMK2A gene and the performance in a spatial and a non-spatial working memory (non-SWM) task in two independent human samples.

Rodent models have shown that a dysfunction of alpha Ca2+/calmodulin dependent protein kinase II severely impairs learning and memory formation3, 4, 5 and emotional behavior.6 Although the association between alpha Ca2+/calmodulin dependent protein kinase II and learning and memory deficits has been well established in rodent models, an association has not yet been reported in humans. In the present study, we investigated the genetic association of 31 single-nucleotide polymorphisms (SNPs) in the human CAMK2A gene with performance in a SWM task, as measured by CANTAB (Cambridge Cognition, UK), in a sample of 558 healthy adolescents (269 males and 289 females). Caucasian participants, 13- to 14-year-old, were drawn from the IMAGEN project.7 Participants were genotyped using the Illumina Quad 610 arrays (Illumina, San Diego, CA, USA).7 This array included 31 SNPs located in the CAMK2A gene, which were tested for association with a delayed SWM task condition in the CANTAB battery (Supplementary Table 1). The SWM subtask is a computerized, self-ordered test of the ability to retain spatial information in working memory (full task description: see Supplementary Materials 1). A strategy score indicates the participant's efficiency in completing the task, with lower scores representing more efficient performance. We used linear regression models to examine the association between each SNP and strategy performance on the SWM. All analyzes were adjusted with the following covariates: age, sex, handedness, study site and intelligence quotient. All SNPs were within Hardy-Weinberg Equilibrium (Supplementary Table 2.) and all P-values were corrected using the false discovery rate (FDR) procedure.8 R-square values represent the degree of linkage disequilibrium between two loci. PLINK software (free open source analysis tool) was used for all analysis.

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Author notes

  1. A C Easton, A Lourdusamy, C Fernandes, C P Müller and G Schumann: These authors contributed equally to this work.

Authors and Affiliations

  1. MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London, UK

    A C Easton, A Lourdusamy, E Loth, C Fernandes, C P Müller & G Schumann

  2. Centre National de la Recherche Scientifique, Institute Pasteur, Paris, France

    R Torro

  3. Centre for the Cellular Basis of Behavior, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London and James Black Centre, London, UK

    K P Giese

  4. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany

    J Kornhuber & C P Müller

  5. Division of Cognitive Neuroscience, Department of Psychology, University of Basel, Basel, Switzerland

    D J-F de Quervain

  6. University of Basel, University Psychiatric Clinics, Basel, Switzerland

    D J-F de Quervain & A Papassotiropoulos

  7. Department Biozentrum, Life Sciences Training Facility,

    A Papassotiropoulos

  8. University of Basel, Basel, Switzerland

    A Papassotiropoulos

  9. Department of Psychology, Division of Molecular Neuroscience, University of Basel, Basel, Switzerland

    A Papassotiropoulos

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  1. A C Easton
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  2. A Lourdusamy
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  3. E Loth
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  4. R Torro
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  5. K P Giese
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  7. D J-F de Quervain
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  8. A Papassotiropoulos
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  9. C Fernandes
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  10. C P Müller
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  11. G Schumann
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the IMAGEN Consortium

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Correspondence to C P Müller.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website

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Easton, A., Lourdusamy, A., Loth, E. et al. CAMK2A polymorphisms predict working memory performance in humans. Mol Psychiatry 18, 850–852 (2013). https://doi.org/10.1038/mp.2012.114

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