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Influence of serotonin transporter gene polymorphisms on cognitive decline and cognitive abilities in a nondemented elderly population

Molecular Psychiatry volume 10, pages 1133–1139 (2005)Cite this article

Abstract

Dysfunction of the serotonergic pathway disrupts normal cognitive functioning and is believed to be the underlying basis for a variety of psychiatric disorders. Two functional polymorphisms within the serotonin transporter (SLC6A4) gene (promoter 44 bp insertion/deletion (HTTLPR) and an intron two 16 or 17 bp variable number tandem repeat (VNTR2)) have been extensively studied in psychiatric conditions but not in the cognitive functioning of normal individuals. We have investigated these two polymorphisms for association with both the level of cognitive abilities and their decline with age using a cohort consisting of over 750 elderly nondemented individuals with a follow-up of up to 15 years. We found that volunteers homozygous for the VNTR2 12 allele had a faster rate of decline for all cognitive tests. This reached significance for both tests of fluid intelligence (novel problem solving) (AH1 P=0.002, AH2 P=0.014), the test of semantic memory (P=0.010) and general cognitive ability (P=0.006). No association was observed between the HTTLPR polymorphism and the rate of cognitive decline when analysed either independently or in combination with the VNTR2 polymorphism based on their influence on expression in vitro. No associations were observed between the two polymorphisms and the baseline level of cognitive abilities. This is only the second gene that has been reported to regulate the rate of cognitive decline in nondemented individuals and may be a target for the treatment of cognitive impairment in the elderly.

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Acknowledgements

This work was supported by the Wellcome Trust (Grant number GD045ERG). Blood collection and DNA extraction was partly funded by Research into Ageing.

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Authors and Affiliations

  1. Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK

    A Payton, W Ollier & J Worthington

  2. Clinical Gerontology, University of Manchester, Clinical Sciences Building, Hope Hospital, Salford, Greater Manchester, UK

    L Gibbons, Y Davidson, N Pendleton & M Horan

  3. Age & Cognitive Performance Research Centre, University of Manchester, Manchester, UK

    P Rabbitt

  4. Biostatistics Group, University of Manchester, Manchester, UK

    A Pickles

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  1. A Payton
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Correspondence to A Payton.

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Payton, A., Gibbons, L., Davidson, Y. et al. Influence of serotonin transporter gene polymorphisms on cognitive decline and cognitive abilities in a nondemented elderly population. Mol Psychiatry 10, 1133–1139 (2005). https://doi.org/10.1038/sj.mp.4001733

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