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Behavioural Genetics of the Serotonin Transporter

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Behavioral Neurogenetics

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 12))

Abstract

The serotonin transporter is a key regulator of the bioavailability of serotonin and therefore any modulation in the expression or action of the transporter would be expected to have consequences on behaviour. The transporter has therefore become a target for pharmaceutical intervention in behavioural and mood disorders. The search for polymorphic variants in the transporter that would associate with neurological disorders has been extensive but has become focused on two domains which are both termed variable number tandem repeat (VNTR) polymorphisms. Both of these VNTRs are in non-coding DNA and therefore proposed to be mechanistically involved in a disorder through their ability to modulate transcriptional or post-transcriptional regulation of the transporter. The most extensively studied is in the promoter and is a bi-allelic insertion/deletion found in the 5′ promoter region of the gene 1.2 kb upstream of the transcriptional start site. This VNTR, termed, 5-HTTLPR was initially identified as two variants containing either, 14 (short/deletion) or 16 (long/insertion) copies of a 22 bp repeat. A second widely studied VNTR found in the non-coding region of the transporter is located within intron 2 and comprises 9, 10 or 12 copies of a 16–17 bp repeat termed, STin2.9, STin2.10 and STin2.12, respectively. These VNTR polymorphisms have been associated with a range of behavioural and psychiatric disorders including depression, OCD, anxiety and schizophrenia, however often the lack of reproducibility in different cohorts has led to debate on the actual association of the polymorphisms with this extensive range of neurological conditions. Here we review these two polymorphic VNTRs in depth and relate that to pharmaceutical response, their ability to regulate differential transporter expression, their core involvement in gene-environment interaction and their genetic association with specific disorders.

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Authors and Affiliations

  1. Department of Clinical and Molecular Pharmacology, Institute of Translation Medicine, University of Liverpool, Liverpool, Merseyside, L69 3BX, UK

    K. Haddley, V. J. Bubb & J. P. Quinn

  2. Social, Genetic and Developmental Psychiatric Centre (SGDP MRC), Institute of Psychiatry, King’s College London, DeCrespigny Park, London, SE5 8AF, UK

    G. Breen & U. M. Parades-Esquivel

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  1. K. Haddley
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  2. V. J. Bubb
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  4. U. M. Parades-Esquivel
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  5. J. P. Quinn
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  1. , Dep of Pharmacology and Therapeutics, School of Pharmacy, College Rd, Cork, 30, Ireland

    John F. Cryan

  2. , Department of Psychiatry and Psychothera, University of Würzburg, Füchsleinstrasse 15, Würzburg, 97080, Germany

    Andreas Reif

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Haddley, K., Bubb, V.J., Breen, G., Parades-Esquivel, U.M., Quinn, J.P. (2011). Behavioural Genetics of the Serotonin Transporter. In: Cryan, J., Reif, A. (eds) Behavioral Neurogenetics. Current Topics in Behavioral Neurosciences, vol 12. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2011_186

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