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Decreased regional gray matter volume in S’ allele carriers of the 5-HTTLPR triallelic polymorphism

Molecular Psychiatry volume 16, pages 472–473 (2011)Cite this article

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The short (S) allele of an insertion/deletion variant in the promoter region of the human serotonin transporter (5-HTT) gene (SLC6A4), has been associated with increased risk of depression in stressful life circumstances.1 The way in which this genetic variation influences brain function is the subject of intensive research. Despite suggestive in vitro evidence, current positron emission tomography studies do not show a consistent effect of the promoter variant on the availability of the 5-HTT in the brain in vivo, and attention has shifted to differential effects of the S allele on brain morphology.2, 3 In the present study, we used voxel-based morphometry in a large sample of healthy control subjects to assess the effect of the triallelic 5-HTTLPR polymorphism. This includes an embedded A/G substitution, rs25531 (S/La/Lg), where the Lg allele is considered functionally similar to and grouped together with the S allele (L’=La; S’=S and Lg).2

We studied 113 volunteers (females 43, males 70), mean age 37.6 years (range 18–60 years, s.d. 11.3). There were 22 S’-non-carriers (L’L’ genotype) (mean age 32.7 years, s.d. 11.2) and 91 S’ carriers (mean age 37.6 years, s.d. 11.2). All volunteers were free from any lifetime psychiatric or neurological disorder. Structural magnetic resonance imaging data were acquired at 3T (TR=9.6 ms, TE=4.6 ms, flip angle=8, voxel dimensions 0.94 × 0.94 × 1.2 mm3). Image preprocessing utilized an optimized voxel-based morphometry protocol (FSL v4.1.4). Effects of the 5-HTTLPR on gray matter volume were examined using an analysis of covariance model with age and gender as covariates of no interest. Gray matter volume changes were assessed statistically with one-tailed t-tests using a threshold-free cluster-based approach with correction for multiple comparisons at the whole-brain level. In addition, regions of interest for bilateral amygdala and subgenual cingulate were used. The genetic variants of 5-HTTLPR rs25531polymorphism were determined by the PCR reaction, followed by digestion with MspI restriction enzyme.4

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Authors and Affiliations

  1. University Department of Psychiatry, Psychopharmacology Research Unit (PPRU), University of Oxford, Oxford, UK

    S Selvaraj, B R Godlewska, R Norbury & P J Cowen

  2. MRC Clinical Sciences Centre (Imperial College), Hammersmith Hospital, London, UK

    S Bose, F Turkheimer, P Stokes, R Rhodes & O Howes

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  1. S Selvaraj
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  2. B R Godlewska
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  3. R Norbury
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  4. S Bose
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  5. F Turkheimer
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  6. P Stokes
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  7. R Rhodes
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  8. O Howes
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  9. P J Cowen
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Correspondence to P J Cowen.

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Selvaraj, S., Godlewska, B., Norbury, R. et al. Decreased regional gray matter volume in S’ allele carriers of the 5-HTTLPR triallelic polymorphism. Mol Psychiatry 16, 472–473 (2011). https://doi.org/10.1038/mp.2010.112

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