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Relationship of a 5-HT transporter functional polymorphism to 5-HT1A receptor binding in healthy women

Molecular Psychiatry volume 10, pages 715–716 (2005)Cite this article

SIR—Variations in the gene encoding the serotonin transporter (5-HTT), which regulates reuptake of brain serotonin (5-HT), are thought to affect the levels of 5-HT in the brain. This study reports that LS/SS variants of the human 5-HTT gene (SLC6A4) are associated with increased 5-HT1A receptor binding in cingulate brain regions in healthy women (HW).

A functional polymorphism in the promoter region of the human 5-HTT gene (SLC6A4) has been implicated in the modulation of mood and antidepressant response.1 Several lines of evidence show that the genotype with two copies of the long (L, 528 bp) allele leads to greater 5-HT reuptake compared to genotypes having either one or two copies of the short (S, 484 bp) allele.2 Since 5-HTT regulates 5-HT concentrations in the synaptic cleft by recycling released 5-HT, individuals with the S allele are likely to have higher extracellular 5-HT concentrations during neurodevelopment and, possibly, in the mature 5-HT system. The activity of the 5-HTT is thought to influence the 5-HT1A receptor. For example, chronic administration of serotonin reuptake inhibitors (SRIs) leads to a desensitization of 5-HT1A autoreceptors.3 However, to our knowledge, no studies have investigated the relationship of this 5-HTT polymorphism to 5-HT1A receptor binding in vivo in healthy subjects.

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Acknowledgements

This work was supported by grants from NIMH MH46001, MH42984, and K05-MD01894. UFB was funded by an Erwin–Schrödinger Fellowship of the Austrian Science Fund (Nos. J 2188 and J 2359-B02).

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Authors and Affiliations

  1. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    M Lee & R E Ferrell

  2. Department of Psychiatry, Western Psychiatric Institute and Clinic, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    U F Bailer, G K Frank, S E Henry, C C Meltzer, A R Hariri & W H Kaye

  3. Department of General Psychiatry, Medical University of Vienna, University Hospital of Psychiatry, Vienna, Austria

    U F Bailer

  4. Department of Child and Adolescent Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA

    G K Frank

  5. Department of Radiology, School of Medicine, University of Pittsburgh, Presbyterian University Hospital, Pittsburgh, PA, USA

    C C Meltzer, J C Price & C A Mathis

  6. Department of Neurology, School of Medicine, University of Pittsburgh, Presbyterian University Hospital, Pittsburgh, PA, USA

    C C Meltzer

  7. Department of Environmental Health, Division of Epidemiology and Biostatistics, University of Cincinnati, Cincinnati, OH, USA

    K T Putnam

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  1. M Lee
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Correspondence to W H Kaye.

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Lee, M., Bailer, U., Frank, G. et al. Relationship of a 5-HT transporter functional polymorphism to 5-HT1A receptor binding in healthy women. Mol Psychiatry 10, 715–716 (2005). https://doi.org/10.1038/sj.mp.4001680

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