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Serotonin transporter genotype and function in relation to antidepressant response in Koreans

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Abstract

Rationale

Serotonin transporter (5-HTT) gene polymorphisms are linked with antidepressant response to selective serotonin reuptake inhibitor drugs (SSRIs), though the favorable allelic variant differs by ethnic group (Caucasian versus Korean or Japanese). In Caucasian patients, response also is linked to measures of platelet 5-HTT function.

Objectives

Here, we study both 5-HTT gene polymorphisms and 5-HTT function as determinants of antidepressant response to SSRIs in Korean patients.

Methods

We enrolled 99 patients with major depression and 48 control subjects. For statistical power, both samples were enriched with the l/l 5-HTTLPR polymorphism, which is uncommon in Koreans. Patients were treated with fluoxetine or sertraline. Response was assessed at 6 weeks. Subjects were genotyped for s/l polymorphism in the 5-HTT promoter region (5-HTTLPR). Platelet 5-HTT activity was determined as maximal uptake rate (Vmax) and affinity constant (Km).

Results

Response was differentially associated with the s allele of 5-HTTLPR, which also was significantly associated with Vmax. These associations are opposite to those reported in Caucasian populations. Responders had significantly higher Vmax and Km than nonresponders. In Koreans as well as Caucasians, high Vmax is related to antidepressant response to SSRIs, though the 5-HTTLPR polymorphism associations with both response and function differ by ethnicity.

Conclusions

Both ethnicity and function must be considered in evaluating candidate gene biomarkers of response to SSRIs in depression.

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Acknowledgments

This study was supported by grants from the Korea Science and Engineering Foundation (KOSEF) NRL Program (Grant R0A-2007-000-20129-0), the Korean Health Technology R&D Project from Ministry of Health & Welfare (A110339), Center for Genome Research of Samsung Biomedical Research Institute (GRC-P-10-03), and Samsung Biomedical Research Institute grant (C-A9-205). Dr. Carroll has received royalties from MultiHealth Systems, Toronto (licensee for the Carroll Depression Scales); royalty from Springer Publishing Company (for a published chapter); and honoraria for lectures sponsored by the South Carolina Psychiatric Association and the Brentwood Biomedical Research Institute at The University of California, Los Angeles. The sponsors of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Conflict of interest

The authors have declared that no conflict of interest exists.

Disclosure

All of the authors declare that they have no relationship with the organization supporting this research and no conflict of interest.

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Authors and Affiliations

  1. Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul, 135-710, Korea

    Woojae Myung, Hyeran Kim, Jae Won Chung, Min Young Seo & Doh Kwan Kim

  2. Center for Clinical Research, Samsung Biomedical Research Institute, Seoul, Korea

    Shinn-Won Lim

  3. Biostatistics Team, Samsung Biomedical Research Institute, Seoul, Korea

    Seonwoo Kim

  4. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Jong-Won Kim

  5. Pacific Behavioral Research Foundation, Carmel, CA, USA

    Bernard J. Carroll

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  1. Woojae Myung
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  9. Doh Kwan Kim
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Correspondence to Doh Kwan Kim.

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Myung, W., Lim, SW., Kim, S. et al. Serotonin transporter genotype and function in relation to antidepressant response in Koreans. Psychopharmacology 225, 283–290 (2013). https://doi.org/10.1007/s00213-012-2813-y

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  • DOI: https://doi.org/10.1007/s00213-012-2813-y

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