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A 40-basepair VNTR polymorphism in the dopamine transporter (DAT1) gene and the rapid response to antidepressant treatment

The Pharmacogenomics Journal volume 7, pages 48–55 (2007)Cite this article

Abstract

Finding predictors of the response to antidepressant therapy is a major goal of molecular psychiatry. The genes encoding the serotonin (SERT) and dopamine (DAT1) transporters are among the possible candidate genes modulating an individual's antidepressant response. In a naturalistic prospective cohort study with a total of 190 fully assessed patients, improvement of depression symptoms during the 3 weeks following initiation of antidepressant therapy was recorded using the 21-item Hamilton Depression Rating Scale (HDRS). The SLC6A3 3′ UTR 40-bp variable number of tandem repeats (VNTR) and the SLC6A4 5′ 44-bp insertion/deletion polymorphism were analyzed by polymerase chain reaction. There was a significantly smaller number of rapid responders among homozygous carriers of the DAT1 9-repeat allele (9/9) than among heterozygous (9/10) and homozygous (10/10) carriers of the 10-repeat allele (19 versus 37 versus 52%, respectively, P=0.0037). Median decline in HDRS score was 35, 40, and 52% in patients with the 9/9, 9/10, and 10/10 genotypes, respectively (P=0.013). The effect was found in all classes of medications (selective serotonin reuptake inhibitors (SSRIs), tricyclics, mirtazapine, venlafaxine) and statistically significant also within the subgroup of patients having received SSRIs. The serotonin promoter insertion/deletion genotype had no effect in the entire study group, but there was an insignificant trend of better response in the l/l and l/s carriers who received SSRIs or mirtazapine. In conclusion, the dopamine transporter VNTR polymorphism influenced rapid response to antidepressant therapy. Compared with homozygous carriers of the 10-repeat allele, carriers of the 9/10 genotype had an odds ratio (OR) calculated by logistic regression analysis of 1.6 (95% CI 0.8–3.2) and carriers of the 9/9 genotype had an OR of 6.0 (1.5–24.4) for no or poor response. Further studies are required to confirm this clinical association and to elucidate the underlying mechanisms.

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Acknowledgements

We thank Drs Hildebrand and Zander for their contributions to the clinical characterization of patients and we thank Dr Gabriele Laschinski for thorough revision of the manuscript. This study was supported by the German Ministry of Education and Research, BMBF Grant No. 01 GG 9845/5.

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Authors and Affiliations

  1. Department of Pharmacology of Natural Products & Clinical Pharmacology, University of Ulm, Ulm, Germany

    J Kirchheiner

  2. Institute of Clinical Pharmacology, Charité University Medicine Berlin, Germany

    K Nickchen & I Roots

  3. Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Campus Charité Mitte, Germany

    J Sasse & M Bauer

  4. Department of Clinical Pharmacology, Georg August University, Göttingen, Germany

    J Brockmöller

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  1. J Kirchheiner
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Correspondence to J Kirchheiner.

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Kirchheiner, J., Nickchen, K., Sasse, J. et al. A 40-basepair VNTR polymorphism in the dopamine transporter (DAT1) gene and the rapid response to antidepressant treatment. Pharmacogenomics J 7, 48–55 (2007). https://doi.org/10.1038/sj.tpj.6500398

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