Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 May 23:7:22.
doi: 10.1186/1471-244X-7-22.

Association between 5-HT2A, TPH1 and GNB3 genotypes and response to typical neuroleptics: a serotonergic approach

Sami Anttila  1 , Olli Kampman, Ari Illi, Riikka Rontu, Terho Lehtimäki, Esa Leinonen
Affiliations

Association between 5-HT2A, TPH1 and GNB3 genotypes and response to typical neuroleptics: a serotonergic approach

Sami Anttila et al. BMC Psychiatry. .

Abstract

Background: Schizophrenia is a common psychiatric disease affecting about 1% of population. One major problem in the treatment is finding the right the drug for the right patients. However, pharmacogenetic results in psychiatry can seldom be replicated.

Methods: We selected three candidate genes associated with serotonergic neurotransmission for the study: serotonin 2A (5-HT2A) receptor gene, tryptophan hydroxylase 1 (TPH1) gene, and G-protein beta-3 subunit (GNB3) gene. We recruited 94 schizophrenia patients representing extremes in treatment response to typical neuroleptics: 43 were good responders and 51 were poor responders. The control group consisted of 392 healthy blood donors.

Results: We do, in part, replicate the association between 5-HT2A T102C polymorphism and response to typical neuroleptics. In female patients, C/C genotype was significantly more common in non-responders than in responders [OR = 6.04 (95% Cl 1.67-21.93), p = 0.005] or in the control population [OR = 4.16 (95% CI 1.46-11.84), p = 0.005]. TPH1 A779C C/A genotype was inversely associated with good treatment response when compared with non-responders [OR = 0.59 (95% Cl 0.36-0.98), p = 0.030] or with the controls [OR = 0.44 (95% CI 0.23-0.86, p = 0.016], and GNB3 C825T C/T genotype showed a trend-like positive association among the male patients with a good response compared with non-responders [OR = 3.48 (95% Cl 0.92-13.25), p = 0.061], and a clearer association when compared with the controls [OR = 4.95 (95% CI 1.56-15.70), p = 0.004].

Conclusion: More findings on the consequences of functional polymorphisms for the role of serotonin in the development of brain and serotonergic neurotransmission are needed before more detailed hypotheses regarding susceptibility and outcome in schizophrenia can be formulated. The present results may highlight some of the biological mechanisms in different courses of schizophrenia between men and women.

PubMed Disclaimer

References

    1. Schultz SK, Andreasen NC. Schizophrenia. Lancet. 1999;353:1425–1430. doi: 10.1016/S0140-6736(98)07549-7. - DOI - PubMed
    1. Werkman TR, Glennon JC, Wadman WJ, McCreary AC. Dopamine receptor pharmacology: interactions with serotonin receptors and significance for the aetiology and treatment of schizophrenia. CNS Neurol Disord Drug Targ. 2006;5:3–23. - PubMed
    1. Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I, Brockmoller J. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry. 2004;9:442–473. doi: 10.1038/sj.mp.4001494. - DOI - PubMed
    1. Hanninen K, Katila H, Kampman O, Anttila S, Illi A, Rontu R, Mattila KM, Hietala J, Hurme M, Leinonen E, Lehtimaki T. Association between the C957T polymorphism of the dopamine D2 receptor gene and schizophrenia. Neurosci Lett. 2006;407:195–198. doi: 10.1016/j.neulet.2006.08.041. - DOI - PubMed
    1. Roth BL, Sheffler DJ, Kroeze WK. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nature Reviews Drug Discovery. 2004;3:353–359. doi: 10.1038/nrd1346. - DOI - PubMed

Publication types

MeSH terms