Abstract
BACKGROUND: Allelic association case-control analysis of a deletion/insertion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has suggested associations with unipolar disorder, bipolar disorder, depression, and Alzheimer's disease. Moreover, the heterozygous long form of the 5-HTTLPR has been associated with increased levels of mRNA for the serotonin transporter (5-HTT) and increased serotonin uptake in lymphoblastic cell lines. This study attempts to determine whether there is an association between 5-HTTLPR genotype and schizophrenia or the binding of [3H]paroxetine to the human hippocampal 5-HTT. MATERIALS AND METHODS: DNA from the cerebellum from 58 schizophrenic and 62 control subjects was used to genotype the 5-HTTLPR. In addition, the relationship between 5-HTTLPR genotype and the affinity and density of [3H]paroxetine binding to the hippocampal 5-HTT was assessed. RESULTS: There were no associations between 5-HTTLPR allotype or genotype and/or the parameters of [3H]paroxetine binding to the hippocampal 5-HTT. CONCLUSIONS: Our data suggest that 5-HTTLPR genotype neither confers an increased susceptibility for schizophrenia nor dictates the expression of the 5-HTT in the human hippocampus.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Collier D. A., Stöber G., Li T., Heils A., Catalano M., Di Bella D., Arranz M. J., Murray R. M., Vallada H. P., Bengel D. A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol Psychiatry. 1996 Dec;1(6):453–460. [PubMed] [Google Scholar]
- Dean B., Opeskin K., Pavey G., Naylor L., Hill C., Keks N., Copolov D. L. [3H]paroxetine binding is altered in the hippocampus but not the frontal cortex or caudate nucleus from subjects with schizophrenia. J Neurochem. 1995 Mar;64(3):1197–1202. doi: 10.1046/j.1471-4159.1995.64031197.x. [DOI] [PubMed] [Google Scholar]
- Furlong R. A., Ho L., Walsh C., Rubinsztein J. S., Jain S., Paykel E. S., Easton D. F., Rubinsztein D. C. Analysis and meta-analysis of two serotonin transporter gene polymorphisms in bipolar and unipolar affective disorders. Am J Med Genet. 1998 Feb 7;81(1):58–63. [PubMed] [Google Scholar]
- Hill C., Keks N., Roberts S., Opeskin K., Dean B., MacKinnon A., Copolov D. Problem of diagnosis in postmortem brain studies of schizophrenia. Am J Psychiatry. 1996 Apr;153(4):533–537. doi: 10.1176/ajp.153.4.533. [DOI] [PubMed] [Google Scholar]
- Kendler K. S., Diehl S. R. The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophr Bull. 1993;19(2):261–285. doi: 10.1093/schbul/19.2.261. [DOI] [PubMed] [Google Scholar]
- Lesch K. P., Balling U., Gross J., Strauss K., Wolozin B. L., Murphy D. L., Riederer P. Organization of the human serotonin transporter gene. J Neural Transm Gen Sect. 1994;95(2):157–162. doi: 10.1007/BF01276434. [DOI] [PubMed] [Google Scholar]
- Lesch K. P., Bengel D., Heils A., Sabol S. Z., Greenberg B. D., Petri S., Benjamin J., Müller C. R., Hamer D. H., Murphy D. L. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science. 1996 Nov 29;274(5292):1527–1531. doi: 10.1126/science.274.5292.1527. [DOI] [PubMed] [Google Scholar]
- Li T., Holmes C., Sham P. C., Vallada H., Birkett J., Kirov G., Lesch K. P., Powell J., Lovestone S., Collier D. Allelic functional variation of serotonin transporter expression is a susceptibility factor for late onset Alzheimer's disease. Neuroreport. 1997 Feb 10;8(3):683–686. doi: 10.1097/00001756-199702100-00021. [DOI] [PubMed] [Google Scholar]
- Meltzer H. Serotonergic dysfunction in depression. Br J Psychiatry Suppl. 1989 Dec;(8):25–31. [PubMed] [Google Scholar]
- Mendes de Oliveira J. R., Otto P. A., Vallada H., Lauriano V., Elkis H., Lafer B., Vasquez L., Gentil V., Passos-Bueno M. R., Zatz M. Analysis of a novel functional polymorphism within the promoter region of the serotonin transporter gene (5-HTT) in Brazilian patients affected by bipolar disorder and schizophrenia. Am J Med Genet. 1998 May 8;81(3):225–227. doi: 10.1002/(sici)1096-8628(19980508)81:3<225::aid-ajmg4>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
- Naylor L., Dean B., Opeskin K., Pavey G., Hill C., Keks N., Copolov D. Changes in the serotonin transporter in the hippocampus of subjects with schizophrenia identified using [3H]paroxetine. J Neural Transm (Vienna) 1996;103(6):749–757. doi: 10.1007/BF01271234. [DOI] [PubMed] [Google Scholar]
- Sasieni P. D. From genotypes to genes: doubling the sample size. Biometrics. 1997 Dec;53(4):1253–1261. [PubMed] [Google Scholar]
- Stöber G., Jatzke S., Heils A., Jungkunz G., Fuchs E., Knapp M., Riederer P., Lesch K. P. Susceptibility for schizophrenia is not influenced by a functional insertion/deletion variant in the promoter of the serotonin transporter gene. Eur Arch Psychiatry Clin Neurosci. 1998;248(2):82–86. doi: 10.1007/s004060050022. [DOI] [PubMed] [Google Scholar]