CENTER ON BEHAVIORAL MEDICINE
Behavioral Genetics: Research Article
Vincent, J.B., Masellis, M., et al. (1999). Genetic
Analysis of Serotonin System Genes in Bipolar Affective Disorder.
Am J Psychiatry 1999; 156:136-138.
ABSTRACT: This study examined the putative role of serotonin genes in the etiology of bipolar affective disorder. Objective: This study examined the putative role of serotonin genes in the etiology of bipolar affective disorder. Method: Genetic association analysis was performed for individuals with bipolar affective disorder and unaffected subjects closely matched in age, sex, and ethnic background (N=103 in each group). The allele and genotype frequencies of polymorphisms at the genes for serotonin receptors HTR1A, HTR1D(alph)a, HTR1D(beta), HTR2A, HTR2C, HTR7, tryptophan hydroxylase (TPH), and the serotonin transporter (hSERT) were compared in the two groups of subjects. Results: Statistically significant positive associations were found for HTR2A and hSERT polymorphisms. However, results from an independent replication group of over 100 patients with bipolar affective disorder and their matched comparison subjects failed to confirm these associations. Conclusions: These results suggest that the serotonin genes studied are not associated with bipolar affective disorder, although transmission disequilibrium studies are required in order to confirm this conclusion.
1. Meltzer H: Serotonergic dysfunction in depression. Br J Psychiatry Suppl 1989; 8:25-31
2. Lucas JJ, Hen R: New players in the 5-HT receptor field: genes and knockouts. Trends Pharmacol Sci 1995; 16:246252
3. Gershon ES, Martinez M, Goldin LR, Gejman PV: Genetic mapping of common diseases: the challenges of manic-depressive illness and schizophrenia. Trends Genet 1990; 6: 282-287
4. Gutierrez B, Arranz M, Fananas L, Valles V, Guillamat R, van Os J, Collier D: 5HT2A receptor gene and bipolar affective disorder (letter). Lancet 1995; 346:969
5. Gutierrez B, Fananas L, Arranz M, Valles V, Guillamat R, van Os J, Collier D: Allelic association analysis of the 5HT2C receptor gene in bipolar affective disorder. Neurosci Lett 1996; 212:65-67
6. Ogilvie AD, Battersby S, Bubb VJ, Fink G, Harmar AJ, Goodwin GM, Smith CAD: Polymorphism in serotonin transporter gene associated with susceptibility to major depression. Lancet 1996; 347:731-733
7. Bellivier F, Leboyer M, Courtet P, Buresi C, Beaufils B, Samolyk D, Allilaire JF, Feingold J, Mallet J, Malafosse A: As sociation between the tryptophan hydroxylase gene and manic-depressive illness. Arch Gen Psychiatry 1998; 55:3337
8. Spitzer RL, Endicott J: Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L). New York, New York State Psychiatric Institute, Biometrics Research, 1978
9. Burke KC, Burke JD, Regier DA, Rae DS: Age at onset of selected mental disorders in five community populations. Arch Gen Psychiatry 1990; 47:511-518
10. Bolos AM, Goldman D, Dean M: Dinucleotide repeat and alu repeat polymorphisms at the 5HT^sub 1A^ (HTR1 A) receptor gene. Psychiatr Genet 1993; 3:235-240
11. Erdmann J, Shimron-Abarbanell D, Rietschel M, Albus M, Maier W, Korner J, Bondy B, Chen K, Shih JC, Knapp M, Propping P, Nothen MM: Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: identification of two naturally occurring receptor variants and association analysis in schizophrenia. Hum Genet 1996; 97:614-619
12. Erdmann J, Nothen MM, Shimron-Abarbanell D, Rietschel M, Albus M, Borrmann M, Maier W, Franzek E, Korner J, Weigelt B, Fimmers R, Propping P: The human serotonin 7 (5-HT7) receptor gene: genomic organization and systematic mutation screening in schizophrenia and bipolar affective disorder. Molecular Psychiatry 1996; 1:392-397
13. Warren JT Jr, Peacock ML, Fink JK: A Rsal polymorphism in the human serotonin receptor gene (HTR1A); detection by DGGE and RFLP analysis. Hum Mol Genet 1992; 1:778
14. Erdmann J, Shimron-Abarbanell
S, Albus M, Maier W, Lichtermann D, Minges J, Reuner U, Franzek E, Ertl
MA, Hebebrand J, Remschmidt H, Lehmkuhl H, Lehmkuhl G, Poustka F,
M, Fimmers R, Korner J, Rietschel M, Propping P, Nothen M: Systematic
for mutations in the promoter and the coding region of the 5HT1 A gene.
Am J Med Genet Neuropsychiatr Genet 1995; 60:393-399