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Association of unipolar depression with gene polymorphisms in the serotonergic pathways in Han Chinese

Published online by Cambridge University Press:  24 June 2014

Mei Shi
Affiliation:
Department of Psychiatric and Psychology
Jian Hu
Affiliation:
Department of Psychiatric and Psychology
Xuesong Dong
Affiliation:
The Hepatosplenic Surgery Center/Department of General Surgery, The First Clinical Medical School
Yue Gao
Affiliation:
The Hepatosplenic Surgery Center/Department of General Surgery, The First Clinical Medical School
Ganghui An
Affiliation:
Department of Psychiatric and Psychology
Wei Liu
Affiliation:
Department of Psychiatric and Psychology
Li Chen
Affiliation:
Department of Medical Psychology, The Institute of Public Health, Harbin Medical University, Harbin, China
Xueying Sun*
Affiliation:
The Hepatosplenic Surgery Center/Department of General Surgery, The First Clinical Medical School
*
Dr Xueying Sun, The Hepatosplenic Surgery Center/Department of General Surgery, The First Clinical Medical School, Harbin Medical University, Harbin 150001, China. Tel/Fax: +86 451 53643628; E-mail: kevsun88@hotmail.com

Abstract

Objective:

The present study aims to investigate the association of unipolar depression (UPD) with six serotonergic gene polymorphisms in Han Chinese.

Methods:

One hundred and thirty-two UPD patients and 180 healthy controls were genotyped for polymorphisms of six serotonergic genes, including tryptophan hydroxylase (TPH1 A218C), serotonin transporter promoter region (5-HTTLPR), serotonin receptor 2A (5-HT2AR −1438G/A), serotonin receptor 2C (5-HT2CR Cys23Ser), serotonin receptor 6 (5-HT6R C267T) and serotonin receptor 1Dβ (5-HT1DβR T371G). Symptomatic clusters were evaluated by the 24-item Hamilton Rating Scale for Depression (HAMD).

Results:

The frequencies of S/S genotype and S allele in 5-HTTLPR polymorphism were significantly higher in UPD patients than in healthy controls. There was a significant difference in distributions of genotypes in 5-HT2CR Cys23Ser polymorphism between UPD patients and control subjects, but the difference became no significant when the data were further stratified by gender. The patients with genotypes G/G and T/G of 5-HT1DβR T371G polymorphism had significantly lower scores of diurnal variation evaluated by HAMD than those with genotype T/T, while the patients with genotype T/G had significantly higher scores of hopelessness than those with genotypes G/G and T/T. There were no significant differences in genotypic and allelic distributions of TPH1 A218C, 5-HT2AR −1438G/A or 5-HT6R C267T polymorphisms between the case and control groups.

Conclusion:

The study demonstrates that 5-HTTLPR and 5-HT2CR Cys23Ser polymorphisms might contribute to susceptibility of UPD, and the genotype T/T in 5-HT1DβR T371G polymorphism might be a risk factor for diurnal variation, while T/G might be a protective factor against hopelessness in Han Chinese populations.

Type
Research Article
Copyright
Copyright © 2008 Blackwell Munksgaard

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References

Wittchen, HU, Essau, CA, VonZerssen, D, Krieg, JC, Zaudig, M. Lifetime and six-month prevalence of mental disorders in the Munich Follow-Up Study. Eur Arch Psychiatry Clin Neurosci 1992;241:247258. CrossRefGoogle ScholarPubMed
Nemeroff, CB, Owens, HJ. Treatment of mood disorders. Nat Neurosci 2002;5(Suppl.):10681070. CrossRefGoogle ScholarPubMed
Wong, ML, Licinio, J. Research and treatment approaches to depression. Nat Rev Neurosci 2001;2:343351. CrossRefGoogle ScholarPubMed
Souery, D, Van Gestel, S, Massat, Iet al. Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: a multicenter association study. Biol Psychiatry 2001;49:405409. CrossRefGoogle ScholarPubMed
Anguelova, M, Benkelfat, C, Turecki, G. A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders. Mol Psychiatry 2003;8:574591. CrossRefGoogle ScholarPubMed
Bonnier, B, Gorwood, P, Hamon, M, Sarfati, Y, Boni, C, Hardy-Bayle, MC. Association of 5-HT (2A) receptor gene polymorphism with major affective disorders: the case of a subgroup of bipolar disorder with low suicide risk. Biol Psychiatry 2002;51:762765. CrossRefGoogle ScholarPubMed
Correa, H, Campi-Azevedo, AC, De Marco, Let al. Familial suicide behavior: association with probands suicide attempt characteristics and 5-HTTLPR polymorphism. Acta Psychiatr Scand 2004;110:459464. CrossRefGoogle ScholarPubMed
Massat, I, Souery, D, Lipp, Oet al. A European multi-center association study of HTR2A receptor polymorphism in bipolar affective disorder. Am J Med Genet 2000;96:130140. 3.0.CO;2-S>CrossRefGoogle Scholar
Chee, IS, Lee, SW, Kim, JLet al. 5-HT2A receptor gene promoter polymorphism −1438A/G and bipolar disorder. Psychiatr Genet 2001;11:111114. CrossRefGoogle ScholarPubMed
Lerer, B, Macciardi, F, Segman, RHet al. Variability of 5-HT2C Cys23Ser polymorphism among European populations and vulnerability to affective disorder. Mol Psychiatry 2001;6:579585. CrossRefGoogle ScholarPubMed
Ohmori, O, Shinkai, T, Hori, H, Nakamura, J. Novel polymorphism in the 5′- upstream region of the human 5-HT6 receptor gene and schizophrenia. Neurosci Lett 2001;310:1720. CrossRefGoogle ScholarPubMed
Crabbe, JC, Phillips, TJ, Feller, DJet al. Elevated alcohol consumption in null mutant mice lacking 5-HT1B serotonin receptor. Nat Genet 1996;14:98101. CrossRefGoogle Scholar
Fava, GA, Kellner, R, Munari, F, Pavan, L. The Hamilton depression rating scale in normals and depressives. Acta Psychiatr Scand 1982;66:2632. CrossRefGoogle ScholarPubMed
Heils, A, Mossner, R, Lesch, KP. The human serotonin transporter gene polymorphism-basic research and clinical implications. J Neural Transm 1997;104:10051014. CrossRefGoogle ScholarPubMed
Spurlock, G, Heils, A, Holmans, Pet al. A family based association study of T102C polymorphism in 5HT2A and schizophrenia plus identification of new polymorphisms in the promoter. Mol Psychiatry 1998;3:4249. CrossRefGoogle ScholarPubMed
Johansson, C, Smedh, C, Partonen, Tet al. Seasonal affective disorder and serotonin-related polymorphisms. Neurobiol Dis 2001;8:351357. CrossRefGoogle ScholarPubMed
Shinkai, T, Ohmori, O, Kojima, H, Terao, T, Suzuki, T, Abe, K. Association study of the 5-HT6 receptor gene in schizophrenia. Am J Med Genet 1999;88:120122. 3.0.CO;2-Y>CrossRefGoogle Scholar
Mundo, E, Zai, G, Lee, L, Parikh, SV, Kennedy, JL. The 5HT1Dbeta receptor gene in bipolar disorder: a family-based association study. Neuropsychopharmacology 2001;25:608613. CrossRefGoogle ScholarPubMed
Rietschel, M, Schorr, A, Albus, Met al. Association study of the tryptophan hydroxylase gene and bipolar affective disorder using family-based internal controls. Am J Med Genet 2000;96:310311. 3.0.CO;2-H>CrossRefGoogle ScholarPubMed
Kunugi, H, Ishida, S, Kato, Tet al. No evidence for an association of polymorphisms of the tryptophan hydroxylase gene with affective disorders or attempted suicide among Japanese patients. Am J Psychiatry 1999;156:774776. CrossRefGoogle ScholarPubMed
Du, L, Bakish, D, Pavel, D. Tryptophan hydroxylase gene 218A/C polymorphism is associated with somatic anxiety in major depressive disorder. J Affect Disord 2001;65:3744. CrossRefGoogle ScholarPubMed
Tsai, SJ, Hong, CJ, Wang, YC. Tryptophan hydroxylase gene polymorphism (A218C) and suicidal behaviors. Neuroreport 1999;10:37733775. CrossRefGoogle ScholarPubMed
Tan, EC, Chan, AO, Tan, CH, Mahendran, R, Wang, A, Chua, HC. Case-control and linkage disequilibrium studies of the tryptophan hydroxylase gene polymorphisms and major depressive disorder. Psychiatr Genet 2003;13:151154. CrossRefGoogle ScholarPubMed
Zhang, X, Beaulieu, JM, Sotnikova, TD, Gainetdinov, RR, Caron, MG. Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science 2004;305:217. CrossRefGoogle ScholarPubMed
Patel, PD, Pontrello, C, Burke, S. Robust and tissue-specific expression of TPH2 versus TPH1 in rat raphe and pineal gland. Biol Psychiatry 2004;55:428433. CrossRefGoogle ScholarPubMed
Walther, DJ, Bader, M. A unique central tryptophan hydroxylase isoform. Biochem Pharmacol 2003;66:16731680. CrossRefGoogle ScholarPubMed
Lesch, KP, Bengel, D, Heils, Aet al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996;274:15271531. CrossRefGoogle ScholarPubMed
Collier, DA, Stober, G, Li, Tet al. A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol Psychiatry 1996;1:453460. Google ScholarPubMed
Kirov, G, Rees, M, Jones, I, MacCandless, F, Owen, MJ, Craddock, N. Bipolar disorder and the serotonin transporter gene: a family-based association study. Psychol Med 1999;29:12491254. CrossRefGoogle ScholarPubMed
Mundo, E, Walker, M, Cate, T, Macciardi, F, Kennedy, JL. The role of serotonin transporter protein gene in antidepressant-induced mania in bipolar disorder: preliminary findings. Arch Gen Psychiatry 2001;58:539544. CrossRefGoogle ScholarPubMed
Smeraldi, E, Benedetti, F, Zanardi, R. Serotonin transporter promoter genotype and illness recurrence in mood disorders. Eur Neuropsychopharmacol 2002;12:7375. CrossRefGoogle ScholarPubMed
Hoefgen, B, Schulze, TG, Ohlraun, Set al. The power of sample size and homogenous sampling: association between the 5-HTTLPR serotonin transporter polymorphism and major depressive disorder. Biol Psychiatry 2005;57:247251. CrossRefGoogle ScholarPubMed
Frisch, A, Postilnick, D, Rockah, Ret al. Association of unipolar major depressive disorder with genes of the serotonergic and dopaminergic pathways. Mol Psychiatry 1999;4:389392. CrossRefGoogle ScholarPubMed
Kunugi, H, Hattori, M, Kato, Tet al. Serotonin transporter gene polymorphisms: ethnic difference and possible association with bipolar affective disorder. Mol Psychiatry 1997;2:457462. CrossRefGoogle ScholarPubMed
Rees, M, Rees, M, Norton, Net al. Association studies of bipolar disorder at the human serotonin transporter gene (hSERT; 5HTT). Mol Psychiatry 1997;2:398402. CrossRefGoogle ScholarPubMed
Furlong, RA, Ho, L, Walsh, Cet al. Analysis and meta-analysis of two serotonin transporter gene polymorphisms in bipolar and unipolar affective disorders. Am J Med Genet 1998;81:5863. 3.0.CO;2-V>CrossRefGoogle ScholarPubMed
Hoehe, MR, Wendel, B, Grunewald, Iet al. Serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorders. Am J Med Genet 1998;81:13. 3.0.CO;2-2>CrossRefGoogle Scholar
Serretti, A, Lilli, R, Lorenzi, C, Lattuada, E, Smeraldi, E. Serotonin-2C and serotonin-1A receptor genes are not associated with psychotic symptomatology of mood disorders. Am J Med Genet 2000;96:161166. 3.0.CO;2-9>CrossRefGoogle Scholar
Choi, MJ, Lee, HJ, Lee, HJet al. Association between major depressive disorder and the −1438A/G polymorphism of the serotonin 2A receptor gene. Neuropsychobiology 2004;49:3841. CrossRefGoogle ScholarPubMed
Ono, H, Ono, H, Shirakawa, Oet al. Serotonin 2A receptor gene polymorphism is not associated with completed suicide. J Psychiatr Res 2001;35:173176. CrossRefGoogle Scholar
Cao, L, Li, T, Xu, K, Liu, X. Association analysis of attempted suicide and 5-HT2A receptor gene. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2001;18:195197 (in Chinese).Google ScholarPubMed
Gutierrez, B, Fananas, L, Arranz, MJet al. Allelic association analysis of the 5-HT2C receptor gene in bipolar affective disorder. Neurosci Lett 1996;212:6567. CrossRefGoogle ScholarPubMed
Oruc, L, Verheyen, GR, Furac, Iet al. Association analysis of the 5-HT2C receptor and 5-HT transporter genes in bipolar disorder. Am J Med Genet 1997;74:504506. 3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Serretti, A, Lilli, R, Lorenzi, C, Lattuada, E, Cusin, C, Smeraldi, E. Serotonin transporter gene (5-HTTLPR) and major psychoses. Mol Psychiatry 2002;7:9599. CrossRefGoogle ScholarPubMed
Hong, CJ, Tsai, SJ, Cheng, CY, Liao, WY, Song, HL, Lai, HC. Association analysis of the 5-HT6 receptor polymorphism (C267T) in mood disorders. Am J Med Genet 1999;88:601602. 3.0.CO;2-1>CrossRefGoogle ScholarPubMed
Wu, WH, Huo, SJ, Cheng, CY, Hong, CJ, Tsai, SJ. Association study of the 5-HT6 receptor polymorphism (C267T) and symptomatology and antidepressant response in major depressive disorders. Neuropsychobiology 2001;44:172175. CrossRefGoogle ScholarPubMed
Vogt, IR, Shimron-Abarbanell, D, Neidt, Het al. Investigation of the human serotonin 6 [5-HT6] receptor gene to bipolar affective disorder and schizophrenia. Am J Med Genet 2000;96:217221. 3.0.CO;2-0>CrossRefGoogle ScholarPubMed
Chang, H-A, Lu, RB, Lin, WWet al. Lack of association between dopamine D3 receptor Ser9Gly polymorphism and schizophrenia in Han Chinese population. Acta Neuropsychiatrica 2007;19:344350. CrossRefGoogle ScholarPubMed