Variations in tryptophan hydroxylase 2 linked to decreased serotonergic activity are associated with elevated risk for metabolic syndrome in depression

Molecular Psychiatry

Volumn 15, Issue 7, 2010, Pages 736-747

  Kloiber, S ^a   Kohli, M A ^a   Brueckl, T ^a   Ripke, S ^a   Ising, M ^a   Uhr, M ^a   Menke, A ^a   Unschuld, P G ^a   Horstmann, S ^a   Salyakina, D ^a   Muller Myhsok, B ^a   Binder, E B ^a   Holsboer, F ^a   Lucae, S ^a  

^a MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

Author keywords

depression; genetics; metabolic syndrome; serotoninxs; TPH2

Indexed keywords

5 HYDROXYINDOLEACETIC ACID; MESSENGER RNA; SEROTONIN; TRYPTOPHAN HYDROXYLASE 2; TPH2 PROTEIN, HUMAN; TRYPTOPHAN HYDROXYLASE;

ADULT; ARTICLE; BRAIN REGION; CEREBROSPINAL FLUID LEVEL; CONTROLLED STUDY; EXON; FEMALE; GENE; GENE EXPRESSION; GENE LOCATION; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOTYPE; HAPLOTYPE; HIGH RISK PATIENT; HUMAN; INTRON; MAJOR CLINICAL STUDY; MAJOR DEPRESSION; MALE; METABOLIC SYNDROME X; NEUROTRANSMISSION; PRIORITY JOURNAL; RISK ASSESSMENT; SEROTONINERGIC SYSTEM; SINGLE NUCLEOTIDE POLYMORPHISM; TPH2 GENE; BIOSYNTHESIS; CASE CONTROL STUDY; COMPLICATION; DEPRESSION; ENZYMOLOGY; GENETIC PREDISPOSITION; GENETICS; MIDDLE AGED;

CASE-CONTROL STUDIES; DEPRESSIVE DISORDER; FEMALE; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; MALE; METABOLIC SYNDROME X; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; SEROTONIN; TRYPTOPHAN HYDROXYLASE;

EID: 77953914140     PISSN: 13594184     EISSN: 14765578     Source Type: Journal    
DOI: 10.1038/mp.2008.142     Document Type: Article

References (71)

1. Park Y-W, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med 2003; 163: 427-436. (Pubitemid 36241019)
2. Steinbaum SR. The metabolic syndrome: an emerging health epidemic in women. Prog Cardiovasc Dis 2004; 46: 321.
3. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US Adults: Findings From the Third National Health and Nutrition Examination Survey. JAMA 2002; 287: 356-359.
4. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994; 51: 8-19.
5. Stover E, Fenton W, Rosenfeld A, Insel TR. Depression and comorbid medical illness: the National Institute of Mental Health perspective. Biol Psychiatry 2003; 54: 184.
6. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005; 365: 1415.
7. Sacks FM. Metabolic syndrome: epidemiology and consequences. J Clin Psychiatry 2004; 65: 3-12.
8. Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 1998; 55: 580-592.
9. Scherrer JF, Xian H, Bucholz KK, Eisen SA, Lyons MJ, Goldberg J et al. A twin study of depression symptoms, hypertension, and heart disease in middle-aged men. Psychosom Med 2003; 65: 548-557.
10. Kinder LS, Carnethon MR, Palaniappan LP, King AC, Fortmann SP. Depression and the metabolic syndrome in young adults: findings from the Third National Health and Nutrition Examination Survey. Psychosom Med 2004; 66: 316-322.
11. Raikkonen K, Matthews KA, Kuller LH. The relationship between psychological risk attributes and the metabolic syndrome in healthy women: antecedent or consequence? Metabolism 2002; 51: 1573-1577.
12. Skilton MR, Moulin P, Terra J-L, Bonnet F. Associations between anxiety, depression, and the metabolic syndrome. Biol Psychiatry 62: 1251-1257.
13. Timonen M, Laakso M, Jokelainen J, Rajala U, Meyer-Rochow VB, Keinanen-Kiukaanniemi S. Insulin resistance and depression: cross sectional study. BMJ 2005; 330: 17-18. (Pubitemid 40070469)
14. Hasler G, Lissek S, Ajdacic V, Milos G, Gamma A, Eich D et al. Major depression predicts an increase in long-term body weight variability in young adults. Obes Res 2005; 13: 1991-1998.
15. Toker S, Shirom A, Melamed S. Depression and the metabolic syndrome: gender-dependent associations. Depress Anxiety 2008; 25: 661-669.
16. Hu FB, Stampfer M, Manson JE. Physical activity and cardiovascular risk in diabetic women\response. Ann Intern Med 2001; 135: 931.
17. Chen W, Srinivasan SR, Elkasabany A, Berenson GS. The association of cardiovascular risk factor clustering related to insulin resistance syndrome (Syndrome X) between young parents and their offspring: the Bogalusa Heart Study. Atherosclerosis 1999; 145: 197-205. (Pubitemid 29292716)
18. Carmelli D, Cardon LR, Fabsitz R. Clustering of hypertension, diabetes, and obesity in adult male twins\same genes or same environments. Am J Hum Genet 1994; 55: 566-573.
19. Phillips C, Lopez-Miranda J, Perez-Jimenez F, McManus R, Roche HM. Genetic and nutrient determinants of the metabolic syndrome. Curr Opin Cardiol 2006; 21: 185-193.
20. Pollex RL, Hegele RA. Genetic determinants of the metabolic syndrome. Nat Clin Prac Cardiovasc Med 2006; 3: 482-489.
21. McGuffin P, Katz R, Watkins S, Rutherford J. A hospital-based twin register of the heritability of DSM-IV unipolar depression. Arch Gen Psychiatry 1996; 53: 129-136.
22. Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry 2000; 157: 1552-1562.
23. Hamet P, Tremblay J. Genetics and genomics of depression. Metabolism 2005; 54(5 Suppl 1): 10.
24. Levinson DF. The genetics of depression: a review. Biol Psychiatry 2006; 60: 84-92.
25. Wurtman RJ, Wurtman JJ. Serotoninergic mechanisms and obesity. J Nutr Biochem 1998; 9: 511-515.
26. Muldoon MF, Mackey RH, Korytkowski MT, Flory JD, Pollock BG, Manuck SB. The metabolic syndrome is associated with reduced central serotonergic responsivity in healthy community volunteers. J Clin Endocrinol Metab 2006; 91: 718-721.
27. Rosmond R. Obesity and depression: same disease, different names? Med Hypotheses 2004; 62: 976-979.
28. Muldoon MF, Mackey RH, Williams KV, Korytkowski MT, Flory JD, Manuck SB. Low central nervous system serotonergic responsivity is associated with the metabolic syndrome and physical inactivity. J Clin Endocrinol Metab 2004; 89: 266-271.
29. Meltzer H. Serotonergic dysfunction in depression. Br J Psychiatry 1989; 155: 25-31.
30. Placidi GPA, Oquendo MA, Malone KM, Huang YY, Ellis SP, Mann JJ. Aggressivity, suicide attempts, and depression: relationship to cerebrospinal fluid monoamine metabolite levels. Biol Psychiatry 2001; 50: 783-791.
31. Williams Jr JW, Mulrow CD, Chiquette E, Noel PH, Aguilar C, Cornell J. A systematic review of newer pharmacothera-pies for depression in adults: evidence report summary: clinical guideline, part 2. Ann Intern Med 2000; 132: 743-756.
32. Aronne LJ. Therapeutic options for modifying cardiometabolic risk factors. Am J Med 2007; 120(3 Suppl 1): S26.
33. Padwal RS, Majumdar SR. Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet 2007; 369: 71-77.
34. Von Ruden AE, Adson DE, Kotlyar M. Effect of selective serotonin reuptake inhibitors on cardiovascular morbidity and mortality. J Cardiovasc Pharmacol Ther 2008; 13: 32-40.
35. Zhang X, Beaulieu J-M, Sotnikova TD, Gainetdinov RR, Caron MG. Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science 2004; 305: 217.
36. Zill P, Buttner A, Eisenmenger W, Moller H-J, Ackenheil M, Bondy B. Analysis of tryptophan hydroxylase I and II mRNA expression in the human brain: a post-mortem study. J Psychiatr Res 2007; 41(1-2): 168.
37. Paresh DP, Crystal P, Sharon B. Robust and tissue-specific expression of TPH2 versus TPH1 in rat raphe and pineal gland. Biol Psychiatry 2004; 55: 428.
38. Lin Y-MJ, Chao S-C, Chen T-M, Lai T-J, Chen J-S, Sun HS. Association of functional polymorphisms of the human trypto-phan hydroxylase 2 gene with risk for bipolar disorder in Han Chinese. Arch Gen Psychiatry 2007; 64: 1015-1024.
39. Lopez VA, Detera-Wadleigh S, Cardona I, Kassem L, McMahon FJ. Nested association between genetic variation in tryptophan hydroxylase II, bipolar affective disorder, and suicide attempts. Biol Psychiatry 2007; 61: 181-186.
40. Van Den Bogaert A, Sleegers K, De Zutter S, Heyrman L, Norrback KF, Adolfsson R et al. Association of brain-specific tryptophan hydroxylase, TPH2, with unipolar and bipolar disorder in a Northern Swedish, isolated population. Arch Gen Psychiatry 2006; 63: 1103-1110. (Pubitemid 44498389)
41. Zhang X, Gainetdinov RR, Beaulieu JM, Sotnikova TD, Burch LH, Williams RB et al. Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Neuron 2005; 45: 11.
42. Zhou Z, Roy A, Lipsky R, Kuchipudi K, Zhu G, Taubman J et al. Haplotype-based linkage of tryptophan hydroxylase 2 to suicide attempt, major depression, and cerebrospinal fluid 5-hydroxyin-doleacetic acid in 4 populations. Arch Gen Psychiatry 2005; 62: 1109-1118.
43. Zill P, Buttner A, Eisenmenger W, Moller H-J, Bondy B, Ackenheil M. Single nucleotide polymorphism and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene in suicide victims. Biol Psychiatry 2004; 56: 581.
44. Cichon S, Winge I, Mattheisen M, Georgi A, Karpushova A, Freudenberg J et al. Brain-specific tryptophan hydroxylase 2 (TPH2): a functional Pro206Ser substitution and variation in the 5-region are associated with bipolar affective disorder. Hum Mol Genet 2008; 17: 87-97.
45. Harvey M, Gagne B, Labbe M, Barden N. Polymorphisms in the neuronal isoform of tryptophan hydroxylase 2 are associated with bipolar disorder in French Canadian pedigrees. Psychiatr Genet 2007; 17: 17-22.
46. Kloiber S, Ising M, Reppermund S, Horstmann S, Dose T, Majer M et al. Overweight and obesity affect treatment response in major depression. Biol Psychiatry 2007; 62: 321.
47. Lucae S, Salyakina D, Barden N, Harvey M, Gagné B, Labbé M et al. P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder. Hum Mol Genet 2006; 15: 2438-2445.
48. Celik C. Computer Assisted Personal Interviewing Application for the Schedules for the Clinical Assessment in Neuropsychiatry Version 2.1 and Diagnostic Algorithms for WHO ICD10 chapter V DCR and for Statistical Manual IV./Release 1 Ed. 1.0.3.5 Win9xNT. World Health Organization: Geneva, 2003.
49. Wittchen HU, Höfler M, Gander F. Screening for mental disorders: performance of the Composite International Diagnostic\Screener (CID-S). Methods Psychiatr Res 1999; 8: 59-79.
50. Alberti KGMM, Zimmet P, Shaw J. The metabolic syndrome\a new worldwide definition. Lancet 2005; 366: 1059.
51. Pruitt KD, Tatusova T, Maglott DR. NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res 2005; 33: D501-D504.
52. Tang K, Fu D-J, Julien D, Braun A, Cantor CR, Koster H. Chip-based genotyping by mass spectrometry. Proc Natl Acad Sci USA 1999; 96: 10016-10020.
53. Hill WG, Robertson A. Linkage disequilibrium in finite populations. Theor Appl Genet 1968; 38: 226.
54. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263-265.
55. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B et al. The structure of haplotype blocks in the human genome. Science 2002; 296: 2225-2229.
56. Purcell S, Cherny SS, Sham PC. Genetic power calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 2003; 19: 149-150.
57. Wigginton JE, Cutler DJ, Abecasis GR. A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 2005; 76: 887-893.
58. Chiano MN, Clayton DG. Genotypic relative risks under ordered restriction. Genet Epidemiol 1998; 15: 135-146.
59. Westfall PH, Stanley Y. Resampling-based Multiple Testing. Wiley: New York, 1993.
60. Chen GL, Novak MA, Hakim S, Xie Z, Miller GM. Tryptophan hydroxylase-2 gene polymorphisms in rhesus monkeys: association with hypothalamic-pituitary- adrenal axis function and in vitro gene expression. Mol Psychiatry 2006; 11: 914.
61. Lim JE, Pinsonneault J, Sadee W, Saffen D. Tryptophan hydro-xylase 2 (TPH2) haplotypes predict levels of TPH2 mRNA expression in human pons. Mol Psychiatry 2006; 12: 491.
62. Lucki I. The spectrum of behaviors influenced by serotonin. Biol Psychiatry 1998; 44: 151-162.
63. Mann JJ, Arango V, Underwood MD. Serotonin and suicidal-behavior. Ann NY Acad Sci 1990; 600: 476-485.
64. Hainer V, Kabrnova K, Aldhoon B, Kunesova M, Wagenknecht M. Serotonin and norepinephrine reuptake inhibition and eating behavior. Ann NY Acad Sci 2006; 1083: 252-269.
65. Peñalva RG, Flachskamm C, Zimmermann S, Wurst W, Holsboer F, Reul JM et al. Corticotropin-releasing hormone receptor type 1-deficiency enhances hippocampal serotonergic neurotransmis-sion: an in vivo microdialysis study in mutant mice. Neuroscience 2002; 109: 253.
66. Clark JA, Flick RB, Pai LY, Szalayova I, Key S, Conley RK et al. Glucocorticoid modulation of tryptophan hydroxylase-2 protein in raphe nuclei and 5-hydroxytryptophan concentrations in frontal cortex of C57//Bl6 mice. Mol Psychiatry 2008; 13: 498-506.
67. Malek ZS, Sage D, Pevet P, Raison S. Daily rhythm of tryptophan hydroxylase-2 mRNA within raphe neurons is induced by corticoid daily surge and modulated by enhanced locomotor activity. Endocrinology 2007; 148: 5165-5172: en: 2007-10526
68. Molnar D. The prevalence of the metabolic syndrome and type 2 diabetes mellitus in children and adolescents. Int J Obes Relat Metab Disord 2004; 28(S3): S70.
69. Herva A, Rasanen P, Miettunen J, Timonen M, Läksy K, Veijola J et al. Co-occurrence of metabolic syndrome with depression and anxiety in young adults: the Northern Finland 1966 Birth Cohort Study. Psychosom Med 2006; 68: 213-216. (Pubitemid 43740123)
70. Zimmermann U, Kraus T, Himmerich H, Schuld A, Pollmacher T. Epidemiology, implications and mechanisms underlying drug-induced weight gain in psychiatric patients. J Psychiatr Res 2003; 37: 193-220.
71. Holsboer F. How can we realize the promise of personalized antidepressant medicines? Nat Rev Neurosci 2008; 9: 638.