Neurobiology of Aging
Volume 29, Issue 3 , Pages 341-347 , March 2008

Role of 5HT2A and 5HT2C polymorphisms in behavioural and psychological symptoms of Alzheimer's disease

  • Antonia L. Pritchard

      Affiliations

    • Department of Human Genetics, G Floor CBCRC Building, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia
    • Corresponding Author InformationCorresponding author. Fax: +61 7 33620323.
    • ,
  • Judith Harris

      Affiliations

    • Molecular Psychiatry Group, Institute of Biomedical Research, University of Birmingham, Vincent Drive B15 2TT, UK
    • ,
  • Colin W. Pritchard

      Affiliations

    • R&D Support Unit, Treliske Hospital, Truro, Cornwall TR1 3HD, UK
    • ,
  • John Coates

      Affiliations

    • Molecular Psychiatry Group, Institute of Biomedical Research, University of Birmingham, Vincent Drive B15 2TT, UK
    • ,
  • Sayeed Haque

      Affiliations

    • Department of Psychiatry, Queen Elizabeth Psychiatric Hospital, University of Birmingham, Mindelson Way B15 2QZ, UK
    • ,
  • Roger Holder

      Affiliations

    • Department of Psychiatry, Queen Elizabeth Psychiatric Hospital, University of Birmingham, Mindelson Way B15 2QZ, UK
    • ,
  • Peter Bentham

      Affiliations

    • Department of Psychiatry, Queen Elizabeth Psychiatric Hospital, University of Birmingham, Mindelson Way B15 2QZ, UK
    • ,
  • Corinne L. Lendon

      Affiliations

    • Department of Human Genetics, G Floor CBCRC Building, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia
    • Molecular Psychiatry Group, Institute of Biomedical Research, University of Birmingham, Vincent Drive B15 2TT, UK

Received 17 March 2006 ,Revised 28 September 2006 ,Accepted 10 October 2006.

References 

  1. Abdolmaleky HM, Faraone SV, Glatt SJ, Tsuang MT. Meta-analysis of association between the T102C polymorphism of the 5HT2a receptor gene and schizophrenia. Schizophr. Res. 2004;67:53–62
  2. Assal F, Alarcon M, Soloman E, Masterman D, Geshwind D, Cummings J. Association of the serotonin transporter and receptor gene polymorphisms in neuropsychiatric symptoms in Alzheimer's disease. Arch. Neurol. 2004;61:1249–1253
  3. Barnes N, Sharp T. A review of central 5HT receptors and their functions. Neuropharmacology. 1999;38:1083–1152
  4. Caligiuri M, Peavy G, Salmon DP, Galasko D, Thal L. Neuromotor abnormalities and risk for psychosis in Alzheimer's disease. Neurology. 2003;61:954–958
  5. Courtney C, Farrell D, Gray R, Hills R, Lynch L, Sellwood E, et al. Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial. Lancet. 2004;363:2105–2115
  6. Cummings JL, Mega M, Gray K. The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44:2308–2314
  7. de Quervain DJ, Henke K, Aerni A, Coluccia D, Wollmer MA, Hock C, et al. A functional genetic variation of the 5-HT2a receptor affects human memory. Nat. Neurosci. 2003;6:1141–1142
  8. Enoch MA, Kaye WH, Rotondo A, Greenberg BD, Murphy DL, Goldman D. 5-HT2A promoter polymorphism -1438G/A, anorexia nervosa, and obsessive-compulsive disorder. Lancet. 1998;351:1785–1786
  9. Eustace A, Coen R, Walsh C, Cunningham C, Walsh J, Coakley D, et al. A longitudinal evaluation of behavioural and psychological symptomsof probable Alzheimer's disease. Int. J. Geriatric Psychiatry. 2002;17:968–973
  10. Finkel S. Behavioural and psychological symptoms of dementia. Clin. Geriatric Med. 2003;19:799–824
  11. Fiorella D, Rabin R, Winter J. Role of the 5HT2A and 5HT2C receptors in the stimulus effects of hallucinogenic drugs. II. Reassessment of LSD false positives. Psychopharmacology. 1995;121:357–363
  12. Heisler L, Cowley M, Tecott L, Fan W, Low M, Smart J, et al. Activation of central melanocortin pathways by fenfluramine. Science. 2002;297:609–611
  13. Holmes C, Arranz M, Collier D, Powell J, Lovestone S. Depression in Alzheimer's disease: the effect of serotonin receptor gene variation. Am. J. Med. Genet. (Neuropsychiatric Genet.). 2003;119B:40–43
  14. Holmes C, Arranz M, Powell J, Collier D, Lovestone S. 5HT2A and 5HT2C receptor polymorphisms and psychopathology in late onset Alzheimer's disease. Hum. Mol. Genet. 1998;7:1507–1509
  15. Hope T, Keene J, Fairburn C, Jacoby R, McShane R. Natural history of behavioural changes and psychiatric symptoms in Alzheimer's disease: a longitudinal study. Br. J. Psychiatry. 1999;174:39–44
  16. Lappalainen J, Zhang L, Dean M, Oz M, Ozaki N, Yu D-h, et al. Identification, expression and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2C receptor gene (HTR2C). Genomics. 1995;27:274–279
  17. Lyketsos CG, Tune L, Pearlson G, Steele C. Major depression in Alzheimer's disease. An interaction between gender and family history. Psychosomatics. 1996;37:380–384
  18. Nacmias B, Tedde A, Forleo P, Piacentini S, Guarnieri B, Bartoli A, et al. Association between 5HT2A receptor polymorphism and psychotic symptoms in Alzheimer's disease. Biol. Psychiatry. 2001;50:472–475
  19. Norton N, Owen M. HTR2A: association and expression studies in neuropsychiatric genetics. Ann. Med. 2005;37:121–129
  20. Ott B, Tate C, Gordon N, Heindel W. Gender differences in the behavioural manifestations of Alzheimer's disease. J. Am. Geriatric Soc. 1996;44:583–587
  21. Pearlson G, Ross C, Lohr W, Rovner B, Chase GA, Folstein M. Association between family history of affective disorder and the depressive syndrome of Alzheimer's disease. Am. J. Psychiatry. 1990;147:452–456
  22. Pritchard, A., Harris, J., Pritchard, C., Coates, J., Haque, S., Holder, R., Bentham, P., Lendon, C., 2006. The effect of APOE gene polymorphisms and haplotypes on behavioural and psychological symptoms in probable Alzheimer's disease, J Neurol Neurosurg Psychiatry, in press.
  23. Rocchi A, Micheli R, Ceravolvo M, Manca M, Tognoni G, Siciliano G, et al. Serotonergic polymorphisms (5-HTTLPR and 5-HT2A): association studies with psychosis in Alzheimer's disease. Genet. Test. 2003;7:309–314
  24. Schneider L, Dagerman K. Psychosis of Alzheimer's disease: clinical characteristics and history. J. Psychiatric Res. 2004;38:105–111
  25. Steele C, Rovner B, Chase GA, Folstein M. Psychiatric symptoms and nursing home placement of patients with Alzheimer's disease. Am. J. Psychiatry. 1990;147:1049–1051
  26. Strauss M, Ogrocki P. Confirmation of an association between family history of affective disorder and the depressive syndrome in Alzheimer's disease. Am. J. Psychiatry. 1996;153:1340–1342
  27. Sweet RA, Nimganokar V, Devlin B, Lopez O, DeKosky S. Increased familial risk of the psychotic phenotype of Alzheimer's disease. Neurology. 2002;58:907–911
  28. Tecott L, Sun L, Akana S, Strack A, Lowenstein D, Dallman M, et al. Eating disorder and epilepsy in mice lacking 5HT2C serotonin receptors. Nature. 1995;374:542–546
  29. Tunstall N, Owen M, Williams J, Rice F, Carty S, Lillystone S, et al. Familial influence on variation in age of onset and behavioural phenotype in Alzheimer's disease. Br. J. Psychiatry. 2000;176:156–159
  30. Wa Lam L, Tang N, Ma S, Zhang W, Fung H, Chiu K. 5-HT2A T102C receptor polymorphism and neuropsychiatric symptoms in Alzheimer's disease. Int. J. Geriatric Psychiatry. 2004;19:523–526
  31. Walitza S, Wewetzer C, Warnke A, Gerlach M, Geller F, Gerber G, et al. 5-HT2A promoter polymorphism -1438G/A in children and adolescents with obsessive-compulsive disorders. Mol. Psychiatry. 2002;7:1054–1057
  32. Xie E, Zhu L, Zhao L, Chang L. The human serotonin 5-HT2C receptor: complete cDNA, genomic structure and alternatively spliced variant. Genomics. 1996;35:551–561

PII: S0197-4580(06)00388-5

doi: 10.1016/j.neurobiolaging.2006.10.011

Neurobiology of Aging
Volume 29, Issue 3 , Pages 341-347 , March 2008

Article Tools