From genes to psychoses and back: the role of the 5HT2α-receptor and prepulse inhibition in schizophrenia
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Decomposition of schizophrenia into neurobiological vulnerability traits is necessary to understand the complex genetic underpinnings of this phenomenologically defined disorder. This issue is discussed with a focus on prepulse inhibition (PPI) as a neurobiological phenotype and the 5HT2a-receptor as a candidate gene. A series of recent studies illuminates that PPI and 5HT2a-receptors present as vulnerability markers for schizophrenia; a functional sequence variant in the 5HT2a-gene is contributing to this relationship and might consequently contribute to the genetic predisposition to schizophrenia with a very small risk increase.
Keywordsschizophrenia endophenotypes prepulse inhibition serotonin 2α-receptor (5HT2a) 5HT2a-gene
Conflict of interest statement
The authors have no conflict of interest to declare.
- 2.Cadenhead KS, Swerdlow NR, Shafer KM, Diaz M, Braff DL (2000) Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits. Am J Psychiatry 157:1660–1668PubMedCrossRefGoogle Scholar
- 7.Meyer-Lindenberg A, Weinberger DR (2006) Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nature 7:818–827Google Scholar
- 8.O’Donovan MC, Craddock N, Norton N, Williams H, Peirce T, Moskvina V, Nikolov I, Hamshere M, Carroll L, Georgieva L, Dwyer S, Holmans P, Marchini JL, Spencer CC, Howie B, Leung HT, Hartmann AM, Möller HJ, Morris DW, Shi Y, Feng G, Hoffmann P, Propping P, Vasilescu C, Maier W, Rietschel M, Zammit S, Schumacher J, Quinn EM, Schulze TG, Williams NM, Giegling I, Iwata N, Ikeda M, Darvasi A, Shifman S, He L, Duan J, Sanders AR, Levinson DF, Gejman PV; Molecular Genetics of Schizophrenia Collaboration, Gejman PV, Sanders AR, Duan J, Levinson DF, Buccola NG, Mowry BJ, Freedman R, Amin F, Black DW, Silverman JM, Byerley WF, Cloninger CR, Cichon S, Nöthen MM, Gill M, Corvin A, Rujescu D, Kirov G, Owen MJ. (2008) Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet 30 Jul 2008. [Epub ahead of print]Google Scholar
- 11.Quednow BB, Frommann I, Berning J, Kühn KU, Maier W, Wagner M (2008) Impaired sensorimotor gating of the acoustic startle response in the prodrome of schizophrenia. Biol Psychiatry 29 May 2008 [Epub ahead of print]Google Scholar
- 13.Quednow BB, Wagner M, Mössner R, Maier W, Kühn K-U (2008) Sensorimotor gating of schizophrenia patients depends on catechol O-methyl-transferase Val158Met polymorphism. Schizophr Bull 17 July 2008 [Epub ahead of print]Google Scholar
- 14.Sanders AR, Duan J, Levinson DF, Shi J, He D, Hou C, Burrel GJ, Rice JP, Nertney DA, Olincy A, Rozic P, Vinogradov S, Buccola NG (2008) No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: Implications for psychiatric genetics. Am J Psychiatry 165:497–506PubMedCrossRefGoogle Scholar