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TAAR6 variation effect on clinic presentation and outcome in a sample of schizophrenic in-patients: An open label study

Published online by Cambridge University Press:  16 April 2020

Chi-Un Pae ,
Antonio Drago ,
Jung-Jin Kim ,
Ashwin A. Patkar ,
Tae-Youn Jun ,
Chul Lee ,
Laura Mandelli ,
Diana De Ronchi ,
In-Ho Paik  and
Alessandro Serretti
Chi-Un Pae*
Affiliation:
Department of Psychiatry, Kangnam St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea Department of Psychiatry and Behavioural Sciences, Duke University, United States
Antonio Drago
Affiliation:
Institute of Psychiatry, University of Bologna, Italy
Jung-Jin Kim
Affiliation:
Department of Psychiatry, Kangnam St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea
Ashwin A. Patkar
Affiliation:
Department of Psychiatry and Behavioural Sciences, Duke University, United States
Tae-Youn Jun
Affiliation:
Department of Psychiatry, Kangnam St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea
Chul Lee
Affiliation:
Department of Psychiatry, Kangnam St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea
Laura Mandelli
Affiliation:
Institute of Psychiatry, University of Bologna, Italy
Diana De Ronchi
Affiliation:
Institute of Psychiatry, University of Bologna, Italy
In-Ho Paik
Affiliation:
Department of Psychiatry, Kangnam St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea
Alessandro Serretti*
Affiliation:
Institute of Psychiatry, University of Bologna, Italy
*
*Corresponding author. Department of Psychiatry, Kangnam St. Mary's Hospital, The Catholic University of Korea College of Medicine, 505 Banpo-Dong, Seocho-Gu, Seoul 137-701, Republic of Korea. Tel.: +82 2 590 1532; fax: +82 2 536 8744. E-mail address: pae@catholic.ac.kr (C.-U. Pae), alessandro.serretti@unibo.it (A. Serretti).
**Corresponding author. Institute of Psychiatry “Paolo Ottonello”, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy. Tel.: +39 051 6584233; fax: +39 051 521030.
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Abstract

We recently reported an association between TAAR6 (trace amine associated receptor 6 gene) variations and schizophrenia (SZ). We now report an association of a set of TAAR6 variations and clinical presentation and outcome in a sample of 240 SZ Korean patients. Patients were selected by a Structured Clinical Interview, DSM-IV Axis I disorders – Clinical Version (SCID-CV). Other psychiatric or neurologic disorders, as well as medical diseases, were exclusion criteria. To assess symptom severity, patients were administered the CGI scale and the PANSS at baseline and at the moment of discharge, 1 month later on average. TAAR6 variations rs6903874, rs7452939, rs8192625 and rs4305745 were investigated; rs6903874, rs7452939 and rs8192625 entered the statistical investigation after LD analysis. Rs8192625 G/G homozygosis was found to be significantly associated both with a worse clinical presentation at PANSS total and positive scores and with a shorter period of illness before hospitalization. No haplotype significant findings were found. The present study stands for a role of the TAAR6 in the clinical presentation of SZ. Moreover, our results show that this genetic effect may be counteracted by a correct treatment. Haplotype analysis was not informative in our sample, probably also because of the incomplete SNPs' coverage of the gene we performed. Further studies in this direction are warranted.

Keywords

Trace amine associated receptor 6SchizophreniaGeneAssociation
Type
Original article
Information
European Psychiatry , Volume 23 , Issue 6 , September 2008 , pp. 390 - 395
Copyright
Copyright © Elsevier Masson SAS 2008

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References

Abou Jamra, R.Sircar, I.Becker, T.Freudenberg-Hua, Y.Ohlraun, S.Freudenberg, J.et al.A family-based and case-control association study of trace amine receptor genes on chromosome 6q23 in bipolar affective disorder Mol Psychiatry. 7 2005 618–620CrossRefGoogle Scholar
Amann, D.Avidan, N.Kanyas, K.Kohn, Y.Hamdan, A.Ben-Asher, E.et al.The trace amine receptor 4 gene is not associated with schizophrenia in a sample linked to chromosome 6q23 Mol Psychiatry. 2 2006 119–121CrossRefGoogle Scholar
Bailer, U.Leisch, F.Meszaros, K.Lenzinger, E.Willinger, U.Strobl, R.et al.Genome scan for susceptibility loci for schizophrenia Neuropsychobiology. 4 2000 175–182CrossRefGoogle Scholar
Borowsky, B.Adham, N.Jones, K.A.Raddatz, R.Artymyshyn, R.Ogozalek, K.L.et al.Trace amines: identification of a family of mammalian G protein-coupled receptors Proc Natl Acad Sci U S A. 16 2001 8966–8971CrossRefGoogle Scholar
Bunzow, J.R.Sonders, M.S.Arttamangkul, S.Harrison, L.M.Zhang, G.Quigley, D.I.et al.Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor Mol Pharmacol. 6 2001 1181–1188CrossRefGoogle Scholar
Burchett, S.A.Hicks, T.P.The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain Prog Neurobiol. 5–6 2006 223–246CrossRefGoogle Scholar
Cao, Q.Martinez, M.Zhang, J.Sanders, A.R.Badner, J.A.Cravchik, A.et al.Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees Genomics. 1 1997 1–8CrossRefGoogle Scholar
Cavalli Sforza, L.The history and geography of human genes 1994 Princeton University Press PrincetonGoogle Scholar
Craddock, N.O'Donovan, M.C.Owen, M.J.Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology Schizophr Bull. 1 2006 9–16Google Scholar
Davis, B.Boulton, A.The trace amines and their acidic metabolites in depression – an overview Prog Neuropsychopharmacol Biol Psychiatry. 1 1994 17–45CrossRefGoogle Scholar
Duan, J.Martinez, M.Sanders, A.R.Hou, C.Saitou, N.Kitano, T.et al.Polymorphisms in the trace amine receptor 4 (TRAR4) gene on chromosome 6q23.2 are associated with susceptibility to schizophrenia Am J Hum Genet. 4 2004 624–638CrossRefGoogle Scholar
Faul, F.Erdfelder, E.Lang, A.G.Buchner, A.G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences Behav Res Methods. 2 2007 175–191CrossRefGoogle Scholar
Guy, W.Assessment manual for psychopharmacology – revised 1976 DHEW Publ Rockville p. 218–22Google Scholar
Hofer, A.M.Lefkimmiatis, K.Extracellular calcium and cAMP: second messengers as “third messengers”? Physiology (Bethesda). 2007 320–327CrossRefGoogle Scholar
Ikeda, M.Iwata, N.Suzuki, T.Kitajima, T.Yamanouchi, Y.Kinoshita, Y.et al.No association of haplotype-tagging SNPs in TRAR4 with schizophrenia in Japanese patients Schizophr Res. 2–3 2005 127–130CrossRefGoogle Scholar
Jacob, M.S.Presti, D.E.Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine Med Hypotheses. 5 2005 930–937CrossRefGoogle Scholar
Kamenetsky, M.Middelhaufe, S.Bank, E.M.Levin, L.R.Buck, J.Steegborn, C.Molecular details of cAMP generation in mammalian cells: a tale of two systems J Mol Biol. 4 2006 623–639CrossRefGoogle Scholar
Kaufmann, C.A.Suarez, B.Malaspina, D.Pepple, J.Svrakic, D.Markel, P.D.et al.NIMH Genetics Initiative Millennium Schizophrenia Consortium: linkage analysis of African-American pedigrees Am J Med Genet. 4 1998 282–2893.0.CO;2-W>CrossRefGoogle Scholar
Kay, S.R.Fiszbein, A.Opler, L.A.The positive and negative syndrome scale (PANSS) for schizophrenia Schizophr Bull. 2 1987 261–276CrossRefGoogle Scholar
Kay, S.R.Opler, L.A.The positive–negative dimension in schizophrenia: its validity and significance Psychiatr Dev. 2 1987 79–103Google Scholar
Lerer, B.Segman, R.H.Hamdan, A.Kanyas, K.Karni, O.Kohn, Y.et al.Genome scan of Arab Israeli families maps a schizophrenia susceptibility gene to chromosome 6q23 and supports a locus at chromosome 10q24 Mol Psychiatry. 5 2003 488–498CrossRefGoogle Scholar
Levinson, D.F.Holmans, P.Straub, R.E.Owen, M.J.Wildenauer, D.B.Gejman, P.V.et al.Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: schizophrenia linkage collaborative group III Am J Hum Genet. 3 2000 652–663CrossRefGoogle Scholar
Lewis, C.M.Levinson, D.F.Wise, L.H.DeLisi, L.E.Straub, R.E.Hovatta, I.et al.Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: schizophrenia Am J Hum Genet. 1 2003 34–48CrossRefGoogle Scholar
Lindemann, L.Ebeling, M.Kratochwil, N.A.Bunzow, J.R.Grandy, D.K.Hoener, M.C.Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors Genomics. 3 2005 372–385CrossRefGoogle Scholar
Lindholm, E.Ekholm, B.Shaw, S.Jalonen, P.Johansson, G.Pettersson, U.et al.A schizophrenia-susceptibility locus at 6q25, in one of the world's largest reported pedigrees Am J Hum Genet. 1 2001 96–105CrossRefGoogle Scholar
Maier, W.Hofgen, B.Zobel, A.Rietschel, M.Genetic models of schizophrenia and bipolar disorder: overlapping inheritance or discrete genotypes? Eur Arch Psychiatry Clin Neurosci. 3 2005 159–166CrossRefGoogle Scholar
Martinez, M.Goldin, L.R.Cao, Q.Zhang, J.Sanders, A.R.Nancarrow, D.J.et al.Follow-up study on a susceptibility locus for schizophrenia on chromosome 6q Am J Med Genet. 4 1999 337–3433.0.CO;2-A>CrossRefGoogle Scholar
Pae, C.U.Yu, H.S.Amann, D.Kim, J.J.Lee, C.U.Lee, S.J.et al.Association of the trace amine associated receptor 6 (TAAR6) gene with schizophrenia and bipolar disorder in a Korean case control sample J Psychiatr Res. 1 2008 35–40CrossRefGoogle Scholar
Potkin, S.G.Karoum, F.Chuang, L.W.Cannon-Spoor, H.E.Phillips, I.Wyatt, R.J.Phenylethylamine in paranoid chronic schizophrenia Science. 4417 1979 470–471CrossRefGoogle Scholar
Sandler, M.Ruthven, C.R.Goodwin, B.L.Coppen, A.Decreased cerebrospinal fluid concentration of free phenylacetic acid in depressive illness Clin Chim Acta. 1 1979 169–171CrossRefGoogle Scholar
Vladimirov, V.Thiselton, D.L.Kuo, P.H.McClay, J.Fanous, A.Wormley, B.et al.A region of 35 kb containing the trace amine associated receptor 6 (TAAR6) gene is associated with schizophrenia in the Irish study of high-density schizophrenia families Mol Psychiatry. 9 2007 842–853CrossRefGoogle Scholar
Walss-Bass, C.Escamilla, M.A.Raventos, H.Montero, A.P.Armas, R.Dassori, A.et al.Evidence of genetic overlap of schizophrenia and bipolar disorder: linkage disequilibrium analysis of chromosome 18 in the Costa Rican population Am J Med Genet B Neuropsychiatr Genet. 1 2005 54–60CrossRefGoogle Scholar
Wolinsky, T.D.Swanson, C.J.Smith, K.E.Zhong, H.Borowsky, B.Seeman, P.et al.The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia Genes Brain Behav. 7 2007 628–639CrossRefGoogle Scholar
Zucchi, R.Chiellini, G.Scanlan, T.S.Grandy, D.K.Trace amine-associated receptors and their ligands Br J Pharmacol. 8 2006 967–978Google Scholar
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