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Titolo:
Variability of 5-HT2C receptor cys23ser polymorphism among European populations and vulnerability to affective disorder
Autore:
Lerer, B; Macciardi, F; Segman, RH; Adolfsson, R; Blackwood, D; Blairy, S; Del Favero, J; Dikeos, DG; Kaneva, R; Lilli, R; Massat, I; Milanova, V; Muir, W; Noethen, M; Oruc, L; Petrova, T; Papadimitriou, GN; Rietschel, M; Serretti, A; Souery, D; Van Gestel, S; Van Broeckhoven, C; Mendlewicz, J;
Indirizzi:
Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Psychiat, Biol Psychiat Lab,Hadassah Med Org, IL-91120 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91120 -91120 Jerusalem, Israel CAMH, Clarke Div, Neurogenet Sect, Unit Biostat & Genet Epidemiol, Toronto, ON, Canada CAMH Toronto ON Canada it Biostat & Genet Epidemiol, Toronto, ON, Canada Umea Univ, Dept Psychiat, Umea, Sweden Umea Univ Umea SwedenUmea Univ, Dept Psychiat, Umea, Sweden Univ Edinburgh, Dept Psychiat, Edinburgh EH8 9YL, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland EH8 9YL Midlothian, Scotland Univ Edinburgh, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland burgh, Midlothian, Scotland Free Univ Brussels, Erasme Hosp, Univ Clin Brussels, Dept Psychiat, B-1050Brussels, Belgium Free Univ Brussels Brussels Belgium B-1050 hiat, B-1050Brussels, Belgium Univ Antwerp, Dept Biochem, Born Bunge Fdn,VIB,BBS, Flanders Interuniv Inst Biotechnol,Neurogenet Lab, B-2020 Antwerp, Belgium Univ Antwerp AntwerpBelgium B-2020 rogenet Lab, B-2020 Antwerp, Belgium Univ Athens, Sch Med, Dept Psychiat, GR-11527 Athens, Greece Univ Athens Athens Greece GR-11527 ept Psychiat, GR-11527 Athens, Greece Univ Athens, Mental Hlth Res Inst, Athens, Greece Univ Athens Athens Greece Athens, Mental Hlth Res Inst, Athens, Greece Med Univ Sofia, Matern Univ Hosp Obstet, Lab Mol Pathol, Sofia, Bulgaria Med Univ Sofia Sofia Bulgaria p Obstet, Lab Mol Pathol, Sofia, Bulgaria Univ Milan, Sch Med, Dept Neuropsychiat Sci, Inst Sci Osped San Raffaele, Milan, Italy Univ Milan Milan Italy t Sci, Inst Sci Osped San Raffaele, Milan, Italy Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany Univ Bonn Bonn GermanyD-5300 nn, Inst Human Genet, D-5300 Bonn, Germany Univ Zagreb, Univ Hosp Rebro, Dept Psychiat, Zagreb 41000, Croatia Univ Zagreb Zagreb Croatia 41000 o, Dept Psychiat, Zagreb 41000, Croatia
Titolo Testata:
MOLECULAR PSYCHIATRY
fascicolo: 5, volume: 6, anno: 2001,
pagine: 579 - 585
SICI:
1359-4184(200109)6:5<579:VO5RCP>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
BIPOLAR AFFECTIVE-DISORDER; ASSOCIATION ANALYSIS; M-CHLOROPHENYLPIPERAZINE; FENFLURAMINE CHALLENGE; GENETIC ASSOCIATION; LITHIUM; MICE;
Keywords:
bipolar disorder; major depression; unipolar disorder; affective disorder; 5-HT2C receptor gene; HT2CR; genetic polymorphism; genetic association; population genetics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Lerer, B Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Psychiat, Biol Psychiat Lab,Hadassah Med Org, IL-91120 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91120 rusalem, Israel
Citazione:
B. Lerer et al., "Variability of 5-HT2C receptor cys23ser polymorphism among European populations and vulnerability to affective disorder", MOL PSYCHI, 6(5), 2001, pp. 579-585

Abstract

Substantial evidence supports a role for dysfunction of brain serotonergic(5-HT) systems in the pathogenesis of major affective disorder, both unipolar (recurrent major depression) and bipolar.(1) Modification of serotonergic neurotransmission is pivotally implicated in the mechanism of action of antidepressant drugs(2) and also in the action of mood stabilizing agents, particularly lithium carbonate.(3) Accordingly, genes that code for the multiple subtypes of serotonin receptors that have been cloned and are expressed in brain,(4) are strong candidates for a role in the genetic etiology ofaffective illness. We examined a structural variant of the serotonin 2C (5-HT2C) receptor gene (HTR2C) that gives rise to a cysteine to serine substitution in the N terminal extracellular domain of the receptor protein (cys23ser),(5) in 513 patients with recurrent major depression (MDD-R), 649 patients with bipolar (BP) affective disorder and 901 normal controls. The subjects were drawn from nine European countries participating in the European Collaborative Project on Affective Disorders. There was significant variation in the frequency of the HT2CR ser23 allele among the 10 population groups included in the sample (from 24.6% in Greek control subjects to 9.2% in Scots, chi (2)=20.9, df 9, P=0.01). Logistic regression analysis demonstrated that over and above this interpopulation variability, there was a significant excess of HT2CR ser23 allele carriers in patients compared to normal controls that was demonstrable for both the MDD (chi (2) = 7.34, df 1, P = 0.006) and BP (chi (2) = 5.45, df 1, P = 0.02) patients. These findings support a possible role for genetically based structural variation in 5-HT2C receptors in the pathogenesis of major affective disorder.

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Documento generato il 21/01/20 alle ore 06:55:59