Abstract
Serotoninergic neurotransmitter systems have been implicated in the pathogenesis of major psychoses. A functional polymorphism (5-HTTLPR) in the upstream regulatory region of the gene (SLC6A4) has been associated with a number of psychiatric disturbances, but conflicting replication followed. The aim of this study was to investigate the possibility that the 5-HTTLPR might be associated with major psychoses. One thousand, eight hundred and twenty inpatients (789 bipolars, 667 major depressives, 66 delusionals, 261 schizophrenics, 37 psychotics not otherwise specified—NOS) and 457 control subjects were included in this study. A subsample of 1235 patients (523 bipolars, 359 major depressives, 259 schizophrenics, 66 delusionals, 28 psychotic NOS) were evaluated for lifetime psychotic symptomatology using the Operational Criteria for Psychotic illness (OPCRIT) checklist. The subjects were also typed for 5-HTTLPR variants using PCR techniques. 5-HTTLPR allele frequencies were not significantly different between controls and bipolars, major depressives, schizophrenics, delusionals and psychotic NOS; genotype analysis also did not show any association. The analysis of symptomatology did not show significant differences. Consideration of possible stratification factors such as sex and age of onset did not significantly influence results. 5-HTTLPR variants are not therefore a liability factor for major psychoses or for major psychoses symptomatology.
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References
Lesch K, Gross J, Franzek F, Wolozin B, Riederer P, Murphy D . Primary structure of the serotonin transporter in unipolar depression and bipolar disorder Biol Psychiatry 1995 37: 215–223
Ogilvie AD, Battersby S, Bubb VJ, Fink G, Harmar AJ, Goodwin GM et al. Polymorphism in serotonin transporter gene associated with susceptibility to major depression Lancet 1996 347: 731–733
Kunugi H, Hattori M, Kato T, Tatsumi M, Sakai T, Sasaki T et al. Serotonin transporter gene polymorphisms: ethnic difference and possible association with bipolar affective disorder Mol Psychiatry 1997 2: 457–462
Liu W, Gu N, Feng G, Zhang J, Li S, Bai S et al. Association of VNTR region of the human serotonin transporter gene with bipolar disorder among the Han Chinese Chung Hua I Hsueh I Chuan Hsueh Tsa Chih 1998 15: 345–348
Collier DA, Arranz MJ, Sham P, Battersby S, Vallada H, Gill P et al. The serotonin transporter is a potential susceptibility factor for bipolar affective disorder Neuroreport 1996 7: 1675–1679
Rees M, Norton N, Jones I, McCandless F, Scourfield J, Holmans P et al. Association studies of bipolar disorder at the human serotonin transporter gene (hSERT; 5HTT) Mol Psychiatry 1997 2: 398–402
Coyle N, Jones I, Robertson E, Lendon C, Craddock N . Variation at the serotonin transporter gene influences susceptibility to bipolar affective puerperal psychosis Lancet 2000 356: 1490–1491
Bellivier F, Laplanche JL, Leboyer M, Feingold J, Bottos C, Allilaire JF et al. Serotonin transporter gene and manic depressive illness: an association study Biol Psychiatry 1997 41: 750–752
Furlong RA, Ho L, Walsh C, Rubinsztein JS, Jain S, Paykel ES et al. Analysis and meta-analysis of two serotonin transporter gene polymorphisms in bipolar and unipolar affective disorders Am J Med Gen 1998 81: 58–63
Gutierrez B, Arranz MJ, Collier DA, Valles V, Guillamat R, Bertranpetit J et al. Serotonin transporter gene and risk for bipolar affective disorder—an association study in a Spanish population Biol Psychiatry 1998 43: 843–847
Oruc L, Verheyen GR, Furac I, Jakovljevic M, Ivezic S, Raeymaekers P et al. Association analysis of the 5-HT2C receptor and 5-HT transporter genes in bipolar disorder Am J Med Gen 1997 74: 504–506
Ospina-Duque J, Duque C, Carvajal-Carmona L, Ortiz-Barrientos D, Soto I, Pineda N et al. An association study of bipolar mood disorder (type I) with the 5-HTTLPR serotonin transporter polymorphism in a human population isolate from colombia Neurosci Lett 2000 292: 199–202
Heils A, Teufel A, Petri S, Stöber G, Riederer P, Bengel D et al. Allelic variation of human serotonin transporter gene expression J Neurochem 1996 66: 2621–2624
Lesch K, Bengel D, Heils A, Sabol S, Greenberg B, Petri S et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region Science 1996 274: 1527–1530
Serretti A, Cusin C, Lattuada E, Di Bella D, Catalano M, Smeraldi E . Serotonin transporter gene (5-HTTLPR) is not associated with depressive symptomatology in mood disorders Mol Psychiatry 1999 4: 280–283
Rosenthal N, Mazzanti C, Barnett R, Hardin T, Turner E, Lam G et al. Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonality and seasonal affective disorder Mol Psychiatry 1998 3: 175–177
Klauck SM, Poustka F, Benner A, Lesch KP, Poustka A . Serotonin transporter (5-HTT) gene variants associated with autism? Hum Mol Genet 1997 6: 2233–2238
Sander T, Harms H, Lesch KP, Dufeu P, Kuhn S, Hoehe M et al. Association analysis of a regulatory variation of the serotonin transporter gene with severe alcohol dependence Alcohol Clin Exp Res 1997 21: 1356–1359
Bellivier F, Szoke A, Henry C, Lacoste J, Bottos C, Nosten-Bertrand M et al. Possible association between serotonin transporter gene polymorphism and violent suicidal behavior in mood disorders Biol Psychiatry 2000 48: 319–322
Malhotra AK, Goldman D, Mazzanti C, Clifton A, Breier A, Pickar D . A functional serotonin transporter (5-HTT) polymorphism is associated with psychosis in neuroleptic-free schizophrenics Mol Psychiatry 1998 3: 328–332
Hranilovic D, Schwab SG, Jernej B, Knapp M, Lerer B, Albus M et al. Serotonin transporter gene and schizophrenia: evidence for association/linkage disequilibrium in families with affected siblings Mol Psychiatry 2000 5: 91–95
Tsuang M, Faraone S . The Genetics of Mood Disorders The Johns Hopkins University Press: Baltimore 1990
Jacobs BL, Fornal CA . Serotonin and behavior. A general hypothesis. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology: The Fourth Generation of Progress Raven Press: New York 1995 pp 461–469
Serretti A, Macciardi F, Smeraldi E . Identification of symptomatologic patterns common to major psychoses: proposal for a phenotype definition Am J Med Gen 1996 67: 393–400
Cardno AG, Jones LA, Murphy KC, Asherson P, Scott LC, Williams J et al. Factor analysis of schizophrenic symptoms using the OPCRIT checklist Schizophr Res 1996 22: 233–239
Cloninger C . Turning point in the design of linkage studies of schizophrenia Am J Med Gen 1994 54: 83–92
Serretti A, Lattuada E, Catalano M, Smeraldi E . Serotonin transporter gene not associated with psychotic symptomatology of mood disorders Psychiatry Res 1999 86: 59–65
Serretti A, Catalano M, Smeraldi E . Serotonin transporter gene is not associated with symptomatology of schizophrenia Schizophr Res 1999 35: 33–39
Risch N . Linkage strategies for genetically complex traits: I. Multilocus models Am J Med Gen 1990 46: 222–228
Carey G . Genetic association study in psychiatry: analytical evaluation and a recommendation Am J Med Gen 1994 54: 311–317
Collier D, Stöber G, Li T, Heils A, Catalano M, Di Bella D et al. A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders Mol Psychiatry 1996 1: 453–460
Kelsoe J, Remick R, Sadovnick A, Kristbjarnarson H, Flodman P, Spence M et al. Genetic linkage study of bipolar disorder and the serotonin transporter Am J Med Gen 1996 67: 215–217
Stober G, Jatzke S, Heils A, Jungkunz G, Fuchs E, Knapp M et al. Susceptibility for schizophrenia is not Influenced by a functional insertion/deletion variant in the promoter of the serotonin transporter gene Eur Arch Psychiatry Clin Neurosci 1998 248: 82–86
Benedetti F, Serretti A, Colombo C, Campori E, Barbini B, Di Bella D et al. Influence of a functional polymorphism within the promoter of the serotonin transporter gene on the effects of total sleep deprivation in bipolar depression Am J Psychiatry 1999 156: 1450–1452
Serretti A, Zanardi R, Rossini D, Cusin C, Lilli R, Smeraldi E . Influence of tryptophan hydroxylase and serotonin transporter genes on fluvoxamine antidepressant activity Mol Psychiatry 2001 6: 586–592
Smeraldi E, Zanardi R, Benedetti F, Dibella D, Perez J, Catalano M . Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine Mol Psychiatry 1998 3: 508–511
Zanardi R, Serretti A, Rossini D, Franchini L, Cusin C, Lattuada E et al. Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional depression Biol Psychiatry (in press)
Zanardi R, Benedetti F, DiBella D, Catalano M, Smeraldi E . Efficacy of paroxetine in depression is influenced by a functional polymorphism within the promoter of serotonin transporter gene J Clin Psychopharmacol 2000 20: 105–107
Ohara K, Nagai M, Suzuki Y, Ochiai M . Association between anxiety disorders and a functional polymorphism in the serotonin transporter gene Psychiatry Res 1998 81: 277–279
Coryell W, Akiskal HS, Leon AC, Winokur G, Maser JD, Mueller TI et al. The time course of nonchronic major depressive disorder. Uniformity across episodes and samples. National Institute of Mental Health Collaborative Program on the Psychobiology of Depression—Clinical Studies Arch Gen Psychiatry 1994 51: 405–410
Maziade M, Bouchard S, Gingras N, Charron L, Cardinal A, Roy MA et al. Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. II: Postnegative distinction and childhood predictors of adult outcome Br J Psychiatry 1996 169: 371–378
Maziade M, Roy MA, Martinez M, Cliche D, Fournier JP, Garneau Y et al. Negative, psychoticism, and disorganized dimensions in patients with familial schizophrenia or bipolar disorder: continuity and discontinuity between the major psychoses Am J Psychiatry 1995 152: 1458–1463
Van Os J, Marcelis M, Sham P, Jones P, Gilvarry K, Murray R . Psychopathological syndromes and familial morbid risk of psychosis Br J Psychiatry 1997 170: 241–246
Kendler KS, Karkowski-Shuman L, FA ON, Straub RE, MacLean CJ, Walsh D . Resemblance of psychotic symptoms and syndromes in affected sibling pairs from the Irish study of high-density schizophrenia families: evidence for possible etiologic heterogeneity Am J Psychiatry 1997 154: 191–198
Chua SE, Wright IC, Poline JB, Liddle PF, Murray RM, Frackowiak RS et al. Grey matter correlates of syndromes in schizophrenia. A semi-automated analysis of structural magnetic resonance images Br J Psychiatry 1997 170: 406–410
Leckman JF, Sholomskas D, Thompson WD, Belanger A, Weissman MM . Best estimate of lifetime psychiatric diagnosis: a methodological study Arch Gen Psychiatry 1982 39: 879–883
Flattem NL, Blakely RD . Modified structure of the human serotonin transporter promoter Mol Psychiatry 2000 5: 110–115
Lesch KP, Jatzke S, Meyer J, Stober G, Okladnova O, Mossner R et al. Mosaicism for a serotonin transporter gene promoter-associated deletion: decreased recombination in depression J Neural Transm 1999 106: 1223–1230
Gasparini P, Estivill X, Volpini V, Totaro A, Castellvi-Bel S, Govea N et al. Linkage of DFNB1 to non-syndromic neurosensory autosomal-recessive deafness in Mediterranean families Eur J Hum Genet 1997 5: 83–88
Souery D, Lipp O, Serretti A, Mahieu B, Rivelli SK, Cavallini C et al. European Collaborative Project on Affective Disorders: Interactions between genetic and psychosocial vulnerability factors Psychiatr Genet 1998 8: 197–205
McGuffin P, Farmer A, Harvey I . A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system Arch Gen Psychiatry 1991 48: 764–770
Lahiri DK, Nurnberger JIJ . A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies Nucleic Acid Res 1991 19: 5444
Cohen J . Statistical Power Analysis for the Behavioral Sciences Lawrence Erlbaum Associates: Hillsdale, NJ 1988
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This work was partially supported by the BIOMED 2 grant BMH4-CT97-2307.
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Serretti, A., Lilli, R., Lorenzi, C. et al. Serotonin transporter gene (5-HTTLPR) and major psychoses. Mol Psychiatry 7, 95–99 (2002). https://doi.org/10.1038/sj.mp.4000936
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DOI: https://doi.org/10.1038/sj.mp.4000936
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