Abstract
The gene for COMT is located on chromosome 22q11, an area that has been implicated in the pathogenesis of schizophrenia through linkage studies and through the detection of deletions in schizophrenics and velocardiofacial syndrome patients that often present psychotic symptomatology. Additionally catechol-O-methyl transferase activity has been found increased in schizophrenia and a functional polymorphism in the COMT gene itself has been associated with the disease, as well as with aggression in patients. We tested the hypothesis that COMT genotype for the functional Val158Met might contribute to the variance of self reported schizotypy and aggression scores in the normal population. We genotyped 379 healthy 18- to 24-year-old male individuals who had completed the PAS, SPQ and AQ questionnaires. Our results showed that self-reported schizotypy scores in both questionnaires were significantly related to COMT genotype (P = 0.028 for the PAS and P = 0.015 for the SPQ) with individuals homozygous for the high activity allele showing the highest scores. No significant differences were detected for AQ scores. We conclude that the COMT genotype for the functional Val158Met polymorphism is correlated to self-reported schizotypy in healthy males. This finding is in the same direction as reported findings on schizophrenia and it adds to the list of evidence that COMT or a nearby gene in linkage disequilibrium is involved in the pathogenesis of the disease.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Pulver AE, Karayiorgou M, Wolyniec PS, Lasseter VK, Kasch L, Nestadt G et al. Sequential strategy to identify a susceptibility gene for schizophrenia: report of potential linkage on chromosome 22q12–q13.1: Part 1 Am J Med Genet 1994; 54: 36–43
Coon H, Jensen S, Holik J, Hoff M, Myles-Worsley M, Reimherr F et al. Genomic scan for genes predisposing to schizophrenia Am J Med Genet 1994; 54: 59–71
Lasseter VK, Pulver AE, Wolyniec PS, Nestadt G, Meyers D, Karayiorgou M et al. Follow-up report of potential linkage for schizophrenia on chromosome 22q: Part 3 Am J Med Genet 1995; 60: 172–173
Gill M, Vallada H, Collier D, Sham P, Holmans P, Murray R et al. A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Schizophrenia Collaborative Linkage Group (Chromosome 22) Am J Med Genet 1996; 67: 40–45
Wildenauer DB, Hallmayer J, Schwab SG, Albus M, Eckstein GN, Zill P et al. Searching for susceptibility genes in schizophrenia by genetic linkage analysis Cold Spring Harb Symp Quant Biol 1996; 61: 845–850
Shaw SH, Kelly M, Smith AB, Shields G, Hopkins PJ, Loftus J et al. A genome-wide search for schizophrenia susceptibility genes Am J Med Genet 1998; 81: 364–376
Pulver AE, Nestadt G, Goldberg R, Shprintzen RJ, Lamacz M, Wolyniec PS et al. Psychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives J Nerv Ment Dis 1994; 182: 476–478
Murphy KC, Jones LA, Owen MJ . High rates of schizophrenia in adults with velo-cardio-facial syndrome Arch Gen Psychiatry 1999; 56: 940–945
Karayiorgou M, Morris MA, Morrow B, Shprintzen RJ, Goldberg R, Borrow J et al. Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11 Proc Natl Acad Sci USA 1995; 92: 7612–7616
Axelrod J . Methylation reactions in the formation and metabolism of catecholamines and other biogenic amines Pharmacol Rev 1966; 18: 95–113
Matthysse S, Baldessarini RJ . S-adenosylmethionine and catechol-O-methyl-transferase in schizophrenia Am J Psychiatry 1972; 128: 1310–1312
Poitou P, Assicot M, Bohuon C . Soluble and membrane catechol-o-methyl transferases in red blood cells of schizophrenic patients Biomedicine 1974; 21: 91–93
White HL, McLeod MN, Davidson JR . Catechol O-methyltransferase in red blood cells of schizophrenic, depressed, and normal human subjects Br J Psychiatry 1976; 128: 184–187
Ebstein R, Belmaker RH, Benbenisty D, Rimon R . Electrophoretic pattern of red blood cell catechol-o-methyltransferase in schizophrenia and manic-depressive illness Biol Psychiatry 1976; 11: 613–623
Groshong R, Baldessarini RJ, Gibson DA, Lipinski JF, Axelrod D, Pope A . Activities of types A and B MAO and catechol-o-methyltransferase in blood cells and skin fibroblasts of normal and chronic schizophrenic subjects Arch Gen Psychiatry 1978; 35: 1198–1205
Baron M, Gruen R, Levitt M, Hunter C, Asnis L . Erythrocytecatechol O-methyltransferase activity in schizophrenia: analysis of family data Am J Psychiatry 1984; 141: 29–32
Weinshilboum RM, Raymond FA . Inheritance of low erythrocyte catechol-o-methyltransferase activity in man Am J Hum Genet 1977; 29: 125–135
Spielman RS, Weinshilboum RM . Genetics of red cell COMT activity: analysis of thermal stability and family data Am J Med Genet 1981; 10: 279–290
Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melen K, Julkunen I et al. Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme Biochemistry 1995; 34: 4202–4210
Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM . Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders Pharmacogenetics 1996; 6: 243–250
Li T, Sham PC, Vallada H, Xie T, Tang X, Murray RM et al. Preferential transmission of the high activity allele of COMT in schizophrenia Psychiatr Genet 1996; 6: 131–133
Kunugi H, Vallada HP, Sham PC, Hoda F, Arranz MJ, Li T et al. Catechol-O-methyltransferase polymorphisms and schizophrenia: a transmission disequilibrium study in multiply affected families Psychiatr Genet 1997; 7: 97–101
Li T, Ball D, Zhao J, Murray RM, Liu X, Sham PC et al. Family-based linkage disequilibrium mapping using SNP marker haplotypes: application to a potential locus for schizophrenia at chromosome 22q11 Mol Psychiatry 2000; 5: 77–84
Wei J, Hemmings GP . Lack of evidence for association between the COMT locus and schizophrenia Psychiatr Genet 1999; 9: 183–186
Karayiorgou M, Gogos JA, Galke BL, Wolyniec PS, Nestadt G, Antonarakis SE et al. Identification of sequence variants and analysis of the role of the catechol-O-methyl-transferase gene in schizophrenia susceptibility Biol Psychiatry 1998; 43: 425–431
Strous RD, Bark N, Woerner M, Lachman HM . Lack of association of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia Biol Psychiatry 1997; 41: 493–495
Risch N . Genetic linkage and complex diseases, with special reference to psychiatric disorders Genet Epidemiol 1990; 7: 3–16
Tyrka AR, Cannon TD, Haslam N, Mednick SA, Schulsinger F, Schulsinger H et al. The latent structure of schizotypy: I. Premorbid indicators of a taxon of individuals at risk for schizophrenia-spectrum disorders J Abnorm Psychol 1995; 104: 173–183
Webb CT, Levinson DF . Schizotypal and paranoid personality disorder in the relatives of patients with schizophrenia and affective disorders: a review Schizophr Res 1993; 11: 81–92
Maier W, Lichtermann D, Minges J, Heun R . Personality disorders among the relatives of schizophrenia patients Schizophr Bull 1994; 20: 481–493
Kremen WS, Faraone SV, Toomey R, Seidman LJ, Tsuang MT . Sex differences in self-reported schizotypal traits in relatives of schizophrenic probands Schizophr Res 1998; 34: 27–37
Yaralian PS, Raine A, Lencz T, Hooley JM, Bihrle SE, Mills S et al. Elevated levels of cognitive-perceptual deficits in individuals with a family history of schizophrenia spectrum disorders Schizophr Res 2000; 46: 57–63
Lyons MJ, Toomey R, Faraone SV, Kremen WS, Yeung AS, Tsuang MT . Correlates of psychosis proneness in relatives of schizophrenic patients J Abnorm Psychol 1995; 104: 390–394
Torgersen S, Lygren S, Oien PA, Skre I, Onstad S, Edvardsen J et al. A twin study of personality disorders Compr Psychiatry 2000; 41: 416–425
Fanous A, Gardner C, Walsh D, Kendler KS . Relationship between positive and negative symptoms of schizophrenia and schizotypal symptoms in nonpsychotic relatives Arch Gen Psychiatry 2001; 58: 669–673
Raine A . The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria Schizophr Bull 1991; 17: 555–564
Chapman LJ, Chapman JP, Raulin ML . Scales for physical and social anhedonia J Abnorm Psychol 1976; 85: 374–382
Coleman MJ, Levy DL, Lenzenweger MF, Holzman PS . Thought disorder, perceptual aberrations, and schizotypy J Abnorm Psychol 1996; 105: 469–473
Laurent A, Biloa-Tang M, Bougerol T, Duly D, Anchisi AM, Bosson JL et al. Executive/attentional performance and measures of schizotypy in patients with schizophrenia and in their nonpsychotic first-degree relatives Schizophr Res 2000; 46: 269–283
Strous RD, Bark N, Parsia SS, Volavka J, Lachman HM . Analysis of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia: evidence for association with aggressive and antisocial behavior Psychiatry Res 1997; 69: 71–77
Lachman HM, Nolan KA, Mohr P, Saito T, Volavka J . Association between catechol O-methyltransferase genotype and violence in schizophrenia and schizoaffective disorder Am J Psychiatry 1998; 155: 835–837
Buss AH, Perry M . The aggression questionnaire J Pers Soc Psychol 1992; 63: 452–459
Cloninger CR, Svrakic DM, Przybeck TR . A psychobiological model of temperament and character Arch Gen Psychiatry 1993; 50: 975–990
de Vries HG, Collee JM, van Veldhuizen MH, Achterhof L, Smit Sibinga CT, Scheffer H et al. Validation of the determination of deltaF508 mutations of the cystic fibrosis gene in over 11 000 mouthwashes Hum Genet 1996; 97: 334–336
Kirov G, Murphy KC, Arranz MJ, Jones I, McCandles F, Kunugi H et al. Low activity allele of catechol-O-methyltransferase gene associated with rapid cycling bipolar disorder Mol Psychiatry 1998; 3: 342–345
Adler LE, Freedman R, Ross RG, Olincy A, Waldo MC . Elementary phenotypes in the neurobiological and genetic study of schizophrenia Biol Psychiatry 1999; 46: 8–18
Arolt V, Lencer R, Nolte A, Muller-Myhsok B, Purmann S, Schurmann M et al. Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease Am J Med Genet 1996; 67: 564–579
Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A, Davis A et al. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus Proc Natl Acad Sci USA 1997; 94: 587–592
Myles-Worsley M, Coon H, McDowell J, Brenner C, Hoff M, Lind B et al. Linkage of a composite inhibitory phenotype to a chromosome 22q locus in eight Utah families Am J Med Genet 1999; 88: 544–550
Schwab SG, Albus M, Hallmayer J, Honig S, Borrmann M, Lichtermann D et al. Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib-pair linkage analysis Nat Genet 1995; 11: 325–327
Riley BP, Makoff A, Mogudi-Carter M, Jenkins T, Williamson R, Collier D et al. Haplotype transmission disequilibrium and evidence for linkage of the CHRNA7 gene region to schizophrenia in Southern African Bantu families Am J Med Genet 2000; 96: 196–201
Karoum F, Chrapusta SJ, Egan MF . 3-Methoxytyramine is the major metabolite of released dopamine in the rat frontal cortex: reassessment of the effects of antipsychotics on the dynamics of dopamine release and metabolism in the frontal cortex, nucleus accumbens, and striatum by a simple two pool model J Neurochem 1994; 63: 972–979
Gogos JA, Morgan M, Luine V, Santha M, Ogawa S, Pfaff D et al. Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior Proc Natl Acad Sci USA 1998; 95: 9991–9996
Kneavel M, Gogos JA, Karayiorgou M, Luine V . Interaction of COMT gene deletion and environment on cognition Soc Neurosci Abstracts 2000; 26: 571.20
Weinberger DR, Berman KF, Zec RF . Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence Arch Gen Psychiatry 1986; 43: 114–124
Carter CS, Perlstein W, Ganguli R, Brar J, Mintun M, Cohen JD . Functional hypofrontality and working memory dysfunction in schizophrenia Am J Psychiatry 1998; 155: 1285–1287
Callicott JH, Bertolino A, Mattay VS, Langheim FJ, Duyn J, Coppola R et al. Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited Cereb Cortex 2000; 10: 1078–1092
Park S, Holzman PS, Goldman-Rakic PS . Spatial working memory deficits in the relatives of schizophrenic patients Arch Gen Psychiatry 1995; 52: 821–828
Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia Proc Natl Acad Sci USA 2001; 98: 6917–6922
Acknowledgements
This work was supported by GSRT grant 97EKBAN107 to CNS.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Avramopoulos, D., Stefanis, N., Hantoumi, I. et al. Higher scores of self reported schizotypy in healthy young males carrying the COMT high activity allele. Mol Psychiatry 7, 706–711 (2002). https://doi.org/10.1038/sj.mp.4001070
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.mp.4001070
Keywords
This article is cited by
-
Developmental Aspects of Schizotypy and Suspiciousness: a Review
Current Behavioral Neuroscience Reports (2018)
-
Cognitive and oculomotor performance in subjects with low and high schizotypy: implications for translational drug development studies
Translational Psychiatry (2016)
-
Examining the Psychosis Continuum
Current Behavioral Neuroscience Reports (2015)
-
Schizotypal Personality Disorder: A Current Review
Current Psychiatry Reports (2014)
-
Effects of risperidone, amisulpride and nicotine on eye movement control and their modulation by schizotypy
Psychopharmacology (2013)