Catechol-o-Methyltransferase Genotype and Childhood Trauma May Interact to Impact Schizotypal Personality Traits
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We attempt to identify gene by childhood abuse interactions which predispose to the development of schizotypal traits in a familial bipolar disorder (BD) sample. Self-report measures of schizotypal personality traits (Schizotypal Personality Scale) and childhood maltreatment (Childhood Trauma Questionnaire) were administered to 222 participants from 44 families with BD. Variants of catechol-o-methyltransferase (COMT) and four other dopamine pathway-related genes: DRD4, DRD2,MAOA, and SLC6A3, were typed. BD type I (BD I) subjects scored significantly higher than their unaffected relatives on the Schizotypal Personality Scale. The val allele of the Val158 Met polymorphism of the COMT gene was associated with increased schizotypal personality trait scores in individuals exposed to higher levels of self-reported childhood trauma (p < 0.05). There was no direct effect of the val158met polymorphism on schizotypal personality traits. Further, no passive correlation between COMT genotype and childhood trauma was found. We raise the possibility that genetically-driven variation in COMT may interact with childhood trauma to contribute to the risk of developing schizotypal personality traits.
KeywordsBipolar disorder Comt Childhood abuse Gene–environment interaction Schizotypal personality Gene–environment correlation Psychosis
The authors would like to thank Elize Pietersen and Gameda Benefeld for conducting psychological interviews. The support of the University of Cape Town’s Brain-Behaviour Initiative and the Medical Research Council of South Africa is acknowledged.
Conflicts of interest
No conflicts of interest are declared.
- Beck AT, Steer RA (1993) Manual for the beck depression inventory. The Psychological Corporation, San AntonioGoogle Scholar
- Bernstein DP, Fink L (1998) Childhood Trauma Questionnaire. Psychological Corporation, San AntonioGoogle Scholar
- Caspi A, Moffitt TE, Cannon M, McClay J, Murray R, Harrington H, Taylor A, Arseneault L, Williams B, Braithwaite A, Poulton R, Craig IW (2005) Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry 57:1117–1127CrossRefPubMedGoogle Scholar
- Henquet C, Rosa A, Krabbendam L, Papiol S, Fananas L, Drukker M, Ramaekers JG, van Os J (2006) An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology 31:2748–2757CrossRefPubMedGoogle Scholar
- Hewitt JK, Claridge G (1989) The factor structure of schizotypy in a normal population. In: Personality and individual differences. pp 323–329Google Scholar
- Massat I, Souery D, Del-Favero J, Nothen M, Blackwood D, Muir W, Kaneva R, Serretti A, Lorenzi C, Rietschel M, Milanova V, Papadimitriou GN, Dikeos D, Van Broekhoven C, Mendlewicz J (2005) Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study. Mol Psychiatry 10:598–605CrossRefPubMedGoogle Scholar
- Ohnishi T, Hashimoto R, Mori T, Nemoto K, Moriguchi Y, Iida H, Noguchi H, Nakabayashi T, Hori H, Ohmori M, Tsukue R, Anami K, Hirabayashi N, Harada S, Arima K, Saitoh O, Kunugi H (2006) The association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and morphological abnormalities of the brain in chronic schizophrenia. Brain 129:399–410CrossRefPubMedGoogle Scholar
- Schurhoff F, Szoke A, Chevalier F, Roy I, Meary A, Bellivier F, Giros B, Leboyer M (2007) Schizotypal dimensions: an intermediate phenotype associated with the COMT high activity allele. Am J Med Genet B Neuropsychiatr Genet 144:64–68Google Scholar
- Shifman S, Bronstein M, Sternfeld M, Pisante-Shalom A, Lev-Lehman E, Weizman A, Reznik I, Spivak B, Grisaru N, Karp L, Schiffer R, Kotler M, Strous RD, Swartz-Vanetik M, Knobler HY, Shinar E, Beckmann JS, Yakir B, Risch N, Zak NB, Darvasi A (2002) A highly significant association between a COMT haplotype and schizophrenia. Am J Hum Genet 71:1296–1302CrossRefPubMedGoogle Scholar
- Shifman S, Bronstein M, Sternfeld M, Pisante A, Weizman A, Reznik I, Spivak B, Grisaru N, Karp L, Schiffer R, Kotler M, Strous RD, Swartz-Vanetik M, Knobler HY, Shinar E, Yakir B, Zak NB, Darvasi A (2004) COMT: a common susceptibility gene in bipolar disorder and schizophrenia. Am J Med Genet B Neuropsychiatr Genet 128:61–64CrossRefGoogle Scholar
- Thomas DC (2004) Statistical methods in genetic epidemiology. Oxford University Press, New YorkGoogle Scholar
- Tost H, Alam T, Meyer-Lindenberg A (2009) Dopamine and psychosis: theory, pathomechanisms and intermediate phenotypes. Neurosci Biobehav RevGoogle Scholar
- van Winkel R, Isusi P, Galdos P, Echevarria E, Bilbao JR, Martin-Pagola A, Castano L, Papiol S, Mengelers R, Krabbendam L, van Os J, Myin-Germeys I (2008) Evidence that the COMTVal158Met polymorphism moderates subclinical psychotic and affective symptoms in unaffected first-degree relatives of patients with schizophrenia. Eur Psychiatry 23:219–222CrossRefPubMedGoogle Scholar
- Wolfradt U, Straube ER (1998) Factor structure of schizotypal traits among adolescents. In: Personality and individual differences. pp 201–206Google Scholar