Skip to main content
SpringerLink
Log in

Catechol-o-Methyltransferase Genotype and Childhood Trauma May Interact to Impact Schizotypal Personality Traits

  • Brief Communication
  • Published:
Behavior Genetics Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  • Abecasis GR, Cardon LR, Cookson WO (2000a) A general test of association for quantitative traits in nuclear families. Am J Hum Genet 66:279–292

    Article  PubMed  Google Scholar 

  • Abecasis GR, Cookson WO, Cardon LR (2000b) Pedigree tests of transmission disequilibrium. Eur J Hum Genet 8:545–551

    Article  PubMed  Google Scholar 

  • Altman EG, Hedeker D, Peterson JL, Davis JM (1997) The Altman Self-Rating Mania Scale. Biol Psychiatry 42:948–955

    Article  PubMed  Google Scholar 

  • Avramopoulos D, Stefanis NC, Hantoumi I, Smyrnis N, Evdokimidis I, Stefanis CN (2002) Higher scores of self reported schizotypy in healthy young males carrying the COMT high activity allele. Mol Psychiatry 7:706–711

    Article  PubMed  Google Scholar 

  • Barnett JH, Heron J, Goldman D, Jones PB, Xu K (2009) Effects of catechol-O-methyltransferase on normal variation in the cognitive function of children. Am J Psychiatry 166:909–916

    Article  PubMed  Google Scholar 

  • Beck AT, Steer RA (1993) Manual for the beck depression inventory. The Psychological Corporation, San Antonio

    Google Scholar 

  • Berenbaum H, McGrew J (1993) Familial resemblance of schizotypic traits. Psychol Med 23:327–333

    Article  PubMed  Google Scholar 

  • Berenbaum H, Valera EM, Kerns JG (2003) Psychological trauma and schizotypal symptoms. Schizophr Bull 29:143–152

    PubMed  Google Scholar 

  • Bernstein DP, Fink L (1998) Childhood Trauma Questionnaire. Psychological Corporation, San Antonio

    Google Scholar 

  • Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T, Stokes J, Handelsman L, Medrano M, Desmond D, Zule W (2003) Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse Negl 27:169–190

    Article  PubMed  Google 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 57:1117–1127

    Article  PubMed  Google Scholar 

  • Claridge G, Broks P (1984) Schizotypy and hemisphere function-I. Personality Individ Differ 5:633–648

    Article  Google Scholar 

  • Coolidge FL, Thede LL, Jang KL (2001) Heritability of personality disorders in childhood: a preliminary investigation. J Personal Disord 15:33–40

    Article  Google Scholar 

  • Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldman D, Weinberger DR (2001) Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 98:6917–6922

    Article  PubMed  Google Scholar 

  • Farmer A, Elkin A, McGuffin P (2007) The genetics of bipolar affective disorder. Curr Opin Psychiatry 20:8–12

    Article  PubMed  Google Scholar 

  • Hammersley P, Dias A, Todd G, Bowen-Jones K, Reilly B, Bentall RP (2003) Childhood trauma and hallucinations in bipolar affective disorder: preliminary investigation. Br J Psychiatry 182:543–547

    Article  PubMed  Google 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 31:2748–2757

    Article  PubMed  Google Scholar 

  • Heron J, Jones I, Williams J, Owen MJ, Craddock N, Jones LA (2003) Self-reported schizotypy and bipolar disorder: demonstration of a lack of specificity of the Kings Schizotypy Questionnaire. Schizophr Res 65:153–158

    Article  PubMed  Google Scholar 

  • Hewitt JK, Claridge G (1989) The factor structure of schizotypy in a normal population. In: Personality and individual differences. pp 323–329

  • Jackson M, Claridge G (1991) Reliability and validity of a psychotic traits questionnaire (STQ). Br J Clin Psychol 30(Pt 4):311–323

    PubMed  Google Scholar 

  • Kendler KS (1985) Diagnostic approaches to schizotypal personality disorder: a historical perspective. Schizophr Bull 11:538–553

    PubMed  Google Scholar 

  • Lin CC, Su CH, Kuo PH, Hsiao CK, Soong WT, Chen WJ (2007) Genetic and environmental influences on schizotypy among adolescents in Taiwan: a multivariate twin/sibling analysis. Behav Genet 37:334–344

    Article  PubMed  Google Scholar 

  • Linney YM, Murray RM, Peters ER, MacDonald AM, Rijsdijk F, Sham PC (2003) A quantitative genetic analysis of schizotypal personality traits. Psychol Med 33:803–816

    Article  PubMed  Google Scholar 

  • Lopez Leon S, Croes EA, Sayed-Tabatabaei FA, Claes S, Van Broeckhoven C, van Duijn CM (2005) The dopamine D4 receptor gene 48-base-pair-repeat polymorphism and mood disorders: a meta-analysis. Biol Psychiatry 57:999–1003

    Article  PubMed  Google 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 10:598–605

    Article  PubMed  Google Scholar 

  • Nackley AG, Shabalina SA, Tchivileva IE, Satterfield K, Korchynskyi O, Makarov SS, Maixner W, Diatchenko L (2006) Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science 314:1930–1933

    Article  PubMed  Google 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 129:399–410

    Article  PubMed  Google Scholar 

  • Pani L, Porcella A, Gessa GL (2000) The role of stress in the pathophysiology of the dopaminergic system. Mol Psychiatry 5:14–21

    Article  PubMed  Google Scholar 

  • Preisig M, Ferrero F, Malafosse A (2005) Monoamine oxidase a and tryptophan hydroxylase gene polymorphisms: are they associated with bipolar disorder? Am J Pharmacogenomics 5:45–52

    Article  PubMed  Google Scholar 

  • Prescott A, Bank L, Reid JB, Knutson JF, Burraston BO, Eddy JM (2000) The veridicality of punitive childhood experiences reported by adolescents and young adults. Child Abuse Negl 24:411–423

    Article  PubMed  Google Scholar 

  • Rawlings D, Claridge G, Freeman JL (2001) Principal components analysis of the Schizotypal Personality Scale (STA) and the Borderline Personality Scale (STB). Personality Individ Differ 31:409–419

    Article  Google Scholar 

  • Read J, van Os J, Morrison AP, Ross CA (2005) Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications. Acta Psychiatr Scand 112:330–350

    Article  PubMed  Google Scholar 

  • Rossi A, Daneluzzo E (2002) Schizotypal dimensions in normals and schizophrenic patients: a comparison with other clinical samples. Schizophr Res 54:67–75

    Article  PubMed  Google Scholar 

  • Savitz JB, Ramesar RS (2004) Genetic variants implicated in personality: a review of the more promising candidates. Am J Med Genet B Neuropsychiatr Genet 131:20–32

    Article  Google Scholar 

  • Schurhoff F, Laguerre A, Szoke A, Meary A, Leboyer M (2005) Schizotypal dimensions: continuity between schizophrenia and bipolar disorders. Schizophr Res 80:235–242

    Article  PubMed  Google 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 144:64–68

    Google Scholar 

  • Serretti A, Mandelli L (2008) The genetics of bipolar disorder: genome ‘hot regions’, genes, new potential candidates and future directions. Mol Psychiatry 13:742–771

    Article  PubMed  Google 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 71:1296–1302

    Article  PubMed  Google 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 128:61–64

    Article  Google Scholar 

  • Simons CJ, Wichers M, Derom C, Thiery E, Myin-Germeys I, Krabbendam L, van Os J (2009) Subtle gene–environment interactions driving paranoia in daily life. Genes Brain Behav 8:5–12

    Article  PubMed  Google Scholar 

  • Spauwen J, Krabbendam L, Lieb R, Wittchen HU, van Os J (2006) Impact of psychological trauma on the development of psychotic symptoms: relationship with psychosis proneness. Br J Psychiatry 188:527–533

    Article  PubMed  Google Scholar 

  • Startup M (1999) Schizotypy, dissociative experiences and childhood abuse: relationships among self-report measures. Br J Clin Psychol 38(Pt 4):333–344

    Article  PubMed  Google Scholar 

  • Stefanis NC, Hanssen M, Smirnis NK, Avramopoulos DA, Evdokimidis IK, Stefanis CN, Verdoux H, Van Os J (2002) Evidence that three dimensions of psychosis have a distribution in the general population. Psychol Med 32:347–358

    Article  PubMed  Google Scholar 

  • Stefanis NC, Van Os J, Avramopoulos D, Smyrnis N, Evdokimidis I, Hantoumi I, Stefanis CN (2004) Variation in catechol-o-methyltransferase val158 met genotype associated with schizotypy but not cognition: a population study in 543 young men. Biol Psychiatry 56:510–515

    Article  PubMed  Google Scholar 

  • Stefanis NC, Vitoratou S, Smyrnis N, Constantinidis T, Evdokimidis I, Hatzimanolis I, Ntzoufras I, Stefanis CN (2006) Mixed handedness is associated with the disorganization dimension of schizotypy in a young male population. Schizophr Res 87:289–296

    Article  PubMed  Google Scholar 

  • Stefanis NC, Henquet C, Avramopoulos D, Smyrnis N, Evdokimidis I, Myin-Germeys I, Stefanis CN, Van Os J (2007) COMT Val158Met moderation of stress-induced psychosis. Psychol Med 37:1651–1656

    Article  PubMed  Google Scholar 

  • Stein DJ, Newman TK, Savitz J, Ramesar R (2006) Warriors versus worriers: the role of COMT gene variants. CNS Spectr. 11:745–748

    PubMed  Google Scholar 

  • Thomas DC (2004) Statistical methods in genetic epidemiology. Oxford University Press, New York

    Google Scholar 

  • Tost H, Alam T, Meyer-Lindenberg A (2009) Dopamine and psychosis: theory, pathomechanisms and intermediate phenotypes. Neurosci Biobehav Rev

  • van Os J, Hanssen M, Bijl RV, Ravelli A (2000) Strauss (1969) revisited: a psychosis continuum in the general population? Schizophr Res 45:11–20

    Article  PubMed  Google 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 23:219–222

    Article  PubMed  Google Scholar 

  • Wigginton JE, Abecasis GR (2005) PEDSTATS: descriptive statistics, graphics and quality assessment for gene mapping data. Bioinformatics 21:3445–3447

    Article  PubMed  Google Scholar 

  • Wolfradt U, Straube ER (1998) Factor structure of schizotypal traits among adolescents. In: Personality and individual differences. pp 201–206

Download references

Acknowledgments

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.

Author information

Authors and Affiliations

  1. MRC/UCT Human Genetics Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

    Jonathan Savitz & Raj Ramesar

  2. Biostatistics Unit, Medical Research Council of South Africa and Department of Statistics, University of the Western Cape, Bellville, South Africa

    Lize van der Merwe

  3. Department of Psychiatry, University of Cape Town, Cape Town, South Africa

    Timothy K. Newman & Dan J. Stein

Authors
  1. Jonathan Savitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lize van der Merwe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Timothy K. Newman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dan J. Stein
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Raj Ramesar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan Savitz.

Additional information

Edited by Michael Lyons.

Appendix

Appendix

Mood state of sample

Table 8 lists the mood state of the sample at the time of testing as measured with the Beck Depression Inventory and Altman Self-Rating Mania Scale.

Table 8 Mood state of sample at the time of testing
Full size table

Genotyping

Table 9 lists the polymorphisms typed in the study.

Variable Number Tandem Repeats (VNTR) and insertion/deletion polymorphisms were scored on the Applied Biosystems (ABI) 3100 sequencer using GeneMapper software, while the DRD2 Taq1A single nucleotide polymorphism (SNP) was genotyped using restriction digests and scored on a polyacrylamide gel. Primer sequences were obtained from the literature or designed online.

In cases where the variant had more than two alleles, we converted them to two pseudo-alleles. For SLC6A3 (DAT), we compared the 9R allele to all the others (only two individuals in the sample did not carry a 9R or a 10R allele). For DRD4 we coded 2R, 3R, and 4R variants as short, and 7R and 8R variants as long. There are data to suggest differences in function between short and long alleles and this analytical approach has been followed by other researchers (Savitz and Ramesar 2004). Because MAO-A is X-linked, we coded males as homozygous (instead of hemizygous) for the particular allele that they carry (see Tables 10, 11).

Table 9 Genetic variants typed in the study
Full size table
Table 10 Frequency of COMT val and met alleles and genotypes across cohorts of Afrikaner and British origin
Full size table
Table 11 HWE scores for the genotyped variants
Full size table

Rights and permissions

Reprints and permissions

About this article

Cite this article

Savitz, J., van der Merwe, L., Newman, T.K. et al. Catechol-o-Methyltransferase Genotype and Childhood Trauma May Interact to Impact Schizotypal Personality Traits. Behav Genet 40, 415–423 (2010). https://doi.org/10.1007/s10519-009-9323-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10519-009-9323-7

Keywords

Search

Navigation