Hostname: page-component-78c5997874-94fs2 Total loading time: 0 Render date: 2024-11-10T07:39:38.329Z Has data issue: false hasContentIssue false
  • English
  • Français

COMT Val158Met moderation of stress-induced psychosis

Published online by Cambridge University Press:  20 July 2007

NICHOLAS C. STEFANIS ,
CÉCILE HENQUET ,
DIMITRIOS AVRAMOPOULOS ,
NIKOLAOS SMYRNIS ,
IOANNIS EVDOKIMIDIS ,
INEZ MYIN-GERMEYS ,
COSTAS N. STEFANIS  and
JIM VAN OS
NICHOLAS C. STEFANIS*
Affiliation:
University Mental Health Research Institute, Athens, Greece Eginition Hospital, Department of Psychiatry, National and Kapodistrian University of Athens, Greece Division of Psychological Medicine, Institute of Psychiatry, London, UK
CÉCILE HENQUET
Affiliation:
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands
DIMITRIOS AVRAMOPOULOS
Affiliation:
University Mental Health Research Institute, Athens, Greece
NIKOLAOS SMYRNIS
Affiliation:
University Mental Health Research Institute, Athens, Greece Eginition Hospital, Department of Psychiatry, National and Kapodistrian University of Athens, Greece
IOANNIS EVDOKIMIDIS
Affiliation:
University Mental Health Research Institute, Athens, Greece
INEZ MYIN-GERMEYS
Affiliation:
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands
COSTAS N. STEFANIS
Affiliation:
University Mental Health Research Institute, Athens, Greece
JIM VAN OS
Affiliation:
Division of Psychological Medicine, Institute of Psychiatry, London, UK Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands
*
*Address for correspondence: Dr Nicholas C. Stefanis, Assistant Professor in Psychiatry, Department of Psychiatry, National and Kapodistrian University of Athens, Eginition Hospital, 74 Vas. Sofias Avenue, Athens11528, Greece. (Email: nistefan@med.uoa.gr)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Exposure to stressful life events increases the risk of developing a psychotic disorder. Moreover, increased reactivity to stress seems to represent part of the vulnerability for psychosis. This study aimed to investigate whether a functional polymorphism in the catechol-O-methyltransferase (COMT Val158Met) gene moderates the psychosis-inducing effects of stress.

Method

A semi-experimental stress exposure paradigm was used in a sample of 306 genotyped young men (aged 19–24 years), in whom measures of psychotic symptoms were obtained at recruitment in the Greek army (exposed condition) and again after 18 months of military training (unexposed condition).

Results

Stress exposure at army induction was associated with an increased level of psychotic symptoms. In addition, carriers of the COMT Val158Met Val allele were more susceptible to the effect of stress on the psychosis outcome than those with the Met/Met genotype (test for interaction: χ2=5·02, df=1, p=0·025).

Conclusion

The COMT Val158Met genotype may moderate the effect of stress on psychotic symptoms.

Type
Original Article
Information
Psychological Medicine , Volume 37 , Issue 11 , November 2007 , pp. 1651 - 1656
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Akil, M., Kolachana, B. S., Rothmond, D. A., Hyde, T. M., Weinberger, D. R. & Kleinman, J. E. (2003). Catechol-O-methyltransferase genotype and dopamine regulation in the human brain. Journal of Neuroscience 23, 2008–2013.CrossRefGoogle ScholarPubMed
Bebbington, P., Wilkins, S., Jones, P., Foerster, A., Murray, R., Toone, B. & Lewis, S. (1993). Life events and psychosis. Initial results from the Camberwell Collaborative Psychosis Study. British Journal of Psychiatry 162, 72–79.CrossRefGoogle ScholarPubMed
Bergeman, C. S., Plomin, R., Pedersen, N. L. & McClearn, G. E. (1991). Genetic mediation of the relationship between social support and psychological well-being. Psychology and Aging 6, 640–646.CrossRefGoogle ScholarPubMed
Bilder, R. M., Volavka, J., Lachman, H. M. & Grace, A. A. (2004). The catechol-O-methyltransferase polymorphism: relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology 29, 1943–1961.CrossRefGoogle Scholar
Caspi, A. & Moffitt, T. E. (2006). Gene–environment interactions in psychiatry: joining forces with neuroscience. Nature Reviews. Neuroscience 7, 583–590.Google Scholar
Caspi, A., Moffitt, T. E., Cannon, M., McClay, J., Murray, R., Harrington, H., Taylor, A., Arseneault, L., Williams, B., Braithwaite, A., Poulton, R. & Craig, I. W. (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×environment interaction. Biological Psychiatry 57, 1117–1127.CrossRefGoogle Scholar
Chapman, L. J., Chapman, J. P. & Raulin, M. L. (1978). Body-image aberration in schizophrenia. Journal of Abnormal Psychology 87, 399–407.CrossRefGoogle ScholarPubMed
Clemons, E. P. (1996). Monitoring anxiety levels and coping skills among military recruits. Military Medicine 161, 18–21.CrossRefGoogle ScholarPubMed
Drabant, E. M., Hariri, A. R., Meyer-Lindenberg, A., Munoz, K. E., Mattay, V. S., Kolachana, B. S., Egan, M. F. & Weinberger, D. R. (2006). Catechol O-methyltransferase val158met genotype and neural mechanisms related to affective arousal and regulation. Archives of General Psychiatry 63, 1396–1406.Google Scholar
Enoch, M. A., Xu, K., Ferro, E., Harris, C. R. & Goldman, D. (2003). Genetic origins of anxiety in women: a role for a functional catechol-O-methyltransferase polymorphism. Psychiatric Genetics 13, 33–41.CrossRefGoogle ScholarPubMed
Fan, J. B., Zhang, C. S., Gu, N. F., Li, X. W., Sun, W. W., Wang, H. Y., Feng, G. Y., St Clair, D. & He, L. (2005). Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis. Biological Psychiatry 57, 139–144.CrossRefGoogle ScholarPubMed
Flint, J. & Munafo, M. R. (2007). The endophenotype concept in psychiatric genetics. Psychological Medicine 37, 163–180.Google Scholar
Grace, A. A. (1991). Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41, 1–24.Google Scholar
Hatzitaskos, P., Soldatos, C., Giouzelis, G., Karvelis, D. & Spilioti, M. (1997). Psychotic symptomatology first appeared in the military environment. Psychiatriki 8, 41–48.Google Scholar
Henquet, C., Krabbendam, L., Spauwen, J., Kaplan, C., Lieb, R., Wittchen, H. U. & van Os, J. (2005). Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. British Medical Journal 330, 11–15.CrossRefGoogle ScholarPubMed
Henquet, C., Rosa, A., Krabbendam, L., Papiol, S., Fananas, L., Drukker, M., Ramaekers, J. G. & van Os, J. (2006). An experimental study of catechol-O-methyltransferase val(158)met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology 31, 2748–2757.Google Scholar
Kapur, S. (2003). Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry 160, 13–23.CrossRefGoogle ScholarPubMed
Kirov, G., Murphy, K. C., Arranz, M. J., Jones, I., McCandles, F., Kunugi, H., Murray, R. M., McGuffin, P., Collier, D. A., Owen, M. J. & Craddock, N. (1998). Low activity allele of catechol-O-methyltransferase gene associated with rapid cycling bipolar disorder. Molecular Psychiatry 3, 342–345.CrossRefGoogle ScholarPubMed
Lachman, H. M., Papolos, D. F., Saito, T., Yu, Y. M., Szumlanski, C. L. & Weinshilboum, R. M. (1996). Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 6, 243–250.CrossRefGoogle ScholarPubMed
Larson, G. E., Booth-Kewley, S., Merrill, L. L. & Stander, V. A. (2001). Physical symptoms as indicators of depression and anxiety. Military Medicine 166, 796–799.CrossRefGoogle ScholarPubMed
Laruelle, M. (2000). The role of endogenous sensitization in the pathophysiology of schizophrenia: implications from recent brain imaging studies. Brain Research. Brain Research Reviews 31, 371–384.Google Scholar
Lataster, T., van Os, J., Drukker, M., Henquet, C., Feron, F., Gunther, N. & Myin-Germeys, I. (2006). Childhood victimisation and developmental expression of non-clinical delusional ideation and hallucinatory experiences: victimisation and non-clinical psychotic experiences. Social Psychiatry and Psychiatric Epidemiology 41, 423–428.CrossRefGoogle ScholarPubMed
Lerew, D. R., Schmidt, N. B. & Jackson, R. J. (1999). Evaluation of psychological risk factors: prospective prediction of psychopathology during basic training. Military Medicine 164, 509–513.CrossRefGoogle ScholarPubMed
Lotta, T., Vidgren, J., Tilgmann, C., Ulmanen, I., Melen, K., Julkunen, I. & Taskinen, J. (1995). Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry 34, 4202–4210.Google Scholar
Lukoff, D., Snyder, K., Ventura, J. & Nuechterlein, K. H. (1984). Life events, familial stress, and coping in the developmental course of schizophrenia. Schizophrenia Bulletin 10, 258–292.CrossRefGoogle ScholarPubMed
Martin, P. D., Williamson, D. A., Alfonso, A. J. & Ryan, D. H. (2006). Psychological adjustment during Army basic training. Military Medicine 171, 157–160.CrossRefGoogle ScholarPubMed
Meyer-Lindenberg, A., Kohn, P. D., Kolachana, B., Kippenhan, S., McInerney-Leo, A., Nussbaum, R., Weinberger, D. R. & Berman, K. F. (2005). Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype. Nature Neuroscience 8, 594–596.CrossRefGoogle ScholarPubMed
Myin-Germeys, I., Delespaul, P. & van Os, J. (2005). Behavioural sensitization to daily life stress in psychosis. Psychological Medicine 35, 733–741.CrossRefGoogle ScholarPubMed
Myin-Germeys, I., Krabbendam, L., Delespaul, P. A. & Van Os, J. (2003). Do life events have their effect on psychosis by influencing the emotional reactivity to daily life stress? Psychological Medicine 33, 327–333.CrossRefGoogle ScholarPubMed
Raine, A. (1991). The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. Schizophrenia Bulletin 17, 555–564.CrossRefGoogle ScholarPubMed
Read, J., van Os, J., Morrison, A. P. & Ross, C. A. (2005). Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications. Acta Psychiatrica Scandinavica 112, 330–350.CrossRefGoogle ScholarPubMed
Schmidt, N. B., Lerew, D. R. & Joiner, T. E. Jr. (2000). Prospective evaluation of the etiology of anxiety sensitivity: test of a scar model. Behaviour Research and Therapy 38, 1083–1095.CrossRefGoogle ScholarPubMed
Smolka, M. N., Schumann, G., Wrase, J., Grusser, S. M., Flor, H., Mann, K., Braus, D. F., Goldman, D., Buchel, C. & Heinz, A. (2005). Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex. Journal of Neuroscience 25, 836–842.CrossRefGoogle ScholarPubMed
Stefanis, N. C., Van Os, J., Avramopoulos, D., Smyrnis, N., Evdokimidis, I., Hantoumi, I. & Stefanis, C. N. (2004). Variation in catechol-O-methyltransferase val158 met genotype associated with schizotypy but not cognition: a population study in 543 young men. Biological Psychiatry 56, 510–515.Google Scholar
Stefanis, N. C., Vitoratou, S., Ntzoufras, I., Smyrnis, N., Evdokimidis, I. & Stefanis, C. N. (2006). Psychometric properties of the Greek version of the Schizotypal Personality Questionnaire (SPQ) in young male obligatory conscripts: a two years test–retest study. Personality and Individual Differences 41, 1275–1286.Google Scholar
Stein, M. B., Fallin, M. D., Schork, N. J. & Gelernter, J. (2005). COMT polymorphisms and anxiety-related personality traits. Neuropsychopharmacology 30, 2092–2102.Google Scholar
Steinberg, H. R. & Durell, J. (1968). A stressful social situation as a precipitant of schizophrenic symptoms: an epidemiological study. British Journal of Psychiatry 114, 1097–1105.CrossRefGoogle ScholarPubMed
Tunbridge, E. M., Harrison, P. J. & Weinberger, D. R. (2006). Catechol-O-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biological Psychiatry 60, 141–151.Google Scholar
van Os, J., Hanssen, M., Bak, M., Bijl, R. V. & Vollebergh, W. (2003). Do urbanicity and familial liability coparticipate in causing psychosis? American Journal of Psychiatry 160, 477–482.Google Scholar
van Os, J., Hanssen, M., Bijl, R. V. & Vollebergh, W. (2001). Prevalence of psychotic disorder and community level of psychotic symptoms: an urban–rural comparison. Archives of General Psychiatry 58, 663–668.CrossRefGoogle ScholarPubMed