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Genetic variation in the schizophrenia-risk gene neuregulin1 correlates with personality traits in healthy individuals

Published online by Cambridge University Press:  16 April 2020

Axel Krug ,
Valentin Markov ,
Dirk Leube ,
Klaus Zerres ,
Thomas Eggermann ,
Markus M. Nöthen ,
Markus H. Skowronek ,
Marcella Rietschel  and
Tilo Kircher
Axel Krug
Affiliation:
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Pauwelsstrasse 30, D-52074Aachen, Germany
Valentin Markov
Affiliation:
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Pauwelsstrasse 30, D-52074Aachen, Germany
Dirk Leube
Affiliation:
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Pauwelsstrasse 30, D-52074Aachen, Germany
Klaus Zerres
Affiliation:
Institute of Human Genetics, RWTH Aachen University, Pauwelsstrasse 30, D-52074Aachen, Germany
Thomas Eggermann
Affiliation:
Institute of Human Genetics, RWTH Aachen University, Pauwelsstrasse 30, D-52074Aachen, Germany
Markus M. Nöthen
Affiliation:
Department of Genomics, Life and Brain Center, University of Bonn, Sigmund-Freud-Strasse 25, D-53127Bonn, Germany
Markus H. Skowronek
Affiliation:
Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, J5, D-68159Mannheim, Germany
Marcella Rietschel
Affiliation:
Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, J5, D-68159Mannheim, Germany
Tilo Kircher*
Affiliation:
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Pauwelsstrasse 30, D-52074Aachen, Germany
*
*Corresponding author. Tel.: +49 241 8088637; fax: +49 241 8082422. E-mail addresses: akrug@ukaachen.de (A. Krug), vmarkov@ukaachen.de (V. Markov), kzerres@ukaachen.de (K. Zerres), teggermann@ukaachen.de (T. Eggermann), genomics@lifeandbrain.com (M.M. Nöthen), markus. skowronek@zi-mannheim.de (M.H. Skowronek), marcella.rietschel@zi-mannheim.de (M. Rietschel), tkircher@ukaachen.de (T. Kircher).
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Abstract

Background

Differences in personality traits have long been acknowledged as potential risk factors in developing psychiatric disorders. Lately, several susceptibility genes of different psychiatric disorders have been linked to personality traits. This has not been done for schizophrenia yet. Neuregulin1 has been repeatedly shown to be associated with schizophrenia and is involved in numerous neurodevelopmental functions such as neuronal migration and myelination. The impact of this gene might also modulate personality traits in healthy subjects.

Methods

The NRG1 status of 523 healthy subjects was determined with a single nucleotide polymorphism (SNP8NRG221533) which has been described as a tagging marker being part of the core at-risk haplotype for schizophrenia. Genotype was correlated with personality traits using the NEO-FFI questionnaire.

Results

Subjects with the NRG1 risk allele scored higher on neuroticism (p <.05) and lower on conscientiousness (p <.05). Further, interactions of genotype by gender for extraversion (p <.05), openness (p <.05) and conscientiousness (p <.05) were found with men carrying the risk allele scoring the lowest.

Conclusions

The data indicate that the NRG1 gene which has found to be associated with schizophrenia may also influence personality differences in healthy subjects.

Keywords

Personality traitsNEO-FFINeuregulinNRG1Genotype
Type
Original article
Information
European Psychiatry , Volume 23 , Issue 5 , August 2008 , pp. 344 - 349
Copyright
Copyright © Elsevier Masson SAS 2008

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References

Abou Jamra, R.Schmael, C.Cichon, S.Rietschel, M.Schumacher, J.Nothen, M.M.The G72/G30 gene locus in psychiatric disorders: a challenge to diagnostic boundaries? Schizophrenia Bulletin 32 4 2006 599–608.Google Scholar
Addington, A.M.Gornick, M.C.Shaw, P.Seal, J.Gogtay, N.Greenstein, D. et al Neuregulin 1 (8p12) and childhood-onset schizophrenia: susceptibility haplotypes for diagnosis and brain developmental trajectories Molecular Psychiatry 12 2 2007 195–205.Google Scholar
Angst, J.Clayton, P.Premorbid personality of depressive, bipolar, and schizophrenic patients with special reference to suicidal issues Comprehensive Psychiatry 27 6 1986 511–532.Google Scholar
Angst, J.Isele, R.Scharfetter, C.Scheidegger, P.Premorbid personality of schizophrenic patients Schweizer Archiv fur Neurologie und Psychiatrie 136 1 1985 45–53.Google Scholar
Anton, E.S.Marchionni, M.A.Lee, K.F.Rakic, P.Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex Development 124 18 1997 3501–3510.Google Scholar
Bagby, R.M.Bindseil, K.D.Schuller, D.R.Rector, N.A.Young, L.T.Cooke, R.G. et al Relationship between the five-factor model of personality and unipolar, bipolar and schizophrenic patients Psychiatry Research 70 2 1997 83–94.Google Scholar
Bagby, R.M.Costa, P.T. Jr.McCrae, R.R.Livesley, W.J.Kennedy, S.H.Levitan, R.D. et al Replicating the five factor model of personality in a psychiatric sample Personality and Individual Differences 27 6 1999 1135–1139.CrossRefGoogle Scholar
Bakker, S.C.Hoogendoorn, M.L.Selten, J.P.Verduijn, W.Pearson, P.L.Sinke, R.J. et al Neuregulin 1: genetic support for schizophrenia subtypes Molecular Psychiatry 9 12 2004 1061–1063.Google Scholar
Berenbaum, H.Fujita, F.Schizophrenia and personality: exploring the boundaries and connections between vulnerability and outcome Journal of Abnormal Psychology 103 1 1994 148–158.Google Scholar
Borkenau, P.Ostendorf, F.NEO Fünf Faktoren Inventar 1993 Göttingen: Hogrefe.Google Scholar
Camisa, K.M.Bockbrader, M.A.Lysaker, P.Rae, L.L.Brenner, C.A.O'Donnell, B.F.Personality traits in schizophrenia and related personality disorders Psychiatry Research 133 1 2005 23–33.Google Scholar
Cannon, T.D.Thompson, P.M.van Erp, T.G.Toga, A.W.Poutanen, V.P.Huttunen, M. et al Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia Proceedings of the National Academy of Sciences of the United States of America 99 5 2002 3228–3233.Google Scholar
Carmine, A.Chheda, M.G.Jonsson, E.G.Sedvall, G.C.Farde, L.Gustavsson, J.P. et al Two NOTCH4 polymorphisms and their relation to schizophrenia susceptibility and different personality traits Psychiatric Genetics 13 1 2003 23–28.Google Scholar
Chapman, L.J.Chapman, J.P.Kwapil, T.R.Eckblad, M.Zinser, M.C.Putatively psychosis-prone subjects 10 years later Journal of Abnormal Psychology 103 2 1994 171–183.Google Scholar
Chen, S.Velardez, M.O.Warot, X.Yu, Z.X.Miller, S.J.Cros, D. et al Neuregulin 1-erbB signaling is necessary for normal myelination and sensory function Journal of Neuroscience 26 12 2006 3079–3086.Google Scholar
Chumakov, I.Blumenfeld, M.Guerassimenko, O.Cavarec, L.Palicio, M.Abderrahim, H. et al Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia Proceedings of the National Academy of Sciences of the United States of America 99 21 2002 13675–13680.Google Scholar
Corfas, G.Roy, K.Buxbaum, J.D.Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia Nature Neuroscience 7 6 2004 575–580.Google Scholar
Costa, P.M.McCrae, R.R.Professional manual for the revised NEO personality inventory 1992 Odessa, FL: Psychological Assessment Resources.Google Scholar
Dinzeo, T.J.Docherty, N.M.Normal personality characteristics in schizophrenia: a review of the literature involving the FFM Journal of Nervous and Mental Disease 195 5 2007 421–429.Google Scholar
Domschke, K.Freitag, C.M.Kuhlenbaumer, G.Schirmacher, A.Sand, P.Nyhuis, P. et al Association of the functional V158M catechol-O-methyltransferase polymorphism with panic disorder in women International Journal of Neuropsychopharmacology/Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) 7 2 2004 183–188.CrossRefGoogle Scholar
Elston, R.C.Forthofer, R.Testing for Hardy–Weinberg equilibrium in small samples Biometrics 33 1977 536–542.Google Scholar
Enoch, M.A.Xu, K.Ferro, E.Harris, C.R.Goldman, D.Genetic origins of anxiety in women: a role for a functional catechol-O-methyltransferase polymorphism Psychiatric Genetics 13 1 2003 33–41.Google Scholar
Falls, D.L.Neuregulins: functions, forms, and signaling strategies Experimental Cell Research 284 1 2003 14–30.Google Scholar
Gardner, M.Gonzalez-Neira, A.Lao, O.Calafell, F.Bertranpetit, J.Comas, D.Extreme population differences across Neuregulin 1 gene, with implications for association studies Molecular Psychiatry 11 1 2006 66–75.Google Scholar
Ghashghaei, H.T.Weber, J.Pevny, L.Schmid, R.Schwab, M.H.Lloyd, K.C. et al The role of neuregulin–ErbB4 interactions on the proliferation and organization of cells in the subventricular zone Proceedings of the National Academy of Sciences of the United States of America 103 6 2006 1930–1935.Google Scholar
Glatt, S.J.Stone, W.S.Faraone, S.V.Seidman, L.J.Tsuang, M.T.Psychopathology, personality traits and social development of young first-degree relatives of patients with schizophrenia British Journal of Psychiatry 189 2006 337–345.Google Scholar
Hahn, C.G.Wang, H.Y.Cho, D.S.Talbot, K.Gur, R.E.Berrettini, W.H. et al Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia Nature Medicine 12 7 2006 824–828.Google Scholar
Harrison, P.J.Law, A.J.Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology Biological Psychiatry 60 2 2006 132–140.Google Scholar
Iwata, N.Suzuki, T.Ikeda, M.Kitajima, T.Yamanouchi, Y.Inada, T. et al No association with the neuregulin 1 haplotype to Japanese schizophrenia Molecular Psychiatry 9 2 2004 126–127.Google Scholar
Jacob, C.P.Strobel, A.Hohenberger, K.Ringel, T.Gutknecht, L.Reif, A. et al Association between allelic variation of serotonin transporter function and neuroticism in anxious cluster C personality disorders American Journal of Psychiatry 161 3 2004 569–572.Google Scholar
Jang, K.L.Livesley, W.J.Vernon, P.A.Heritability of the big five personality dimensions and their facets: a twin study Journal of Personality 64 3 1996 577–591.Google Scholar
Khan, A.A.Jacobson, K.C.Gardner, C.O.Prescott, C.A.Kendler, K.S.Personality and comorbidity of common psychiatric disorders British Journal of Psychiatry 186 2005 190–196.Google Scholar
Krabbendam, L.Janssen, I.Bak, M.Bijl, R.V.de Graaf, R.van Os, J.Neuroticism and low self-esteem as risk factors for psychosis Social Psychiatry and Psychiatric Epidemiology 37 1 2002 1–6.CrossRefGoogle Scholar
Lang, U.E.Bajbouj, M.Sander, T.Gallinat, J.Gender-dependent association of the functional catechol-O-methyltransferase Val158Met genotype with sensation seeking personality trait Neuropsychopharmacology 32 2007 1950–1955.Google Scholar
Li, D.Collier, D.A.He, L.Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia Human Molecular Genetics 15 12 2006 1995–2002.Google Scholar
Liu, Y.Ford, B.Mann, M.A.Fischbach, G.D.Neuregulins increase alpha7 nicotinic acetylcholine receptors and enhance excitatory synaptic transmission in GABAergic interneurons of the hippocampus Journal of Neuroscience 21 15 2001 5660–5669.Google Scholar
Luo, X.Kranzler, H.R.Zuo, L.Wang, S.Gelernter, J.Personality traits of agreeableness and extraversion are associated with ADH4 variation Biological Psychiatry 61 5 2007 599–608.Google Scholar
Luo, X.Kranzler, H.R.Zuo, L.Zhang, H.Wang, S.Gelernter, J.CHRM2 variation predisposes to personality traits of agreeableness and conscientiousness Human Molecular Genetics 16 13 2007 1557–1568.Google Scholar
Luo, X.Zuo, L.Kranzler, H.Zhang, H.Wang, S.Gelernter, J.Multiple OPR genes influence personality traits in substance dependent and healthy subjects in two American populations American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics 2008 10.1002/ajmg.b.30701.Google Scholar
Maier, W.Minges, J.Lichtermann, D.Heun, R.Franke, P.Personality variations in healthy relatives of schizophrenics Schizophrenia Research 12 1 1994 81–88.Google Scholar
Munafo, M.R.Thiselton, D.L.Clark, T.G.Flint, J.Association of the NRG1 gene and schizophrenia: a meta-analysis Molecular Psychiatry 11 6 2006 539–546.Google Scholar
Nave, K.A.Salzer, J.L.Axonal regulation of myelination by neuregulin 1 Current Opinion in Neurobiology 16 5 2006 492–500.CrossRefGoogle Scholar
Ozaki, M.Sasner, M.Yano, R.Lu, H.S.Buonanno, A.Neuregulin-beta induces expression of an NMDA-receptor subunit Nature 390 6661 1997 691–694.Google Scholar
Porteous, D.J.Thomson, P.Brandon, N.J.Millar, J.K.The genetics and biology of DISC1–an emerging role in psychosis and cognition Biological Psychiatry 60 2 2006 123–131.Google Scholar
Schwab, S.G.Knapp, M.Mondabon, S.Hallmayer, J.Borrmann-Hassenbach, M.Albus, M. et al Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families American Journal of Human Genetics 72 1 2003 185–190.Google Scholar
Stefansson, H.Sarginson, J.Kong, A.Yates, P.Steinthorsdottir, V.Gudfinnsson, E. et al Association of neuregulin 1 with schizophrenia confirmed in a Scottish population American Journal of Human Genetics 72 1 2003 83–87.Google Scholar
Stefansson, H.Sigurdsson, E.Steinthorsdottir, V.Bjornsdottir, S.Sigmundsson, T.Ghosh, S. et al Neuregulin 1 and susceptibility to schizophrenia American Journal of Human Genetics 71 4 2002 877–892.Google Scholar
Stein, M.B.Fallin, M.D.Schork, N.J.Gelernter, J.COMT polymorphisms and anxiety-related personality traits Neuropsychopharmacology 30 11 2005 2092–2102.Google Scholar
Thiselton, D.L.Webb, B.T.Neale, B.M.Ribble, R.C.O'Neill, F.A.Walsh, D. et al No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF) Molecular Psychiatry 9 8 2004 777–783 image 29.Google Scholar
Thorup, A.Waltoft, B.L.Pedersen, C.B.Mortensen, P.B.Nordentoft, M.Young males have a higher risk of developing schizophrenia: a Danish register study Psychological Medicine 37 4 2007 479–484.Google Scholar
Tosato, S.Dazzan, P.Collier, D.Association between the neuregulin 1 gene and schizophrenia: a systematic review Schizophrenia Bulletin 31 3 2005 613–617.Google Scholar
Van Den Bogaert, A.Schumacher, J.Schulze, T.G.Otte, A.C.Ohlraun, S.Kovalenko, S. et al The DTNBP1 (dysbindin) gene contributes to schizophrenia, depending on family history of the disease American Journal of Human Genetics 73 6 2003 1438–1443.Google Scholar
World Health Organisation The ICD-10 classification of mental and behavioural disorders. Diagnostic criteria for research 1993 Geneva: WHO.Google Scholar
Wright, C.I.Williams, D.Feczko, E.Barrett, L.F.Dickerson, B.C.Schwartz, C.E. et al Neuroanatomical correlates of extraversion and neuroticism Cerebral Cortex 16 12 2006 1809–1819.CrossRefGoogle Scholar
Zhao, X.Shi, Y.Tang, J.Tang, R.Yu, L.Gu, N. et al A case control and family based association study of the neuregulin1 gene and schizophrenia Journal of Medical Genetics 41 1 2004 31–34.Google Scholar
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