Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-22T19:42:17.288Z Has data issue: false hasContentIssue false

Association of a functional variant of the nitric oxide synthase 1 gene with personality, anxiety, and depressiveness

Published online by Cambridge University Press:  15 October 2012

Triin Kurrikoff
Affiliation:
University of Tartu
Klaus-Peter Lesch
Affiliation:
University of Würzburg
Evelyn Kiive
Affiliation:
University of Tartu
Kenn Konstabel
Affiliation:
University of Tartu National Institute for Health Development
Sabine Herterich
Affiliation:
University of Würzburg
Toomas Veidebaum
Affiliation:
National Institute for Health Development
Andreas Reif
Affiliation:
University of Würzburg
Jaanus Harro*
Affiliation:
University of Tartu
*
Address correspondence and reprint requests to: Jaanus Harro, University of Tartu, Tiigi 78, EE 50410, Tartu, Estonia; E-mail: [email protected].

Abstract

A functional promoter polymorphism of the nitric oxide synthase 1 gene first exon 1f variable number tandem repeat (NOS1 ex1f-VNTR) is associated with impulsivity and related psychopathology. Facets of impulsivity are strongly associated with personality traits; maladaptive impulsivity with neuroticism; and adaptive impulsivity with extraversion. Both high neuroticism and low extraversion predict anxiety and depressive symptoms. The aim of the present study was to evaluate the effect of the NOS1 ex1f-VNTR genotype and possible interaction with environmental factors on personality, anxiety, and depressiveness in a population-representative sample. Short allele carriers had higher neuroticism and anxiety than individuals with the long/long (l/l) genotype. Male short/short homozygotes also had higher extraversion. In the face of environmental adversity, females with a short allele had higher scores of neuroticism, anxiety, and depressiveness compared to the l/l genotype. Males were more sensitive to environmental conditions when they had the l/l genotype and low extraversion. In conclusion, the NOS1 ex1f-VNTR influences personality and emotional regulation dependent on gender and environment. Together with previous findings on the effect of the NOS1 genotype on impulse control, these data suggest that NOS1 should be considered another plasticity gene, because its variants are associated with different coping strategies.

Type
Articles
Copyright
Copyright © Cambridge University Press 2012

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

Aluja, A., García, Ó., & García, L. (2003). Relationships among extraversion, openness to experience, and sensation seeking. Personality and Individual Differences, 35, 671680.CrossRefGoogle Scholar
Belsky, J., Jonassaint, C., Pluess, M., Stanton, M., Brummett, B., & Williams, R. (2009). Vulnerability genes or plasticity genes? Molecular Psychiatry, 14, 746754.Google Scholar
Chioqueta, A. P., & Stiles, T. C. (2005). Personality traits and the development of depression, hopelessness, and suicide ideation. Personality and Individual Differences, 38, 12831291.CrossRefGoogle Scholar
Congdon, E., & Canli, T. (2008). A neurogenetic approach to impulsivity. Journal of Personality, 76, 14471484.Google Scholar
Cremers, H., van Tol, M. J., Roelofs, K., Aleman, A., Zitman, F. G., van Buchem, M. A., et al. (2011). Extraversion is linked to volume of the orbitofrontal cortex and amygdala. PLoS One, 6, e28421.Google Scholar
DeYoung, C. G., Hirsh, J. B., Shane, M. S., Papademetris, X., Rajeevan, N., & Gray, J. R. (2010). Testing predictions from personality neuroscience: Brain structure and the Big Five. Psychological Science, 21, 820828.Google Scholar
Dickman, S. J. (1990). Functional and dysfunctional impulsivity: Personality and cognitive correlates. Journal of Personality and Social Psychology, 58, 95102.Google Scholar
Duncan, L. E., & Keller, M. C. (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. American Journal of Psychiatry, 168, 10411049.CrossRefGoogle ScholarPubMed
Eley, T. C., Hudson, J. L., Creswell, C., Tropeano, M., Lester, K. J., Cooper, P., et al. (2012). Therapygenetics: The 5HTTLPR and response to psychological therapy. Molecular Psychiatry, 17, 236237.Google Scholar
Evenden, J. L. (1999). Varieties of impulsivity. Psychopharmacology, 146, 348361.Google Scholar
Frydman, C., Camerer, C., Bossaerts, P., & Rangel, A. (2011). MAOA-L carriers are better at making optimal financial decisions under risk. Proceedings of the Royal Society B: Biological Sciences, 278, 20532059.CrossRefGoogle ScholarPubMed
Geschwind, N., Nicolson, N. A., Peeters, F., van Os, J., Barge-Schaapveld, D., & Wichers, M. (2011). Early improvement in positive rather than negative emotion predicts remission from depression after pharmacotherapy. European Neuropsychopharmacology, 21, 241247.Google Scholar
Harro, J. (2010). Interindividual differences in neurobiology as vulnerability factors for affective disorders: Implications for psychopharmacology. Pharmacology & Therapeutics, 125, 402422.CrossRefGoogle ScholarPubMed
Harro, M., Eensoo, D., Kiive, E., Merenäkk, L., Alep, J., Oreland, L., et al. (2001). Platelet monoamine oxidase in healthy 9- and 15-year-old children: The effect of gender, smoking, and puberty. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 25, 14971511.CrossRefGoogle Scholar
Harro, J., Merenäkk, L., Nordquist, N., Konstabel, K., Comasco, E., & Oreland, L. (2009). Personality and the serotonin transporter gene: Associations in a longitudinal population-based study. Biological Psychology, 81, 913.Google Scholar
Homberg, J. R., & Lesch, K. P. (2011). Looking on the bright side of serotonin transporter gene variation. Biological Psychiatry, 69, 513519.Google Scholar
Insel, T. R. (2010). Rethinking schizophrenia. Nature, 468, 187193.Google Scholar
Jylhä, P., & Isometsä, E. (2006). The relationship of neuroticism and extraversion to symptoms of anxiety and depression in the general population. Depression and Anxiety, 23, 281289.CrossRefGoogle ScholarPubMed
Kendler, K. S., Gatz, M., Gardner, C. O., & Pedersen, N. L. (2006). Personality and major depression: A Swedish longitudinal, population-based twin study. Archives of General Psychiatry, 63, 11131120.Google Scholar
Kerscher, A. J., Rapee, R. M., & Schniering, C. A. (2009). Neuroticism, life events, and negative thoughts in the development of depression in adolescent girls. Journal of Abnormal Child Psychology, 37, 903915.Google Scholar
Kestler, L. P., Malhotra, A. K., Finch, C., Adler, C., & Breier, A. (2000). The relation between dopamine D2 receptor density and personality: Preliminary evidence from the NEO personality inventory—Revised. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 13, 4852.Google Scholar
Kirmayer, L. J., Robbins, J. M., Dworkind, M., & Yaffe, M. J. (1993). Somatization and the recognition of depression and anxiety in primary care. American Journal of Psychiatry, 150, 734741.Google Scholar
Kiss, J. P., & Vizi, E. S. (2001). Nitric oxide: A novel link between synaptic and nonsynaptic transmission. Trends in Neurosciences, 24, 211215.CrossRefGoogle ScholarPubMed
Konstabel, K., Lönnqvist, J.-L., Walkowitz, G., Konstabel, K., & Verkasalo, M. (2012). The “Short Five” (S5): Measuring personality traits using comprehensive single items. European Journal of Personality, 26, 1329.Google Scholar
Kriegebaum, C., Gutknecht, L., Schmitt, A., Lesch, K. P., & Reif, A. (2010). Serotonin now: Part 2. Behavioral genetics and psychopathology. Fortschritte der Neurologie—Psychiatrie, 78, 332342.CrossRefGoogle ScholarPubMed
Laas, K., Reif, A., Herterich, S., Eensoo, D., Lesch, K.-P., & Harro, J. (2010). The effect of a functional NOS1 promoter polymorphism on impulsivity is moderated by platelet MAO activity. Psychopharmacology, 209, 255261.Google Scholar
Lönnqvist, J.-E., Verkasalo, M., Mäkinen, S., & Henriksson, M. (2009). High neuroticism at age 20 predicts history of mental disorders and low self-esteem at age 35. Journal of Clinical Psychology, 65, 781790.Google Scholar
Lucas, R. E., Le, K., & Dyrenforth, P. S. (2008). Explaining the extraversion/positive affect relation: Sociability cannot account for extraverts’ greater happiness. Journal of Personality, 76, 385414.CrossRefGoogle ScholarPubMed
Malloy-Diniz, L., Fuentes, D., Borges Leite, W., Correa, H., & Bechara, A. (2007). Impulsive behavior in adults with attention deficit/hyperactivity disorder: Characterization of attentional, motor, and cognitive impulsiveness. Journal of the International Neuropsychological Society, 13, 693698.Google Scholar
McLaughlin, K. A., Fox, N. A., Zeanah, C. H., & Nelson, C. A. (2011). Adverse rearing environments and neural development in children: The development of frontal electroencephalogram asymmetry. Biological Psychiatry, 70, 10081015.Google Scholar
Montgomery, S. A., & Åsberg, M. (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134, 382389.Google Scholar
Mõttus, R., Pullmann, H., & Allik, J. (2006). Towards more readable Big Five personality inventories. European Journal of Psychological Assessment, 22, 149157.Google Scholar
Muris, P., Bos, A. E. R., Mayer, B., Verkade, R., Thewissen, V., & Dell'Avvento, V. (2009). Relations among behavioral inhibition, Big Five personality factors, and anxiety disorder symptoms in nonclinical children. Personality and Individual Differences, 46, 525529.Google Scholar
Nelson, R. J., Trainor, B. C., Chiavegatto, S., & Demas, G. E. (2006). Pleiotropic contributions of nitric oxide to aggressive behavior. Neuroscience and Biobehavioral Reviews, 30, 346355.Google Scholar
Oreland, L., Nordquist, N., Hallman, J., Harro, J., & Nilsson, K. W. (2010). Environment and the serotonergic system. European Psychiatry, 25, 304306.CrossRefGoogle ScholarPubMed
Paaver, M., Kurrikoff, T., Nordquist, N., Oreland, L., & Harro, J. (2008). The effect of 5-HTT gene promoter polymorphism on impulsivity depends on family relations in girls. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 32, 12631268.Google Scholar
Reif, A., Herterich, S., Strobel, A., Ehlis, A.-C., Saur, D., Jacob, C. P., et al. (2006). A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function. Molecular Psychiatry, 11, 286300.Google Scholar
Reif, A., Jacob, C. P., Rujescu, D., Herterich, S., Lang, S., Gutknech, L., et al. (2009). Influence of functional variant of neuronal nitric oxide synthase on impulsive behaviors in humans. Archives of General Psychiatry, 66, 4150.Google Scholar
Reif, A., Kiive, E., Kurrikoff, T., Paaver, M., Herterich, S., Konstabel, K., et al. (2011). A functional NOS1 promoter polymorphism interacts with adverse environment on functional and dysfunctional impulsivity. Psychopharmacology, 214, 239248.Google Scholar
Reiner, I., & Spangler, G. (2011). Dopamine D4 receptor exon III polymorphism, adverse life events, and personality traits in a nonclinical German adult sample. Neuropsychobiology, 63, 5258.Google Scholar
Rife, T., Rasoul, B., Pullen, N., Mitchell, D., Grathwol, K., & Kurth, J. (2009). The effect of a promoter polymorphism on the transcription of nitric oxide synthase 1 and its relevance to Parkinson's disease. Journal of Neuroscience Research, 87, 23192325.Google Scholar
Roberts, B. W., Walton, K. E., & Viechtbauer, W. (2006). Patterns of mean-level change in personality traits across the life course: A meta-analysis of longitudinal studies. Psychological Bulletin, 132, 125.CrossRefGoogle ScholarPubMed
Schmitt, D. P., Realo, A., Voracek, M., & Allik, J. (2008). Why can't a man be more like a woman? Sex differences in Big Five personality traits across 55 cultures. Journal of Personality and Social Psychology, 94, 168182.CrossRefGoogle Scholar
Smillie, L. D., Cooper, A. J., Proitsi, P., Powell, J. F., & Pickering, A. D. (2010). Variation in DRD2 dopamine gene predicts extraverted personality. Neuroscience Letters, 468, 234237.Google Scholar
Smillie, L. D., & Jackson, C. J. (2006). Functional impulsivity and reinforcement sensitivity theory. Journal of Personality, 74, 4783.CrossRefGoogle ScholarPubMed
Spielberger, C. D. (Ed.). (1983). Manual for the State–Trait Anxiety Inventory (STAI). Palo Alto, CA: Consulting Psychologists Press.Google Scholar
ten Have, M., Oldehinkel, A., Vollebergh, W., & Ormel, J. (2005). Does neuroticism explain variations in care service use for mental health problems in the general population? Results from the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Social Psychiatry and Psychiatric Epidemiology, 40, 425431.Google Scholar
Trainor, B. C., Workman, J. L., Jessen, R., & Nelson, R. J. (2007). Impaired nitric oxide synthase signaling dissociates social investigation and aggression. Behavioural Neuroscience, 121, 362369.Google Scholar
Uher, R., & McGuffin, P. (2010). The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Molecular Psychiatry, 15, 1822.Google Scholar
Van de Velde, S., Bracke, P., & Levecque, K. (2010). Gender differences in depression in 23 European countries: Cross-national variation in the gender gap in depression. Social Science & Medicine, 71, 305313.Google Scholar
Workman, J. L., Trainor, B. C., Finly, M. S., & Nelson, R. J. (2008). Inhibition of neuronal nitric oxide reduces anxiety-like responses to pair housing. Behavioral Brain Research, 187, 109115.Google Scholar
Wultsch, T., Chourbaji, S., Fritzen, S., Kittel, S., Grünblatt, E., Gerlach, M., et al. (2007). Behavioural and expressional phenotyping of nitric oxide synthase-I knockdown animals. Jounal of Neural Transmission, 72(Suppl.), 6985.Google Scholar
Zadravec, T., Bucik, V., & Sočan, G. (2005). The place of dysfunctional and functional impulsivity in the personality structure. Horizons of Psychology, 14, 3950.Google Scholar
Zhang, J., Huang, X. Y., Ye, M. L., Luo, C. X., Wu, H. Y., Hu, Y., et al. (2010). Neuronal nitric oxide synthase alteration accounts for the role of 5-HT1A receptor in modulating anxiety-related behaviors. Journal of Neuroscience, 30, 24332441.Google Scholar
Zhou, Q.-G., Hu, Y., Hua, Y., Hu, M., Luo, C.-X., Han, X., et al. (2007). Neuronal nitric oxide synthase contributes to chronic stress-induced depression by suppressing hippocampal neurogenesis. Journal of Neurochemistry, 103, 18431854.Google Scholar