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

  • Triin Kurrikoff (a1), Klaus-Peter Lesch (a2), Evelyn Kiive (a1), Kenn Konstabel (a1) (a3), Sabine Herterich (a2), Toomas Veidebaum (a3), Andreas Reif (a2) and Jaanus Harro (a1)...

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.

Corresponding author
Address correspondence and reprint requests to: Jaanus Harro, University of Tartu, Tiigi 78, EE 50410, Tartu, Estonia; E-mail:
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A. Aluja , Ó. García , & L. García (2003). Relationships among extraversion, openness to experience, and sensation seeking. Personality and Individual Differences, 35, 671680.

J. Belsky , C. Jonassaint , M. Pluess , M. Stanton , B. Brummett , & R. Williams (2009). Vulnerability genes or plasticity genes? Molecular Psychiatry, 14, 746754.

A. P. Chioqueta , & T. C. Stiles (2005). Personality traits and the development of depression, hopelessness, and suicide ideation. Personality and Individual Differences, 38, 12831291.

H. Cremers , M. J. van Tol , K. Roelofs , A. Aleman , F. G. Zitman , M. A. van Buchem , (2011). Extraversion is linked to volume of the orbitofrontal cortex and amygdala. PLoS One, 6, e28421.

C. G. DeYoung , J. B. Hirsh , M. S. Shane , X. Papademetris , N. Rajeevan , & J. R. Gray (2010). Testing predictions from personality neuroscience: Brain structure and the Big Five. Psychological Science, 21, 820828.

S. J. Dickman (1990). Functional and dysfunctional impulsivity: Personality and cognitive correlates. Journal of Personality and Social Psychology, 58, 95102.

L. E. Duncan , & M. C. Keller (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. American Journal of Psychiatry, 168, 10411049.

T. C. Eley , J. L. Hudson , C. Creswell , M. Tropeano , K. J. Lester , P. Cooper , (2012). Therapygenetics: The 5HTTLPR and response to psychological therapy. Molecular Psychiatry, 17, 236237.

J. L. Evenden (1999). Varieties of impulsivity. Psychopharmacology, 146, 348361.

C. Frydman , C. Camerer , P. Bossaerts , & A. Rangel (2011). MAOA-L carriers are better at making optimal financial decisions under risk. Proceedings of the Royal Society B: Biological Sciences, 278, 20532059.

N. Geschwind , N. A. Nicolson , F. Peeters , J. van Os , D. Barge-Schaapveld , & M. Wichers (2011). Early improvement in positive rather than negative emotion predicts remission from depression after pharmacotherapy. European Neuropsychopharmacology, 21, 241247.

J. Harro (2010). Interindividual differences in neurobiology as vulnerability factors for affective disorders: Implications for psychopharmacology. Pharmacology & Therapeutics, 125, 402422.

M. Harro , D. Eensoo , E. Kiive , L. Merenäkk , J. Alep , L. Oreland , (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.

J. Harro , L. Merenäkk , N. Nordquist , K. Konstabel , E. Comasco , & L. Oreland (2009). Personality and the serotonin transporter gene: Associations in a longitudinal population-based study. Biological Psychology, 81, 913.

J. R. Homberg , & K. P. Lesch (2011). Looking on the bright side of serotonin transporter gene variation. Biological Psychiatry, 69, 513519.

T. R. Insel (2010). Rethinking schizophrenia. Nature, 468, 187193.

P. Jylhä , & E. Isometsä (2006). The relationship of neuroticism and extraversion to symptoms of anxiety and depression in the general population. Depression and Anxiety, 23, 281289.

K. S. Kendler , M. Gatz , C. O. Gardner , & N. L. Pedersen (2006). Personality and major depression: A Swedish longitudinal, population-based twin study. Archives of General Psychiatry, 63, 11131120.

A. J. Kerscher , R. M. Rapee , & C. A. Schniering (2009). Neuroticism, life events, and negative thoughts in the development of depression in adolescent girls. Journal of Abnormal Child Psychology, 37, 903915.

J. P. Kiss , & E. S. Vizi (2001). Nitric oxide: A novel link between synaptic and nonsynaptic transmission. Trends in Neurosciences, 24, 211215.

K. Konstabel , J.-L. Lönnqvist , G. Walkowitz , K. Konstabel , & M. Verkasalo (2012). The “Short Five” (S5): Measuring personality traits using comprehensive single items. European Journal of Personality, 26, 1329.

C. Kriegebaum , L. Gutknecht , A. Schmitt , K. P. Lesch , & A. Reif (2010). Serotonin now: Part 2. Behavioral genetics and psychopathology. Fortschritte der Neurologie—Psychiatrie, 78, 332342.

K. Laas , A. Reif , S. Herterich , D. Eensoo , K.-P. Lesch , & J. Harro (2010). The effect of a functional NOS1 promoter polymorphism on impulsivity is moderated by platelet MAO activity. Psychopharmacology, 209, 255261.

J.-E. Lönnqvist , M. Verkasalo , S. Mäkinen , & M. Henriksson (2009). High neuroticism at age 20 predicts history of mental disorders and low self-esteem at age 35. Journal of Clinical Psychology, 65, 781790.

R. E. Lucas , K. Le , & P. S. Dyrenforth (2008). Explaining the extraversion/positive affect relation: Sociability cannot account for extraverts’ greater happiness. Journal of Personality, 76, 385414.

L. Malloy-Diniz , D. Fuentes , W. Borges Leite , H. Correa , & A. Bechara (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.

K. A. McLaughlin , N. A. Fox , C. H. Zeanah , & C. A. Nelson (2011). Adverse rearing environments and neural development in children: The development of frontal electroencephalogram asymmetry. Biological Psychiatry, 70, 10081015.

S. A. Montgomery , & M. Åsberg (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134, 382389.

R. Mõttus , H. Pullmann , & J. Allik (2006). Towards more readable Big Five personality inventories. European Journal of Psychological Assessment, 22, 149157.

P. Muris , A. E. R. Bos , B. Mayer , R. Verkade , V. Thewissen , & V. Dell'Avvento (2009). Relations among behavioral inhibition, Big Five personality factors, and anxiety disorder symptoms in nonclinical children. Personality and Individual Differences, 46, 525529.

R. J. Nelson , B. C. Trainor , S. Chiavegatto , & G. E. Demas (2006). Pleiotropic contributions of nitric oxide to aggressive behavior. Neuroscience and Biobehavioral Reviews, 30, 346355.

L. Oreland , N. Nordquist , J. Hallman , J. Harro , & K. W. Nilsson (2010). Environment and the serotonergic system. European Psychiatry, 25, 304306.

M. Paaver , T. Kurrikoff , N. Nordquist , L. Oreland , & J. Harro (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.

A. Reif , S. Herterich , A. Strobel , A.-C. Ehlis , D. Saur , C. P. Jacob , (2006). A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function. Molecular Psychiatry, 11, 286300.

A. Reif , C. P. Jacob , D. Rujescu , S. Herterich , S. Lang , L. Gutknech , (2009). Influence of functional variant of neuronal nitric oxide synthase on impulsive behaviors in humans. Archives of General Psychiatry, 66, 4150.

A. Reif , E. Kiive , T. Kurrikoff , M. Paaver , S. Herterich , K. Konstabel , (2011). A functional NOS1 promoter polymorphism interacts with adverse environment on functional and dysfunctional impulsivity. Psychopharmacology, 214, 239248.

I. Reiner , & G. Spangler (2011). Dopamine D4 receptor exon III polymorphism, adverse life events, and personality traits in a nonclinical German adult sample. Neuropsychobiology, 63, 5258.

T. Rife , B. Rasoul , N. Pullen , D. Mitchell , K. Grathwol , & J. Kurth (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.

B. W. Roberts , K. E. Walton , & W. Viechtbauer (2006). Patterns of mean-level change in personality traits across the life course: A meta-analysis of longitudinal studies. Psychological Bulletin, 132, 125.

D. P. Schmitt , A. Realo , M. Voracek , & J. Allik (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.

L. D. Smillie , A. J. Cooper , P. Proitsi , J. F. Powell , & A. D. Pickering (2010). Variation in DRD2 dopamine gene predicts extraverted personality. Neuroscience Letters, 468, 234237.

L. D. Smillie , & C. J. Jackson (2006). Functional impulsivity and reinforcement sensitivity theory. Journal of Personality, 74, 4783.

M. ten Have , A. Oldehinkel , W. Vollebergh , & J. Ormel (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.

B. C. Trainor , J. L. Workman , R. Jessen , & R. J. Nelson (2007). Impaired nitric oxide synthase signaling dissociates social investigation and aggression. Behavioural Neuroscience, 121, 362369.

R. Uher , & P. McGuffin (2010). The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Molecular Psychiatry, 15, 1822.

S. Van de Velde , P. Bracke , & K. Levecque (2010). Gender differences in depression in 23 European countries: Cross-national variation in the gender gap in depression. Social Science & Medicine, 71, 305313.

J. L. Workman , B. C. Trainor , M. S. Finly , & R. J. Nelson (2008). Inhibition of neuronal nitric oxide reduces anxiety-like responses to pair housing. Behavioral Brain Research, 187, 109115.

T. Wultsch , S. Chourbaji , S. Fritzen , S. Kittel , E. Grünblatt , M. Gerlach , (2007). Behavioural and expressional phenotyping of nitric oxide synthase-I knockdown animals. Jounal of Neural Transmission, 72(Suppl.), 6985.

J. Zhang , X. Y. Huang , M. L. Ye , C. X. Luo , H. Y. Wu , Y. Hu , (2010). Neuronal nitric oxide synthase alteration accounts for the role of 5-HT1A receptor in modulating anxiety-related behaviors. Journal of Neuroscience, 30, 24332441.

Q.-G. Zhou , Y. Hu , Y. Hua , M. Hu , C.-X. Luo , X. Han , (2007). Neuronal nitric oxide synthase contributes to chronic stress-induced depression by suppressing hippocampal neurogenesis. Journal of Neurochemistry, 103, 18431854.

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