Skip to main content Accessibility help

Relationship of monoamine oxidase A binding to adaptive and maladaptive personality traits

  • A. Soliman (a1) (a2), R. M. Bagby (a3), A. A. Wilson (a1), L. Miler (a1), M. Clark (a1), P. Rusjan (a1), J. Sacher (a1) (a2) (a4), S. Houle (a1) and J. H. Meyer (a1) (a2)...



Monoamine oxidase A (MAOA) is an important enzyme that metabolizes monoamines such as serotonin, norepinephrine and dopamine in the brain. In prefrontal cortex, low MAOA binding is associated with aggression and high binding is associated with major depressive disorder (MDD) and also risk for recurrence of depressive episodes. In rodent models, low MAOA levels are associated with increased aggression and fear conditioning, and decreased social and exploratory investigative behaviors. Our objective was to measure MAOA binding in prefrontal cortex and concurrently evaluate a broad range of validated personality traits. We hypothesized that prefrontal MAOA binding would correlate negatively with angry-hostility, a trait related to aggression/anger, and positively with traits intuitively related to adaptive investigative behavior.


Participants were aged 19–49 years, healthy and non-smoking. MAOA binding was measured with [11C]harmine positron emission tomography (PET) in prefrontal brain regions and personality traits were measured with the NEO Personality Inventory Revised (NEO PI-R).


Prefrontal MAOA binding correlated negatively with angry-hostility (r=−0.515, p=0.001) and positively with deliberation (r=0.514, p=0.001). In a two-factor regression model, these facets explained 38% of variance in prefrontal MAOA binding. A similar relationship was found in prefrontal cortex subregions.


We propose a new continuum describing the relationship between personality and MAOA: deliberate/thoughtful contrasting aggressive/impulsive. Additionally, the association between high MAOA binding and greater deliberation may explain why some people have moderately high levels of MAOA, although very high levels occur during MDD. In health, higher MAOA binding is associated with an adaptive personality facet.


Corresponding author

*Address for correspondence: Dr J. H. Meyer, College Street Site, Centre for Addiction and Mental Health, PET Centre, 250 College St, Toronto, Ontario, Canada M5T 1R8. (Email:


Hide All
Alia-Klein, N, Goldstein, RZ, Kriplani, A, Logan, J, Tomasi, D, Williams, B, Telang, F, Shumay, E, Biegon, A, Craig, IW, Henn, F, Wang, GJ, Volkow, ND, Fowler, JS (2008). Brain monoamine oxidase A activity predicts trait aggression. Journal of Neuroscience 28, 50995104.
Aluja, A, García, Ó, García, LF, Seisdedos, N (2005). Invariance of the ‘NEO-PI-R’ factor structure across exploratory and confirmatory factor analyses. Personality and Individual Differences 38, 18791889.
Ashburner, J, Friston, K (1997). Multimodal image coregistration and partitioning – a unified framework. NeuroImage 6, 209217.
Ashburner, J, Friston, KJ (1999). Nonlinear spatial normalization using basis functions. Human Brain Mapping 7, 254266.
Barrash, J, Tranel, D, Anderson, SW (2000). Acquired personality disturbances associated with bilateral damage to the ventromedial prefrontal region. Developmental Neuropsychology 18, 355381.
Berlin, HA, Rolls, ET, Kischka, U (2004). Impulsivity, time perception, emotion and reinforcement sensitivity in patients with orbitofrontal cortex lesions. Brain 127, 11081126.
Bortolato, M, Chen, K, Shih, JC (2008). Monoamine oxidase inactivation: from pathophysiology to therapeutics. Advanced Drug Delivery Reviews 60, 15271533.
Brown, GL, Goodwin, FK, Ballenger, JC, Goyer, PF, Major, LF (1979). Aggression in humans correlates with cerebrospinal fluid amine metabolites. Psychiatry Research 1, 131139.
Brunner, HG, Nelen, M, Breakefield, XO, Ropers, HH, van Oost, BA (1993). Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 262, 578580.
Buckholtz, JW, Callicott, JH, Kolachana, B, Hariri, AR, Goldberg, TE, Genderson, M, Egan, MF, Mattay, VS, Weinberger, DR, Meyer-Lindenberg, A (2008). Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality. Molecular Psychiatry 13, 313324.
Burger, JM (1993). Personality. Brooks/Cole Publishing Company: Pacific Grove, CA.
Caramaschi, D, de Boer, SF, de Vries, H, Koolhaas, JM (2008). Development of violence in mice through repeated victory along with changes in prefrontal cortex neurochemistry. Behavioural Brain Research 189, 263272.
Cases, O, Seif, I, Grimsby, J, Gaspar, P, Chen, K, Pournin, S, Müller, U, Aguet, M, Babinet, C, Shih, JC, Maeyer, ED (1995). Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science 268, 17631766.
Cases, O, Vitalis, T, Seif, I, De Maeyer, E, Sotelo, C, Gaspar, P (1996). Lack of barrels in the somatosensory cortex of monoamine oxidase A-deficient mice: role of a serotonin excess during the critical period. Neuron 16, 297307.
Caspi, A, McClay, J, Moffitt, TE, Mill, J, Martin, J, Craig, IW, Taylor, A, Poulton, R (2002). Role of genotype in the cycle of violence in maltreated children. Science 297, 851854.
Centers for Disease and Control Prevention (2008). Smoking-attributable mortality, years of potential life lost, and productivity losses – United States, 2000–2004. Morbidity and Mortality Weekly Report 57, 12261228.
Chen, K, Cases, O, Rebrin, I, Wu, W, Gallaher, TK, Seif, I, Shih, JC (2007). Forebrain-specific expression of monoamine oxidase A reduces neurotransmitter levels, restores the brain structure, and rescues aggressive behavior in monoamine oxidase A-deficient mice. Journal of Biological Chemistry 282, 115123.
Chow, TW (2000). Personality in frontal lobe disorders. Current Psychiatry Reports 2, 446451.
Compton, WM, Conway, KP, Stinson, FS, Colliver, JD, Grant, BF (2005). Prevalence, correlates, and comorbidity of DSM-IV antisocial personality syndromes and alcohol and specific drug use disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Journal of Clinical Psychiatry 66, 677685.
Costa, Jr. PT, McCrae, RR (1988). Personality in adulthood: a six-year longitudinal study of self-reports and spouse ratings on the NEO Personality Inventory. Journal of Personality and Social Psychology 54, 853863.
Costa, PT, McCrae, RR (1992). Revised NEO Personality Inventory and NEO Five-Factor Inventory Professional Manual. Psychological Assessment Resources: Odessa, FL.
Courbasson, CMA (2006). Reflective activity and its measurement. International Journal of Mental Health and Addiction 4, 133149.
Damasio, AR (1995). On some functions of the human prefrontal cortex. Annals of the New York Academy of Sciences 769, 241251.
Digman, JM (1990). Personality structure: emergence of the five-factor model. Annual Review of Psychology 41, 417440.
Drevets, WC (2000). Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression. Progress in Brain Research 126, 413431.
Farde, L, Gustavsson, JP, Jonsson, E (1997). D2 dopamine receptors and personality traits. Nature 385, 590.
First, M, Spitzer, R, Williams, J, Gibbon, M (1995). Structured Clinical Interview for DSM-IV, Non-Patient Edition (SCID-NP, Version 1.0). American Psychiatric Press: Washington, DC.
Fischer, S, Smith, GT (2004). Deliberation affects risk taking beyond sensation seeking. Personality and Individual Differences 36, 527537.
Fowler, JS, Volkow, ND, Wang, GJ, Pappas, N, Logan, J, Shea, C, Alexoff, D, MacGregor, RR, Schlyer, DJ, Zezulkova, I, Wolf, AP (1996). Brain monoamine oxidase A inhibition in cigarette smokers. Proceedings of the National Academy of Sciences USA 93, 1406514069.
Frokjaer, VG, Mortensen, EL, Nielsen, FA, Haugbol, S, Pinborg, LH, Adams, KH, Svarer, C, Hasselbalch, SG, Holm, S, Paulson, OB, Knudsen, GM (2008). Frontolimbic serotonin 2A receptor binding in healthy subjects is associated with personality risk factors for affective disorder. Biological Psychiatry 63, 569576.
Garrick, NA, Seppala, T, Linnoila, M, Murphy, DL (1985). Rhesus monkey cerebrospinal fluid amine metabolite changes following treatment with the reversible monoamine oxidase type-A inhibitor cimoxatone. Psychopharmacology 86, 265269.
Ginovart, N, Meyer, JH, Boovariwala, A, Hussey, D, Rabiner, EA, Houle, S, Wilson, AA (2006). Positron emission tomography quantification of [11C]-harmine binding to monoamine oxidase-A in the human brain. Journal of Cerebral Blood Flow and Metabolism 26, 330344.
Goldberg, LR (1990). An alternative ‘description of personality’: the Big-Five factor structure. Journal of Personality and Social Psychology 59, 12161229.
Grace, AA (1991). Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41, 124.
Haefely, W, Burkard, WP, Cesura, AM, Kettler, R, Lorez, HP, Martin, JR, Richards, JG, Scherschlicht, R, Da Prada, M (1992). Biochemistry and pharmacology of moclobemide, a prototype RIMA. Psychopharmacology 106 (Suppl.), S6–S14.
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.
Harkness, KL, Bagby, RM, Joffe, RT, Levitt, A (2002). Major depression, chronic minor depression, and the Five-Factor Model of Personality. European Journal of Personality 16, 271281.
Holschneider, DP, Scremin, OU, Huynh, L, Chen, K, Seif, I, Shih, JC (2000). Regional cerebral cortical activation in monoamine oxidase A-deficient mice: differential effects of chronic versus acute elevations in serotonin and norepinephrine. Neuroscience 101, 869877.
Kalbitzer, J, Frokjaer, VG, Erritzoe, D, Svarer, C, Cumming, P, Nielsen, FA, Hashemi, SH, Baare, WF, Madsen, J, Hasselbalch, SG, Kringelbach, ML, Mortensen, EL, Knudsen, GM (2009). The personality trait openness is related to cerebral 5-HTT levels. NeuroImage 45, 280285.
Kawahara, H, Yoshida, M, Yokoo, H, Nishi, M, Tanaka, M (1993). Psychological stress increases serotonin release in the rat amygdala and prefrontal cortex assessed by in vivo microdialysis. Neuroscience Letters 162, 8184.
Kim, JJ, Shih, JC, Chen, K, Chen, L, Bao, S, Maren, S, Anagnostaras, SG, Fanselow, MS, De Maeyer, E, Seif, I, Thompson, RF (1997). Selective enhancement of emotional, but not motor, learning in monoamine oxidase A-deficient mice. Proceedings of the National Academy of Sciences USA 94, 59295933.
Kim-Cohen, J, Caspi, A, Taylor, A, Williams, B, Newcombe, R, Craig, IW, Moffitt, TE (2006). MAOA, maltreatment, and gene-environment interaction predicting children's mental health: new evidence and a meta-analysis. Molecular Psychiatry 11, 903913.
Lebrand, C, Cases, O, Adelbrecht, C, Doye, A, Alvarez, C, El Mestikawy, S, Seif, I, Gaspar, P (1996). Transient uptake and storage of serotonin in developing thalamic neurons. Neuron 17, 823835.
Lieberman, JA, Sheitman, BB, Kinon, BJ (1997). Neurochemical sensitization in the pathophysiology of schizophrenia: deficits and dysfunction in neuronal regulation and plasticity. Neuropsychopharmacology 17, 205229.
Linnoila, M, Virkkunen, M, Scheinin, M, Nuutila, A, Rimon, R, Goodwin, FK (1983). Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. Life Sciences 33, 26092614.
Linnoila, VM, Virkkunen, M (1992). Aggression, suicidality, and serotonin. Journal of Clinical Psychiatry 53 (Suppl.), 4651.
Logan, J, Fowler, JS, Volkow, ND, Wolf, AP, Dewey, SL, Schlyer, DJ, MacGregor, RR, Hitzemann, R, Bendriem, B, Gatley, SJ (1990). Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11C-methyl]-(-)-cocaine PET studies in human subjects. Journal of Cerebral Blood Flow and Metabolism 10, 740747.
Love, TM, Stohler, CS, Zubieta, J-K (2009). Positron emission tomography measures of endogenous opioid neurotransmission and impulsiveness traits in humans. Archives of General Psychiatry 66, 11241134.
Luciano, M, Wainwright, MA, Wright, MJ, Martin, NG (2006). The heritability of conscientiousness facets and their relationship to IQ and academic achievement. Personality and Individual Differences 40, 11891199.
Matsuo, K, Nicoletti, M, Nemoto, K, Hatch, JP, Peluso, MA, Nery, FG, Soares, JC (2009). A voxel-based morphometry study of frontal gray matter correlates of impulsivity. Human Brain Mapping 30, 11881195.
Meyer, JH, Ginovart, N, Boovariwala, A, Sagrati, S, Hussey, D, Garcia, A, Young, T, Praschak-Rieder, N, Wilson, AA, Houle, S (2006). Elevated monoamine oxidase A levels in the brain: an explanation for the monoamine imbalance of major depression. Archives of General Psychiatry 63, 12091216.
Meyer, JH, Wilson, AA, Sagrati, S, Miler, L, Rusjan, P, Bloomfield, PM, Clark, M, Sacher, J, Voineskos, AN, Houle, S (2009). Brain monoamine oxidase A binding in major depressive disorder: relationship to selective serotonin reuptake inhibitor treatment, recovery, and recurrence. Archives of General Psychiatry 66, 13041312.
Meyer-Lindenberg, A, Buckholtz, JW, Kolachana, B, Hariri, AR, Pezawas, L, Blasi, G, Wabnitz, A, Honea, R, Verchinski, B, Callicott, JH, Egan, M, Mattay, V, Weinberger, DR (2006). Neural mechanisms of genetic risk for impulsivity and violence in humans. Proceedings of the National Academy of Sciences USA 103, 62696274.
Mickey, BJ, Ducci, F, Hodgkinson, CA, Langenecker, SA, Goldman, D, Zubieta, JK (2008). Monoamine oxidase A genotype predicts human serotonin 1A receptor availability in vivo. Journal of Neuroscience 28, 1135411359.
Murphy, JM, Laird, NM, Monson, RR, Sobol, AM, Leighton, AH (2000). A 40-year perspective on the prevalence of depression: the Stirling County Study. Archives of General Psychiatry 57, 209215.
New, AS, Hazlett, EA, Newmark, RE, Zhang, J, Triebwasser, J, Meyerson, D, Lazarus, S, Trisdorfer, R, Goldstein, KE, Goodman, M, Koenigsberg, HW, Flory, JD, Siever, LJ, Buchsbaum, MS (2009). Laboratory induced aggression: a positron emission tomography study of aggressive individuals with borderline personality disorder. Biological Psychiatry 66, 11071114.
Popova, NK, Skrinskaya, YA, Amstislavskaya, TG, Vishnivetskaya, GB, Seif, I, de Meier, E (2001). Behavioral characteristics of mice with genetic knockout of monoamine oxidase type A. Neuroscience and Behavioral Physiology 31, 597602.
Popova, NK, Vishnivetskaya, GB, Ivanova, EA, Skrinskaya, JA, Seif, I (2000). Altered behavior and alcohol tolerance in transgenic mice lacking MAO A: a comparison with effects of MAO A inhibitor clorgyline. Pharmacology, Biochemistry and Behavior 67, 719727.
Pruessner, JC, Champagne, F, Meaney, MJ, Dagher, A (2004). Dopamine release in response to a psychological stress in humans and its relationship to early life maternal care: a positron emission tomography study using [11C]raclopride. Journal of Neuroscience 24, 28252831.
Quirk, GJ, Beer, JS, Quirk, GJ, Beer, JS (2006). Prefrontal involvement in the regulation of emotion: convergence of rat and human studies. Current Opinion in Neurobiology 16, 723727.
Raine, A, Lencz, T, Bihrle, S, LaCasse, L, Colletti, P (2000). Reduced prefrontal gray matter volume and reduced autonomic activity in antisocial personality disorder. Archives of General Psychiatry 57, 119127; discussion 128–129.
Ressler, KJ, Mayberg, HS (2007). Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nature Neuroscience 10, 11161124.
Rusjan, P, Mamo, D, Ginovart, N, Hussey, D, Vitcu, I, Yasuno, F, Tetsuya, S, Houle, S, Kapur, S (2006). An automated method for the extraction of regional data from PET images. Psychiatry Research 147, 7989.
Sacher, J, Wilson, AA, Houle, S, Rusjan, P, Hassan, S, Bloomfield, PM, Stewart, DE, Meyer, JH (2010). Elevated brain monoamine oxidase A binding in the early postpartum period. Archives of General Psychiatry 67, 468474.
Saura, J, Andrés, N, Andrade, C, Ojuel, J, Eriksson, K, Mahy, N (1997). Biphasic and region-specific MAO-B response to aging in normal human brain. Neurobiology of Aging 18, 497507.
Saura, J, Bleuel, Z, Ulrich, J, Mendelowitsch, A, Chen, K, Shih, JC, Malherbe, P, Da Prada, M, Richards, JG (1996). Molecular neuroanatomy of human monoamine oxidases A and B revealed by quantitative enzyme radioautography and in situ hybridization histochemistry. Neuroscience 70, 755774.
Saura, J, Kettler, R, Da Prada, M, Richards, JG (1992). Quantitative enzyme radioautography with 3H-Ro 41-1049 and 3H-Ro 19-6327 in vitro: localization and abundance of MAO-A and MAO-B in rat CNS, peripheral organs, and human brain. Journal of Neuroscience 12, 19771999.
Scott, S, Knapp, M, Henderson, J, Maughan, B (2001). Financial cost of social exclusion: follow up study of antisocial children into adulthood. British Medical Journal 323, 191.
Shih, JC (2004). Cloning, after cloning, knock-out mice, and physiological functions of MAO A and B. Neurotoxicology 25, 2130.
Shih, JC, Chen, K, Ridd, MJ (1999 a). Monoamine oxidase: from genes to behavior. Annual Review of Neuroscience 22, 197217.
Shih, JC, Ridd, MJ, Chen, K, Meehan, WP, Kung, MP, Seif, I, De Maeyer, E (1999 b). Ketanserin and tetrabenazine abolish aggression in mice lacking monoamine oxidase A. Brain Research 835, 104112.
Siever, LJ, Buchsbaum, MS, New, AS, Spiegel-Cohen, J, Wei, T, Hazlett, EA, Sevin, E, Nunn, M, Mitropoulou, V (1999). d,l-fenfluramine response in impulsive personality disorder assessed with [18F]fluorodeoxyglucose positron emission tomography. Neuropsychopharmacology 20, 413423.
Soliman, A, O'Driscoll, GA, Pruessner, J, Holahan, ALV, Boileau, I, Gagnon, D, Dagher, A (2008). Stress-induced dopamine release in humans at risk of psychosis: a [C-11]raclopride PET study. Neuropsychopharmacology 33, 20332041.
Studholme, C, Hill, D, Hawkes, D (1999). An overlap invariant entropy measure of 3D medical image alignment. Pattern Recognition 32, 7186.
Upton, AL, Salichon, N, Lebrand, C, Ravary, A, Blakely, R, Seif, I, Gaspar, P (1999). Excess of serotonin (5-HT) alters the segregation of ispilateral and contralateral retinal projections in monoamine oxidase A knock-out mice: possible role of 5-HT uptake in retinal ganglion cells during development. Journal of Neuroscience 19, 70077024.
Ustun, TB, Ayuso-Mateos, JL, Chatterji, S, Mathers, C, Murray, CJ (2004). Global burden of depressive disorders in the year 2000. British Journal of Psychiatry 184, 386392.
Vitalis, T, Cases, O, Callebert, J, Launay, JM, Price, DJ, Seif, I, Gaspar, P (1998). Effects of monoamine oxidase A inhibition on barrel formation in the mouse somatosensory cortex: determination of a sensitive developmental period. Journal of Comparative Neurology 393, 169184.
Waldmeier, PC, Baumann, PA (1983). Effects of CGP 11305 A, a new reversible and selective inhibitor of MAO A, on biogenic amine levels and metabolism in the rat brain. Naunyn-Schmiedebergs Archives of Pharmacology 324, 2026.
Whiteside, SP, Lynam, DR (2001). The Five Factor Model and impulsivity: using a structural model of personality to understand impulsivity. Personality and Individual Differences 30, 669689.
Yang, Z, Seif, I, Armstrong-James, M (2001). Differences in somatosensory processing in S1 barrel cortex between normal and monoamine oxidase A knockout (Tg8) adult mice. Cerebral Cortex 11, 2636.
Youdim, MB, Edmondson, D, Tipton, KF (2006). The therapeutic potential of monoamine oxidase inhibitors. Nature Reviews Neuroscience 7, 295309.
Young, MS, Schinka, JA (2001). Research validity scales for the NEO-PI-R: additional evidence for reliability and validity. Journal of Personality Assessment 76, 412420.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed