Skip to main content
SpringerLink
Log in

From aggression to autism: new perspectives on the behavioral sequelae of monoamine oxidase deficiency

  • Psychiatry and Preclinical Psychiatric Studies - Review Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

The two monoamine oxidase (MAO) enzymes, A and B, catalyze the metabolism of monoamine neurotransmitters, such as serotonin, norepinephrine, and dopamine. The phenotypic outcomes of MAO congenital deficiency have been studied in humans and animal models, to explore the role of these enzymes in behavioral regulation. The clinical condition caused by MAOA deficiency, Brunner syndrome, was first described as a disorder characterized by overt antisocial and aggressive conduct. Building on this discovery, subsequent studies were focused on the characterization of the role of MAOA in the neurobiology of antisocial conduct. MAO A knockout mice were found to display high levels of intermale aggression; however, further analyses of these mutants unveiled additional behavioral abnormalities mimicking the core symptoms of autism-spectrum disorder. These findings were strikingly confirmed in newly reported cases of Brunner syndrome. The role of MAOB in behavioral regulation remains less well-understood, even though Maob-deficient mice have been found to exhibit greater behavioral disinhibition and risk-taking responses, supporting previous clinical studies showing associations between low MAO B activity and impulsivity. Furthermore, lack of MAOB was found to exacerbate the severity of psychopathological deficits induced by concurrent MAOA deficiency. Here, we summarize how the convergence of clinical reports and behavioral phenotyping in mutant mice has helped frame a complex picture of psychopathological features in MAO-deficient individuals, which encompass a broad spectrum of neurodevelopmental problems. This emerging knowledge poses novel conceptual challenges towards the identification of the endophenotypes shared by autism-spectrum disorder, antisocial behavior and impulse-control problems, as well as their monoaminergic underpinnings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aguinaga D, Medrano M, Vega-Quiroga I, Gysling K, Canela EI, Navarro G, Franco R (2018) Cocaine effects on dopaminergic transmission depend on a balance between sigma-1 and sigma-2 receptor expression. Front Mol Neurosci 11:17

    PubMed  PubMed Central  Google Scholar 

  • Alon A, Schmidt HR, Wood MD, Sahn JJ, Martin SF, Kruse AC (2017) Identification of the gene that codes for the σ(2) receptor. Proc Natl Acad Sci USA 114:7160–7165

    CAS  PubMed  Google Scholar 

  • Ambroziak W, Pietruszko R (1991) Human aldehyde dehydrogenase. Activity with aldehyde metabolites of monoamines, diamines, and polyamines. J Biol Chem 266:13011–13018

    CAS  PubMed  Google Scholar 

  • Anichtchik O, Sallinen V, Peitsaro N, Panula P (2006) Distinct structure and activity of monoamine oxidase in the brain of zebrafish (Danio rerio). J Comp Neurol 498:593–610

    CAS  PubMed  Google Scholar 

  • Arnsten AF (2009) Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci 10:410–422

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bach AW, Lan NC, Johnson DL, Abell CW, Bembenek ME, Kwan SW, Seeburg PH, Shih JC (1988) cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc Natl Acad Sci USA 85:4934–4938

    CAS  PubMed  Google Scholar 

  • Beckmann H, Waldmeier P, Lauber J, Gattaz WF. (1983) Phenylethylamine and monoamine metabolites in CSF of schizophrenics: effects of neuroleptic treatment. J Neural Transm 57: 103–110

    CAS  PubMed  Google Scholar 

  • Berry MD (2007) The potential of trace amines and their receptors for treating neurological and psychiatric diseases. Rev Recent Clin Trials 2:3–19

    CAS  PubMed  Google Scholar 

  • Black KJ, Hershey T, Koller JM, Videen TO, Mintun MA, Price JL, Perlmutter JS (2002) A possible substrate for dopamine-related changes in mood and behavior: prefrontal and limbic effects of a D3-preferring dopamine agonist. Proc Natl Acad Sci USA 99:17113–17118

    CAS  PubMed  Google Scholar 

  • Blanco C, Orensanz-Muñoz L, Blanco-Jerez C, Saiz-Ruiz J (1996) Pathological gambling and platelet MAO activity: a psychobiological study. Am J Psychiatr 153:119–121

    CAS  PubMed  Google Scholar 

  • Bond PA, Cundall RL (1977) Properties of monoamine oxidase (MAO) in human blood platelets, plasma, lymphocytes and granulocytes. Clin Chim Acta 80:317–326

    CAS  PubMed  Google Scholar 

  • Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C (2001) Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci USA 98:8966–8971

    CAS  PubMed  Google Scholar 

  • Bortolato M, Shih JC (2011) Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence. Int Rev Neurobiol 100:13–42

    PubMed  PubMed Central  Google Scholar 

  • Bortolato M, Chen K, Shih JC (2008) Monoamine oxidase inactivation: from pathophysiology to therapeutics. Adv Drug Deliv Rev 60:1527–1533

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bortolato M, Godar SC, Davarian S, Chen K, Shih JC (2009) Behavioral disinhibition and reduced anxiety-like behaviors in monoamine oxidase B-deficient mice. Neuropsychopharmacology 34:2746–2757

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bortolato M, Godar SC, Melis M, Soggiu A, Roncada P, Casu A, Flore G, Chen K, Frau R, Urbani A, Castelli MP, Devoto P, Shih JC (2012) NMDARs mediate the role of monoamine oxidase A in pathological aggression. J Neurosci 32:8574–8582

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bortolato M, Godar SC, Tambaro S, Li FG, Devoto P, Coba MP, Chen K, Shih JC (2013a) Early postnatal inhibition of serotonin synthesis results in long-term reductions of perseverative behaviors, but not aggression, in MAO A-deficient mice. Neuropharmacology 75:223–232

    CAS  PubMed  Google Scholar 

  • Bortolato M, Godar SC, Alzghoul L, Zhang J, Darling RD, Simpson KL, Bini V, Chen K, Wellman CL, Lin RC, Shih JC (2013b) Monoamine oxidase A and A/B knockout mice display autistic-like features. Int J Neuropsychopharmacol 16:869–888

    CAS  PubMed  Google Scholar 

  • Boutet I, Tanguy A, Moraga D (2004) Molecular identification and expression of two non-P450 enzymes, monoamine oxidase A and flavin-containing monooxygenase 2, involved in phase I of xenobiotic biotransformation in the Pacific oyster, Crassostrea gigas. Biochim Biophys Acta 1679:29–36

    CAS  PubMed  Google Scholar 

  • Boylan CB, Bennett-Clarke CA, Crissman RS, Mooney RD, Rhoades RW (2000) Clorgyline treatment elevates cortical serotonin and temporarily disrupts the vibrissae-related pattern in rat somatosensory cortex. J Comp Neurol 427: 139–49

    CAS  PubMed  Google Scholar 

  • Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA (1993a) Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 262:578–580

    CAS  PubMed  Google Scholar 

  • Brunner HG, Nelen MR, van Zandvoort P, Abeling NG, van Gennip AH, Wolters EC, Kuiper MA, Ropers HH, van Oost BA (1993b) X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism. Am J Hum Genet 52:1032–1039

    CAS  PubMed  PubMed Central  Google Scholar 

  • Buchsbaum MS, Coursey RD, Murphy DL (1976) The biochemical high-risk paradigm: behavioral and familial correlates of low platelet monoamine oxidase activity. Science 194:339–341

    CAS  PubMed  Google Scholar 

  • Buckholtz JW, Meyer-Lindenberg A (2008) MAO A and the neurogenetic architecture of human aggression. Trends Neurosci 31:120–129

    CAS  PubMed  Google Scholar 

  • Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S, Muller U, Aguet M, Babinet C, Shih JC (1995) Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science 268:1763–1766

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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 297:851–854

    CAS  PubMed  Google Scholar 

  • Cerasa A, Gioia MC, Labate A, Lanza P, Magariello A, Muglia M, Quattrone A (2008) MAO A VNTR polymorphism and variation in human morphology: a VBM study. Neuroreport 19:1107–1110

    PubMed  Google Scholar 

  • Cerasa A, Cherubini A, Quattrone A, Gioia MC, Magariello A, Muglia M, Manna I, Assogna F, Caltagirone C, Spalletta G (2010) Morphological correlates of MAO A VNTR polymorphism: new evidence from cortical thickness measurement. Behav Brain Res 211:118–124

    CAS  PubMed  Google Scholar 

  • Chen L, He M, Sibille E, Thompson A, Sarnyai Z, Baker H, Shippenberg T, Toth M (1999) Adaptive changes in postsynaptic dopamine receptors despite unaltered dopamine dynamics in mice lacking monoamine oxidase B. J Neurochem 73:647–655

    CAS  PubMed  Google Scholar 

  • Chen K, Holschneider DP, Wu W, Rebrin I, Shih JC (2004) A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior. J Biol Chem 279:39645–3965

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng A, Scott AL, Ladenheim B, Chen K, Ouyang X, Lathia JD, Mughal M, Cadet JL, Mattson MP, Shih JC (2010) Monoamine oxidases regulate telencephalic neural progenitors in late embryonic and early postnatal development. J Neurosci 30:10752–10762

    CAS  PubMed  PubMed Central  Google Scholar 

  • Coccini T, Crevani A, Rossi G, Assandri F, Balottin U, Nardo RD, Manzo L (2009) Reduced platelet monoamine oxidase type B activity and lymphocyte muscarinic receptor binding in unmedicated children with attention deficit hyperactivity disorder. Biomarkers 14:513–522

    CAS  PubMed  Google Scholar 

  • Collins FA, Murphy DL, Reiss AL, Sims KB, Lewis JG, Freund L, Karoum F, Zhu D, Maumenee IH, Antonarakis SE (1992) Clinical, biochemical, and neuropsychiatric evaluation of a patient with a contiguous gene syndrome due to a microdeletion Xp11.3 including the Norrie disease locus and monoamine oxidase (MAOA and MAOB) genes. Am J Med Genet 42:127–134

    CAS  PubMed  Google Scholar 

  • Contini V, Marques FZ, Garcia CE, Hutz MH, Bau CH (2006) MAOA-uVNTR polymorphism in a Brazilian sample: further support for the association with impulsive behaviors and alcohol dependence. Am J Med Genet B Neuropsychiatr Genet 141:305–308

    Google Scholar 

  • Dahlstroem A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand Suppl 232:1–55

    Google Scholar 

  • Deckert J, Catalano M, Syagailo YV, Bosi M, Okladnova O, Di Bella D, Nöthen MM, Maffei P, Franke P, Fritze J, Maier W, Propping P, Beckmann H, Bellodi L, Lesch K-P (1999) Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Hum Mol Genet 8:621–624

    CAS  PubMed  Google Scholar 

  • Denney RM, Koch H, Craig IW (1999) Association between monoamine oxidase A activity in human male skin fibroblasts and genotype of the MAO-A promoter-associated variable number tandem repeat. Hum Genet 105:542–551

    CAS  PubMed  Google Scholar 

  • Donnelly CH, Murphy DL (1977) Substrate- and inhibitor-related characteristics of human platelet. Biochem Pharmacol 26:853–858

    CAS  PubMed  Google Scholar 

  • Doran N, Sanders PE, Bekman NM, Worley MJ, Monreal TK, McGee E, Cummins K, Brown SA (2011) Mediating influences of negative affect and risk perception on the relationship between sensation seeking and adolescent cigarette smoking. Nicotine Tob Res 13:457–465

    PubMed  PubMed Central  Google Scholar 

  • Dubrovina NI, Popova NK, Gilinskii MA, Tomilenko RA, Seif I (2006) Acquisition and extinction of a conditioned passive avoidance reflex in mice with genetic knockout of monoamine oxidase A. Neurosci Behav Physiol 36:335–339

    CAS  PubMed  Google Scholar 

  • Edmondson DE, Mattevi A, Binda C, Li M, Hubálek F (2004) Structure and mechanism of monoamine oxidase. Curr Med Chem 11:1983–1993

    CAS  PubMed  Google Scholar 

  • Ekblom J, Jossan SS, Bergström M, Oreland L, Walum E, Aquilonius SM (1993) Monoamine oxidase-B in astrocytes. Glia 8:122–132

    CAS  PubMed  Google Scholar 

  • Erzurumlu RS, Gaspar P (2012) Development and critical period plasticity of the barrel cortex. Eur J Neurosci 35:1540–1553

    PubMed  PubMed Central  Google Scholar 

  • Feldstein A, Williamson O (1968) 5-Hydroxytryptamine metabolism in rat brain and liver homogenates. Br J Pharmacol 34(1):38–42

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fitzpatrick PF, Chadegani F, Zhang S, Roberts KM, Hinck CS (2016) Mechanism of the flavoprotein l-hydroxynicotine oxidase: kinetic mechanism, substrate specificity, reaction product, and roles of active-site residues. Biochemistry 55:697–703

    CAS  PubMed  PubMed Central  Google Scholar 

  • Foley DL, Eaves LJ, Wormley B, Silberg JL et al (2004) Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder. Arch Gen Psychiatr 61:738–744

    CAS  PubMed  Google Scholar 

  • Fontanilla D, Johannessen M, Hajipour AR, Cozzi NV, Jackson MB, Ruoho AE (2009) The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science 323:934–937

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fowler CJ, von Knorring L, Oreland L (1980) Platelet monoamine oxidase activity in sensation seekers. Psychiatr Res 3:273–279

    CAS  Google Scholar 

  • Fowler JS, Volkow ND, Wang GJ, Pappas N, Logan J, MacGregor R, Alexoff D, Wolf AP, Warner D, Cilento R, Zezulkova I (1998) Neuropharmacological actions of cigarette smoke: brain monoamine oxidase B (MAO B) inhibition. J Addict Dis 17:23–34

    CAS  PubMed  Google Scholar 

  • Garpenstrand H, Ekblom J, Forslund K, Rylander G, Oreland L (2000) Platelet monoamine oxidase activity is related to MAOB intron 13 genotype. J Neural Transm 107:523–530

    CAS  PubMed  Google Scholar 

  • Garrick NA, Murphy DL (1980) Species differences in the deamination of dopamine and other substrates for monoamine oxidase in brain. Psychopharmacology 72:27–33

    CAS  PubMed  Google Scholar 

  • Glover V, Sandler M, Owen F, Riley GJ (1977) Dopamine is a monoamine oxidase B substrate in man. Nature 265:80–81

    CAS  PubMed  Google Scholar 

  • Godar SC, Bortolato M, Frau R, Dousti M, Chen K, Shih JC (2011) Maladaptive defensive behaviours in monoamine oxidase A-deficient mice. Int J Neuropsychopharmacol 14:1195–1207

    CAS  PubMed  Google Scholar 

  • Godar SC, Bortolato M, Castelli MP, Casti A, Casu A, Chen K, Ennas MG, Tambaro S, Shih JC (2014) The aggression and behavioral abnormalities associated with monoamine oxidase A deficiency are rescued by acute inhibition of serotonin reuptake. J Psychiatr Res 56:1–9

    PubMed  PubMed Central  Google Scholar 

  • Godar SC, Bortolato M, Richards SE, Li FG, Chen K, Wellman CL, Shih JC (2015) Monoamine oxidase A is required for rapid dendritic remodeling in response to stress. Int J Neuropsychopharmacol. https://doi.org/10.1093/ijnp/pyv035

    Article  PubMed  PubMed Central  Google Scholar 

  • Godar SC, Fite PJ, McFarlin KM, Bortolato M (2016) The role of monoamine oxidase A in aggression: current translational developments and future challenges. Prog Neuropsychopharmacol Biol Psychiatr 69:90–100

    CAS  Google Scholar 

  • Grimsby J, Lan NC, Neve R, Chen K, Shih JC (1990) Tissue distribution of human monoamine oxidase A and B mRNA. J Neurochem 55:1166–1169

    CAS  PubMed  Google Scholar 

  • Grimsby J, Chen K, Wang LJ, Lan NC, Shih JC (1991) Human monoamine oxidase A and B genes exhibit identical exon–intron organization. Proc Natl Acad Sci USA 88:3637–3641

    CAS  PubMed  Google Scholar 

  • Grimsby J, Toth M, Chen K, Kumazawa T, Klaidman L, Adams JD, Karoum F, Gal J, Shih JC (1997) Increased stress response and beta-phenylethylamine in MAOB-deficient mice. Nat Genet 17:206–210

    CAS  PubMed  Google Scholar 

  • Guo L, Zhen X (2015) Sigma-2 receptor ligands: neurobiological effects. Curr Med Chem 22:989–1003

    CAS  PubMed  Google Scholar 

  • Huang Y-Y, Cate SP, Battistuzzi C, Oquendo MA, Brent D, Mann JJ (2004) An association between a functional polymorphism in the monoamine oxidase A gene promoter, impulsive traits and early abuse experiences. Neuropsychopharmacology 29:1498–1505

    CAS  PubMed  Google Scholar 

  • Hutsler JJ, Casanova MF (2016) Review: cortical construction in autism spectrum disorder: columns, connectivity and the subplate. Neuropathol Appl Neurobiol 42:115–134

    PubMed  Google Scholar 

  • Jahng JW, Houpt TA, Wessel TC, Chen K, Shih JC, Joh TH (1997) Localization of monoamine oxidase A and B mRNA in the rat brain by in situ hybridization. Synapse 25:30–36

    CAS  PubMed  Google Scholar 

  • Jones P, Suggett A (1968) The catalase-hydrogen peroxide system. A theoretical appraisal of the mechanism of catalase action. Biochem J 110:621–629

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jonsson EG, Norton N, Gustavsson JP, Oreland L, Owen MJ, Sedvall GC (2000) A promoter polymorphism in the monoamine oxidase A gene and its relationships to monoamine metabolite concentrations in CSF of healthy volunteers. J Psychiatr Res 34:239–244

    CAS  PubMed  Google Scholar 

  • Jossan SS, Gillberg PG, Gottfries CG, Karlsson I, Oreland L (1991) Monoamine oxidase B in brains from patients with Alzheimer’s disease: a biochemical and autoradiographical study. Neuroscience 45:1–12

    CAS  PubMed  Google Scholar 

  • Karmakar A, Maitra S, Chakraborti B, Verma D, Sinha S, Mohanakumar KP, Rajamma U, Mukhopadhyay K (2016) Monoamine oxidase B gene variants associated with attention deficit hyperactivity disorder in the Indo-Caucasoid population from West Bengal. BMC Genet 24:92

    Google Scholar 

  • Karmakar A, Goswami R, Saha T, Maitra S, Roychowdhury A, Panda CK, Sinha S, Ray A, Mohanakumar KP, Rajamma U, Mukhopadhyay K (2017) Pilot study indicate role of preferentially transmitted monoamine oxidase gene variants in behavioral problems of male ADHD probands. BMC Med Genet 18:109

    PubMed  PubMed Central  Google Scholar 

  • 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. Proc Natl Acad Sci USA 94:5929–5933

    CAS  PubMed  Google Scholar 

  • 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. Mol Psychiatr 11:903–913

    CAS  Google Scholar 

  • Kitahama K, Denney RM, Maeda T, Jouvet M (1991) Distribution of type B monoamine oxidase immunoreactivity in the cat brain with reference to enzyme histochemistry. Neuroscience 44:185–204

    CAS  PubMed  Google Scholar 

  • Knoll J (1993) The pharmacological basis of the beneficial effects of (-)deprenyl (selegiline) in Parkinson’s and Alzheimer’s diseases. J Neural Transm Suppl 40:69–91

    CAS  PubMed  Google Scholar 

  • Kuroki T, Tsutsumi T, Hirano M, Matsumoto T, Tatebayashi Y, Nishiyama K, Uchimura H, Shiraishi A, Nakahara T, Nakamura K (1990) Behavioral sensitization to beta-phenylethylamine (PEA): enduring modifications of specific dopaminergic neuron systems in the rat. Psychopharmacology 102:5–10

    CAS  PubMed  Google Scholar 

  • Lan NC, Heinzmann C, Gal A, Klisak I, Orth U, Lai E, Grimsby J, Sparkes RS, Mohandas T, Shih JC (1989) Human monoamine oxidase A and B genes map to Xp 11.23 and are deleted in a patient with Norrie disease. Genomics 4:552–559

    CAS  PubMed  Google Scholar 

  • Lee BT, Ham BJ (2008) Monoamine oxidase A-uVNTR genotype affects limbic brain activity in response to affective facial stimuli. Neuroreport 19:515–519

    CAS  PubMed  Google Scholar 

  • Lenders JW, Eisenhofer G, Abeling NG, Berger W, Murphy DL, Konings CH, Wagemakers LM, Kopin IJ, Karoum F, van Gennip AH, Brunner HG (1996) Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes. J Clin Invest 97:1010–1019

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Wang Y, Hu S, Zhou R, Yu X, Wang B, Guan L, Yang L, Zhang F, Faraone SV (2008) The monoamine oxidase B gene exhibits significant association to ADHD. Am J Med Genet B Neuropsychiatr Genet 147:370–374

    PubMed  Google Scholar 

  • Liberles SD, Buck LB (2006) A second class of chemosensory receptors in the olfactory epithelium. Nature 442:645–650

    CAS  PubMed  Google Scholar 

  • Lindemann L, Ebeling M, Kratochwil NA, Bunzow JR, Grandy DK, Hoener MC (2005) Trace amine associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors. Genomics 85:372–385

    CAS  PubMed  Google Scholar 

  • Luque JM, Kwan SW, Abell CW, Da Prada M, Richards JG (1995) Cellular expression of mRNAs encoding monoamine oxidases A and B in the rat central nervous system. J Comp Neurol 363:665–680

    CAS  PubMed  Google Scholar 

  • Matson JL, Rivet TT (2008) Characteristics of challenging behaviours in adults with autistic disorder, PDD-NOS, and intellectual disability. J Intellect Dev Disabil 33:323–329

    PubMed  Google Scholar 

  • Megens AA, Niemegeers CJ, Awouters FH (1992) Behavioral disinhibition and depression in amphetaminized rats: a comparison of risperidone, ocaperidone and haloperidol. J Pharmacol Exp Ther 260:160–167

    CAS  PubMed  Google Scholar 

  • Mejia JM, Ervin FR, Palmour RM, Tremblay RE (2001) Aggressive behavior and Brunner syndrome: no evidence for the C936T mutation in a population sample. Am J Med Genet 105:396–397

    CAS  PubMed  Google Scholar 

  • Mejia JM, Ervin FR, Baker GB, Palmour RM (2002) Monoamine oxidase inhibition during brain development induces pathological aggressive behavior in mice. Biol Psychiatr 52:811–821

    CAS  Google Scholar 

  • Meyer-Lindenberg A, Buckholtz JW, Kolachana BR, Hariri AR, Pezawas L, Blasi G, Wabnitz A, Honea R, Verchinski B, Callicott JH, Egan M, Matty V, Weinberger DR (2006) Neural mechanisms of genetic risk for impulsivity and violence in humans. Proc Natl Acad Sci USA 103:6269–6274

    CAS  PubMed  Google Scholar 

  • Minshew NJ, Williams DL (2007) The new neurobiology of autism: cortex, connectivity, and neuronal organization. Arch Neurol 64:1464

    Google Scholar 

  • Muller CL, Anacker AMJ, Veenstra-VanderWeele J (2016) The serotonin system in autism spectrum disorder: from biomarker to animal models. Neuroscience 321:24–41

    CAS  PubMed  Google Scholar 

  • Murphy DL, Sims KB, Karoum F, de la Chapelle A, Norio R, Sankila EM, Breakefield XO (1990) Marked amine and amine metabolite changes in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase. J Neurochem 54:242–247

    CAS  PubMed  Google Scholar 

  • Murphy DL, Karoum F, Pickar D, Cohen RM, Lipper S, Mellow AM, Tariot PN, Sunderland T (1998) Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (clorgyline) or MAO-B (selegiline and pargyline). J Neural Transm Suppl 52:39–48

    CAS  PubMed  Google Scholar 

  • Nakamura S, Kawamata T, Akiguchi I, Kameyama M, Nakamura N, Kimura H (1990) Expression of monoamine oxidase B activity in astrocytes of senile plaques. Acta Neuropathol 80:419–425

    CAS  PubMed  Google Scholar 

  • Nedic G, Pivac N, Hercigonja DK, Jovancevic M, Curkovic KD, Muck-Seler D (2010) Platelet monoamine oxidase activity in children with attention-deficit/hyperactivity disorder. Psychiatr Res 175:252–255

    CAS  Google Scholar 

  • Nicotra A, Pierucci F, Parvez H, Senatori O (2004) Monoamine oxidase expression during development and aging. Neurotoxicology 25:155–165

    CAS  PubMed  Google Scholar 

  • O’Reilly R, Davis BA, Durden DA, Thorpe L, Machnee H, Boulton AA (1991) Plasma phenylethylamine in schizophrenic patients. Biol Psychiatr 30:145–150

    Google Scholar 

  • Oreland L, Hallman J (1995) The correlation between platelet MAO activity and personality: short review of findings and a discussion on possible mechanisms. Prog Brain Res 106:77–84

    CAS  PubMed  Google Scholar 

  • Oreland L, Nilsson K, Damberg M, Hallman J (2007) Monoamine oxidases: activities, genotypes and the shaping of behaviour. J Neural Transm 114:817–822

    CAS  PubMed  Google Scholar 

  • Oxenstierna G, Edman G, Iselius L, Oreland L, Ross SB, Sedvall G (1986) Concentrations of monoamine metabolites in the cerebrospinal fluid of twins and unrelated individuals—a genetic study. J Psychiatr Res 20:19–29

    CAS  PubMed  Google Scholar 

  • Palmer EE, Leffler M, Rogers C, Shaw M, Carroll R, Earl J, Cheung NW, Champion B, Hu H, Haas SA, Kalscheuer VM, Gecz J, Field M (2016) New insights into Brunner syndrome and potential for targeted therapy. Clin Genet 89:120–127

    CAS  PubMed  Google Scholar 

  • Passamonti L, Fera F, Magariello A, Cerasa A, Gioia MC, Muglia M, Nicoletti G, Gallo O, Provinciali L, Quattrone A (2006) Monoamine oxidase-a genetic variations influence brain activity associated with inhibitory control: new insight into the neural correlates of impulsivity. Biol Psychiatr 59:334–340

    CAS  Google Scholar 

  • Pedersen NL, Oreland L, Reynolds C, McClearn GE. (1993) Importance of genetic effects for monoamine oxidase activity in thrombocytes in twins reared apart and twins reared together. Psychiatr Res 46: 239–51

    CAS  Google Scholar 

  • Picazo O, Chuc-Meza E, Anaya-Martinez V, Jimenez I, Aceves J, Garcia-Ramirez M (2009) 6-Hydroxydopamine lesion in thalamic reticular nucleus reduces anxiety behaviour in the rat. Behav Brain Res 197:317–322

    CAS  PubMed  Google Scholar 

  • Piton A, Poquet H, Redin C, Masurel A, Lauer J, Muller J, Thevenon J, Herenger Y, Chancenotte S, Bonnet M, Pinoit JM, Huet F, Thauvin-Robinet C, Jaeger AS, Le Gras S, Jost B, Gérard B, Peoc’h K, Launay JM, Faivre L, Mandel JL (2014) 20 ans après: a second mutation in MAOA identified by targeted high-throughput sequencing in a family with altered behavior and cognition. Eur J Hum Genet 22:776–783

    CAS  PubMed  Google Scholar 

  • Pizzinat N, Copin N, Vindis C, Parini A, Cambon C (1999) Reactive oxygen species production by monoamine oxidases in intact cells. Naunyn Schmiedebergs Arch Pharmacol 359:428–431

    CAS  PubMed  Google Scholar 

  • Popova NK, Maslova LN, Morosova EA, Bulygina VV, Seif I (2006) MAO A knockout attenuates adrenocortical response to various kinds of stress. Psychoneuroendocrinology 31:179–186

    CAS  PubMed  Google Scholar 

  • Reist C, Haier RJ, DeMet E, Chicz-DeMet A (1990) Platelet MAO activity in personality disorders and normal controls. Psychiatr Res 33:221–227

    CAS  Google Scholar 

  • Revel FG, Moreau JL, Gainetdinov RR, Bradaia A, Sotnikova TD, Mory R, Durkin S, Zbinden KG, Norcross R, Meyer CA, Metzler V, Chaboz S, Ozmen L, Trube G, Pouzet B, Bettler B, Caron MG, Wettstein JG, Hoener MC (2011) TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity. Proc Natl Acad Sci USA 108:8485–8490

    CAS  PubMed  Google Scholar 

  • Revel FG, Moreau JL, Pouzet B, Mory R, Bradaia A, Buchy D, Metzler V, Chabo S, Groebke Zbinden K, Galley G, Norcross RD, Tuerck D, Bruns A, Morairty SR, Kilduff TS, Wallace TL, Risterucci C, Wettstein JG, Hoener MC (2013) A new perspective for schizophrenia: TAAR1 agonists reveal antipsychotic- and antidepressant-like activity, improve cognition and control body weight. Mol Psychiatr 18:543–556

    CAS  Google Scholar 

  • Ribasés M, Ramos-Quiroga JA, Hervás A, Bosch R, Bielsa A, Gastaminza X, Artigas J, Rodriguez-Ben S, Estivill X, Casas M, Cormand B, Bayés M (2009) Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB. Mol Psychiatr 14:71–85

    Google Scholar 

  • Rich-Edwards JW, Spiegelman D, Lividoti Hibert EN, Jun HJ, Todd TJ, Kawachi I, Wright RJ (2010) Abuse in childhood and adolescence as a predictor of type 2 diabetes in adult women. Am J Prev Med 39:529–536

    PubMed  PubMed Central  Google Scholar 

  • Rose CF, Verkhratsky A, Parpura V (2013) Astrocyte glutamine synthetase: pivotal in health and disease. Biochem Soc Trans 41:1518–1524

    CAS  PubMed  Google Scholar 

  • Ruchkin VV, Koposov RA, af Klinteberg B, Oreland L, Grigorenko EL. (2005) Platelet MAO-B, personality, and psychopathology. J Abnorm Psychol 114: 477–482

    PubMed  Google Scholar 

  • Rutigliano G, Accorroni A, Zucchi R (2018) The case for TAAR1 as a modulator of central nervous system function. Front Pharmacol 8:987

    PubMed  PubMed Central  Google Scholar 

  • Sabelli HC, Javaid JI (1995) Phenylethylamine modulation of affect: therapeutic and diagnostic implications. J Neuropsychiatr Clin Neurosci 7:6–14

    CAS  Google Scholar 

  • Sabol SZ, Hu S, Hamer D (1998) A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet 103:273–279

    CAS  PubMed  Google Scholar 

  • Saito M, Yamagata T, Matsumoto A, Shiba Y, Nagashima M, Taniguchi S, Jimbo E, Momoi MY (2014) MAOA/B deletion syndrome in male siblings with severe developmental delay and sudden loss of muscle tonus. Brain Dev 36:64–69

    PubMed  Google Scholar 

  • Salichon N, Gaspar P, Upton AL, Picaud S, Hanoun N, Hamon M, De Maeyer E, Murphy DL, Mossner R, Lesch KP, Hen R, Seif I (2001) Excessive activation of serotonin (5-HT) 1B receptors disrupts the formation of sensory maps in monoamine oxidase a and 5-ht transporter knock-out mice. J Neurosci 21:884–896

    CAS  PubMed  Google Scholar 

  • Samochowiec J, Lesch KP, Rottmann M, Smolka M, Syagailo YV, Okladnova O, Rommelspacher H, Winterer G, Schmidt LG, Sander T (1999) Association of a regulatory polymorphism in the promoter region of the monoamine oxidase A gene with antisocial alcoholism. Psychiatr Res 86:67–72

    CAS  Google Scholar 

  • Saura J, Richards JG, Mahy N (1994) Age-related changes on MAO in Bl/C57 mouse tissues: a quantitative radioautographic study. J Neural Transm 41:89–94

    CAS  Google Scholar 

  • Schilling B, Lerch K (1995) Cloning, sequencing and heterologous expression of the monoamine oxidase gene from Aspergillus niger. Mol Gen Genet 247:430–438

    CAS  PubMed  Google Scholar 

  • Schuback DE, Mulligan EL, Sims KB, Tivol EA, Greenberg BD, Chang SF, Yang SL, Mau YC, Shen CY, Ho MS, Yang NH, Butler MG, Fink S, Schwartz CE, Berlin F, Breakefield XO, Murphy DL, Hsu YP (1999) Screen for MAOA mutations in target human groups. Am J Med Genet 88:25–28

    CAS  PubMed  PubMed Central  Google Scholar 

  • Scott AL, Bortolato M, Chen K, Shih JC (2008) Novel monoamine oxidase A knock out mice with human-like spontaneous mutation. Neuroreport 19:739–743

    CAS  PubMed  PubMed Central  Google Scholar 

  • Setini A, Pierucci F, Senatori O, Nicotra A (2005) Molecular characterization of monoamine oxidase in zebrafish (Danio rerio). Comp Biochem Physiol B Biochem Mol Biol 140:153–161

    PubMed  Google Scholar 

  • Shabanov PD, Lebedev AA, Meshcherov ShK, Strel’tsov VF (2005) The effects of neurochemical lesioning of dopaminergic terminals in early ontogenesis on behavior in adult rats. Neurosci Behav Physiol 35:535–544

    CAS  PubMed  Google Scholar 

  • Shekim WO, Bylund DB, Alexson J, Glaser RD, Jones SB, Hodges K, Perdue S (1986) Platelet MAO and measures of attention and impulsivity in boys with attention deficit disorder and hyperactivity. Psychiatr Res 18:179–188

    CAS  Google Scholar 

  • Sims KB, de la Chapelle A, Norio R, Sankila EM, Hsu YP, Rinehart WB, Corey TJ, Ozelius L, Powell JF, Bruns G et al (1989) Monoamine oxidase deficiency in males with an X chromosome deletion. Neuron 2:1069–1076

    CAS  PubMed  Google Scholar 

  • Singh C, Bortolato M, Bali N, Godar SC, Scott AL, Chen K, Thompson RF, Shih JC (2013) Cognitive abnormalities and hippocampal alterations in monoamine oxidase A and B knockout mice. Proc Natl Acad Sci USA 110:12816–12821

    CAS  PubMed  Google Scholar 

  • Sotnikova TD, Budygin EA, Jones SR, Dykstra LA, Caron MG, Gainetdinov RR (2004) Dopamine transporter-dependent and -independent actions of trace amine beta-phenylethylamine. J Neurochem 91:362–373

    CAS  PubMed  Google Scholar 

  • Stäubert C, Böselt I, Bohnekamp J, Römpler H, Enard W, Schöneberg T (2010) Structural and functional evolution of the trace amine-associated receptors TAAR3, TAAR4 and TAAR5 in primates. PLoS One 5:e11133

    PubMed  PubMed Central  Google Scholar 

  • Suárez I, Bodega G, Fernández B (2002) Glutamine synthetase in brain: effect of ammonia. Neurochem Int 41:123–142

    PubMed  Google Scholar 

  • Szymanski HV, Naylor EW, Karoum F (1987) Plasma phenylethylamine and phenylalanine in chronic schizophrenic patients. Biol Psychiatr 22:194–198

    CAS  Google Scholar 

  • Tank AW, Weiner H, Thurman JA (1981) Enzymology and subcellular localization of aldehyde oxidation in rat liver. Oxidation of 3,4-dihydroxyphenylacetaldehyde derived from dopamine to 3,4-dihydroxyphenylacetic acid. Biochem Pharmacol 30:3265–3275

    CAS  PubMed  Google Scholar 

  • Tank AW, Deitrich RA, Weiner H (1986) Effects of induction of rat liver cytosolic aldehyde dehydrogenase on the oxidation of biogenic aldehydes. Biochem Pharmacol 35:4563–4569

    CAS  PubMed  Google Scholar 

  • Thompson AM, Thompson GC (2009) Serotonin-immunoreactive neurons in the postnatal MAO-A KO mouse lateral superior olive project to the inferior colliculus. Neurosci Lett 460:47–51

    CAS  PubMed  Google Scholar 

  • van Gaalen MM, Brueggeman RJ, Bronius PF, Schoffelmeer AN, Vanderschuren LJ (2006) Behavioral disinhibition requires dopamine receptor activation. Psychopharmacology 187:73–85

    CAS  PubMed  Google Scholar 

  • 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. J Comp Neurol 393:169–184

    CAS  PubMed  Google Scholar 

  • von Knorring L, Oreland L, Winblad B (1984) Personality traits related to monoamine oxidase activity in platelets. Psychiatr Res 12:11–26

    Google Scholar 

  • Whibley A, Urquhart J, Dore J, Willatt L, Parkin G, Gaunt L, Black G, Donnai D, Raymond FL (2010) Deletion of MAOA and MAOB in a male patient causes severe developmental delay, intermittent hypotonia and stereotypical hand movements. Eur J Hum Genet 18:1095–1099

    PubMed  PubMed Central  Google Scholar 

  • Whitaker-Azmitia PM, Zhang X, Clarke C (1994) Effects of gestational exposure to monoamine oxidase inhibitors in rats: preliminary behavioral and neurochemical studies. Neuropsychopharmacology 11:125–132

    CAS  PubMed  Google Scholar 

  • Williams LM, Gatt JM, Kuan SA, Dobson-Stone C et al (2009) A polymorphism of the MAOA gene is associated with emotional brain markers and personality traits on an antisocial index. Neuropsychopharmacology 34:1797–1809

    CAS  PubMed  Google Scholar 

  • Yu Q, Teixeira CM, Mahadevia D, Huang Y, Balsam D, Mann JJ, Gingrich JA, Ansorge MS (2014) Dopamine and serotonin signaling during two sensitive developmental periods differentially impact adult aggressive and affective behaviors in mice. Mol Psychiatr 19:688–698

    CAS  Google Scholar 

Download references

Acknowledgements

The present study was supported by the National Institute of Health grant R01 MH104603-01 (to M.B.).

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, L.S. Skaggs Hall, 30 S 2000 E, Salt Lake City, UT, 84112, USA

    Marco Bortolato & Gabriele Floris

  2. Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA

    Jean C. Shih

  3. Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA, USA

    Jean C. Shih

Authors
  1. Marco Bortolato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriele Floris
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jean C. Shih
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marco Bortolato.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bortolato, M., Floris, G. & Shih, J.C. From aggression to autism: new perspectives on the behavioral sequelae of monoamine oxidase deficiency. J Neural Transm 125, 1589–1599 (2018). https://doi.org/10.1007/s00702-018-1888-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-018-1888-y

Keywords

Search

Navigation