Abnormal Behavior Associated with a Point Mutation in the Structural Gene for Monoamine Oxidase A
Abstract
Genetic and metabolic studies have been done on a large kindred in which several males are affected by a syndrome of borderline mental retardation and abnormal behavior. The types of behavior that occurred include impulsive aggression, arson, attempted rape, and exhibitionism. Analysis of 24-hour urine samples indicated markedly disturbed monoamine metabolism. This syndrome was associated with a complete and selective deficiency of enzymatic activity of monoamine oxidase A (MAOA). In each of five affected males, a point mutation was identified in the eighth exon of the MAOA structural gene, which changes a glutamine to a termination codon. Thus, isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.
Get full access to this article
View all available purchase options and get full access to this article.
References
BACH, AWJ, CDNA CLONING OF HUMAN-LIVER MONOAMINE OXIDASE-A AND OXIDASE-B - MOLECULAR-BASIS OF DIFFERENCES IN ENZYMATIC-PROPERTIES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 85: 4934 (1988).
BERGER, W, ISOLATION OF A CANDIDATE GENE FOR NORRIE DISEASE BY POSITIONAL CLONING, NATURE GENETICS 1: 199 (1992).
BLEEKERWAGEMAKE.EM, NORRIE DISEASE AS PART OF A COMPLEX SYNDROME EXPLAINED BY A SUBMICROSCOPIC DELETION OF THE X-CHROMOSOME, OPHTHALMIC PAEDIATRICS AND GENETICS 9: 137 (1988).
BLIER, P, MODIFICATION OF SEROTONERGIC AND NORADRENERGIC NEUROTRANSMISSIONS BY REPEATED ADMINISTRATION OF MONOAMINE-OXIDASE INHIBITORS - ELECTROPHYSIOLOGICAL STUDIES IN THE RAT CENTRAL-NERVOUS-SYSTEM, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 237: 987 (1986).
BRADFORD, M.M., RAPID AND SENSITIVE METHOD FOR QUANTITATION OF MICROGRAM QUANTITIES OF PROTEIN UTILIZING PRINCIPLE OF PROTEIN-DYE BINDING, ANALYTICAL BIOCHEMISTRY 72: 248 (1976).
Breakefield, X. O., Genetic Research Strategies in Psychobiology and Psychiatry: 129 (1981).
BROWN, G.L., AGGRESSION IN HUMANS CORRELATES WITH CEREBROSPINAL-FLUID AMINE METABOLITES, PSYCHIATRY RESEARCH 1: 131 (1979).
BRUNNER, H.G., X-LINKED BORDERLINE MENTAL-RETARDATION WITH PROMINENT BEHAVIORAL DISTURBANCE - PHENOTYPE, GENETIC LOCALIZATION, AND EVIDENCE FOR DISTURBED MONOAMINE METABOLISM, AMERICAN JOURNAL OF HUMAN GENETICS 52: 1032 (1993).
Chen, Z.-Y., Nucleic Acids Research 19: 4537 (1992).
CHOMCZYNSKI, P, SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION, ANALYTICAL BIOCHEMISTRY 162: 156 (1987).
COCCARO, E.F., CENTRAL SEROTONIN AND IMPULSIVE AGGRESSION, BRITISH JOURNAL OF PSYCHIATRY 155: 52 (1989).
COHEN, R.M., REM-SLEEP SUPPRESSION INDUCED BY SELECTIVE MONOAMINE-OXIDASE INHIBITORS, PSYCHOPHARMACOLOGY 78: 137 (1982).
COLLINS, F.A., 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, AMERICAN JOURNAL OF MEDICAL GENETICS 42: 127 (1992).
DELACHAPELLE, A, NORRIE DISEASE CAUSED BY A GENE DELETION ALLOWING CARRIER DETECTION AND PRENATAL-DIAGNOSIS, CLINICAL GENETICS 28: 317 (1985).
DONNAI, D, NORRIE DISEASE RESULTING FROM A GENE DELETION - CLINICAL-FEATURES AND DNA STUDIES, JOURNAL OF MEDICAL GENETICS 25: 73 (1988).
EDELSTEIN, S.B., DEXAMETHASONE SELECTIVELY INCREASES MONOAMINE-OXIDASE TYPE-A IN HUMAN-SKIN FIBROBLASTS, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 98: 836 (1981).
EDELSTEIN, S.B., MONOAMINE OXIDASE-A AND OXIDASE-B ARE DIFFERENTIALLY REGULATED BY GLUCOCORTICOIDS AND AGING IN HUMAN-SKIN FIBROBLASTS, CELLULAR AND MOLECULAR NEUROBIOLOGY 6: 121 (1986).
EDELSTEIN, S.B., MONO-AMINE OXIDASE ACTIVITY IN NORMAL AND LESCH-NYHAN FIBROBLASTS, JOURNAL OF NEUROCHEMISTRY 31: 1247 (1978).
EICHELMAN, B, AGGRESSIVE MONOAMINES, BIOLOGICAL PSYCHIATRY 6: 143 (1973).
EICHELMAN, B, FACILITATED SHOCK-INDUCED AGGRESSION FOLLOWING ANTIDEPRESSIVE MEDICATION IN RAT, PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR 3: 601 (1975).
GREENSHAW, A.J., CHRONIC EFFECTS OF TRANYLCYPROMINE AND 4-FLUOROTRANYLCYPROMINE ON REGIONAL BRAIN MONOAMINE METABOLISM IN RATS - A COMPARISON WITH CLORGYLINE, BIOLOGICAL PSYCHIATRY 25: 1014 (1989).
HIGLEY, J.D., CEREBROSPINAL-FLUID MONOAMINE AND ADRENAL CORRELATES OF AGGRESSION IN FREE-RANGING RHESUS-MONKEYS, ARCHIVES OF GENERAL PSYCHIATRY 49: 436 (1992).
HOTAMISLIGIL, G.S., HUMAN MONOAMINE OXIDASE-A GENE DETERMINES LEVELS OF ENZYME-ACTIVITY, AMERICAN JOURNAL OF HUMAN GENETICS 49: 383 (1991).
HSU, YPP, STRUCTURAL FEATURES OF HUMAN MONOAMINE OXIDASE-A ELUCIDATED FROM CDNA AND PEPTIDE SEQUENCES, JOURNAL OF NEUROCHEMISTRY 51: 1321 (1988).
KANTAK, K.M., EFFECTS OF DIETARY-SUPPLEMENTS AND A TRYPTOPHAN-FREE DIET ON AGGRESSIVE-BEHAVIOR IN RATS, PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR 12: 173 (1980).
KRUESI, MJP, CEREBROSPINAL-FLUID MONOAMINE METABOLITES, AGGRESSION, AND IMPULSIVITY IN DISRUPTIVE BEHAVIOR DISORDERS OF CHILDREN AND ADOLESCENTS, ARCHIVES OF GENERAL PSYCHIATRY 47: 419 (1990).
LATHROP, G.M., EASY CALCULATIONS OF LOD SCORES AND GENETIC RISKS ON SMALL COMPUTERS, AMERICAN JOURNAL OF HUMAN GENETICS 36: 460 (1984).
LINNOILA, M, LOW CEREBROSPINAL-FLUID 5-HYDROXYINDOLEACETIC ACID CONCENTRATION DIFFERENTIATES IMPULSIVE FROM NONIMPULSIVE VIOLENT BEHAVIOR, LIFE SCIENCES 33: 2609 (1983).
MORDEN, B, EFFECTS OF RAPID EYE MOVEMENT (REM) SLEEP DEPRIVATION ON SHOCK-INDUCED FIGHTING, PHYSIOLOGY & BEHAVIOR 3: 425 (1968).
Murphy, D. L., Antidepressants: 209 (1983).
NIKULINA, E.M., SELECTION FOR REDUCED AGGRESSIVENESS TOWARDS MAN AND DOPAMINERGIC ACTIVITY IN NORWAY RATS, AGGRESSIVE BEHAVIOR 18: 65 (1992).
PICKAR, D, SELECTIVE AND NON-SELECTIVE MONOAMINE-OXIDASE INHIBITORS, ARCHIVES OF GENERAL PSYCHIATRY 39: 535 (1982).
POPOVA, N.K., SEROTONIN METABOLISM AND SEROTONERGIC RECEPTORS IN NORWAY RATS SELECTED FOR LOW AGGRESSIVENESS TO MAN, AGGRESSIVE BEHAVIOR 17: 207 (1991).
REIS, D. J., RESEARCH PUBLICATIONS. ASSOCIATION FOR RESEARCH IN NERVOUS AND MENTAL DISEASE 50: 266 (1972).
SIMS, K.B., MONOAMINE-OXIDASE DEFICIENCY IN MALES WITH AN X-CHROMOSOME DELETION, NEURON 2: 1069 (1989).
SLEIGHT, A.J., RELATIONSHIP BETWEEN EXTRACELLULAR 5-HYDROXYTRYPTAMINE AND BEHAVIOR FOLLOWING MONOAMINE-OXIDASE INHIBITION AND L-TRYPTOPHAN, BRITISH JOURNAL OF PHARMACOLOGY 93: 303 (1988).
TRONCONE, LRP, EFFECTS OF SELECTIVE ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON AGGRESSIVE-BEHAVIOR ELICITED BY APOMORPHINE, DL-DOPA AND FUSARIC ACID IN REM-SLEEP-DEPRIVED RATS, PHYSIOLOGY & BEHAVIOR 50: 173 (1991).
TUFIK, S, DOES REM-SLEEP DEPRIVATION INDUCE A SUPERSENSITIVITY OF DOPAMINERGIC RECEPTORS IN RAT-BRAIN, PHARMACOLOGY 16: 98 (1978).
VALZELLI, L, SEROTONERGIC INHIBITORY CONTROL OF EXPERIMENTAL AGGRESSION, PHARMACOLOGICAL RESEARCH COMMUNICATIONS 14: 1 (1982).
Valzelli, L., Psychobiology of Aggression and Violence (1981).
VANDENOUWELAND, AMW, MUTATIONS IN THE VASOPRESSIN TYPE-2 RECEPTOR GENE (AVPR2) ASSOCIATED WITH NEPHROGENIC DIABETES-INSIPIDUS, NATURE GENETICS 2: 99 (1992).
WINSLOW, J.T., HABITUATION OF AGGRESSION IN MICE - PHARMACOLOGICAL EVIDENCE OF CATECHOLAMINERGIC AND SEROTONERGIC MEDIATION, PSYCHOPHARMACOLOGY 81: 286 (1983).
ZHU, D.P., MICRODELETION IN THE X-CHROMOSOME AND PRENATAL-DIAGNOSIS IN A FAMILY WITH NORRIE DISEASE, AMERICAN JOURNAL OF MEDICAL GENETICS 33: 485 (1989).
(0)eLetters
eLetters is a forum for ongoing peer review. eLetters are not edited, proofread, or indexed, but they are screened. eLetters should provide substantive and scholarly commentary on the article. Embedded figures cannot be submitted, and we discourage the use of figures within eLetters in general. If a figure is essential, please include a link to the figure within the text of the eLetter. Please read our Terms of Service before submitting an eLetter.
Log In to Submit a ResponseNo eLetters have been published for this article yet.
Information & Authors
Information
Published In
Science
Volume 262 | Issue 5133
22 October 1993
22 October 1993
Copyright
© 1993.
Submission history
Published in print: 22 October 1993
Authors
Metrics & Citations
Metrics
Article Usage
Altmetrics
Citations
Cite as
- H. G. Brunner et al.
Export citation
Select the format you want to export the citation of this publication.
Cited by
- Targeting monoamine oxidase A for T cell–based cancer immunotherapy, Science Immunology, 6, 59, (2021)./doi/10.1126/sciimmunol.abh2383
- The rise and fall of the “warrior gene” defense, Science, 371, 6536, (1320-1320), (2021)./doi/10.1126/science.abh4479
- Role of Genotype in the Cycle of Violence in Maltreated Children, Science, 297, 5582, (851-854), (2002)./doi/10.1126/science.1072290
- Aggressive Behavior and Altered Amounts of Brain Serotonin and Norepinephrine in Mice Lacking MAOA, Science, 268, 5218, (1763-1766), (1995)./doi/10.1126/science.7792602
- Response: Aggression in Mice and Men?, Science, 270, 5235, (363-363), (1995)./doi/10.1126/science.270.5235.363
- Aggression in Mice and Men?, Science, 270, 5235, (362-363), (1995)./doi/10.1126/science.270.5235.362
- The Genetic Basis of Complex Human Behaviors, Science, 264, 5166, (1733-1739), (1994)./doi/10.1126/science.8209254
- Violence study hits a nerve in Germany, Science, 264, 5159, (653-653), (1994)./doi/10.1126/science.8171314
- Abnormal Fear Response and Aggressive Behavior in Mutant Mice Deficient for α-Calcium-Calmodulin Kinase II, Science, 266, 5183, (291-294), (1994)./doi/10.1126/science.7939668
Loading...
View Options
Check Access
Log in to view the full text
AAAS login provides access to Science for AAAS Members, and access to other journals in the Science family to users who have purchased individual subscriptions.
- Become a AAAS Member
- Activate your AAAS ID
- Purchase Access to Other Journals in the Science Family
- Account Help
Log in via OpenAthens.
Log in via Shibboleth.
More options
Purchase digital access to this article
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
View options
PDF format
Download this article as a PDF file
Download PDF