Document Detail


A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity.
MedLine Citation:
PMID:  10904119     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study presents preliminary evidence of an association between polymorphic variation in the gene for monoamine oxidase-A (MAOA) and interindividual variability in aggressiveness, impulsivity and central nervous system (CNS) serotonergic responsivity. An apparently functional 30-bp VNTR in the promoter region of the X-chromosomal MAOA gene (MAOA-uVNTR), as well as a dinucleotide repeat in intron 2 (MAOA-CAn), was genotyped in a community sample of 110 men. All participants had completed standard interview and questionnaire measures of impulsivity, hostility and lifetime aggression history; in a majority of subjects (n=75), central serotonergic activity was also assessed by neuropsychopharmacologic challenge (prolactin response to fenfluramine hydrochloride). The four repeat variants of the MAOA-uVNTR polymorphism were grouped for analysis (alleles '1+ 4' vs. '2+3') based on prior evidence of enhanced transcriptional activity in MAOA promoter constructs with alleles 2 and 3 (repeats of intermediate length). Men in the 1/4 allele group scored significantly lower on a composite measure of dispositional aggressiveness and impulsivity (P<0.015) and showed more pronounced CNS serotonergic responsivity (P<0.02) than men in the 2/3 allele group. These associations were also significant on comparison of the more prevalent one and three alleles alone (encompassing 93% of subjects). Although in linkage disequilibrium with the MAOA-uVNTR polymorphism, MAOA-CAn repeat length variation did not vary significantly with respect to behavior or fenflluramine challenge in this sample. We conclude that the MAOA-uVNTR regulatory polymorphism may contribute, in part, to individual differences in both CNS serotonergic responsivity and personality traits germane to impulse control and antagonistic behavior.
Authors:
S B Manuck; J D Flory; R E Ferrell; J J Mann; M F Muldoon
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Psychiatry research     Volume:  95     ISSN:  0165-1781     ISO Abbreviation:  Psychiatry Res     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-09-26     Completed Date:  2000-09-26     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7911385     Medline TA:  Psychiatry Res     Country:  IRELAND    
Other Details:
Languages:  eng     Pagination:  9-23     Citation Subset:  IM    
Affiliation:
Department of Psychology, Behavioral Physiology Laboratory, University of Pittsburgh, PA 15260, USA. manuck@pitt.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Aggression / physiology*
Alleles
Brain / physiopathology*
Dinucleotide Repeats / genetics
Gene Expression Regulation, Enzymologic / physiology
Genes, Regulator / genetics*
Genotype
Hostility
Humans
Impulsive Behavior / genetics*,  physiopathology
Male
Middle Aged
Minisatellite Repeats
Monoamine Oxidase / genetics*,  physiology
Polymorphism, Genetic / genetics*
Promoter Regions, Genetic
Receptors, Serotonin / genetics*,  physiology
Serotonin / physiology
Grant Support
ID/Acronym/Agency:
HL-40962/HL/NHLBI NIH HHS; HL-48238/HL/NHLBI NIH HHS; MH-46745/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Serotonin; 50-67-9/Serotonin; EC 1.4.3.4/Monoamine Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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