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==Clinical significance==
==Clinical significance==
In humans, there is a 30-base [[Variable number tandem repeat|repeat sequence]] repeated in one of several different numbers of times in the [[Promoter (biology)|promoter region]] of the gene coding for MAOA. There are 2R (two repeats), 3R, 3.5R, 4R, and 5R variants of the repeat sequence, with the 3R and 4R variants most common in Caucasians. The 3.5R and 4R variants have been found to be more highly active than 3R or 5R, in a study which did not examine the 2R variant.<ref name="pmid18212819">{{cite journal | author = Guo G, Ou XM, Roettger M, Shih JC | title = The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: associations and MAOA promoter activity | journal = Eur. J. Hum. Genet. | volume = 16 | issue = 5 | pages = 626–34 | year = 2008 | month = May | pmid = 18212819 | pmc = 2922855 | doi = 10.1038/sj.ejhg.5201999 }}</ref> An association between a rare 2R repeat of the [[variable number tandem repeat|VNTR]] region of the gene and an increase in the likelihood of committing serious crime or violence has been found.<ref name="Guo_ Roettger_ Shih_2008">{{cite journal | author = Guo G, Roettger M, Shih JC | title = The integration of genetic propensities into social-control models of delinquency and violence among male youths | journal = American Sociological Review | volume=73 | issue = 4 | pages = 543–568 | year = 2008 | month = August | doi = 10.1177/000312240807300402 | url = http://www.asanet.org/galleries/default-file/Aug08ASRFeature.pdf | format = }} {{dead link|date=July 2010}}</ref><ref name="pmid18212819" />
In humans, there is a 30-base [[Variable number tandem repeat|repeat sequence]] repeated in one of several different numbers of times in the [[Promoter (biology)|promoter region]] of the gene coding for MAOA. There are 2R (two repeats), 3R, 3.5R, 4R, and 5R variants of the repeat sequence, with the 3R and 4R variants most common in Caucasians. The 3.5R and 4R variants have been found to be more highly active than 3R or 5R, in a study which did not examine the 2R variant.<ref name="pmid18212819">{{cite journal | author = Guo G, Ou XM, Roettger M, Shih JC | title = The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: associations and MAOA promoter activity | journal = Eur. J. Hum. Genet. | volume = 16 | issue = 5 | pages = 626–34 | year = 2008 | month = May | pmid = 18212819 | pmc = 2922855 | doi = 10.1038/sj.ejhg.5201999 }}</ref> An association between the 2R allele of the [[variable number tandem repeat|VNTR]] region of the gene and an increase in the likelihood of committing serious crime or violence has been found.<ref name="Guo_ Roettger_ Shih_2008">{{cite journal | author = Guo G, Roettger M, Shih JC | title = The integration of genetic propensities into social-control models of delinquency and violence among male youths | journal = American Sociological Review | volume=73 | issue = 4 | pages = 543–568 | year = 2008 | month = August | doi = 10.1177/000312240807300402 | url = http://www.asanet.org/galleries/default-file/Aug08ASRFeature.pdf | format = }} {{dead link|date=July 2010}}</ref><ref name="pmid18212819" /><ref name="beaver2012">{{cite journal |author=Beaver KM, ''et al.'' |title=Exploring the association between the 2-repeat allele of the MAOA gene promoter polymorphism and psychopathic personality traits, arrests, incarceration, and lifetime antisocial behavior |journal=Personality and Individual Differences |year=2012 |doi=10.1016/j.paid.2012.08.014 |url=http://www.sciencedirect.com/science/article/pii/S0191886912004047}}</ref>


MAO-A levels in the brain as measured using [[positron emission tomography]] are elevated by an average of 34% in patients with [[major depressive disorder]].<ref name="pmid17088501">{{cite journal | author = Meyer JH, Ginovart N, Boovariwala A, Sagrati S, Hussey D, Garcia A, Young T, Praschak-Rieder N, Wilson AA, Houle S | title = Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression | journal = Arch. Gen. Psychiatry | volume = 63 | issue = 11 | pages = 1209–16 | year = 2006 | month = November | pmid = 17088501 | doi = 10.1001/archpsyc.63.11.1209 }}</ref> Genetic association studies examining the relationship between high-activity MAO-A variants and depression have produced mixed results, with some studies linking the high-activity variants to major depression in females,<ref name="pmid11121185">{{cite journal | author = Schulze TG, Müller DJ, Krauss H, Scherk H, Ohlraun S, Syagailo YV, Windemuth C, Neidt H, Grässle M, Papassotiropoulos A, Heun R, Nöthen MM, Maier W, Lesch KP, Rietschel M | title = Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder | journal = Am. J. Med. Genet. | volume = 96 | issue = 6 | pages = 801–3 | year = 2000 | month = December | pmid = 11121185 | doi = 10.1002/1096-8628(20001204)96:6<801::AID-AJMG21>3.0.CO;2-4 }}</ref> depressed suicide in males,<ref name="pmid12151768">{{cite journal | author = Du L, Faludi G, Palkovits M, Sotonyi P, Bakish D, Hrdina PD | title = High activity-related allele of MAO-A gene associated with depressed suicide in males | journal = NeuroReport | volume = 13 | issue = 9 | pages = 1195–8 | year = 2002 | month = July | pmid = 12151768 | doi = 10.1097/00001756-200207020-00025 }}</ref> major depression and sleep disturbance in males<ref name="pmid15486489">{{cite journal | author = Du L, Bakish D, Ravindran A, Hrdina PD | title = MAO-A gene polymorphisms are associated with major depression and sleep disturbance in males | journal = NeuroReport | volume = 15 | issue = 13 | pages = 2097–101 | year = 2004 | month = September | pmid = 15486489 | doi = 10.1097/00001756-200409150-00020 }}</ref> and major depressive disorder in both males and females.<ref name="pmid15956990">{{cite journal | author = Yu YW, Tsai SJ, Hong CJ, Chen TJ, Chen MC, Yang CW | title = Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and antidepressant response | journal = Neuropsychopharmacology | volume = 30 | issue = 9 | pages = 1719–23 | year = 2005 | month = September | pmid = 15956990 | doi = 10.1038/sj.npp.1300785 }}</ref> Other studies failed to find a significant relationship between high-activity variants of the MAO-A gene and major depressive disorder.<ref name="pmid11992558">{{cite journal | author = Serretti A, Cristina S, Lilli R, Cusin C, Lattuada E, Lorenzi C, Corradi B, Grieco G, Costa A, Santorelli F, Barale F, Nappi G, Smeraldi E | title = Family-based association study of 5-HTTLPR, TPH, MAO-A, and DRD4 polymorphisms in mood disorders | journal = Am. J. Med. Genet. | volume = 114 | issue = 4 | pages = 361–9 | year = 2002 | month = May | pmid = 11992558 | doi = 10.1002/ajmg.10356 }}</ref><ref name="pmid19224413">{{cite journal | author = Huang SY, Lin MT, Lin WW, Huang CC, Shy MJ, Lu RB | title = Association of monoamine oxidase A (MAOA) polymorphisms and clinical subgroups of major depressive disorders in the Han Chinese population | journal = World J. Biol. Psychiatry | volume = 10 | issue = 4 Pt 2 | pages = 544–51 | year = 2009 | pmid = 19224413 | doi = 10.1080/15622970701816506 }}</ref> In patients with [[major depressive disorder]], those with MAO-A G/T polymorphisms (rs6323) coding for the highest-activity form of the enzyme have a significantly lower magnitude of [[placebo]] response than those with other genotypes.<ref name="pmid19593178">{{cite journal | author = Leuchter AF, McCracken JT, Hunter AM, Cook IA, Alpert JE | title = Monoamine oxidase a and catechol-o-methyltransferase functional polymorphisms and the placebo response in major depressive disorder | journal = J Clin Psychopharmacol | volume = 29 | issue = 4 | pages = 372–7 | year = 2009 | month = August | pmid = 19593178 | doi = 10.1097/JCP.0b013e3181ac4aaf }}</ref>
MAO-A levels in the brain as measured using [[positron emission tomography]] are elevated by an average of 34% in patients with [[major depressive disorder]].<ref name="pmid17088501">{{cite journal | author = Meyer JH, Ginovart N, Boovariwala A, Sagrati S, Hussey D, Garcia A, Young T, Praschak-Rieder N, Wilson AA, Houle S | title = Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression | journal = Arch. Gen. Psychiatry | volume = 63 | issue = 11 | pages = 1209–16 | year = 2006 | month = November | pmid = 17088501 | doi = 10.1001/archpsyc.63.11.1209 }}</ref> Genetic association studies examining the relationship between high-activity MAO-A variants and depression have produced mixed results, with some studies linking the high-activity variants to major depression in females,<ref name="pmid11121185">{{cite journal | author = Schulze TG, Müller DJ, Krauss H, Scherk H, Ohlraun S, Syagailo YV, Windemuth C, Neidt H, Grässle M, Papassotiropoulos A, Heun R, Nöthen MM, Maier W, Lesch KP, Rietschel M | title = Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder | journal = Am. J. Med. Genet. | volume = 96 | issue = 6 | pages = 801–3 | year = 2000 | month = December | pmid = 11121185 | doi = 10.1002/1096-8628(20001204)96:6<801::AID-AJMG21>3.0.CO;2-4 }}</ref> depressed suicide in males,<ref name="pmid12151768">{{cite journal | author = Du L, Faludi G, Palkovits M, Sotonyi P, Bakish D, Hrdina PD | title = High activity-related allele of MAO-A gene associated with depressed suicide in males | journal = NeuroReport | volume = 13 | issue = 9 | pages = 1195–8 | year = 2002 | month = July | pmid = 12151768 | doi = 10.1097/00001756-200207020-00025 }}</ref> major depression and sleep disturbance in males<ref name="pmid15486489">{{cite journal | author = Du L, Bakish D, Ravindran A, Hrdina PD | title = MAO-A gene polymorphisms are associated with major depression and sleep disturbance in males | journal = NeuroReport | volume = 15 | issue = 13 | pages = 2097–101 | year = 2004 | month = September | pmid = 15486489 | doi = 10.1097/00001756-200409150-00020 }}</ref> and major depressive disorder in both males and females.<ref name="pmid15956990">{{cite journal | author = Yu YW, Tsai SJ, Hong CJ, Chen TJ, Chen MC, Yang CW | title = Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and antidepressant response | journal = Neuropsychopharmacology | volume = 30 | issue = 9 | pages = 1719–23 | year = 2005 | month = September | pmid = 15956990 | doi = 10.1038/sj.npp.1300785 }}</ref> Other studies failed to find a significant relationship between high-activity variants of the MAO-A gene and major depressive disorder.<ref name="pmid11992558">{{cite journal | author = Serretti A, Cristina S, Lilli R, Cusin C, Lattuada E, Lorenzi C, Corradi B, Grieco G, Costa A, Santorelli F, Barale F, Nappi G, Smeraldi E | title = Family-based association study of 5-HTTLPR, TPH, MAO-A, and DRD4 polymorphisms in mood disorders | journal = Am. J. Med. Genet. | volume = 114 | issue = 4 | pages = 361–9 | year = 2002 | month = May | pmid = 11992558 | doi = 10.1002/ajmg.10356 }}</ref><ref name="pmid19224413">{{cite journal | author = Huang SY, Lin MT, Lin WW, Huang CC, Shy MJ, Lu RB | title = Association of monoamine oxidase A (MAOA) polymorphisms and clinical subgroups of major depressive disorders in the Han Chinese population | journal = World J. Biol. Psychiatry | volume = 10 | issue = 4 Pt 2 | pages = 544–51 | year = 2009 | pmid = 19224413 | doi = 10.1080/15622970701816506 }}</ref> In patients with [[major depressive disorder]], those with MAO-A G/T polymorphisms (rs6323) coding for the highest-activity form of the enzyme have a significantly lower magnitude of [[placebo]] response than those with other genotypes.<ref name="pmid19593178">{{cite journal | author = Leuchter AF, McCracken JT, Hunter AM, Cook IA, Alpert JE | title = Monoamine oxidase a and catechol-o-methyltransferase functional polymorphisms and the placebo response in major depressive disorder | journal = J Clin Psychopharmacol | volume = 29 | issue = 4 | pages = 372–7 | year = 2009 | month = August | pmid = 19593178 | doi = 10.1097/JCP.0b013e3181ac4aaf }}</ref>
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==Aggression and "Warrior gene"==
==Aggression and "Warrior gene"==


A dysfunctional MAO-A gene has been correlated with increased aggression levels in mice,<ref name="Novel">{{cite journal | author = Scott AL, Bortolato M, Chen K, Shih JC | title = Novel monoamine oxidase A knock out mice with human-like spontaneous mutation | journal = NeuroReport | volume = 19 | issue = 7 | pages = 739–43 | year = 2008 | month = May | pmid = 18418249 | doi = 10.1097/WNR.0b013e3282fd6e88 }}</ref><ref name="pmid17441000">{{cite journal | author = Vishnivetskaya GB, Skrinskaya JA, Seif I, Popova NK | title = Effect of MAO A deficiency on different kinds of aggression and social investigation in mice | journal = Aggress Behav | volume = 33 | issue = 1 | pages = 1–6 | year = 2007 | pmid = 17441000 | doi = 10.1002/ab.20161 }}</ref> and in some studies, has been correlated with heightened levels of aggression in humans.<ref name="Abnormal">{{cite journal | author = Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA | title = Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A | journal = Science | volume = 262 | issue = 5133 | pages = 578–80 | year = 1993 | month = October | pmid = 8211186 | doi = 10.1126/science.8211186 }}</ref> In mice, a dysfunction MAO-A gene is created through insertional mutagenesis (called ‘Tg8’). <ref name="Novel" /> Tg8 is a transgenic mouse strain that lacks a functional MAO-A enzymatic activity. Mice that lacked a functional MAO-A gene exhibited increased aggression towards intruder mice. <ref name="Novel" /> <ref>{{cite journal|last=Vishnivetskaya|first=Galina B.|coauthors=Skrinskaya, Julia A., Seif, Isabelle, Popova, Nina K.|title=Effect of MAO A deficiency on different kinds of aggression and social investigation in mice|journal=Aggressive Behavior|date=1 January 2007|volume=33|issue=1|pages=1–6|doi=10.1002/ab.20161|pmid=17441000}}</ref> Some types of aggression exhibited by these mice were territorial aggression, predatory aggression, and isolation induced aggression. <ref name="pmid17441000" /> The MAO-A deficient mice that exhibited increased isolation induced aggression reveals that an MAO-A deficiency may also contribute to a disruption in social interactions. The correlation between a dysfunctional MAO-A gene and heightened levels of aggression in humans remains controversial.<ref name="pmid7649563">{{cite journal | author = Hebebrand J, Klug B | title = Specification of the phenotype required for men with monoamine oxidase type A deficiency | journal = Hum. Genet. | volume = 96 | issue = 3 | pages = 372–6 | year = 1995 | month = September | pmid = 7649563 | doi = 10.1007/BF00210430 }}</ref> However, there is research in both humans and mice to support that a spontaneous point nonsense mutation in the eighth exon of the MAO-A gene is responsible for impulsive aggressiveness due to a complete MAO-A deficiency.<ref name="Novel"/><ref name="Abnormal"/>
A dysfunctional MAO-A gene has been correlated with increased aggression levels in mice,<ref name="Novel">{{cite journal | author = Scott AL, Bortolato M, Chen K, Shih JC | title = Novel monoamine oxidase A knock out mice with human-like spontaneous mutation | journal = NeuroReport | volume = 19 | issue = 7 | pages = 739–43 | year = 2008 | month = May | pmid = 18418249 | doi = 10.1097/WNR.0b013e3282fd6e88 }}</ref><ref name="pmid17441000">{{cite journal | author = Vishnivetskaya GB, Skrinskaya JA, Seif I, Popova NK | title = Effect of MAO A deficiency on different kinds of aggression and social investigation in mice | journal = Aggress Behav | volume = 33 | issue = 1 | pages = 1–6 | year = 2007 | pmid = 17441000 | doi = 10.1002/ab.20161 }}</ref> and has been correlated with heightened levels of aggression in humans.<ref name="Abnormal">{{cite journal | author = Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA | title = Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A | journal = Science | volume = 262 | issue = 5133 | pages = 578–80 | year = 1993 | month = October | pmid = 8211186 | doi = 10.1126/science.8211186 }}</ref> In mice, a dysfunction MAO-A gene is created through insertional mutagenesis (called ‘Tg8’). <ref name="Novel" /> Tg8 is a transgenic mouse strain that lacks a functional MAO-A enzymatic activity. Mice that lacked a functional MAO-A gene exhibited increased aggression towards intruder mice. <ref name="Novel" /> <ref>{{cite journal|last=Vishnivetskaya|first=Galina B.|coauthors=Skrinskaya, Julia A., Seif, Isabelle, Popova, Nina K.|title=Effect of MAO A deficiency on different kinds of aggression and social investigation in mice|journal=Aggressive Behavior|date=1 January 2007|volume=33|issue=1|pages=1–6|doi=10.1002/ab.20161|pmid=17441000}}</ref> Some types of aggression exhibited by these mice were territorial aggression, predatory aggression, and isolation induced aggression. <ref name="pmid17441000" /> The MAO-A deficient mice that exhibited increased isolation induced aggression reveals that an MAO-A deficiency may also contribute to a disruption in social interactions.<ref name="pmid7649563">{{cite journal | author = Hebebrand J, Klug B | title = Specification of the phenotype required for men with monoamine oxidase type A deficiency | journal = Hum. Genet. | volume = 96 | issue = 3 | pages = 372–6 | year = 1995 | month = September | pmid = 7649563 | doi = 10.1007/BF00210430 }}</ref> There is research in both humans and mice to support that a spontaneous point nonsense mutation in the eighth exon of the MAO-A gene is responsible for impulsive aggressiveness due to a complete MAO-A deficiency.<ref name="Novel"/><ref name="Abnormal"/>


A version of the [[monoamine oxidase]]-A gene has been popularly referred to as the ''warrior gene''. Several different versions of the gene are found in different individuals, although a functional gene is present in most humans (with the exception of a few individuals with [[Brunner syndrome]]).<ref name="maoa">{{OMIM|309850|MONOAMINE OXIDASE A; MAOA.}}</ref> In the variant, the allele associated with behavioural traits is shorter (30 [[base pair|bases]]) and may produce less MAO-A enzyme.<ref name="pmid9799080">{{cite journal | author = Sabol SZ, Hu S, Hamer D | title = A functional polymorphism in the monoamine oxidase A gene promoter | journal = Hum. Genet. | volume = 103 | issue = 3 | pages = 273–9 | year = 1998 | month = September | pmid = 9799080 | doi = 10.1007/s004390050816 }}</ref> This gene variation is in a regulatory [[promoter (biology)|promoter]] region about 1000 [[bases]] from the [[start codon|start]] of the region that [[translation (genetics)|encodes]] the MAO-A enzyme.
A version of the [[monoamine oxidase]]-A gene has been popularly referred to as the ''warrior gene''. Several different versions of the gene are found in different individuals, although a functional gene is present in most humans (with the exception of a few individuals with [[Brunner syndrome]]).<ref name="maoa">{{OMIM|309850|MONOAMINE OXIDASE A; MAOA.}}</ref> In the variant, the allele associated with behavioural traits is shorter (30 [[base pair|bases]]) and may produce less MAO-A enzyme.<ref name="pmid9799080">{{cite journal | author = Sabol SZ, Hu S, Hamer D | title = A functional polymorphism in the monoamine oxidase A gene promoter | journal = Hum. Genet. | volume = 103 | issue = 3 | pages = 273–9 | year = 1998 | month = September | pmid = 9799080 | doi = 10.1007/s004390050816 }}</ref> This gene variation is in a regulatory [[promoter (biology)|promoter]] region about 1000 [[bases]] from the [[start codon|start]] of the region that [[translation (genetics)|encodes]] the MAO-A enzyme.


A 2002 study found a connection between a version of the [[monoamine oxidase]]-A gene and several types of antisocial behavior. This study was performed within the ''[[Dunedin Multidisciplinary Health and Development Study]]''. The authors divided participants into two bins of "low" and "high" MAO-A activity. They then diagnosed participants according to four criteria of antisocial behaviour. Overall MAO-A had no statistically significant effect on antisocial behavior. However, there was an effect on these children who had been maltreated. The study found that maltreated children with genes causing high level of MAO-A were less likely to develop antisocial behavior.<ref name= "pmid12161658">{{cite journal |author=Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R | title = Role of genotype in the cycle of violence in maltreated children | journal = Science | volume = 297 | issue = 5582 | pages = 851–4 | year = 2002 | month = August | pmid = 12161658 | doi = 10.1126/science.1072290 | laysummary = http://www.eurekalert.org/pub_releases/2002-08/uow-gmp072602.php | laysource = eurekalert.org | laydate = 2002-08-01 }}</ref> This finding is not universal; it was shown in Caucasian but not non-white Americans.<ref name="pmid17339895"/> Follow-up studies have sometimes replicated a relationship and sometimes not. The differences may be due to different measures of behaviors and environmental risk factors. Frazzetto et al. (2007) found that low MAO-A activity in combination with abuse experienced during childhood results in an increased risk of aggressive behaviour as an adult.<ref>{{cite journal |author=Frazzetto G, Di Lorenzo G, Carola V, ''et al.'' |title=Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype |journal=PLoS ONE |volume=2 |issue=5 |pages=e486 |year=2007 |pmid=17534436 |pmc=1872046 |doi=10.1371/journal.pone.0000486 |url= |editor1-last=Baune |editor1-first=Bernhard}}</ref>
A 2002 study found a connection between a version of the [[monoamine oxidase]]-A gene (3R) and several types of antisocial behavior. This study was performed within the ''[[Dunedin Multidisciplinary Health and Development Study]]''. The authors divided participants into two bins of "low" and "high" MAO-A activity. They then diagnosed participants according to four criteria of antisocial behaviour. Overall MAO-A had no statistically significant effect on antisocial behavior. However, there was an effect on these children who had been maltreated. The study found that maltreated children with genes causing high level of MAO-A were less likely to develop antisocial behavior.<ref name= "pmid12161658">{{cite journal |author=Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R | title = Role of genotype in the cycle of violence in maltreated children | journal = Science | volume = 297 | issue = 5582 | pages = 851–4 | year = 2002 | month = August | pmid = 12161658 | doi = 10.1126/science.1072290 | laysummary = http://www.eurekalert.org/pub_releases/2002-08/uow-gmp072602.php | laysource = eurekalert.org | laydate = 2002-08-01 }}</ref> Frazzetto et al. (2007) found that low MAO-A activity in combination with abuse experienced during childhood results in an increased risk of aggressive behaviour as an adult.<ref>{{cite journal |author=Frazzetto G, Di Lorenzo G, Carola V, ''et al.'' |title=Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype |journal=PLoS ONE |volume=2 |issue=5 |pages=e486 |year=2007 |pmid=17534436 |pmc=1872046 |doi=10.1371/journal.pone.0000486 |url= |editor1-last=Baune |editor1-first=Bernhard}}</ref> Other studies have found that high testosterone, maternal tobacco smoking during pregnancy, poor material living standards, dropping out of school, and low IQ can also trigger violent behavior in men with the low-activity alleles (which are overwhelmingly the 3R allele).<ref>{{cite journal |author=Fergusson DM, ''et al.'' |title=Moderating role of the MAOA genotype in antisocial behaviour. |journal=The British Journal of Psychiatry |volume=200 |issue=2 |pages=116-23 |year=2012 |month=February |pmid=22297589 |doi=10.1192/bjp.bp.111.093328 |url=http://bjp.rcpsych.org/content/200/2/116.short}}</ref><ref>{{cite journal |author=Sjoberg RL, ''et al.'' |title=A non-additive interaction of a functional MAO-A VNTR and testosterone predicts antisocial behavior. |journal=Neuropsychopharmacology |volume=33 |issue=2 |pages=425-30 |year=2008 |month=January |pmid=17429405 |pmc=2665792 |doi=10.1038/sj.npp.1301417 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/pmc2665792/}}</ref>


The frequency distribution of variants of the MAO-A gene differs between ethnic groups<ref name="pmid9799080"/><ref name="pmid17339897">{{cite journal | author = Lea R, Chambers G | title = Monoamine oxidase, addiction, and the "warrior" gene hypothesis | journal = N. Z. Med. J. | volume = 120 | issue = 1250 | pages = U2441 | year = 2007 | pmid = 17339897 | doi = | url = http://journal.nzma.org.nz/journal/120-1250/2441/ }}</ref> &mdash; as is the case for many genotypes. The variant was found to vary widely in demographic prevalence among different ethnic groups, with around 80% of Chinese, 60% of Maori, 60% of Africans, and 30% of Caucasians carrying the genetic variant.<ref name="pmid17339897" /> Due to the sensitive political nature of the findings, the research has been heavily scrutinised. It has been claimed that MAO-A may be related to social problems among the Maori. Several objections have been raised, such as the small sample size regarding the prevalence among Maori (17 persons), the extrapolation of non-Maori studies to the Maori population, and an effect only being found in maltreated children. In addition, ideological objections were raised, as well as concerns about announcing such findings in the early stages of research.<ref name="pmid17339895">{{cite journal |author=Crampton P, Parkin C |title=Warrior genes and risk-taking science |journal=N. Z. Med. J. |volume = 120 | issue = 1250 |pages = U2439 | year = 2007 | pmid = 17339895 | url = http://journal.nzma.org.nz/journal/120-1250/2439/}}</ref><ref name= "urlMaori warrior gene claims appalling, says geneticist - Health - ">{{cite web | url = http://www.nzherald.co.nz/category/story.cfm?c_id=204&objectid=10395491 | title = Maori 'warrior gene' claims appalling, says geneticist |work=News |publisher=[[NZ Herald]] News | accessdate = 2009-01-27}}</ref><ref name="urlwww.hrc.govt.nz">{{cite book | url = http://www.hrc.govt.nz/assets/pdfs/publications/Hui%20Report%2006%20FINAL.pdf | title = Hui Whakapiripiri Report | author = Whanau Tu, Whanau Ora | year = 2007 | publisher = www.hrc.govt.nz | accessdate = 2009-01-27 | isbn = 978-0-908700-73-3 {{Please check ISBN|reason=Check digit (3) does not correspond to calculated figure.}} }}</ref><ref name= "url Scientist debunks 'warrior gene' ">{{cite web | url = http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10596821 | title = Scientist debunks 'warrior gene' | work = News | publisher = NZ Herald News | accessdate = 2009-09-11}}</ref>
The frequency distribution of variants of the MAO-A gene differs between ethnic groups.<ref name="pmid9799080"/><ref name="pmid17339897">{{cite journal | author = Lea R, Chambers G | title = Monoamine oxidase, addiction, and the "warrior" gene hypothesis | journal = N. Z. Med. J. | volume = 120 | issue = 1250 | pages = U2441 | year = 2007 | pmid = 17339897 | doi = | url = http://journal.nzma.org.nz/journal/120-1250/2441/ }}</ref> 59% of African-American men, 56% of Maori men, 54% of Chinese men, and 34% of Caucasian men carry the 3R allele. 5.5% of African-American men, 0.1% of Caucasian men, and 0.00067% of Asian men carry the 2R allele.<ref name="pmid17339897" /><ref>{{cite journal |author=Lu R, ''et al.'' |title=Neither Antisocial Personality Disorder Nor Antisocial Alcoholism Is Associated With the MAO-A Gene in Han Chinese Males |journal=Alcoholism: Clinical and Experimental Research |volume=27 |issue=6 |pages=889-893 |year=2003 |month=June |pmid=12824808 |doi=10.1111/j.1530-0277.2003.tb04412.x |url=http://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.2003.tb04412.x/abstract}}</ref><ref name="beaver2012"/><ref>{{cite journal |author=Zhang M, ''et al.'' |title=The association between infants' self-regulatory behavior and MAOA gene polymorphism. |journal=Developmental Science |volume=14 |issue=5 |pages=1059-1065 |year=2011 |month=September |pmid=21884321 |doi=10.1111/j.1467-7687.2011.01047.x |url=http://onlinelibrary.wiley.com/doi/10.1111/j.1467-7687.2011.01047.x/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false}}</ref><ref>{{cite journal |author=Zhou Q, ''et al.'' |title=The developmental trajectories of attention focusing, attentional and behavioral persistence, and externalizing problems during school-age years. |journal=Developmental Psychology |volume=43 |issue=2 |pages=369-85 |year=2007 |month=March |pmid=17352545 |pmc=1832154 |doi=10.1037/0012-1649.43.2.369 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1832154/}}</ref><ref>{{cite journal |author=Chen S, ''et al.'' |title=Androgen and glucocorticoid receptor heterodimer formation. A possible mechanism for mutual inhibition of transcriptional activity. |journal=Journal of Biological Chemistry |volume=272 |issue=22 |pages=14087-92 |year=1997 |month=May |pmid=9162033 |doi=10.1074/jbc.272.22.14087 |url=http://www.jbc.org/content/272/22/14087.full}}</ref><ref name="pmid9799080"/><ref>{{cite journal |author=Ono H, ''et al.'' |title=No evidence of an association between a functional monoamine oxidase a gene polymorphism and completed suicides. |journal=American Journal of Medical Genetics |volume=114 |issue=3 |pages=340-342 |year=2002 |month=April |pmid=11920860 |doi=10.1002/ajmg.10237 |url=http://onlinelibrary.wiley.com/doi/10.1002/ajmg.10237/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false}}</ref><ref>{{cite journal |author=Wang TJ, ''et al.'' |title=Possible interaction between MAOA and DRD2 genes associated with antisocial alcoholism among Han Chinese men in Taiwan. |journal=Progress in Neuro-psychopharmacology and Biological Psychiatry |volume=31 |issue=1 |pages=108-114 |year=2007 |month=January |pmid=17007976 |doi=10.1016/j.pnpbp.2006.08.010 |url=http://ukpmc.ac.uk/abstract/MED/17007976}}</ref><ref>{{cite journal |author=Lee SY, ''et al.'' |title=MAOA interacts with the ALDH2 gene in anxiety-depression alcohol dependence. |journal=Alcoholism: Clinical and Experimental Research |volume=34 |issue=7 |pages=1212-8 |year=2010 |month=July |pmid=20477771 |doi=10.1111/j.1530-0277.2010.01198.x |url=http://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.2010.01198.x/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false}}</ref>


In a 2009 criminal trial in the United States, an argument based on a combination of "warrior gene" and history of [[child abuse]] was successfully used to avoid a conviction of [[first-degree murder]] and the death penalty; however, the convicted murderer was sentenced to 32 years in jail.<ref name="url_Psychology_Today">{{cite web | url = http://www.psychologytoday.com/blog/the-human-beast/201007/pity-the-poor-murderer-his-genes-made-him-do-it | title = Pity the poor murderer, his genes made him do it | author = Barber N | date = 2010-07-13 | work =The Human Beast: Why we do what we do | publisher = Psychology Today | accessdate = 2010-10-17 }}</ref><ref name="url_NPR">{{cite web | url = http://www.npr.org/templates/story/story.php?storyId=128043329 | title = Can Your Genes Make You Murder? | author = Hagerty BB | date = 2010-07-01 | work = News > Science > Inside The Criminal Brain | publisher = National Public Radio | accessdate = 2010-10-17 }}</ref>
In a 2009 criminal trial in the United States, an argument based on a combination of "warrior gene" and history of [[child abuse]] was successfully used to avoid a conviction of [[first-degree murder]] and the death penalty; however, the convicted murderer was sentenced to 32 years in jail.<ref name="url_Psychology_Today">{{cite web | url = http://www.psychologytoday.com/blog/the-human-beast/201007/pity-the-poor-murderer-his-genes-made-him-do-it | title = Pity the poor murderer, his genes made him do it | author = Barber N | date = 2010-07-13 | work =The Human Beast: Why we do what we do | publisher = Psychology Today | accessdate = 2010-10-17 }}</ref><ref name="url_NPR">{{cite web | url = http://www.npr.org/templates/story/story.php?storyId=128043329 | title = Can Your Genes Make You Murder? | author = Hagerty BB | date = 2010-07-01 | work = News > Science > Inside The Criminal Brain | publisher = National Public Radio | accessdate = 2010-10-17 }}</ref>

Revision as of 09:58, 13 October 2012

Template:PBB Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the MAO-A gene.[1][2] Monoamine oxidase A is an isozyme of monoamine oxidase. It preferentially deaminates norepinephrine (noradrenaline), epinephrine (adrenaline), serotonin, and dopamine (dopamine is equally deaminated by MAO-A and MAO-B). It is inhibited by clorgiline and befloxatone. Inhibition of both MAO-A and MAO-B using a monoamine oxidase inhibitor (MAO inhibitor) is used in the treatment of clinical depression and anxiety.

Function

Monoamine oxidase A is an enzyme that degrades amine neurotransmitters, such as dopamine, norepinephrine, and serotonin. The protein localizes to the outer mitochondrial membrane. Its encoding gene is adjacent to a related gene (MAO-B) on the opposite strand of the X chromosome. Mutation in this gene results in monoamine oxidase deficiency, or Brunner syndrome.[3]

Clinical significance

In humans, there is a 30-base repeat sequence repeated in one of several different numbers of times in the promoter region of the gene coding for MAOA. There are 2R (two repeats), 3R, 3.5R, 4R, and 5R variants of the repeat sequence, with the 3R and 4R variants most common in Caucasians. The 3.5R and 4R variants have been found to be more highly active than 3R or 5R, in a study which did not examine the 2R variant.[4] An association between the 2R allele of the VNTR region of the gene and an increase in the likelihood of committing serious crime or violence has been found.[5][4][6]

MAO-A levels in the brain as measured using positron emission tomography are elevated by an average of 34% in patients with major depressive disorder.[7] Genetic association studies examining the relationship between high-activity MAO-A variants and depression have produced mixed results, with some studies linking the high-activity variants to major depression in females,[8] depressed suicide in males,[9] major depression and sleep disturbance in males[10] and major depressive disorder in both males and females.[11] Other studies failed to find a significant relationship between high-activity variants of the MAO-A gene and major depressive disorder.[12][13] In patients with major depressive disorder, those with MAO-A G/T polymorphisms (rs6323) coding for the highest-activity form of the enzyme have a significantly lower magnitude of placebo response than those with other genotypes.[14]

Aggression and "Warrior gene"

A dysfunctional MAO-A gene has been correlated with increased aggression levels in mice,[15][16] and has been correlated with heightened levels of aggression in humans.[17] In mice, a dysfunction MAO-A gene is created through insertional mutagenesis (called ‘Tg8’). [15] Tg8 is a transgenic mouse strain that lacks a functional MAO-A enzymatic activity. Mice that lacked a functional MAO-A gene exhibited increased aggression towards intruder mice. [15] [18] Some types of aggression exhibited by these mice were territorial aggression, predatory aggression, and isolation induced aggression. [16] The MAO-A deficient mice that exhibited increased isolation induced aggression reveals that an MAO-A deficiency may also contribute to a disruption in social interactions.[19] There is research in both humans and mice to support that a spontaneous point nonsense mutation in the eighth exon of the MAO-A gene is responsible for impulsive aggressiveness due to a complete MAO-A deficiency.[15][17]

A version of the monoamine oxidase-A gene has been popularly referred to as the warrior gene. Several different versions of the gene are found in different individuals, although a functional gene is present in most humans (with the exception of a few individuals with Brunner syndrome).[20] In the variant, the allele associated with behavioural traits is shorter (30 bases) and may produce less MAO-A enzyme.[21] This gene variation is in a regulatory promoter region about 1000 bases from the start of the region that encodes the MAO-A enzyme.

A 2002 study found a connection between a version of the monoamine oxidase-A gene (3R) and several types of antisocial behavior. This study was performed within the Dunedin Multidisciplinary Health and Development Study. The authors divided participants into two bins of "low" and "high" MAO-A activity. They then diagnosed participants according to four criteria of antisocial behaviour. Overall MAO-A had no statistically significant effect on antisocial behavior. However, there was an effect on these children who had been maltreated. The study found that maltreated children with genes causing high level of MAO-A were less likely to develop antisocial behavior.[22] Frazzetto et al. (2007) found that low MAO-A activity in combination with abuse experienced during childhood results in an increased risk of aggressive behaviour as an adult.[23] Other studies have found that high testosterone, maternal tobacco smoking during pregnancy, poor material living standards, dropping out of school, and low IQ can also trigger violent behavior in men with the low-activity alleles (which are overwhelmingly the 3R allele).[24][25]

The frequency distribution of variants of the MAO-A gene differs between ethnic groups.[21][26] 59% of African-American men, 56% of Maori men, 54% of Chinese men, and 34% of Caucasian men carry the 3R allele. 5.5% of African-American men, 0.1% of Caucasian men, and 0.00067% of Asian men carry the 2R allele.[26][27][6][28][29][30][21][31][32][33]

In a 2009 criminal trial in the United States, an argument based on a combination of "warrior gene" and history of child abuse was successfully used to avoid a conviction of first-degree murder and the death penalty; however, the convicted murderer was sentenced to 32 years in jail.[34][35]

Some MAO-A inhibitors

References

  1. ^ Hotamisligil GS, Breakefield XO (1991). "Human monoamine oxidase A gene determines levels of enzyme activity". Am. J. Hum. Genet. 49 (2): 383–92. PMC 1683299. PMID 1678250. {{cite journal}}: Unknown parameter |month= ignored (help)
  2. ^ 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. U.S.A. 88 (9): 3637–41. doi:10.1073/pnas.88.9.3637. PMC 51507. PMID 2023912. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ "Entrez Gene: MAOA monoamine oxidase A".
  4. ^ a b Guo G, Ou XM, Roettger M, Shih JC (2008). "The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: associations and MAOA promoter activity". Eur. J. Hum. Genet. 16 (5): 626–34. doi:10.1038/sj.ejhg.5201999. PMC 2922855. PMID 18212819. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Guo G, Roettger M, Shih JC (2008). "The integration of genetic propensities into social-control models of delinquency and violence among male youths" (PDF). American Sociological Review. 73 (4): 543–568. doi:10.1177/000312240807300402. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) [dead link]
  6. ^ a b Beaver KM; et al. (2012). "Exploring the association between the 2-repeat allele of the MAOA gene promoter polymorphism and psychopathic personality traits, arrests, incarceration, and lifetime antisocial behavior". Personality and Individual Differences. doi:10.1016/j.paid.2012.08.014. {{cite journal}}: Explicit use of et al. in: |author= (help)
  7. ^ 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". Arch. Gen. Psychiatry. 63 (11): 1209–16. doi:10.1001/archpsyc.63.11.1209. PMID 17088501. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ Schulze TG, Müller DJ, Krauss H, Scherk H, Ohlraun S, Syagailo YV, Windemuth C, Neidt H, Grässle M, Papassotiropoulos A, Heun R, Nöthen MM, Maier W, Lesch KP, Rietschel M (2000). "Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder". Am. J. Med. Genet. 96 (6): 801–3. doi:10.1002/1096-8628(20001204)96:6<801::AID-AJMG21>3.0.CO;2-4. PMID 11121185. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Du L, Faludi G, Palkovits M, Sotonyi P, Bakish D, Hrdina PD (2002). "High activity-related allele of MAO-A gene associated with depressed suicide in males". NeuroReport. 13 (9): 1195–8. doi:10.1097/00001756-200207020-00025. PMID 12151768. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Du L, Bakish D, Ravindran A, Hrdina PD (2004). "MAO-A gene polymorphisms are associated with major depression and sleep disturbance in males". NeuroReport. 15 (13): 2097–101. doi:10.1097/00001756-200409150-00020. PMID 15486489. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  11. ^ Yu YW, Tsai SJ, Hong CJ, Chen TJ, Chen MC, Yang CW (2005). "Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and antidepressant response". Neuropsychopharmacology. 30 (9): 1719–23. doi:10.1038/sj.npp.1300785. PMID 15956990. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Serretti A, Cristina S, Lilli R, Cusin C, Lattuada E, Lorenzi C, Corradi B, Grieco G, Costa A, Santorelli F, Barale F, Nappi G, Smeraldi E (2002). "Family-based association study of 5-HTTLPR, TPH, MAO-A, and DRD4 polymorphisms in mood disorders". Am. J. Med. Genet. 114 (4): 361–9. doi:10.1002/ajmg.10356. PMID 11992558. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  13. ^ Huang SY, Lin MT, Lin WW, Huang CC, Shy MJ, Lu RB (2009). "Association of monoamine oxidase A (MAOA) polymorphisms and clinical subgroups of major depressive disorders in the Han Chinese population". World J. Biol. Psychiatry. 10 (4 Pt 2): 544–51. doi:10.1080/15622970701816506. PMID 19224413.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ Leuchter AF, McCracken JT, Hunter AM, Cook IA, Alpert JE (2009). "Monoamine oxidase a and catechol-o-methyltransferase functional polymorphisms and the placebo response in major depressive disorder". J Clin Psychopharmacol. 29 (4): 372–7. doi:10.1097/JCP.0b013e3181ac4aaf. PMID 19593178. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  15. ^ a b c d Scott AL, Bortolato M, Chen K, Shih JC (2008). "Novel monoamine oxidase A knock out mice with human-like spontaneous mutation". NeuroReport. 19 (7): 739–43. doi:10.1097/WNR.0b013e3282fd6e88. PMID 18418249. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  16. ^ a b Vishnivetskaya GB, Skrinskaya JA, Seif I, Popova NK (2007). "Effect of MAO A deficiency on different kinds of aggression and social investigation in mice". Aggress Behav. 33 (1): 1–6. doi:10.1002/ab.20161. PMID 17441000.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ a b 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 (5133): 578–80. doi:10.1126/science.8211186. PMID 8211186. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  18. ^ Vishnivetskaya, Galina B. (1 January 2007). "Effect of MAO A deficiency on different kinds of aggression and social investigation in mice". Aggressive Behavior. 33 (1): 1–6. doi:10.1002/ab.20161. PMID 17441000. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  19. ^ Hebebrand J, Klug B (1995). "Specification of the phenotype required for men with monoamine oxidase type A deficiency". Hum. Genet. 96 (3): 372–6. doi:10.1007/BF00210430. PMID 7649563. {{cite journal}}: Unknown parameter |month= ignored (help)
  20. ^ Online Mendelian Inheritance in Man (OMIM): MONOAMINE OXIDASE A; MAOA. - 309850
  21. ^ a b c Sabol SZ, Hu S, Hamer D (1998). "A functional polymorphism in the monoamine oxidase A gene promoter". Hum. Genet. 103 (3): 273–9. doi:10.1007/s004390050816. PMID 9799080. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  22. ^ 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 (5582): 851–4. doi:10.1126/science.1072290. PMID 12161658. {{cite journal}}: Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  23. ^ Frazzetto G, Di Lorenzo G, Carola V; et al. (2007). Baune, Bernhard (ed.). "Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype". PLoS ONE. 2 (5): e486. doi:10.1371/journal.pone.0000486. PMC 1872046. PMID 17534436. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  24. ^ Fergusson DM; et al. (2012). "Moderating role of the MAOA genotype in antisocial behaviour". The British Journal of Psychiatry. 200 (2): 116–23. doi:10.1192/bjp.bp.111.093328. PMID 22297589. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)
  25. ^ Sjoberg RL; et al. (2008). "A non-additive interaction of a functional MAO-A VNTR and testosterone predicts antisocial behavior". Neuropsychopharmacology. 33 (2): 425–30. doi:10.1038/sj.npp.1301417. PMC 2665792. PMID 17429405. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)
  26. ^ a b Lea R, Chambers G (2007). "Monoamine oxidase, addiction, and the "warrior" gene hypothesis". N. Z. Med. J. 120 (1250): U2441. PMID 17339897.
  27. ^ Lu R; et al. (2003). "Neither Antisocial Personality Disorder Nor Antisocial Alcoholism Is Associated With the MAO-A Gene in Han Chinese Males". Alcoholism: Clinical and Experimental Research. 27 (6): 889–893. doi:10.1111/j.1530-0277.2003.tb04412.x. PMID 12824808. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)
  28. ^ Zhang M; et al. (2011). "The association between infants' self-regulatory behavior and MAOA gene polymorphism". Developmental Science. 14 (5): 1059–1065. doi:10.1111/j.1467-7687.2011.01047.x. PMID 21884321. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)
  29. ^ Zhou Q; et al. (2007). "The developmental trajectories of attention focusing, attentional and behavioral persistence, and externalizing problems during school-age years". Developmental Psychology. 43 (2): 369–85. doi:10.1037/0012-1649.43.2.369. PMC 1832154. PMID 17352545. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)
  30. ^ Chen S; et al. (1997). "Androgen and glucocorticoid receptor heterodimer formation. A possible mechanism for mutual inhibition of transcriptional activity". Journal of Biological Chemistry. 272 (22): 14087–92. doi:10.1074/jbc.272.22.14087. PMID 9162033. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: unflagged free DOI (link)
  31. ^ Ono H; et al. (2002). "No evidence of an association between a functional monoamine oxidase a gene polymorphism and completed suicides". American Journal of Medical Genetics. 114 (3): 340–342. doi:10.1002/ajmg.10237. PMID 11920860. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)
  32. ^ Wang TJ; et al. (2007). "Possible interaction between MAOA and DRD2 genes associated with antisocial alcoholism among Han Chinese men in Taiwan". Progress in Neuro-psychopharmacology and Biological Psychiatry. 31 (1): 108–114. doi:10.1016/j.pnpbp.2006.08.010. PMID 17007976. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)
  33. ^ Lee SY; et al. (2010). "MAOA interacts with the ALDH2 gene in anxiety-depression alcohol dependence". Alcoholism: Clinical and Experimental Research. 34 (7): 1212–8. doi:10.1111/j.1530-0277.2010.01198.x. PMID 20477771. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)
  34. ^ Barber N (2010-07-13). "Pity the poor murderer, his genes made him do it". The Human Beast: Why we do what we do. Psychology Today. Retrieved 2010-10-17.
  35. ^ Hagerty BB (2010-07-01). "Can Your Genes Make You Murder?". News > Science > Inside The Criminal Brain. National Public Radio. Retrieved 2010-10-17.

Further reading

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