The Monoamine Oxidase A (MAOA) Genetic Predisposition to ... · wrinkles, tattoos, etc. These atavistic traits in crimi-nals showed, according to Lombroso, that crime was the result

ORIGINAL PAPER

The Monoamine Oxidase A (MAOA) Genetic Predispositionto Impulsive Violence: Is It Relevant to Criminal Trials?

Matthew L. Baum

Received: 17 August 2009 /Accepted: 4 April 2011# Springer Science+Business Media B.V. 2011

Abstract In Italy, a judge reduced the sentence of adefendant by 1 year in response to evidence for agenetic predisposition to violence. The best charac-terized of these genetic differences, those in themonoamine oxidase A (MAOA), were cited asespecially relevant. Several months previously in theUSA, MAOA data contributed to a jury reducingcharges from 1st degree murder (a capital offence) tovoluntary manslaughter. Is there a rational basis forthis type of use of MAOA evidence in criminal court?This paper will review in context recent work on theMAOA gene–environment interaction in predisposingindividuals to violence and address the relevance ofsuch findings to murder trials. Interestingly, theMAOA genetic variants impact future violence andaggression only when combined with the adverseenvironmental stimuli of childhood maltreatment.Thus nature and nurture interact to determine theindividual’s risk. Based on current evidence, I arguethere is a weak case for mitigation. But should futureexperiments confirm the hypothesis that individual

differences in impulse control and response toprovocation found in MAOA-L men (without abuse)are significantly magnified when combined withchildhood maltreatment, the case could turn into astronger one.

Keywords Violence . Genetic predisposition .

MAOA .Monoamine Oxidase A . Criminalresponsibility . Neuroethics . Gene × environmentinteraction

Genetic Predispositions Enter the Courts

On 18 September 2009, An Italian appeals courttriggered controversy when it reduced the defendant’ssentence in response to evidence of a geneticpredisposition towards violence [1–3]. In a briefeditorial published in the European Journal of HumanGenetics, Forzano et al. describe the murder case:

“The convicted man [Abdelmalek Bayout] wasan adult male affected by schizophrenia who[…] was found guilty at the first level ofjudgement and was given a reduced sentence(9 years) owing to his mental illness. At theappeal court, a new expert assessment tookplace, and genetic testing was requested by thedefence. […]The judge, however, reduced thesentence from 9 to 8 years, based on the factthat the accused had tested positive for geneticvariants that made him particularly prone to be

NeuroethicsDOI 10.1007/s12152-011-9108-6

M. L. Baum (*)The Ethox Centre, Division of Public Healthand Primary Health Care, University of Oxford,Badenoch Building, Old Road Campus, Headington,Oxford OX3 7LF, UKe-mail: [email protected]

M. L. BaumOxford Centre for Neuroethics, University of Oxford,Littlegate House, Suite 8, 16/17 St Ebbes St,Oxford OX1 1PT, UK

aggressive under stressful circumstances andtherefore he was even more vulnerable becauseof that.” [1].

The court found especially salient the experttestimony on the effect of Monoamine Oxidase A(MAOA)1 genetic variants: “In particular, carrying thelow activity MAOA gene (MAOA-L) could make thesubject more prone to express aggression if provokedor socially excluded. It should be stressed that such“genetic vulnerability” turns out to carry even moresignificant weight in cases in which an individualgrew up in a negative domestic social context, andwas, especially in the early decades of life, exposed toadverse, psychologically traumatic environmentalfactors2” [4].

Forzano et al. decry the judge’s decision, sayingthat such action based on genetic testing “[…] mightconstitute a dangerous precedent [,]” and that “Aperson should be judged on the basis of his actualcondition and mental capacity at the moment of theact, independent of any theoretical predisposition todevelop some disease or inappropriate behaviour—even assuming that there is really a link betweenabnormal behaviour and specific genetic variants” [1].

“I don’t think this could have happened inAmerica, where we have the Daubert ruling (whichsets out stringent criteria for the admission ofscientific evidence)” said Troy Duster, a New YorkUniversity sociologist, when sought by the SundayTimes (UK) to comment on the case in an articlepublished Nov 17, 2009 [2]. Dr Duster was apparent-ly unaware that 6 months previous to his comment, aUS court not only admitted MAOA gene × environ-ment interaction (MAOA-L + childhood abuse)evidence during the guilt phase of the trial of DavisBradley Waldroup, but the jury took it into accountwhen reducing the charge from 1st degree murder (acapital offense) to voluntary manslaughter (a maxi-mum sentence of 6 years) [5, 6]. Waldroup wassentenced to 32 years total [7], as he also wasconvicted of especially aggravated kidnapping andattempted first degree murder.

These cases show that molecular behavioral genet-ics has already entered courts; a discussion of itsrelevance, therefore, is both warranted and pressing.Did these courts make the right rulings? Is there awell supported link between aggression and specificgenetic variants and does it lend support to a case forreduced punishment or charge?

In order to address these questions, I first will paintwith broad strokes the historical background of thegenetics of crime and then describe in detail what isemerging as the modern stage’s principal player: thelow activity gene variant of Monoamine Oxidase A(MAOA).

From Lombroso to Molecular-geneticPredispositions: Important Steppingstones3

The Italian case described above occurred in anappeals court in Trieste. Two months later in Turinon the opposite side of northern Italy, a museumreopened with rooms lined in prison artifacts—criminal skulls, artwork, handwriting, stories, familytrees of criminal families, photographs, and diagrams.The grand reopening of this criminology museum,first established by Italian psychologist and physicianCesare Lombroso, marked the 100th anniversary ofLombroso’s death. It has long been noted that thechildren of criminals seem more likely to commitcrimes. Modern epidemiological research estimatesthat 10% of the families in a given society areresponsible for over 50% of crime [8]. It wasn’t until1876, however, that Lombroso published a shortvolume, L’Uomo Deliquente or The Criminal Man,the first empirical theory of the biology of criminalbehavior [9]. In his preface to this first edition,Lombroso outlines his mission: “To […] decidewhether there is a force in nature that causes crime,[by proceeding] to the direct physical and psycholog-ical study of the criminal[.]” Lombroso came to arguethat some criminals were born, not made, and couldbe identified by their enrichment in characteristically“primitive” or “atavistic” physical traits—cranialstructure, nose size, jaw jutting, jug ears, skin

1 This gene codes for the MAOA protein, which is importantfor the degradation of several neurotransmitters includingserotonin, dopamine, and noradrenalin.2 Translated from the Italian. This quotation, with which thecourt concurs, is from the testimony of the psychologicalexperts and is written in the court’s case report.

3 A thorough treatment of the period in behavioral geneticsfrom Lombroso to the current work on MAOA is beyond thescope of the paper. I hope with this section to draw a humbleoutline of some important events that set the context for modernbehavioral genetics.

M.L. Baum

wrinkles, tattoos, etc. These atavistic traits in crimi-nals showed, according to Lombroso, that crime wasthe result of a regression to a more primitive andviolent evolutionary state. Because biology is unlikelyto change, he continued, the “born criminals” shouldbe punished in proportion to their threat to society [9].“Born criminals” composed only one third of thecriminal population, however. Of the other types ofcriminals, Lombroso argued that the “criminaloid”was predisposed to crime by having some—but notmany—physical traits of criminality and could bedriven to crimes by adverse environments [9].

Though his arguments overstepped their support,reflected racial stereotypes, and have now beenrightfully discredited, Lombroso’s first attempts touse the scientific method in studies of criminalbehavior set the theoretical groundwork for subse-quent research on its hereditary nature.

After his death in 1909, Lombroso’s physical“anomalies” theory was largely rejected [9]. Never-theless, the re-publishing of Mendel’s pioneeringwork on the genetics of pea plants ensured that theseeds of the idea of hereditary criminal behavior tookroot. The success of some researchers, such asCharles Davenport, in finding statistical evidence ofMendelian one-gene-one-trait inheritance in complexbehaviors like Huntington’s disease reinforced ideasof simple genetic determinism and encouraged othersto redouble efforts to look(in vain)for the same simplerelationship in behaviors as wide ranging as “feeble-mindedness” [10]. These early human studies ofbehavioral genetics were complemented by work inanimal models.

With the rise of human genetics came eugenics,gaining in speed during the interwar period. Twinresearch, then the cutting edge, blossomed, allowingresearchers to form better statistical estimates of theheritability of complex traits; because identical twinsare genetically identical, genetic traits should appearwith stronger similarity in identical than fraternaltwins. Of note, Germany became a major powerhousein the field of twin research under Verschuer [11]. Themutually-frenzying relationship of eugenics with poli-cy led to forced sterilization laws and immigrationquotas for those from “feebleminded origins” in theUnited States, and reached its abominable zenith in thehuman genetics laboratories of Nazi Germany [11].

The atrocious human rights violations at Auschwitzin the name of human genetics and the surprising vigor

and international voice with which many Germangeneticists/eugenicists bent their science to the aimsof Nazi racial policy combined to strike a large blow tothe prestige of behavioral genetics [11]. As McGue[12] succinctly notes, “Behavioral genetics was nearlycompletely discredited by its early association with theeugenics movement. Few intellectuals wanted to beassociated with a scientific Endeavour perceived tohave contributed to the Nazi’s repressive policies, nomatter how indirectly.” The inclusion of many of thesame Nazi eugenicists at the first meeting of theAmerican society of human genetics in 1949, however,indicates that the true state of events after the war wasmore complicated [13]. Regardless of the precisecause, in the 1950’s competing behaviorist explana-tions eclipsed hereditary theories of behavior; behav-iorists like B.F. Skinner and John B. Watson arguedthat the baby entered the world as a “blank slate” andthat environment, not heredity, determined all behavior[10, 12].

The success of the field of medical genetics ininborn errors of metabolism, which occurred duringthis period, kept the door open for future behavioralgenetics. Of most relevance here is the story ofPhenylketonuria (PKU) [14]. Inherited in a simplerecessive pattern, PKU is a condition in which theaffected child cannot metabolize the phenylalaninepresent in protein rich foods. Phenylalanine builds totoxic levels that cause irreversible brain damage andmental retardation. In a triumph for molecularscience, however, the discovery of the mechanism(build up of phenylalanine) led to a method of earlydiagnosis and the development of a treatment (a lowPhenylalanine diet) that could avert the mentallyretarded outcome if immediately applied. Thus PKUbecame a striking example that we are not “deter-mined exclusively by our genes,” but that we have thecapacity to modify our environments (diet, here) toovercome previously unavoidable outcomes; geneticknowledge confers empowerment, not helplessness.

Genetic predispositions to complex physical con-ditions gained credibility and public trust with theirsuccess in cardiovascular disease (see [15]), establish-ing terminology and a way of thinking about risk thatwas an essential step towards current moleculargenetics research on predispositions to violence.

Standing atop these steppingstones, several groupsof scientists have begun to reexamine the hypothesisthat crime has a genetic basis. What they have found

Is It Relevant to Criminal Trials?

is a gene × environment interaction, far fromLombroso’s born criminal and even farther from“crime genes.”

What is a Gene × Environment Interaction?4

You take the family car for a spin down MainSt. Unbeknownst to you, the computer software thatcontrols the car’s anti-lock brakes rounds down whenit calculates how many times per second to engage thebrakes. About 35% of cars on the road use this sort ofanti-lock brakes software, but 65% use one thatrounds up. If you were to slam on the brakes withenough force for them to engage the antilock brakes,cars like yours actually pump the brakes fewer timesper second and take longer to stop. Given goodweather and good driving technique, however, whichantilock brakes program you have shouldn’t make adifference. If you never slam on the brakes, you neverengage the anti-lock system, and your car behavesjust like every other.

Now imagine that it begins to snow. Soon, slipperysnowflakes blanket the road. Your muscles tense.Combined with this adverse environment, suddenlyyou have become much more likely to slam on thebreaks and unveil the disadvantage in the computerprogram, which ultimately makes it more likely foryou than for the general population to be in a caraccident.

Importantly, the combination is not deterministic.By this I mean determined only by your computerprogram regardless of what else happens. You maynever slam on the brakes. Even if you do trigger theantilock brakes, the car will still stop; it will just takelonger. Whether you actually get into an accident willdepend not only on the anti-lock brakes program buton your speed, driving experience, alertness, actionsof the other drivers, the distance between you and thenext car, etc.

But what happens if a car surprises you? Itcomes down to a nagging fact: if you, or any of35% of the population like you, drive in the snow,you are more likely than most to get into a caraccident and as a group, do. How should we takeinto account your non-deterministic predispositionto car accidents?

Recent behavioral genetics and neuroscience sug-gests that we may have unearthed an analogoussituation that applies not to car accidents, but toimpulsive violence—and there is no possibility of aparts recall. Instead of an adverse environmentcombining with an antilock-brakes program, it com-bines with a gene variant coding for monoamineoxidase A (MAOA). One variant confers susceptibil-ity to the negative influence of adverse environmentalstimuli like childhood maltreatment to predispose tofuture violence. The other variant confers resilience.Thus both nature and nurture interact to modify theindividual’s risk.

The following will review the science linking theMAOA variants to aggression. Though there are othergenes associated with violent behavior, I concentrateon MAOA for two reasons 1) the comparativerobustness of its supporting evidence and preliminarydata on mechanism make it the most promising casefor this type of research 2) Both the trials in whichmolecular genetic predisposition data has had aneffect, Bayout (2009) and Waldroup (2009), the effectwas due heavily to MAOA.

A Note on Violence

Before continuing, it is important to clarify that thispaper refers to impulsive, reactive violence caused bya stimulus: anger, frustration, or other provocation. Iwill sometimes use aggression and violence inter-changeably, but always I am referring to this reactiveform. Although reactive violence can sometimes beadaptive, as in defending oneself, a reaction that isdisproportional to the provocation, or in response toperceived and not actual provocation, can becomepathological. When it does, this impulsive violencetakes major tolls from society. The World HealthOrganization recently estimated 560,000 people to bedying in a single year as a result of homicide (i.e.greater than 1 person per minute), which is almost 3.5times the number estimated to be dying as a result of

4 A similar scenario actually did happen: “February 8, 2010—Toyota […], today announced it will conduct a voluntary safetyrecall on approximately 133,000 2010 Model Year Priusvehicles to update software in the vehicle’s antilock brakesystem (ABS). [… Some] reported experiencing inconsistentbrake feel during slow and steady application of brakes onrough or slick road surfaces when the ABS is activated” http://www.toyota.com/recall/abs.html

M.L. Baum

http://www.toyota.com/recall/abs.html

http://www.toyota.com/recall/abs.html

collective violence5 [16]. Most of these homicidesrepresent casualties of impulsive aggression; whilesome of the most chilling cases in criminology dealwith individuals who commit acts of premeditatedviolence, these cases are of the extreme minority andwill not be discussed here [17].

MAOA

First Clues from the Netherlands

Brunner and colleagues [18] found the first evidencethat a single gene might be important in violence andaggression. Many of the men in a large Dutch familyexhibited a strange behavioral disorder characterizedby mild retardation and antisocial behavior: inappro-priate aggression, rape, assault, and other violentcrime. Brunner and colleagues identified that a singlenucleotide (one of the As, Ts, Gs, and Cs that link-uptogether in the genetic code) in the MAOA genesequence that was altered in these men artificiallyterminated the production of MAOA protein leadingto its complete absence (C to T, position 936). Asmentioned briefly above, MAOA is involved primar-ily in degradation of the neurotransmitter serotoninand to a lesser extent, noradrenaline and dopamine.Interestingly, mice genetically engineered to bedevoid of MAOA protein have increased levels ofserotonin and are more aggressive [19]. Becausedysregulation of the neurotransmitter, serotonin, hadbeen previously associated with violence [5], adysregulation of its turnover in these Dutch menwas a particularly attractive model for their violentbehavior. The MAOA gene’s location on the Xchromosome carried the potential to explain whyviolent crime and antisocial personality disorder isobserved disproportionately in men in the generalpopulation. Men inherit a single X chromosome whilefemales inherit two, which puts men at greater risk forinheriting no functional copy of the MAOA gene.

Because this non-functional mutation in theMAOA gene turned out to be extremely rare in therest of the population, the results of the Brunner studywere of limited use but set the stage for the researchthat followed.

A Gene × Environment Interaction

Further research revealed that the MAOA gene existsin several common variations. In the gene’s promoter,a region that controls transcription and expressionefficiency, there are a variable number of nucleotidetandem repeats (VNTR) arranged much like links ofsausage. While the VNTRs range from 1 to 5 repeats,genes with three or four repeats are most common.Approximately 30% of the alleles (gene copies) in thegeneral population contain three repeats while ap-proximately 65% contain 4 [20]. Interestingly, in vitrostudies indicate that the variant with three repeats isexpressed significantly less efficiently than the variantwith four repeats [21], although there is conflictingdata about whether this is also true in humans [22].

Caspi and colleagues [21] tested the hypothesisthat the low-expressing variant would correlate withantisocial behavior. They tracked a birth cohort of1037 New Zealand male children at regular intervalsas they grew to 26 years of age. Antisocial behaviorwas measured by convictions for violent crime,diagnosis of adolescent conduct disorder, a psycho-logical assessment of violence-acceptance, and anti-social personality disorder symptoms reported by aninformant.

When the children were grouped by the low (threerepeats; MAOA-low) or high (four repeats; MAOA-high) activity polymorphisms in the MAOA gene,there was no significant correlation between genotypeand antisocial behavior. Consistent with previousstudies, however, there was a significant positivecorrelation between maltreatment and later antisocialbehavior (8% had experienced severe maltreatmentbetween the age of 3 and 11 years). Strikingly, boyswho had been maltreated AND possessed MAOA-low were significantly more likely to exhibit laterantisocial behavior than were maltreated boys withMAOA-high.

Importantly, the boys who were maltreated werenot significantly more likely than non-maltreated boysto possess the MAOA low genotype (P=0.82), whichsuggests that genotype did not predispose the boys toreceive maltreatment, but rather impacted their resil-ience to it. This gene × environment interaction wasstill seen after correction for socioeconomic status andseveral other environmental variables. The lowMAOA variant seemed to confer sensitivity tomaltreatment while the high MAOA conferred a sort

5 170,000 per year were estimated to die of collective violence[16].


of protection. Although only 12% of the boys in thecohort were maltreated and possessed the low MAOAgenotype, they were responsible for 44% of convic-tions for violent crime. This was the first example of agene × environment interaction correlating with abehavior and the first time such an interaction wasshown to predispose anyone to criminal violence (seeFig. 1 for a diagrammatic representation of theinteraction).

MAOA Stands up to Meta-analysis

Several other groups confirmed and expanded uponthis research over the next 5 years [23]. Althoughsome groups were not able to repeat the findings ofCaspi et al. [21] with their own sample groups, thismay have been due to differences in definition ofmaltreatment or of aggression, or to a lack ofstatistical power. This critique highlights an importantshortcoming in the current literature: exactly what isan adverse environment needs to be better defined andmight be the leading reason for discrepancies betweentrials [24]. Some data, moreover, suggests that theresulting predisposition might be proportional to theseverity and duration of the exposure to the adverseenvironment rather than an all or nothing situation[24, 25]. The developmental window of susceptibilitywill also need to be systematically investigated.Despite these technological shortcomings, severalmeta-analyses, which pooled the sample data fromup to eight studies to increase statistical power, and

attempted to further standardize its variables, wereable to show a significant effect for the predispositionof maltreated boys with the low MAOA genotype andaggression [20, 23]. That the interaction held up to themeta-analysis even with the agglomeration of looselydefined “adverse environments” is important andsurprising, as few gene–environment interactions inbehavioral genetics have done so. For example, theother most studied gene × environment interaction,the one between the 5HTT-LPR (the gene coding forthe serotonin transporter), stressful life events, anddepression, did not pass testing by a similar meta-analytical method [26].

Modern Investigations of a Mechanism

These epidemiological findings set off a flurry ofneuroscientific inquiry into mechanism of the effect.Unfortunately, these studies were conducted on theMAOA gene variants alone without knowledge ofexposure to adverse environment; nevertheless, theyprovide important insights. A recent study [27] showsthat the MAOA gene promoter contains glucocorti-coid (stress hormones)/testosterone response elementsthat govern the gene’s transcription, which couldfurther tie MAOA to male violence. Glucocorticoidbinding leads to a larger increase in transcription thandoes testosterone binding, which suggests that anelevated level of testosterone would compete forbinding and actually decrease the net rate of tran-scription. The study went on to show that high

Fig. 1 Diagramatic representation of the MAOA gene ×environment interaction. Approximately 65% of males (largecircle) possess the MAOA high gene variant while approxi-mately 30% possess the MAOA Low variant (small circle).

When equal portions of these groups are exposed to an adverseenvironment during childhood (the oval) only the MAOA lowgroup on average shows a significantly increased probability ofaggression (darker shading)

M.L. Baum

testosterone levels, shown previously to correlate withantisocial personality disorder (ASPD), correlatedwith ASPD and aggression only in males who alsopossessed the MAOA low genotype. Importantly,there was no significant correlation between MAOAhigh males producing high testosterone and ASPD oraggression.

Using positron emission tomography (PET) with aradiolabeled MAOA-specific tagging molecule, clor-gyline, Alia-Klein et al. [28] showed that differencesin the expression of MAOA protein in the humansubjects accounted for greater than 30% of variabilityin trait aggression as assessed by survey.6 Althoughthey detected no correlation between genotype andMAOA activity, they did not look at whether subjectshad a history of childhood maltreatment. It could befeasible that possession of the low MAOA alonewould not diminish the amount of protein to levelsdetectable in this assay unless it had previously beencombined with childhood maltreatment.

Buckholtz and colleagues [29] went on to showthat functional connectivity between the ventromedialprefrontal cortex (vmPFC), a region implicated inimpulse repression, and the amygdala, a regionimplicated in emotional salience, was increased onlyin males with the low MAOA gene. Moreover, whenperforming an emotional face matching task, MAOAlow males showed increased activation of the amyg-dala and decreased activation of the vmPFC ascompared to control subjects. Interestingly, decreasedactivity of vmPFC and increased activity in amygdalahad previously been correlated with antisocial behav-ior, conviction of violent crime, and self reportedviolence. However, the reverse inference problem ofimaging makes it unclear whether the activationpattern (or endophenotype) seen in these previousstudies is cause or consequence of the violentbehavior. The connection between MAOA-low geno-type, this endophenotype, and aggression providessome of the first evidence, however, for a mechanisticrole of the gene in this altered brain activation. Thisneuroimaging study found this effect without differ-entiating between those who had experienced mal-treatment as children. It is intriguing to postulate that

the increased activation of the emotional amygdalaand decreased activation of the inhibitory input fromthe cortex could act like the slower-stopping antilockbrakes did in our analogy.

The authors note that there is no direct anatomicalconnective circuitry between the vmPFC and theamygdala. Using a functional connectivity regressionanalysis, however, they found that this functionalconnectivity seems to be mediated through theperigenual anterior cingulate, a region with anatom-ical connections both to the vmPFC and the amygda-la. The increased activation of the perigenual anteriorcingulate in this circuit is very interesting because ofthis region’s importance in serotonin signaling. Theperigenual anterior cingulate contains the highestconcentration of the serotonin receptor subtype 5-HT2a, a receptor shown by PET to be even furtherupregulated in the cingulate in those who havecommitted violent crime [17]. Moreover, inhibitionof the 5-HT2a receptor decreases impulsivity andaggression in animal models while activationincreases aggression [30].

Finally, MAOA low subjects show greater activa-tion of the anterior cingulate in response to beingexcluded from a virtual “ball-passing” game [31] andincidences of aggression become more frequent andof greater magnitude in response to provocation [32]as compared to MAOA high subjects (see Fig. 2 forschematic mechanism).

MAOA on Trial: Legal Implicationsof an Imperfect Predisposition to Aggressionand Violent Crime

Lombroso believed that there was a corporeal seat ofviolent crime that he could descry in the face of aman. Current research peers behind the face to thegenetic building blocks and neuronal networks thatenable him to learn and react to an ever changingenvironment. This research suggests that some peoplehave genetic susceptibilities to adverse environments.Of those children confronted with an adverse envi-ronment, only those that carry the low expressingvariant of the MAOA gene become more likely tocommit future reactive violence. The result, far from“born criminals,” is a group of individuals that giventhe right combination of gene and environment aremore vulnerable to act on violent impulses.

6 PET is an imaging technique that enables researchers tovisualize the location and density of a protein of interest bylabeling it with a tagged molecule that is injected into theblood.


Historical Application

The first appeal to the MAOA gene and violencesusceptibility was Mobley v. State (1995) [33]. Thedefense requested MAOA genotyping for the raremutation found in the Dutch family in the Brunner etal. study of Stephen Mobley, a 29 year old manaccused of murder. At this time, the MAOA gene ×environment interaction data had yet to surface.Because Mobley’s family tree did not fit the properinheritance pattern for the lack of function MAOAmutation, the judge determined that genotyping wasnot warranted. Mobley was later executed [34].

Since Mobley, discussion about the relevance tocriminal courts of the data like that on MAOA hastreated it like a distant possibility. In 2008, Pieri andcolleagues conducted focus groups of law professio-nals (social workers, parole officers, judges, lawstudents) in which “almost all participants wereskeptical about the possibility that research into thegenetics of aggressiveness and violence might benefit,or even enter, their fields of practice, in the foreseeable

future or ever” [35]. Perhaps surprising is that by 2007,however, genotyping evidence on MAOA variants (ofthe gene × environment type) had been submitted in afew U.S. criminal cases and, while it had no effect onoutcome, had been tolerated7 [34]. Bayout (2009) andWaldroup (2009), force us to acknowledge that it hasindeed breached the courts (see Table 1 for summary ofMAOA cases).

In Bayout (2009), MAOA data was introduced inthe sentencing phase. In Waldroup (2009), it wasintroduced in the pre-conviction (liability) phase. Theserepresent the two main phases at which any evidencemay act. During the liability phase, a case can be madefor a full defense (which if successful will lead to averdict of not guilty), or a partial defense (which ifsuccessful will lead to conviction of a lesser charge)[36]. An example of a full defense is insanity. Anexample of a partial defense is provocation.

Fig. 2 Diagramatic representation of proposed mechanism forMAOA variants (reading from left to right). The hypothesisfollows: presence of the MAOA low variant under normalconditions leads to a slight biasing of the development of neuralsystems that in turn contribute to a hyperactive amygdala andunderactive ventromedial prefrontal cortex (vmPFC) in re-sponse to emotional stimuli. This aberrant activation pattern

may then contribute to exaggerated emotional salience withdecreased impulse control. This creates the risk of provocativestimuli seeming even more provocative and contributing toincreased likelihood and intensity of response. Though moreempirical research is needed, it is hypothesized that the additionof an adverse environment (lightning bolt) supercharges themechanism, thereby leading to even greater effects

7 See [34]. Unfortunately, Bernet et al. does not identify therelevant trials by name, but codes them. Note also that Bernetprovided the expert evidence in the Waldroup trial [5].

M.L. Baum

Evidence that is not strong enough to successfullyserve as a full or partial defense can be offered forconsideration to mitigate the punishment during thesentencing phase. The Crown Prosecution ServicesSentencing Guidelines, for example, lists among itsmitigating factors lack of premeditation, mental disorderor disability, provocation less than defense, any elementof self defense, age and the West law dictionary alsoincludes childhood abuse.8 Though it has elements thatcould be used in several defenses, it might bereasonable to argue that the MAOA interaction couldwield most force at the level of sentence determination(See Table 2). While a thorough discussion ofrelevance of the MAOA data to all the possibilitieslisted in Table 2 is beyond the reach of this paper, Iwill focus on provocation as an illustrative example.9

“Incapability of Repression” is not Requiredfor Relevance in Court

First, let us dispel what seems to be Forzano et al.’s[1] main argument against the legal use of geneticpredispositions: “There is no scientific support todeclare that gene variants, claimed to predispose toaggression, would make the carriers incapable of

repressing an aggressive behaviour and thus unable tochoose appropriate socially acceptable behaviours.”10

Such a declaration would be tantamount to definingthe behavior involuntary action similar to spasm orconvulsion. In this case, the actus reus, or necessaryvoluntary component of the crime, would be negatedand a defense of automatism may be brought forward(see [36]). Forzano et al. are factually correct inpointing out that current scientific evidence isinsufficient to argue that MAOA even when com-bined with severe abuse leads to legally involuntaryaction. Their argument fails to take into account,however, that the vast majority of defenses and partialdefenses—those concerned not with actus reus butmens rea, the guilty mind—as well as sentencingconsiderations, do not require the agent to beincapable of repressing the behavior in this strictinvoluntary sense [36]. Likewise, it is not necessary toprove that MAOA or other genetic variants render anindividual incapable of repressing his behavior fortheir effects to be relevant in court.

Can the Framework of Provocation Stretchto Incorporate MAOA?

In concluding their 2008 paper on the MAOA story,Buckholtz et al. [19] propose “that MAOA genotype8 Although different jurisdictions accept different criteria for

mitigating factors, most of them resemble what I have outlinedhere. Mitigating factors are most relevant in jurisdictions thatstill permit capital punishment.9 I will leave discussion of Insanity and diminished capacity toanother paper, for example.

Table 1 MAOA genotyping in court

Case Brief description Genotype Adverse environment? Result

Mobley (1995) Charged with murder. During trial,asked for genotyping according torare Brunner et al. study

Genotypingrefused

n/a Executed

Waldroup (2009) Charged with murder (capitaloffense) of estranged wife’s friend,attempted murder of wife, and twocounts of kidnapping afterescalating argument

MAOA L Childhood Abuse Voluntary manslaughter (instead ofmurder); two counts of aggravatedkidnapping; attempted 2nd degreemurder. 32 year sentence

Bayout (2009) Defendant assaulted by group ofyouths, after which he buys a knifeand follows victim down street.Kills victim, mistakenly thinkingvictim was one of the assailants.Possibly delusional at time

MAOA L Unclear. Sentence reduced by 1 year forgenetic evidenceCulture shock/social

isolation?

Schizophrenia?

The unnamed cases mentioned in [34] are omitted from the table

10 This comment seems to be reacting against notions of hardgenetic determinism, a misinformed stance responsible forphrases like “crime genes.”


modifies an individual’s ‘socioaffective scaffold’: thebasic neural equipment for social and emotionalexperience, which subserves cognitive routines forcontextualizing social signals, decoding ambiguoussocial interactions and regulating affective response in

the face of perceived interpersonal threat.” Cognitiveexperiments seemed to indicate that MAOA low menare more sensitive to social rejection, have moreintense cognitive responses to fearful and negativestimuli, and decreased cognitive control over the

Table 2 Areas of possible legal relevance for the MAOA interaction

Full defense Negation of guilt MAOA Notes

Duress Requires threat of grievous bodilyharm. Though the strongest casesare where threat is reasonableand immediate, threat can befalsely believed and imminent[36]

Perhaps relevant in so far asMAOA would contribute to afalse belief or false appraisal ofthreat. But likely not so great thatit would lead to the full defense

Duress is not a defense to murder.Also subject to reasonable mantest

Insanity M’Naughten Rules: “A defect ofreason, from diseases of themind, as not to know the natureand the quality of the act he wasdoing; or, if he did know it, thathe did not know he was doingwhat was wrong” [36]

Possible but unlikely: unclearwould count as “disease of mind”or that it would have level ofinterference in knowingwrongness/nature/quality for thisdefense

Some US jurisdictions haveabolished the insanity defense

Partial defense Murder to manslaughter MAOA Notes

DiminishedResponsibility(capacity in US)

HA 1957s2 “1) Where a personkills or is a party to a killing ofanother, he shall not be convictedof murder if he was sufferingfrom such abnormality of mind(whether arising from conditionof arrested or retardeddevelopment of mind or anyinherent causes or induced bydisease or injury) as substantiallyimpaired his mentalresponsibility for his acts andomissions in doing or being aparty to the killing” [36]

Possible: wording here isremarkably loose. MAOA gene ×environment interaction couldpotentially be thought asabnormality of mind arising outof injury (abuse) or simply“inherent causes.”

Not available in many USjurisdictions, especially afterreaction to use as basis for the“twinkie defense” in the killingof Harvey Milk

Provocation Camplin (1978) “the reasonableman is a person having the powerof self-control to be expected ofan ordinary person of the sex andage of the accused, but in otherrespects sharing such of theaccused’s characteristics as theythink would affect the gravity ofthe provocation to him [36].”

Possible: stronger if reasonableman subjectified; could therebyinclude diminished impulsecontrol. As it stands, the over-salience of external social cuesmay make the defendant moresusceptible to provocation (b/c itseems to hold more gravity tohim)

Subjectification of reasonable manpossible. Roiled in debate

Sentencing Mitigation of punishment MAOA Notes

Crown prosecution servicessentencing guidelines mitigatingfactors:

Strongest case. Ticks all the boxes(except for age). Lesspremeditation, elements ofmental disorder, easierprovocation, false beliefs of selfdefense, all combined withchildhood abuse

Most relevant in capital trials.Mitigating factors vary somewhatbetween jurisdictions, but mostresemble what is to the left• Lack of premeditation

• Mental disorder or disability

• Provocation less than defence

• Any extent of self defence

• Age

• Childhood abuse (west law)

M.L. Baum

behavioral output from those interactions. Though itremains untested, the hypothesis is that an adverseenvironment throws that “socioaffective scaffold”even farther of its axis such that the above mecha-nisms become even more intense. If further worksupports this hypothesis, a partial defense that is“provocation-like” may exist for MAOA-L men withchildhood maltreatment. Until further work supportsit, however, there is a weaker case.

Perceived not Actual Provocation

In their 2006 paper, Eastman et al. [37] suggest that aprovocation defense would be implausible: “themental characteristics cannot be ‘proneness to vio-lence’ but must be characteristics that made thedefendant more susceptible to the particular provoca-tion emitted. This seems infertile ground for neuro-scientific evidence.” If the above hypothesis issupported, however, these individuals may be “proneto violence” specifically because they are moresusceptible to the particular provocation. That is,the particular stimulus is perceived as more intense.In practice, the partial defense of provocation ifsuccessful reduces a murder charge to manslaugh-ter. The test of provocation is composed of onesubjective (was the defendant provoked) and twoobjective limbs (would a reasonable man have beenprovoked, would a reasonable man have done asthe defendant did). Camplin (1978) [38] explainedthat “the reasonable man is a person having thepower of self-control to be expected of an ordinaryperson of the sex and age of the accused, but in otherrespects sharing such of the accused’s characteristicsas they think would affect the gravity of theprovocation to him” [36]. The altered evaluation ofstimuli due to the MAOA variants, therefore, mightreasonably qualify as a characteristic that wouldaffect the gravity of provocation to the accused. Itseems also that the increased gravity of the provo-cation would satisfy even the stringent ruling inNewell (1980) [39] that such characteristics wouldneed to have “sufficient degree of permanence tomake it part of individual’s character and personality.More importantly, there must be some real connec-tion between the nature of the provocation and theparticular characteristic of [the defendant] by whichit is sought to modify the reasonable man test”[36].

A Subjective Reasonable Man?

Currently, there is vibrant debate about whetherindividually diminished levels of self-control shouldmodify the reasonable man, making him moresubjective [40]. The reasonable person already makesallowances for individual difference for physicalattributes; for example, physical size and strength orphysical disability [40]. Recent research on impulsecontrol further challenges the physical/mental distinc-tion by revealing that this faculty fatigues much in thesame way that a muscle does [41]. It could be arguedthe reasonable person should take into accountsignificant variations in the size of both the physicalmuscle and the mental one (which arises fromphysical processes) or should reject both. An objec-tively small aggressor could be threatening to anotherman with even smaller muscles; so could a smallimpulse to one with even smaller impulse controlmuscles.

To illustrate this possibility, let us consider a casedescribed by Berns and Swerdlow [42]:

A man who we will refer to as Tim wasconvicted of amassing child pornography. Afterseveral months in prison, Tim began complain-ing of painful headaches. Doctors imaged hisbrain and discovered a large tumor impingingon his orbitofrontal cortex, a region thought tobe involved in impulse control. A tumor growthlike this can interfere with behavior essentiallyby compressing and thereby strangling thetissue’s normal functions. Interestingly, Tim’spedophilic tendencies disappeared when thetumor was removed. Shortly after the surgery,he was deemed fit for release. Several monthslater, however, he again began to stockpile childpornography, was discovered, jailed, and a brainimage revealed that his brain tumor had grownback. Doctors again removed the tumor, andTim’s pedophilic tendencies again vanished.

In the tumor’s absence, Tim behaves in a sociallyacceptable manner. It is only in its presence that hisexecutive functions, including the ability to controlhis unacceptable impulses, become reduced below thebaseline level that would lead to his refrain from childporn in everyday conditions. Should a tumor pressingon the frontal cortex be incorporated into thereasonable man? In Luc Thiet Thuan v. R (1997)


[43], where the defendant had a tumor that may havesimilarly decreased his self-control, the judge ruledthat this condition was not a relevant characteristic.Later that year in Campbell (1997) [44], however, thejudge overturned the decision, explaining, “If theconcept of the reasonable man expressed […] wereaccepted without any qualification, successful pleas ofprovocation would be rare indeed, since it is notaltogether easy to imagine circumstances in which areasonable man would strike a fatal blow with thenecessary mental intention, whatever the provocation.It is in recognition of human frailty that the scope ofthe defence of provocation has, to a very limitedextent, been enlarged.”

A split (3–2) decision in Smith (2000) [45] ruledfurther in favor of the relevance of diminished selfcontrol: “a characteristic of the accused, whethertemporary or permanent, which affected the degreeof control society could reasonably have expected of[the defendant] and which it would be unjust not totake into account” [36]. The dissent, voiced by LordMillet, responded: “The objective element of provo-cation should not be eroded and its moral basissubverted in order to provide a defence of diminishedresponsibility outside the limits within which Parlia-ment has chosen to confine it” [36]. Rowland (2003)[46] and Weller (2003) [47] embraced the majorityapproach. Lord Justice Mantell explained that “thejudge should not tell the jury that they should, as amatter of law, ignore any aspect. He may give themsome guidance as to the weight to be given to someaspects, provided he makes it clear that the question isone which, as the law provides, they are to answer,and not him” [47]. The decision in Smith (2000) wasquestionably overruled by A-G for Jersey v Holley(2005) [48] and Holley (2005) was subsequentlyupheld by James; Karimi (2006) [49]. The currentmeasure is an ordinary level of self-control. Shouldthe debate swing the other way, however, the MAOAstory could pack a double punch with both increasedsalience and decreased self-control modifying thereasonable man.

Before the age of non-invasive brain imaging,tumors would have gone unnoticed and Tim wouldhave been punished too harshly. It is an ethicalimperative, therefore, that legal structures expand toincorporate our understanding of the mind, itsabilities, and its weaknesses. Though they are ofdiffering impact magnitudes, Tim’s tumor and the

MAOA gene × environment interaction share animportant similarity. Namely, the MAOA interactionmay impair the functional connection between thefrontal cortex and the amygdala, which is perhapsequivalent to cutting the power brakes tempering theemotional reaction and decreasing control of violentimpulses.

It may be objected that the inclusion of differencesin impulse control would create a slippery slope thatwould lead to even “mere individual differences” inthe personal level of impulse control serving in anexculpatory fashion. I counter that keeping in mindthe degree of impairment introduces traction. We donot consider all height differences relevant to per-ceived threat. While two inches might not be relevant,two feet might; the impact of MAOA low alone mightnot be found relevant by a jury, but that of MAOAlow combined with childhood abuse and alteredbehavioral measures might.11

Inferring Mental States: Is MAOA Evidence ReallyThat Different from Other Evidence?

There is understandable reticence to including prob-abilistic information in criminal trials because of thepotential for miscarriages of justice. Forzano et al.voice a version of this concern when they say, “aperson should be judged on the basis of his actualcondition and mental capacity at the moment of theact, independent of any theoretical predisposition todevelop some disease or inappropriate behavior.”While it is reasonable to argue that the moment ofthe act is what matters, demanding one prove theactual mental state at any moment is unreasonableand unrealistic. The problem of finding out thismental information is neither new nor restricted to

11 A reasonable argument is that the jury might overweight thiskind of evidence. The basis for overweighting would be a sortof “genetic exceptionalism,” or false belief that geneticevidence is in fact inherently different than other evidence.While there is gravity in this risk and it should be takenseriously, excluding genetic information will likely reinforcethe very ideas of “genetic exceptionalism” that should becombated. Only by becoming comfortable with talking aboutand engaging with genetic information can we hope toovercome the specter of “genetic exceptionalism” and the riskof overweighting genetic evidence in trials if it is relevant to thecase (see Parens 2010 [53] for “why talking about behavioralgenetics is important and difficult”). During the transitionperiod, juries should be guided about how to interpret geneticinformation.

M.L. Baum

genetic predispositions, however. In reality, we can donothing more than infer the mental state, yet this issomething that courts do all the time. What courts relyon are observed behaviors at the moment (if there is awitness) and after-the-fact psychiatric (or other)evaluations, all “mere” correlates to the “actual”condition and mental capacity, in order to build acase for a certain mental state—in other words, tosupport the inference. Though courts would bereticent to define them this way, all inferences areby definition probabilistic. Yet courts recognize theproblem when they point out that “Beyond reasonabledoubt” does not mean “no doubt.” In other words,probabilities do matter (in so far as they help us makebetter inferences of mental states). As a corollary,predispositions matter (in so far as they provideuseful data on probabilities).

Both diagnoses of mental illness in the classicalsense (i.e. according to the DSM IV), for example,and genetic predispositions provide useful probabilis-tic information. They both act as signals that arelevant state is more likely than usual and that thecourt therefore has a responsibility to look forsupporting evidence. MAOA data should be viewedas simply another tool to help in making inferencesabout mental sates. To illustrate, a diagnosis ofschizophrenia can be thought of as a predispositionto (or risk for) hallucinations, delusions, and/or boutsof cripplingly disordered thinking. This would besimilar to classifying a person with epilepsy as beingpredisposed to develop (or at risk for) seizures.12 Inboth cases, having a diagnosis would be onlyprobabilistically related to experiencing hallucina-tions, delusions, seizures, etc. at the time of thecrime.13 Furthermore, experiencing hallucinations,delusions, seizures, etc. at the time of the crimewould only be probabilistically relevant for criminal

responsibility. For example, consider two delusionsthat would have differing relevance in a murder trial:1) Sam believes his child to be replaced by a fairydoppelganger and that if he did not kill thisdoppelganger, Sam’s own child would certainly die;2) Sam believes he would be paid $10,000 for killinghis child. Again, if the court infers that a delusion waspresent at the time of the crime, it would then benecessary to infer which type of delusion was present.In this way, courts build a tower of nested probabil-ities to house the inferred mental state. In thisframework, there is nothing inherently special aboutgenetic predispositions. Difficulties in proving “actualcondition and mental capacity at the moment of theact” are similar in type between risk factors likeschizophrenia and risk factors like gene × environ-ment interactions.

At this point, one may bring up the argument, asForzano et al. do, that “genetic variants associatedwith schizophrenia do not add to the evaluation of thephenotype itself.” I agree that there is an argument fora diagnosis of schizophrenia screening out theusefulness of genetic variants associated with schizo-phrenia, as the diagnosis provides stronger probabi-listic support for a relevant hallucination etc. Thisdoes not mean, however, that genetic variants wouldhave no value. Possessing genetic variants associatedwith schizophrenia—if one had this information butnot psychiatric evaluation—would serve as a flagindicating that one should check for the existence ofthe relevant phenotype. Similarly, if a genetic variantwas significantly associated with delusions of perse-cution or threat (i.e. those delusions particularlypertinent to responsibility as opposed to non-threatening delusions) this information would enrichthe diagnosis of schizophrenia in the court. Geneticvariants whose effects are relevant via a mechanismdistinct from schizophrenia, which seems the casewith the MAOA variants, would also be useful. I amnot arguing that all predisposing markers—whetherpsychiatric diagnosis or genetic variant—carry thesame level of probabilistic information. They obvi-ously do not. Some genetic variants contain lessinformation than others, or only contain moreprobabilistic information when combined with aspecific environmental stressor like childhood abuse.Similarly, a diagnosis of ADD (attention deficitdisorder) would contain lesser probability of arelevant impairment than diagnosis of schizophrenia.

12 One might reasonably object to my conceptual re-organization by pointing out that a diagnosis of Schizophreniaor Epilepsy requires more than just a predisposition to certainbehaviors; rather, it requires one to actually have exhibitedthose behaviors for some period of time. If the defense claimsthe first exhibition of the behavior is during or near the momentof the crime, however, a diagnosis—itself an inference made bythe psychiatrist—should be investigated and if determined byfurther psychiatric evaluation to be warranted can further buildsupport for the existence of the claimed mental state at themoment of the crime.13 Note that one does not need to have schizophrenia to havedelusions or hallucinations.


These individual weights are an empirical issue.While the relative risk of a relevant impairment forsomeone diagnosed with schizophrenia may turn outto be higher than for someone with MAOA low +childhood abuse, the type of information (probabilis-tic) and the difficulty of identifying the actualoccurrence in each case is similar. A rational agentshould either accept both as useful in court or rejectboth.

If the decision is to accept, then in both cases thecourt needs corroborating evidence to build its towertowards a good inference of mental state. For the case ofschizophrenia, interviews and checklist-questionnairesby forensic psychiatrists help identify continued pres-ence and type of delusions or hallucinations, whichwould in turn raise the level of confidence about claimsof a relevant state at the moment of the crime. It seemspossible that one could build similar support in theMAOA case. The same research tools used to establishdifferential susceptibility of the group to social rejection,negative emotions, and corresponding impulse controlcould in principle complement the marker data. Suchtesting might not be warranted, for practical purposes,for every defendant, but might be warranted for thosefound to have MAOA-L and probable maltreatment.These tests would work to embed a mechanistic story inthe otherwise population statistical definition of thegene × environment correlation.14

A Brief Address of Harsher Punishments

Though proper examination of a case for harsherpunishment is beyond the scope of this paper, it isnecessary to mention. The prosecution might argue aperson with a predisposition towards violence is adanger to society, a “ticking time-bomb.” Punishmentshould be extended, therefore, not because the person“deserves” greater punishment, but in order tosafeguard the community. In effect, this shows howgenetic predisposition evidence might cut both ways:

decreasing sentence due to less culpability, andincreasing sentence due to public safety concerns.Even a successful full excuse can be accompanied bythe option of involuntary civil commitment. Whichdirection wins this tug of war in the MAOA case,however, will depend both on political environmentand practical considerations. While the politicalenvironment in the UK at least seems to be growingmore intolerant of deviance,15 our increasing appre-ciation of workings of the brain and the surprisinglydynamic malleability of its neurons16 raise thepossibility that behaviors might be successfullyaltered in new ways that safeguard the communitywithout the need for continued imprisonment. Theadvent of non-invasive brain imaging, for example,enabled the identification and removal of the tumorthat influenced Tim’s undesirable behavior, afterwhich his behavior improved to the point that hewas deemed safe to return to the community. With thedevelopment of a mechanistic understanding comesthe potential to harness the power of modernmedicine, neuroscience, and psychology necessaryto drive toward effective rehabilitation. We need toprotect the public, but this might be achieved througheffective treatment combined with a shorter prisonsentence. Though I will address this possibility onlybriefly in the case of MAOA, mindfulness training,17

Omega-3 supplementation (found in oily fish),18 and

14 Some point menacingly to its statistical nature and theobservation that a majority of those with MAOA-L andchildhood maltreatment do not go on to commit violence (see[1]). While these things are important to remember, they do notform a sound basis upon which to argue that MAOA datashould have no effect in criminal court. The majority of thosewith schizophrenia, epilepsy, etc. do not commit crimes. If theydo, however, the court has a responsibility to investigatewhether these markers are relevant to the crime. The sameshould be true in the MAOA case.

15 The possibility of punishment based solely on risk to societyhovers in the British skies where a person deemed to pose agreater than 50% risk to commit future violent crime isproposed to be diagnosed with Dangerous and Severe Person-ality Disorder (DSPD). DSPD would support an optionalextension of a criminal sentence to life or permanent monitor-ing [54, 55].16 Modern research on epigenetics (in which environmentalinfluences dynamically modify the accessibility and transcrip-tion rates of genes) shows that even genes themselves are lessstatic than we had previously thought (see [24]). The MAOAgene–environment interaction itself may be mediated by such amechanism: the MAOA promoter region contains sites for onemechanism (addition of a methyl group—methylation) ofmetaplasticity and has been shown to be methylated in responseto components in tobacco smoke [56, 57].

18 Omega-3 fatty acids are essential for proper development andfunction of the prefrontal cortex, the area of the brain mostdirectly involved in impulse control, and supplementationshows promises of decreasing impulsive aggression [35, 59]

17 Mindfulness training is an adaptation of a type of Buddhistmeditation that helps individuals recognize and tolerateimpulses and seems especially suited to angry impulses [58]

M.L. Baum

5HT2a receptor antagonists19 all show potential forspecifically addressing effects of MAOA-L (seeTable 3) and should be investigated in a rigorous,evidence-based manner. While it seems intuitive thatthe MAOA interaction would lead to higher rates ofreoffending, moreover, it is important to rememberthat this has yet to be shown empirically and may notnecessarily turn out to be the case.

Returning to Trieste: Bayout (2009)

On the day of the murder, the defendant was accostedby a group of South American youths, who insultedhim (calling him a “faggot”) for wearing blackeyeliner (kohl), which the defendant said he worefor religious reasons [4]. The youths then beat him up,giving him cuts and bruises. The defendant changedhis bloodied clothes at a nearby cultural center,bought a knife, followed down a street and killedthe victim, whom he believed (falsely) to be one ofthe South American youths. The trial judge wasconvinced that on the balance of probabilities therewas some diminution of rational capacity; thedefendant had a history of mental disorder, stoppedtaking medication 6 months prior to the offence, andintended to kill one of his assailants, but mistakenlykilled a random South American person.20 The judgedeemed the evidence not strong enough to support aninsanity defense, however.

Did the defendant experience an adverse environ-ment? The case proceedings make no mention ofchildhood abuse or maltreatment. But as we sawearlier, there is considerable ambiguity about whatcould count as an adverse environment. Buckholtz[19] suggest a very inclusive definition “one typifiedby persistent uncertainty, unpredictable threat, poorbehavioral modeling and social referencing, andinconsistent reinforcement for prosocial decisionmaking.” The defense spends significant time arguingthat the defendant was unsettled by the shock of

uprooting from his native Algerian to Italian culture.Could culture shock and subsequent social isolationcount as an adverse environment? Or could schizo-phrenia itself count as an adverse environment, onetypified by illogical, unpredictable threats and uncer-tainty? Also, the defendant moved to Italy when hewas 24 years old, not when he was a child.Schizophrenia does not typically onset until 17–21 years; also not exactly childhood. Is this too oldfor an adverse environment to have an impact? Thesequestions highlight the need for more research (seeTable 4). The prefrontal cortex does not finishmaturing until the early-mid twenties (coincident withschizophrenia onset) and the brain remains immenselyplastic throughout life, however, both of whichsuggest room for influence [50].

Though theoretically possible, it remains to beshown empirically whether and to what degree thesepotential adverse environments could have impactedthe defendant’s brain. MAOA as marker in this case,therefore, contains very uncertain probabilistic infor-mation. The case for MAOA mitigation wouldcertainly be stronger if Bayout had the “classical”physical abuse during early childhood. Bayout was

19 Remember from the review of the science that MAOA-Lsubjects had increased activation of the perigenual anteriorcingulate, which could be responsible for the aberrant couplingbetween the amygdala and prefrontal cortex. This region is richin 5HT2a receptors and an antagonist applied to an animalmodel decreased aggression.20 [2] mistakenly claims that the victim was one of thedefendant’s assailants.

Table 3 Treatments to be investigated

Treatment Rationale

5HT2a receptorantagonists

• Overactive perigenual nucleus maymediate the disrupted amygdala/PFCcircuit

• Perigenual nucleus rich in 5HT2areceptors

• MAOA deficiency might indicatesurplus of 5HT and overstimulationof area

• 5HT2a antagonists decrease aggressionin mouse model

Omega-3supplements

• Underactive PFC and impulse control

• Omega-3 important for proper PFCfunction

• Omega-3 decrease incidence ofviolence in children and prisoners

Mindfulnesstraining

• Overactive amygdala and overlysalient emotional content

• Mindfulness training helps subjectsrecognize emotions and let them pass

• Mindfulness training decreasesincidence of aggression in certainstudies


put through a modified Stroop test, however, whichsuggested, according to the trial document, that hehad trouble inhibiting his motor impulses (most cuessignaled that the defendant should reach out andtouch a button; on the cues that signaled to hold back,Bayout failed to do so 23 out of 60 times).21 It isdifficult to estimate the extent of the defendant’sbehavioral disinhibition without knowing the exactparameters of the behavior task, but it may providesome independent support of decreased inhibitorycontrol. Again, this would be more relevant if thereasonable man went down the subjective route.Moreover, the provocation seems quite distant to thecrime (∼1.5 h). The South American youths created ahostile, stressful environment and though influence ofsuch an environment of perceived threat and perse-cution should not be all-together ruled out, it remainsto be shown whether hypersensitivity due to MAOAvariants could impact an action so far removed fromthe stimulus.

It is questionable though not completely outlandishthat Bayout experienced an adverse environmentduring a relevant window that could combine withhis MAOA-L gene. Thus it should count at most aweak argument that there is impairment above that ofMAOA-L alone. Behavioral evidence corroboratedthe proposition of impaired impulse control, however,which suggests that at least one component of theMAOA-L effects may be present. Such an associationmay have limited relevance in biasing, via anenvironment of persecution, the channeling of thepsychotic episode to a violent response, and perhapswould support the minor reduction in the sentence(1 year). At this point, it is worth remembering thatthe defense screened for several other genes ofpotential relevance, all with less empirical supportthan the MAOA case; together, however, one couldargue that the minor reduction in sentence is bettersupported.22 If his potential adverse environments anddevelopmental windows were supported by empirical

evidence, however, the decision would certainly reston firmer ground. At its current strength, introductionat the sentencing phase seems most relevant.

Polk County, Tennessee: Waldroup (2009)

The case for the relevance of the MAOA data isstronger in Waldroup’s trial, as it seems he was bothabused as a child and possessed the MAOA-L variant[5]. There was no delay between the triggeringstressful incident and the violent action, moreover.The violence was especially brutal however: adiscussion between Waldroup and his wife abouttheir marital problems escalated and all of a sudden,Waldroup fired his rifle (killing the wife’s femalefriend, who he believed had had an affair with her)and shot his fleeing wife in the back. A struggleensued: the wife kicked the gun away, but Waldrouppulled a pocket knife and cut her. This exchange wasrepeated with a shovel and a machete before the wifesubmitted and was dragged inside the home. Policearrived shortly thereafter and the wife was saved [6].

No corroborating behavioral tests on impulsecontrol or emotional sensitivity were performed.Waldroup’s lawyers, however, did argue that hesuffered from both intermittent explosive disorderand acted in passion, both conditions that could berelated to the MAOA story. Should the increasedemotional sensitivity and lowered impulse controlindeed be magnified when combined with abuse, acase may be made for a partial defense according tothe criteria above (temporary and severe perceivedemotional threat and, if the reasonable man issubjectified, diminished self-control). Until researchcorroborates that hypothesis, however, we will notknow whether the court made the right decision inconsidering the MAOA evidence during the liabilityphase or whether it should have been restricted to thesentencing phase.

A Cautious Conclusion

I recalled a brief history of genetics of crime andbehavior up to the probabilistic association betweenthe MAOA gene × environment interaction andimpulsive violence. I argued that this genetic evidenceis similar to current psychiatric diagnoses as a marker

21 The details of the procedure were not provided in the legaldocument.22 This argument leaves itself open to a challenge that mightarise if we continue down this road: courts may soon be facedwith cases in which the defense presents whole genomes andpoints out thousands of genetic variants each with small butnon-zero associations with violence (and with varying levels ofempirical support).

M.L. Baum

of a potentially relevant condition and could withfuture research form the rational basis for mitigationof criminal responsibility. Before we can knowwhether the decisions in the only two trials in whichthis data has had an effect, Bayout (2009) andWaldroup (2009), were correct, however, we needfurther research (see Table 4), especially corrobora-tion that the deficits in emotional regulation andimpulse control seen in those with MAOA-L aloneare magnified upon addition of an adverse environ-ment; we also need to better delineate the type andwindow of adverse environment that is relevant.

As we move forward toward this goal of building arigorous evidence base, we should keep in mind that it

was less than 100 years ago (during the interwar period)that Yale Psychologist Robert Yerkes stated in an addressto the American Eugenics Council that “the safedevelopment of eugenics is indeed assured by [our]insistence that we should not let application outstripknowledge” [51]. Despite the energies of some of thebrightest minds of the time, the heritability of crime wasoverestimated, was poorly and too generally defined,and resulted in a definition of the “unfit” that closelymimicked existing racial and ethnic prejudices.23

Table 4 Future research needed

Practical concern Research needed Notes

Mechanism of MAOA gene ×environment interaction exaggerateseffect of the gene alone on cognitivemeasures?

Repeat current cognitive neuroscience studieswith both MAOA genotype and childhoodabuse as independent variables

Urgent. Much stronger case for relevance ifinteraction follows the hypothesizedmechanism

What counts as an adverseenvironment?

Abuse: All these need not be investigated. The goalshould be to identify relevantenvironments while knocking downarguments based on irrelevantenvironments. For example, shouldBayout’s move from Algerian to Italiansociety or onset of schizophrenia beconsidered an adverse environment?

• Nuclear family only?

• Continual or single case?

• Severity?

• Bullying at school?

• Exposure to gang violence?

• Cultural conflict (i.e. Israel-Palestine)?

Neglect:

• Maternal rejection only?

• Social isolation?

• Culture shock?

Other:

• Uncertainty in environment?

• Mental or physical illness?

• Maternal smoking during pregnancy?

• Poor nutrition?

A critical period for relevantadversity? If so, what is it?

• Young childhood? Possible that certain adverse environmentsserve as triggers during specific windowsonly—maybe different windows fordifferent environments

• Pre-puberty?

• Before brain fully developed (18–24)?

To whom does the data apply? • White males only? Important for validity of evidence in court

How strong is the impulse controldeficit?

• Like flashing-light induced seizure? Impacts how relevant info is to guilt phaseof trial• Like mosquito-bite induced scratch?

What tests could complement thegenetics in a legal setting?

• Stop-signal test for motor impulse control Critical in building a case for a relevantimpairment of impulse control, oremotional arousal at the time of the crime

• Reaction to negatively valenced faces

• Reaction to simulated social exclusion

• Tendency and degree of punishment in “hotsauce” task [3]

23 The possibility of discrimination exists with the MAOA dataas well and should be safeguarded against in any application:the MAOA-L gene is differentially represented across ethnic-ities (see [60–62]).


Application outpaced knowledge without anyone real-izing it. As a result, the sterilizations and immigrationlaws that aimed to improve society actually damaged it.

The journalist, Walter Lippmann, who lived at thetime, warned, “If [the expert’s] advice is followed,and he is wrong, the consequences may be incalcu-lable.” For “except on a few subjects where ourknowledge is great, we cannot choose between trueand false accounts [52].” The people rely on theexpert. They have learned to trust the prestige ofscience in order to form public opinion. Scientistshave a great responsibility, consequently, to ensurethat any application is reasonably justified by thedata.

In light of this history, it is worth noting that theinvestigation of the mechanism of the MAOA ×environment predisposition has advanced farther thanany of its contemporaries or predecessors in theassociation with impulsive violence. It is linked to aneurotransmitter system and functional differences inbrain areas known to be involved in anger productionand control. Nonetheless, it will be extremely impor-tant to ensure that application of the data onMAOA × environment predispositions toward vio-lence does not outpace a realistic understanding ofmechanism.

Acknowledgments The author would like to thank RussellPerkins for aiding in the translation and understanding of theItalian Appeals Court trial, as well as Julian Savulescu, MarkSheehan, Neil Levy, Owen Schaefer, Ben Edelstein, Paul Troopand one anonymous reviewer for thoughtful comment anddiscussion of the manuscript in its various stages.

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2. Ahuja, A. The get out of jail free gene. The Sunday Times(UK) 2009, (November 17).

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4. Bayout v. Francesco. 2009, RGAssise App. 6/2008 RGNR1685/2007, RG. sent 5, dd 18 settembre 2009.

5. Hagerty, B. 2010. Can your genes make you murder?National Public Radio (July 1): [http://www.npr.org/templates/story/story.php?storyId=128043329]

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