Low-activity Monoamine Oxidase A Research Articles

The role of monoamine oxidase A in the neurobiology of aggressive, antisocial, and violent behavior: A tale of mice and men.

Over the past two decades, research has revealed that genetic factors shape the propensity for aggressive, antisocial, and violent behavior. The best-documented gene implicated in aggression is MAOA (Monoamine oxidase A), which encodes the key enzyme for the degradation of serotonin and catecholamines. Congenital MAOA deficiency, as well as low-activity MAOA variants, has been associated with a higher risk for antisocial behavior (ASB) and violence, particularly in males with a history of child maltreatment. Indeed, the interplay between low MAOA genetic variants and early-life adversity is the best-documented gene × environment (G × E) interaction in the pathophysiology of aggression and ASB. Additional evidence indicates that low MAOA activity in the brain is strongly associated with a higher propensity for aggression; furthermore, MAOA inhibition may be one of the primary mechanisms whereby prenatal smoke exposure increases the risk of ASB. Complementary to these lines of evidence, mouse models of Maoa deficiency and G × E interactions exhibit striking similarities with clinical phenotypes, proving to be valuable tools to investigate the neurobiological mechanisms underlying antisocial and aggressive behavior. Here, we provide a comprehensive overview of the current state of the knowledge on the involvement of MAOA in aggression, as defined by preclinical and clinical evidence. In particular, we show how the convergence of human and animal research is proving helpful to our understanding of how MAOA influences antisocial and violent behavior and how it may assist in the development of preventative and therapeutic strategies for aggressive manifestations.

A Systematic Review and Meta-Analysis Investigating the Relationship between Exposures to Chemical and Non-Chemical Stressors during Prenatal Development and Childhood Externalizing Behaviors.

Childhood behavioral outcomes have been linked to low quality intrauterine environments caused by prenatal exposures to both chemical and non-chemical stressors. The effect(s) from the many stressors a child can be prenatally exposed to may be influenced by complex interactive relationships that are just beginning to be understood. Chemical stressors influence behavioral outcomes by affecting the monoamine oxidase A (MAOA) enzyme, which is involved in serotonin metabolism and the neuroendocrine response to stress. Non-chemical stressors, particularly those associated with violence, have been shown to influence and exacerbate the externalizing behavioral outcomes associated with low MAOA activity and slowed serotonin metabolism. The adverse developmental effects associated with high stress and maternal drug use during pregnancy are well documented. However, research examining the combined effects of other non-chemical and chemical stressors on development and childhood outcomes as a result of gestational exposures is scarce but is an expanding field. In this systematic review, we examined the extant literature to explore the interrelationships between exposures to chemical and non-chemical stressors (specifically stressful/traumatic experiences), MAOA characteristics, and childhood externalizing behaviors. We observed that exposures to chemical stressors (recreational drugs and environmental chemicals) are significantly related to externalizing behavioral outcomes in children. We also observed that existing literature examining the interactions between MAOA characteristics, exposures to chemical stressors, and traumatic experiences and their effects on behavioral outcomes is sparse. We propose that maternal stress and cortisol fluctuations during pregnancy may be an avenue to link these concepts. We recommend that future studies investigating childhood behaviors include chemical and non-chemical stressors as well as children’s inherent genetic characteristics to gain a holistic understanding of the relationship between prenatal exposures and childhood behavioral outcomes.

Sex-Dimorphic Interactions of MAOA Genotype and Child Maltreatment Predispose College Students to Polysubstance Use.

Polysubstance use (PSU) is highly prevalent among college students. Recent evidence indicates that PSU is based on gene x environment (G×E) interactions, yet the specific biosocial factors underlying this problem remain elusive. We recently reported that lifetime use of tobacco and cannabis in college students is influenced by the interaction of the X-linked MAOA (monoamine oxidase A) gene and child maltreatment. Building on these premises, here we evaluated whether the same G×E interaction may also predict PSU in this population. Students of a large Midwestern university (n = 470; 50.9% females) took part in a computer survey for substance use, as well as childhood trauma exposure, using the Child Trauma Questionnaire (CTQ). DNA was extracted from their saliva samples and genotyped for MAOA variable-number of tandem repeat (VNTR) variants. Findings indicated that the highest number of substances were used by male students harboring low-activity MAOA alleles with a history of childhood emotional abuse. In contrast, female homozygous high-activity MAOA carriers with a history of emotional and physical abuse reported consumption of the greatest number of substances. Our results indicate that PSU among college students is influenced by the interaction of MAOA and child maltreatment in a sex-specific fashion. Further studies are warranted to understand the mechanisms of sex differences in the biosocial interplays underlying PSU in this at-risk group.

A systematic review and meta-analysis examining the interrelationships between chemical and non-chemical stressors and inherent characteristics in children with ADHD

Children may be more vulnerable to the combined interactions of chemical and non-chemical stressors from their built, natural, and social environments when compared to adults. Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed childhood neurodevelopmental disorder and is considered a major public health issue, as 75% of childhood cases persist into adulthood. ADHD is characterized by developmentally inappropriate levels of hyperactivity, impulsivity, and inattention, with the neurotransmitter serotonin regulating these symptoms. Monoamine oxidase A (MAOA) aids in serotonin uptake and is often implicated in behavioral and emotional disorders, including ADHD. When children are exposed to cigarette smoke, bisphenol A (BPA), or organophosphate pesticides, MAOA activity is inhibited. Non-chemical stressors, such as traumatic childhood experiences, and lifestyle factors, complicate the relationship between genotype and exposures to chemical stressors. But the co-occurrence among outcomes between exposures to chemical stressors, non-chemical stressors, and the low activity MAOA genotype suggest that mental illness in children may be influenced by multiple interacting factors.In this systematic review, we examine the existing literature that combines exposures to chemical and non-chemical stressors (specifically childhood trauma), MAOA characteristics, and ADHD diagnosis to investigate the interrelationships present. We observe that chemical (lead [Pb], phthalates/plasticizers, persistent organic pollutants, and cigarette smoke) exposure is significantly related to ADHD in children. We also observed that existing literature examining the interaction between MAOA, exposures to chemical stressors, and traumatic experiences and their effect on ADHD outcomes is sparse. We recommend that future studies investigating childhood ADHD include chemical and non-chemical stressors and inherent characteristics to gain a holistic understanding of childhood mental health outcomes.

Tobacco and cannabis use in college students are predicted by sex-dimorphic interactions between MAOA genotype and child abuse.

Postsecondary students in Western countries exhibit a high prevalence of cannabis and tobacco use disorders. The etiology of these problems is contributed by several psychosocial factors, including childhood adversity and trauma; however, the mechanisms whereby these environmental determinants predispose to the use of these substances remain elusive, due to our poor knowledge of genetic and biological moderators. Converging evidence points to the monoamine oxidase A (MAOA) gene as a moderator of the effects of lifetime stress on the initiation of substance use. Building on these premises, in this study, we analyzed whether MAOA upstream variable number tandem repeat (uVNTR) alleles interact with child maltreatment history to predict for lifetime cannabis and tobacco consumption. Five hundred college students (age: 18-25years) from a large Midwestern University were surveyed for their child maltreatment history (encompassing emotional, physical, and sexual abuse, as well as emotional and physical neglect) and lifetime consumption of cannabis and tobacco. Saliva samples were obtained to determine the MAOA uVNTR genotype of each participant. In female students, lifetime tobacco and cannabis use was predicted by the interaction of physical and emotional abuse with high-activity MAOA allelic variants; conversely, in males, the interaction of low-activity MAOA alleles and physical abuse was associated with lifetime use of tobacco, but not cannabis. These findings collectively suggest that the vulnerability to smoke tobacco and cannabis is predicted by sex-dimorphic interactions of MAOA gene with childhood abuse. These biosocial underpinnings of tobacco and cannabis use may prove important in the development of novel personalized preventive strategies for substance use disorders in adolescents.

The interaction between monoamine oxidase A and punitive discipline in the development of antisocial behavior: Mediation by maladaptive social information processing.

Previous studies demonstrate that boys' monoamine oxidase A (MAOA) genotype interacts with adverse rearing environments in early childhood, including punitive discipline, to predict later antisocial behavior. Yet the mechanisms by which MAOA and punitive parenting interact during childhood to amplify risk for antisocial behavior are not well understood. In the present study, hostile attributional bias and aggressive response generation during middle childhood, salient aspects of maladaptive social information processing, were tested as possible mediators of this relation in a sample of 187 low-income men followed prospectively from infancy into early adulthood. Given racial-ethnic variation in MAOA allele frequencies, analyses were conducted separately by race. In both African American and Caucasian men, those with the low-activity MAOA allele who experienced more punitive discipline at age 1.5 generated more aggressive responses to perceived threat at age 10 relative to men with the high-activity variant. In the African American subsample only, formal mediation analyses indicated a marginally significant indirect effect of maternal punitiveness on adult arrest records via aggressive response generation in middle childhood. The findings suggest that maladaptive social information processing may be an important mechanism underlying the association between MAOA × Parenting interactions and antisocial behavior in early adulthood. The present study extends previous work in the field by demonstrating that MAOA and harsh parenting assessed in early childhood interact to not only predict antisocial behavior in early adulthood, but also predict social information processing, a well-established social-cognitive correlate of antisocial behavior.

Post-Stroke Fatigue May Be Associated with the Promoter Region of a Monoamine Oxidase A Gene Polymorphism

Background: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. Methods: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A). Results: Among the 373 patients, 164 (44%) had PSF. All patients were ethnic Koreans. Of the 6 polymorphisms examined, only one marker, that is, low-activity MAO-A was associated with PSF (p < 0.05) in female patients. Multiple logistic regression analyses showed that post-stroke depression (PSD; 95% CI 1.561-14.323, p = 0.006) and low MAO-A activity (95% CI 0.166-0.722, p = 0.005) were factors associated with PSF in female patients, whereas only PSD (95% CI 5.511-65.269, p = 0.000) was associated with PSF in male patients. Conclusions: Our findings suggest that PSF may be associated with a genetic polymorphism involving MAO-A, at least in female stroke patients.

Different brain activity in pons in adolescent males with high- and low- activity MAOA genotype: resting-state fMRI study

Objective To examine the effects of a functional polymorphism of the monoamine oxidase A (MAOA) gene on spontaneous brain activity in healthy male adolescents. Methods Resting-state fMRI was performed on 31 healthy male adolescents with the low-activity MAOA genotype (MAOA-L) and 25 healthy male adolescents with the high-activity MAOA genotype (MAOA-H). The amplitude of low-frequency fluctuation (ALFF) of the blood oxygen level-dependent (BOLD) signal was calculated using REST software, and was compared between two genotype groups. The region ROIs showed significant difference. The ALFF data in ROIs were related to BIS scores. Results Compared with the MAOA-H group, the MAOA-L group showed a significant decrease of ALFF (P<0.001) in the pons (MNI coordinates: –6, –19, –23; 6, –16, –17; –6, –25, –32). In addition, the BIS scores were positively correlated with ALFF in pons in the MAOA-L group (r=0.398, P=0.02), but not in the MAOA-H group. Conclusions There exists relevance between the polymorphism of MAOA and the spontaneous brain activity in pons.And the lower activity of spontaneous brain activity in pons may be a key risk factor for impulsivity and aggression. Key words: Monoamine oxidase A gene; Amplitude of low-frequency fluctuation; Functional magnetic resonance imaging

Androgen metabolites impact CSF amines and axonal serotonin via MAO-A and -B in male macaques

A number of studies have shown that mutations or deletions of the monoamine oxidase-A (MAO-A) gene cause elevated CNS serotonin and elevated impulsive aggression in humans and animal models. In addition, low cerebrospinal fluid (CSF) 5-hydroxyindole acetic acid (5HIAA) has been documented in a limited number of violent criminal populations and in macaques that exhibit impulsive aggression. To reconcile these different analyses, we hypothesized that CSF 5HIAA reflected degradation of serotonin by the activity of MAO-A; and that low MAO-A activity would result in lower CSF 5HIAA, but overall higher serotonin in the CNS. To test this hypothesis, male Japanese macaques (Macaca fuscata) were castrated, rested for 5–7months, and then treated for 3months with [1] placebo, [2] testosterone (T), [3] dihydrotestosterone (DHT; non-aromatizable androgen) and 1,4,6-androstatriene-3,17-dione (ATD) (steroidal aromatase inhibitor), or [4] flutamide (FLUT; androgen antagonist) and ATD (n=5/group). These treatments enable isolation of androgen and estrogen activities. In the dorsal raphe, MAO-A and MAO-B expressions were determined with in situ hybridization (ISH) and protein expression of aromatase was determined with immunohistochemistry (IHC). CSF concentrations of 5HIAA, 3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) were determined with liquid chromatography/mass spectrometry (LC/MS). From the same animals, previously published data on serotonin axon density were used as a proxy for CNS serotonin. Aromatase conversion of T to estrogen (E) suppressed MAO-A (positive pixel area, p=0.0045), but androgens increased MAO-B (positive pixel area, p=0.014). CSF 5HIAA was suppressed by conversion of T to E (Cohen’s d=0.6). CSF 5HIAA was positively correlated with MAO-A-positive pixel area (r2=0.78). CSF 5HIAA was inversely correlated with serotonin axon-positive pixel area (r2=0.69). In summary, CSF 5HIAA reflects MAO-A activity rather than global serotonin. Low CSF 5HIAA may, in this paradigm, reflect higher serotonin activity. Androgens lower MAO-A activity via metabolism to E, thus elevating CNS serotonin and decreasing CSF 5HIAA. Since androgens increase certain types of aggression, these data are consistent with studies demonstrating that lower MAO-A activity is associated with elevated serotonin and increased aggression.

Testing for association of the monoamine oxidase A promoter polymorphism with brain structure volumes in both autism and the fragile X syndrome

BackgroundAutism and the fragile X syndrome (FXS) are related to each other genetically and symptomatically. A cardinal biological feature of both disorders is abnormalities of cerebral cortical brain volumes. We have previously shown that the monoamine oxidase A (MAOA) promoter polymorphism is associated with cerebral cortical volumes in children with autism, and we now sought to determine whether the association was also present in children with FXS.MethodsParticipants included 47 2-year-old Caucasian boys with FXS, some of whom also had autism, as well as 34 2-year-old boys with idiopathic autism analyzed in a previous study. The MAOA promoter polymorphism was genotyped and tested for relationships with gray and white matter volumes of the cerebral cortical lobes and cerebro-spinal fluid volume of the lateral ventricles.ResultsMAOA genotype effects in FXS children were the same as those previously observed in idiopathic autism: the low activity MAOA promoter polymorphism allele was associated with increased gray and white matter volumes in all cerebral lobes. The effect was most pronounced in frontal lobe gray matter and all three white matter regions: frontal gray, F = 4.39, P = 0.04; frontal white, F = 5.71, P = 0.02; temporal white, F = 4.73, P = 0.04; parieto-occipital white, F = 5.00, P = 0.03. Analysis of combined FXS and idiopathic autism samples produced P values for these regions <0.01 and effect sizes of approximately 0.10.ConclusionsThe MAOA promoter polymorphism is similarly associated with brain structure volumes in both idiopathic autism and FXS. These data illuminate a number of important aspects of autism and FXS heritability: a genetic effect on a core biological trait of illness, the specificity/generalizability of the genetic effect, and the utility of examining individual genetic effects on the background of a single gene disorder such as FXS.

Interactions Between Monoamine Oxidase A and Punitive Discipline in African American and Caucasian Men's Antisocial Behavior.

Although previous studies have shown that interactions between monoamine oxidase A (MAOA) genotype and childhood maltreatment predict Caucasian boys' antisocial behavior, the generalizability of this gene-environment interaction to more diverse populations and more common parenting behaviors, such as punitive discipline in early childhood, is not clearly understood. Among 189 low-income men (44% African American, 56% Caucasian) who underwent rigorous assessments of family behavior and social context longitudinally across 20 years, those men with the low activity MAOA allele who experienced more punitive discipline at ages 1.5, 2, and 5 years showed more antisocial behavior from ages 15 through 20 years. Effects of punitive discipline on antisocial behavior differed by caregiver and age at which it occurred, suggesting sensitive periods throughout early childhood in which low MAOA activity elevated boys' vulnerability to harsh parenting and risk for antisocial behavior. This genetic vulnerability to punitive discipline-and not just extreme, maltreatment experiences-may generalize to other male populations at risk for antisocial behavior.

A functional polymorphism of the MAOA gene modulates spontaneous brain activity in pons.

Objective. To investigate the effects of a functional polymorphism of the monoamine oxidase A (MAOA) gene on spontaneous brain activity in healthy male adolescents. Methods. Thirty-one healthy male adolescents with the low-activity MAOA genotype (MAOA-L) and 25 healthy male adolescents with the high-activity MAOA genotype (MAOA-H) completed the 11-item Barratt Impulsiveness Scale (BIS-11) questionnaire and were subjected to resting-state functional magnetic resonance imaging (rs-fMRI) scans. The amplitude of low-frequency fluctuation (ALFF) of the blood oxygen level-dependent (BOLD) signal was calculated using REST software. ALFF data were related to BIS scores and compared between genotype groups. Results. Compared with the MAOA-H group, the MAOA-L group showed significantly lower ALFFs in the pons. There was a significant correlation between the BIS scores and the ALFF values in the pons for MAOA-L group, but not for the MAOA-H group. Further regression analysis showed a significant genotype by ALFF values interaction effect on BIS scores. Conclusions. Lower spontaneous brain activity in the pons of the MAOA-L male adolescents may provide a neural mechanism by which boys with the MAOA-L genotype confers risk for impulsivity and aggression.

Factors associated with post‐stroke anger proneness in ischaemic stroke patients

Factors related to post- stroke anger proneness (PSAP) are poorly studied. The aim of the present study was to determine the frequency of, and the factors related to, PSAP in the acute stage of stroke. Serotonin transporter protein genes and monoamine oxidase A (MAO-A) gene polymorphisms were also examined. A total of 508 patients with acute IS were screened for PSAP at admission after stroke, using the modified Spielberger Trait Anger Scale. Blood samples were collected from each participant for DNA extraction and genotyping. The promoter of serotonin transporter protein (5-HTTLPR), the variable number of tandem repeat polymorphisms within intron 2 (VNTR STin2), and the 30-bp functional VNTR polymorphism in the promoter region of the MAO-A gene (MAOA-uVNTR) were genotyped. Post- stroke anger proneness was present in 15.1% of patients at admission. The factors related to PSAP were diabetes mellitus (P < 0.05), previous stroke (P < 0.01), motor and sensory dysfunction (P < 0.01), National Institutes of Health Stroke Scale (NIHSS) at admission (P < 0.01), and MAO-A gene polymorphism (P < 0.05). Multiple logistic regression analyses showed that previous stroke (95% CI: 1.33-4.25, P < 0.01), NIHSS at admission (95% CI: 1.09-1.26, P < 0.01), and low MAO-A activity (95% CI: 1.19-3.47, P = 0.01) were the factors related to PSAP. Our results show that PSAP is relatively prevalent and that previous stroke, neurological dysfunction and the MAO-A gene are involved in the development of PSAP.

Altered cerebellar organization and function in monoamine oxidase A hypomorphic mice

Monoamine oxidase A (MAO-A) is the key enzyme for the degradation of brain serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE) and dopamine (DA). We recently generated and characterized a novel line of MAO-A hypormorphic mice (MAO-ANeo), featuring elevated monoamine levels, social deficits and perseverative behaviors as well as morphological changes in the basolateral amygdala and orbitofrontal cortex. Here we showed that MAO-ANeo mice displayed deficits in motor control, manifested as subtle disturbances in gait, motor coordination, and balance. Furthermore, magnetic resonance imaging of the cerebellum revealed morphological changes and a moderate reduction in the cerebellar size of MAO-ANeo mice compared to wild type (WT) mice. Histological and immunohistochemical analyses using calbindin-D-28k (CB) expression of Purkinje cells revealed abnormal cerebellar foliation with vermal hypoplasia and decreased in Purkinje cell count and their dendritic density in MAO-ANeo mice compared to WT. Our current findings suggest that congenitally low MAO-A activity leads to abnormal development of the cerebellum.

Influence of prenatal iron deficiency and MAOA genotype on response to social challenge in rhesus monkey infants

Social and emotional behaviors are known to be sensitive to both developmental iron deficiency (ID) and monoamine oxidase A (MAOA) gene polymorphisms. In this study, male rhesus monkey infants deprived of dietary iron in utero were compared with iron sufficient (IS) controls (n = 10/group). Half of each group had low MAOA activity genotypes and half had high MAOA activity genotypes. A series of social response tests were conducted at 3-14 months of age. MAOA genotype influenced attention to a video of aggressive behavior, emotional expression (fear, grimace and sniff) in the social intruder test, social actions (displacement, grooming) in the social dyad test, and aggressive responses to a threatening picture. Interactions between MAOA and prenatal ID were seen in response to the aggressive video, in temperament ratings, in affiliative behavior in the social dyad test, in cortisol response in the social buffering test and in response to a social intruder and to pictures with social and nonsocial themes. In general, the effects of ID were dependent on MAOA genotype in terms of both direction and size of the effect. Nutrition/genotype interactions may shed new light on behavioral consequences of nutritional deprivation during brain development.

Moderating role of the MAOA genotype in antisocial behaviour

Recent studies have examined gene×environment (G×E) interactions involving the monoamine oxidase A (MAOA) gene in moderating the associations between exposure to adversity and antisocial behaviour. The present study examined a novel method for assessing interactions between a single gene and multiple risk factors related to environmental and personal adversity. To test the hypothesis that the presence of the low-activity MAOA genotype was associated with an increased response to a series of risk factors. Participants were 399 males from the Christchurch Health and Development Study who had complete data on: (a) MAOA promoter region variable number tandem repeat genotype; (b) antisocial behaviour (criminal offending) to age 30 and convictions to age 21; and (c) maternal smoking during pregnancy, IQ, childhood maltreatment and school failure. Poisson regression models were fitted to three antisocial behaviour outcomes (property/violent offending ages 15-30; and convictions ages 17-21), using measures of exposure to adverse childhood circumstances. The analyses revealed consistent evidence of G x E interactions, such that those with the low-activity MAOA variant who were exposed to adversity in childhood were significantly more likely to report offending in late adolescence and early adulthood. The present findings add to the evidence suggesting that there is a stable G x E interaction involving MAOA, a range of adverse environmental and personal factors, and antisocial behaviour across the life course. These analyses also demonstrate the utility of using multiple environmental/personal exposures to test G×E interactions.

Child Abuse and Psychiatric Illness

Child Abuse and Psychiatric Illness

Psychopathy, PCL-R, and MAOA genotype as predictors of violent reconvictions

The Revised Psychopathy Checklist (PCL-R) has shown a moderate association with violence. The efficacy of PCL-R in varying monoamine oxidase A ( MAOA) genotypes is, however, unexamined. The aim of this study was to investigate the effect of PCL-R and psychopathy on the risk for violent reconvictions among 167 MAOA genotyped alcoholic offenders. Violent reconvictions and PCL-R scores among violent offenders were assessed after a 7-year non-incarcerated follow-up. Regression analysis was used to evaluate the alcohol exposure and age-adjusted effect of PCL-R score and psychopathy on the risk for reconvictions among differing MAOA genotypes. Results suggest that the PCL-R total score predicts impulsive reconvictions among high-activity MAOA offenders (6.8% risk increase for every one-point increase in PCL-R total score, P = 0.015), but not among low-activity MAOA offenders, whereas antisocial behavior and attitudes predicted reconvictions in both genotypes (17% risk increase among high-activity MAOA offenders and 12.8% increase among low-activity MAOA offenders for every one-point increase in factor 2 score). Both narcissistic self-image with related interpersonal style (factor 1 score) and psychopathy (PCL-R ≥ 30) failed to predict future violence. Results suggest that the efficacy of PCL-R is altered by MAOA genotype, alcohol exposure, and age, which seems important to note when PCL-R is used for risk assessments that will have legal or costly preventive work consequences.

High activity of Monoamine oxidase A is associated with externalizing behaviour in maltreated and nonmaltreated adoptees

Individual differences in a functional polymorphism of the promoter of the Monoamine oxidase A (MAO-A) gene might partly explain the increased vulnerability of maltreated children for externalizing behaviour. A sample of 239 internationally adopted boys was studied. Adoptive parents provided the information about abuse and neglect before the adoption and rated externalizing behaviour of their adopted children, using the Child Behaviour Checklist. MAO-A alleles were classified in high and low activity. We found that individuals with high MAO-A activity had more externalizing behaviour than those with low MAO-A activity. No modifying effect of MAO-A on the relationship between early maltreatment on externalizing behaviour was observed. Our results suggest that in severely maltreated children, high MAO-A activity may not protect against the effects of maltreatment but may convey an increased risk for externalizing behaviour.

Monoamine oxidase A genotype is associated with gang membership and weapon use

Context A functional polymorphism in the promoter region of the monoamine oxidase A (MAOA) gene has been found to be associated with a broad range of antisocial phenotypes, including physical violence. At the same time, it is well known that gang members represent some of the most serious violent offenders. Even so, no research has ever examined the association between MAOA and gang membership. Objectives The aim of this study is to examine the association between MAOA and gang membership and between MAOA and weapon use. Design We examined the effects of MAOA by using a molecular genetic association research design. Setting A nonclinical sample was used in this study. Participants Participants were drawn from the National Longitudinal Study of Adolescent Health (1155 females, 1041 males). Main Outcome Measures The outcome measures of this study are gang membership and weapon use. Results The low MAOA activity alleles conferred an increased risk of joining a gang and using a weapon in a fight for males but not for females. Moreover, among male gang members, those who used weapons in a fight were more likely to have a low MAOA activity allele when compared with male gang members who do not use weapons in a fight. Conclusions Male carriers of low MAOA activity alleles are at risk for becoming a gang member and, once a gang member, are at risk for using weapons in a fight.