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Book ChapterDOI

Neurobiological Mechanisms for Impulsive-Aggression: The Role of MAOA

01 Jan 2013-Current topics in behavioral neurosciences (Curr Top Behav Neurosci)-Vol. 17, pp 297-313
TL;DR: Current data on the genetics and neurobiology of individual differences in impulsive-aggression are reviewed, with particular attention to the role of genetic variation in Monoamine Oxidase A and its impact on serotonergic signaling within corticolimbic circuitry.
Abstract: Aggression may be present across a large part of the spectrum of psychopathology, and underlies costly criminal antisocial behaviors. Human aggression is a complex and underspecified construct, confounding scientific discovery. Nevertheless, some biologically tractable subtypes are apparent, and one in particular—impulsive (reactive) aggression—appears to account for many facets of aggression-related dysfunction in psychiatric illness. Impulsive-aggression is significantly heritable, suggesting genetic transmission. However, the specific neurobiological mechanisms that mediate genetic risk for impulsive-aggression remain unclear. Here, we review extant data on the genetics and neurobiology of individual differences in impulsive-aggression, with particular attention to the role of genetic variation in Monoamine Oxidase A (MAOA) and its impact on serotonergic signaling within corticolimbic circuitry.
Citations
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01 Jan 1996
TL;DR: The preliminary results suggest that deficits localized to the prefrontal cortex may be related to violence in a selected group of offenders, although further studies are needed to establish the generalizability of these findings to violent offenders in the community.
Abstract: This study tests the hypothesis that seriously violent offenders pleading not guilty by reason of insanity or incompetent to stand trial are characterized by prefrontal dysfunction. This hypothesis was tested in a group of 22 subjects accused of murder and 22 age-matched and gender-matched controls by measuring local cerebral uptake of glucose using positron emission tomography during the continuous performance task. Murderers had significantly lower glucose metabolism in both lateral and medial prefrontal cortex relative to controls. No group differences were observed for posterior frontal, temporal, and parietal glucose metabolism, indicating regional specificity for the prefrontal deficit. Group differences were not found to be a function of raised levels of left-handedness, schizophrenia, ethnic minority status, head injury, or motivation deficits in the murder group. These preliminary results suggest that deficits localized to the prefrontal cortex may be related to violence in a selected group of offenders, although further studies are needed to establish the generalizability of these findings to violent offenders in the community.

342 citations

12 Jun 2015
TL;DR: In this article, the authors found that both low monoamine metabolism and neuronal membrane dysfunction are plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5-10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.
Abstract: In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5–10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.

122 citations

Journal ArticleDOI
TL;DR: Low monoamine metabolism and neuronal membrane dysfunction are indicated as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5–10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.
Abstract: In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5–10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.

120 citations

Journal ArticleDOI
TL;DR: How an integrated translational strategy coordinating clinical and preclinical research may prove critical to elucidate important aspects of the pathophysiology of aggression, and identify potential targets for its diagnosis, prevention and treatment is emphasized.
Abstract: Drawing upon the recent resurgence of biological criminology, several studies have highlighted a critical role for genetic factors in the ontogeny of antisocial and violent conduct. In particular, converging lines of evidence have documented that these maladaptive manifestations of aggression are influenced by monoamine oxidase A (MAOA), the enzyme that catalyzes the degradation of brain serotonin, norepinephrine and dopamine. The interest on the link between MAOA and aggression was originally sparked by Han Brunner's discovery of a syndrome characterized by marked antisocial behaviors in male carriers of a nonsense mutation of this gene. Subsequent studies showed that MAOA allelic variants associated with low enzyme activity moderate the impact of early-life maltreatment on aggression propensity. In spite of overwhelming evidence pointing to the relationship between MAOA and aggression, the neurobiological substrates of this link remain surprisingly elusive; very little is also known about the interventions that may reduce the severity of pathological aggression in genetically predisposed subjects. Animal models offer a unique experimental tool to investigate these issues; in particular, several lines of transgenic mice harboring total or partial loss-of-function Maoa mutations have been shown to recapitulate numerous psychological and neurofunctional endophenotypes observed in humans. This review summarizes the current knowledge on the link between MAOA and aggression; in particular, we will emphasize how an integrated translational strategy coordinating clinical and preclinical research may prove critical to elucidate important aspects of the pathophysiology of aggression, and identify potential targets for its diagnosis, prevention and treatment.

67 citations

Journal ArticleDOI
TL;DR: Desirable effects of MAO inhibition include increased availability of monoamine neurotransmitters, decreased oxidative stress, decreased formation of neurotoxins, induction of pro-survival genes and antiapoptotic factors, and improved mitochondrial functions.
Abstract: Progress in understanding the role of monoamine neurotransmission in pathophysiology of neuropsychiatric disorders was made after the discovery of the mechanisms of action of psychoactive drugs, including monoamine oxidase (MAO) inhibitors. The increase in monoamine neurotransmitter availability, decrease in hydrogen peroxide production, and neuroprotective effects evoked by MAO inhibitors represent an important approach in the development of new drugs for the treatment of mental disorders and neurodegenerative diseases. New drugs are synthesized by acting as multitarget-directed ligands, with MAO, acetylcholinesterase, and iron chelation as targets. Basic information is summarized in this paper about the drug-induced regulation of monoaminergic systems in the brain, with a focus on MAO inhibition. Desirable effects of MAO inhibition include increased availability of monoamine neurotransmitters, decreased oxidative stress, decreased formation of neurotoxins, induction of pro-survival genes and antiapoptotic factors, and improved mitochondrial functions.

64 citations


Cites background from "Neurobiological Mechanisms for Impu..."

  • ...tional polymorphisms inMAO-A and serotonin transporters and their impact on serotonergic signaling (Dorfman et al., 2014; Pavlov et al., 2012)....

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  • ...Particular attention has been paid to the role of functional polymorphisms inMAO-A and serotonin transporters and their impact on serotonergic signaling (Dorfman et al., 2014; Pavlov et al., 2012)....

    [...]

References
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Journal ArticleDOI
02 Aug 2002-Science
TL;DR: In this paper, a large sample of male children from birth to adulthood was studied to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not.
Abstract: We studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A (MAOA) was found to moderate the effect of maltreatment. Maltreated children with a genotype conferring high levels of MAOA expression were less likely to develop antisocial problems. These findings may partly explain why not all victims of maltreatment grow up to victimize others, and they provide epidemiological evidence that genotypes can moderate children's sensitivity to environmental insults.

4,151 citations

Journal ArticleDOI
TL;DR: The OMPFC appears to function as a sensory-visceromotor link, especially for eating, which appears to be critical for the guidance of reward-related behavior and for setting of mood.
Abstract: This paper reviews architectonic subdivisions and connections of the orbital and medial prefrontal cortex (OMPFC) in rats, monkeys and humans. Cortico-cortical connections provide the basis for recognition of 'medial' and 'orbital' networks within the OMPFC. These networks also have distinct connections with structures in other parts of the brain. The orbital network receives sensory inputs from several modalities, including olfaction, taste, visceral afferents, somatic sensation and vision, which appear to be especially related to food or eating. In contrast, the medial network provides the major cortical output to visceromotor structures in the hypothalamus and brainstem. The two networks have distinct connections with areas of the striatum and mediodorsal thalamus. In particular, projections to the nucleus accumbens and the adjacent ventromedial caudate and putamen arise predominantly from the medial network. Both networks also have extensive connections with limbic structures. Based on these and other observations, the OMPFC appears to function as a sensory-visceromotor link, especially for eating. This linkage appears to be critical for the guidance of reward-related behavior and for setting of mood. Imaging and histological observations on human brains indicate that clinical depressive disorders are associated with specific functional and cellular changes in the OMPFC, including activity and volume changes, and specific changes in the number of glial cells.

2,522 citations

Journal ArticleDOI
22 Oct 1993-Science
TL;DR: Analytical results indicate that isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.
Abstract: Genetic and metabolic studies have been done on a large kindred in which several males are affected by a syndrome of borderline mental retardation and abnormal behavior. The types of behavior that occurred include impulsive aggression, arson, attempted rape, and exhibitionism. Analysis of 24-hour urine samples indicated markedly disturbed monoamine metabolism. This syndrome was associated with a complete and selective deficiency of enzymatic activity of monoamine oxidase A (MAOA). In each of five affected males, a point mutation was identified in the eighth exon of the MAOA structural gene, which changes a glutamine to a termination codon. Thus, isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.

1,481 citations

Journal ArticleDOI
TL;DR: Early-onset prefrontal damage resulted in a syndrome resembling psychopathy, suggesting that the acquisition of complex social conventions and moral rules had been impaired.
Abstract: The long-term consequences of early prefrontal cortex lesions occurring before 16 months were investigated in two adults. As is the case when such damage occurs in adulthood, the two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities, and showed insensitivity to future consequences of decisions, defective autonomic responses to punishment contingencies and failure to respond to behavioral interventions. Unlike adult-onset patients, however, the two patients had defective social and moral reasoning, suggesting that the acquisition of complex social conventions and moral rules had been impaired. Thus early-onset prefrontal damage resulted in a syndrome resembling psychopathy.

1,426 citations


"Neurobiological Mechanisms for Impu..." refers background in this paper

  • ...Moreover, lesion studies support the notion that disrupting this circuit produces deficits in emotion regulation and impulse control (Anderson et al. 1999; Goursaud and Bachevalier 2007; Machado and Bachevalier 2006; Butter and Snyder 1972; Blair and Cipolotti 2000; Clark and Manes 2004)....

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Journal ArticleDOI
TL;DR: This study has shown that the orbital and medial prefrontal cortex (OMPFC) is extensively connected with medial temporal and cingulate limbic structures, and the organization of these projections was defined in relation to architectonic areas within the OMPFC.
Abstract: Previous studies have shown that the orbital and medial prefrontal cortex (OMPFC) is extensively connected with medial temporal and cingulate limbic structures. In this study, the organization of these projections was defined in relation to architectonic areas within the OMPFC. All of the limbic structures were substantially connected with the following posterior and medial orbital areas: the posteromedial, medial, intermediate, and lateral agranular insular areas (Iapm, Iam, Iai, and Ial, respectively) and areas 11m, 13a, 13b, 14c and 14r. In contrast, lateral orbital areas 12o, 12m, and 12l and medial wall areas 24a,b and 32 were primarily connected with the amygdala, the temporal pole, and the cingulate cortex. Data were not obtained on the posteroventral medial wall. Three distinct projections were recognized from the basal amygdaloid nucleus: 1) The dorsal part projected to area 12l; 2) the ventromedial part projected to most areas in the posterior and medial orbital cortex except for area Iai, 12o, 13a, and 14c; and 3) the ventrolateral part projected to orbital areas 12o, Iai, 13a, 14c, and to the medial wall areas. The accessory basal and lateral amygdaloid nuclei projected most strongly to areas in the posterior and medial orbital cortex. The medial, anterior cortical, and central amygdaloid nuclei and the periamygdaloid cortex were connected with the posterior orbital areas. The projection from the hippocampus originated from the rostral subiculum and terminated in the medial orbital areas. The same region was reciprocally connected with the anteromedial nucleus of the thalamus, which received input from the rostral subiculum. The parahippocampal cortical areas (including the temporal polar, entorhinal, perirhinal, and posterior parahippocampal cortices) were primarily connected with posterior and medial orbital areas, with some projections to the dorsal part of the medial wall. The rostral cingulate cortex sent fibers to the medial wall, to the medial orbital areas, and to lateral areas 12o, 12r, and Iai. The posterior cingulate gyrus, including the caudomedial lobule, was especially strongly connected with area 11m.

1,201 citations