The COMT Met158 allele and violence in schizophrenia: A meta-analysis

Bhakta, Savita; Zhang, Jian-Ping; Malhotra, Anil K.

doi:10.1016/j.schres.2012.06.026

Cited by 41 publications

(35 citation statements)

References 39 publications

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“…Among people with a diagnosis of personality disorder, the low-expressing G allele of the COMT rs165599 SNP is associated with self-reported aggression (Flory et al, 2007). Likewise, among individuals diagnosed with schizophrenia, the low-activity Met allele of the COMT Val158Met polymorphism is associated with high aggression (Bhakta et al, 2012;Gu et al, 2009;Han et al, 2004;Hong et al, 2008;Koh et al, 2012;Kotler et al, 1999;Lachman et al, 1998;Singh et al, 2012;Strous et al, 2003;Volavka et al, 2004c). DRD 2 and DRD 4 gene variants interact to predict adolescent conduct disorder and adult antisocial behavior (Beaver et al, 2007), as well as dysfunctional impulsivity (Colzato et al, 2010), and differences in inhibitory control are associated with the DRD 4 VNTR polymorphism (Congdon et al, 2008).…”

Section: Da and Aggressive Behaviormentioning

confidence: 99%

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Suri

Teixeira

Cagliostro

et al. 2014

Neuropsychopharmacol

141

125

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Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system development, such sensitive periods shape the formation of neurocircuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint as well as the environmental context. While allowing for adaptation, such sensitive periods are also vulnerability windows during which external and internal factors can confer risk to disorders by derailing otherwise resilient developmental programs. Here we review developmental periods that are sensitive to monoamine signaling and impact adult behaviors of relevance to psychiatry. Specifically, we review (1) a serotonin-sensitive period that impacts sensory system development, (2) a serotonin-sensitive period that impacts cognition, anxiety-and depressionrelated behaviors, and (3) a dopamine-and serotonin-sensitive period affecting aggression, impulsivity and behavioral response to psychostimulants. We discuss preclinical data to provide mechanistic insight, as well as epidemiological and clinical data to point out translational relevance. The field of translational developmental neuroscience has progressed exponentially providing solid conceptual advances and unprecedented mechanistic insight. With such knowledge at hand and important methodological innovation ongoing, the field is poised for breakthroughs elucidating the developmental origins of neuropsychiatric disorders, and thus understanding pathophysiology. Such knowledge of sensitive periods that determine the developmental trajectory of complex behaviors is a necessary step towards improving prevention and treatment approaches for neuropsychiatric disorders.

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Section: Da and Aggressive Behaviormentioning

confidence: 99%

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Suri

Teixeira

Cagliostro

et al. 2014

Neuropsychopharmacol

141

125

View full text Add to dashboard Cite

show abstract

“…98 Most of the human association studies between the COMT genetic variants and violence-related traits involve schizophrenics and schizoaffective patients, as recently reported in a meta-analysis showing that males carrying the low activity Met allele, particularly the Met/Met genotype, are at risk for violent behavior. 12 However, since the sample included in the meta-analysis comprised primarily men (80%), its power was limited and a possible relationship in females cannot be excluded. In detail, the Met/Met genotype was associated to higher risk for aggressive and dangerous behavior in schizophrenics with a history of aggressive behavior and in schizophrenics with high scores at the Overt Aggression Scale or the Corrigan Agitated Behavior Scale.…”

Section: Slc6a4 5httlprmentioning

confidence: 99%

“…[2][3][4] The hypothesis that a close linkage between behavior and genetics may exist comes from studies on twins and adoptees, 5 and is supported by several pieces of evidence recently generated by scientific research. 6 A number of candidate genes have been indeed investigated in association with antisocial behavior, especially genes involved in serotonergic [7][8][9][10][11] and dopaminergic [12][13][14] circuits.…”

Section: Introductionmentioning

confidence: 99%

Molecular genetics and antisocial behavior: Where do we stand?

Iofrida

Palumbo

Pellegrini

2014

Exp Biol Med (Maywood)

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Over the last two decades, it has become increasingly evident that control of aggressive behavior is modulated by the individual genetic profile as well. Several candidate genes have been proposed to play a role in the risk to develop antisocial behavior, and distinct brain imaging studies have shown that specific cortical areas may be functionally and/or structurally impaired in impulsive violent subjects on the basis of their genotypes. In this paper, we review the findings regarding four polymorphisms-MAOA (Monoamine oxidase A) uVNTR, SLC6A4 (solute carrier family 6 (neurotransmitter transporter), member 4) 5HTTLPR, COMT (Catechol-O-methyltransferase) Val158Met and DRD4 (dopamine D4 receptor) VNTR 1-11-that all have been found to be associated with an increased vulnerability for antisocial and impulsive behavior in response to aversive environmental conditions. These results, however, have not been replicated by other studies, likely because of crucial methodological discrepancies, including variability in the criteria used to define antisocial behavior and assessment of environmental factors. Finally, it has been recently proposed that these genetic variants may actually increase the individual susceptibility not merely to the negative environmental factors, but to the positive ones as well. In this view, such alleles would play a wider modulatory role, by acting as "plasticity" rather than "vulnerability" genes. Overall, these findings have potential important implications that span well outside of neuroscience and psychiatry, to embrace ethics, philosophy, and the law itself, as they pose new challenges to the very notion of Free Will. Novel properly controlled studies that examine multi-allelic genetic profiles, rather than focusing on distinct single variants, will make it possible to achieve a clearer understanding of the molecular underpinnings of the nature by nurture interaction.

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“…A meta-analysis testing the same association in 14 studies was independently conducted by another group [53]. Similarly, it was found that the Met158 allele of the COMT gene confers a significantly increased risk for violent behavior in schizophrenia.…”

Section: Static Factorsmentioning

confidence: 91%

“…Recently published meta-analyses indicating an association between the polymorphism of the catechol-o-methyl transferase (COMT) gene and violence in schizophrenia [52,53] have pointed to a role of catecholamines in the pathogenesis of violence in schizophrenia. These meta-analyses may therefore rekindle future interest in influencing noradrenergic system as a potential treatment for violent behavior in schizophrenia.…”

Section: Othermentioning

confidence: 99%

Aggression in Psychoses

Volavka

2014

Advances in Psychiatry

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Most individuals diagnosed with a mental illness are not violent, but some mentally ill patients commit violent acts. PubMed database was searched for articles published between 1980 and November 2013 using the combination of key words “schizophrenia” or “bipolar disorder” with “aggression” or “violence.” In comparison with the general population, there is approximately a twofold increase of risk of violence in schizophrenia without substance abuse comorbidity and ninefold with such comorbidity. The risk in bipolar disorder is at least as high as in schizophrenia. Most of the violence in bipolar disorder occurs during the manic phase. Violence among adults with schizophrenia may follow two distinct pathways: one associated with antisocial conduct and another associated with the acute psychopathology, particularly anger and delusions. Clozapine is the most effective treatment of aggressive behavior in schizophrenia. Emerging evidence suggests that olanzapine may be the second most effective treatment. Treatment nonadherence greatly increases the risk of violent behavior, and poor insight as well as hostility is associated with nonadherence. Nonpharmacological methods of treatment of aggression in schizophrenia and bipolar disorder are increasingly important. Cognitive behavioral approaches appear to be effective in cases where pharmacotherapy alone is not sufficient.

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The COMT Met158 allele and violence in schizophrenia: A meta-analysis

Cited by 41 publications

References 39 publications

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Monoamine-Sensitive Developmental Periods Impacting Adult Emotional and Cognitive Behaviors

Molecular genetics and antisocial behavior: Where do we stand?

Aggression in Psychoses

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