COMT but not serotonin-related genes modulates the influence of childhood abuse on anger traits Nader Perroud,1,2,* Isabelle Jaussent,3 Sébastien Guillaume,3,4 Frank Bellivier,5,6 Patrick Baud,1 Fabrice Jollant,3,4 Marion Leboyer,5,6 Cathryn Lewis,2,7 Alain Malafosse,1,3,8 and Philippe Courtet3,4 Author information Copyright and License information Disclaimer The publisher's final edited version of this article is available free at Genes Brain Behav See other articles in PMC that cite the published article. Go to: Abstract Anger-related traits are regulated by genes as well as early environmental factors. Both childhood maltreatment and genes underlie vulnerability to suicidal behaviors, possibly by affecting the constitution of intermediate phenotypes such as anger traits. The aim of this study was to test the interaction between nine candidate genes and childhood maltreatment in modulating anger-related traits in 875 adult suicide attempters. The State-Trait Anger Expression Inventory and the Childhood Trauma Questionnaire were used to examine anger traits and traumatic childhood experiences respectively. The functional polymorphism of the catecholamine-O-methyl-transferase (COMT) gene Val158Met significantly modulated the association between sexual abuse and anger-trait level (p=0.001). In the presence of sexual abuse, individuals carrying the Val high-activity allele displayed greater disposition towards anger than individuals homozygous for the Met allele (p=0.0003). Notably, none of the serotonin-related genes influenced the effect of childhood abuse on anger traits. The results of the present study suggest that anger-trait level is influenced by the interaction between childhood abuse and functional polymorphism in the COMT gene. This study was carried out in a population with a high frequency of childhood abuse and a high disposition towards anger, and replication in healthy subjects is needed.
Keywords: Amino Acid Substitution, Anger, physiology, Catechol O-Methyltransferase, genetics, Child, Child Abuse, statistics & numerical data, Child Abuse, Sexual, statistics & numerical data, Demography, Female, Genotype, Humans, Male, Minisatellite Repeats, Monoamine Oxidase, genetics, Neurotic Disorders, epidemiology, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Psychotic Disorders, epidemiology, Regression Analysis, Serotonin, genetics, Suicide, Attempted, statistics & numerical data Keywords: comt, serotonin, genes, trait anger, suicidal behaviors, sexual abuse Go to: Introduction Anger is a basic, commonly experienced emotional state that consists of feelings of variable intensity, from mild irritation to intense fury and rage. Anger has been related to several phenomena in medicine and several behavioral and psychiatric conditions (Chida & Steptoe, 2009, Lara & Akiskal, 2006). A high level of anger traits has indeed been associated with eating disorders (Fassino et al., 2001), borderline personality disorder (Zanarini et al., 2004), drug addiction (De Moja & Spielberger, 1997), and suicidal behaviors (Baud, 2005, Baud et al., 2007). For the latter, in comparison to controls suicide attempters have indeed been shown to express higher level of anger (Baud, 2005, Baud et al., 2007).
Anger is part of the brain’s fight-or-flight response to a perceived threat. This multidimensional structure is composed of physiological, behavioral and cognitive aspects that have been shown to correlate positively with aggression, hostility and impulsivity (Ramirez & Andreu, 2006). From this perspective, particular attention has been paid to anger in the field of suicidal behaviors. Indeed, subjects with a history of suicide attempts have been shown to display a greater tendency towards anger or greater difficulty in outwardly expressing anger than control (Baud, 2005, Baud et al., 2007).
Knowledge of the sources of individual differences in anger remains sparse but includes genetic and environmental factors. Twin and family studies have indeed suggested that anger-related traits are inheritable (Rebollo & Boomsma, 2006, Sluyter et al., 2000). Several genes involved in serotoninergic and catecholaminergic neurotransmissions have recently been associated with anger traits and/or related measures of anger such as aggression or impulsivity, including tryptophan hydroxylase 1 (TPH1) (Baud et al., 2009, Manuck et al., 1999, Rujescu et al., 2002), several serotonin receptors (5-HTR) (Giegling et al., 2006, Serretti et al., 2007, Zouk et al., 2007), the monoamine oxidase A (MAOA) (Alia-Klein et al., 2008, Manuck et al., 2000) and the catecholamine O-methyl transferase (COMT) genes (Alia-Klein et al., 2008, Baud et al., 2007, Baud et al., 2009, Giegling et al., 2006, Manuck et al., 1999, Rujescu et al., 2002, Serretti et al., 2007, Zouk et al., 2007)
Environmental factors such as childhood maltreatment, lack of social support and negative life events were also found to predict high levels of anger (Springer et al., 2007). Finally, the effects of gene–environment interaction (GxE) on measures of anger are also taken into account although this area has not been thoroughly investigated to date. Exactly how GxE modulates anger related traits is not yet understood. Some studies such as those published by Caspi et al. (Caspi et al., 2002) provide some preliminary evidence pointing to the interaction of MAOA and early maltreatment on aggression and anti-social personality traits.
In this study, we intend to explore the extent to which some GxE underlies inter-individual differences in the expression of anger in a population of suicide attempters. In view of the importance of childhood maltreatment in the development of suicidal behaviors (Dube et al., 2001), the close relationship between suicidal behaviors and anger (Horesh et al., 1997) and the existence of a genetic component in suicidal behaviors (Bellivier et al., 2004), a population composed of suicide attempters is ideal to unravel the environmental and genetic components of anger-related traits.
