Different allele distribution of a regulatory MAOA gene promoter polymorphism in antisocial and anxious-depressive alcoholics

Abstract

Heritable factors account for approximately 40-60% of the total variance of liability to alcohol dependence. The present study tested whether a novel functional polymorphism in the promotor region of the X-chromosomal monoamine oxidase A gene (MAOA) was related to antisocial and anxious-depressive traits in alcoholics. Due to the X-chromosomal localization of the MAOA gene, psychobiological traits were compared separately for both genders of 298 male and 66 female alcoholics. In males, 30 of 59 alcoholics with antisocial personality disorder carried the low-activity 3-repeat allele in contrast to only 7 of 31 anxious-depressive alcoholics (51% vs. 23%; p = 0.02). Likewise, female anxious-depressive alcoholics showed a trend towards a low frequency of genotypes with the 3 repeat allele compared to female alcoholics without these symptoms (29% vs. 53%; p = 0.09). Taken together, these findings suggest that the 3-repeat allele of the MAOA polymorphism contributes modestly to the dimension of overand underreactive behaviors as possible antecedents of alcoholism.

Cluster B Personality Disorders are Associated with Allelic Variation of Monoamine Oxidase A Activity

“…Neuroticism is a normally distributed quantitative anxietyrelated trait, which is consistently associated with an increased risk for anxiety disorders and depression. In agreement with the evidence for a role of MAOA activity in panic disorder (Deckert et al, 1998), these findings further support the notion that the MAOA-LPR contributes modestly to the balance of the dimension of over-(antisocial) and underreactive (anxious-depressive) via several neurotransmitter systems in interaction with environmental factors (Schmidt et al, 2000). It may therefore be hypothesized that this dysbalance may also be involved in pathogenesis of Cluster B personality disorders.…”

A functional polymorphism in the MAOA gene promoter (MAOA-LPR) predicts central dopamine function and body mass index

“…The majority of reports find an increase in the frequency of low activity alleles in patients with externalizing disorders. 5,6,18 However, there are some important exceptions. For example, increased aggression 17 and vulnerability to ADHD 16 were both associated with alleles conferring high MAOA activity.…”

“…3 The key role of MAOA in modulating monoamine turnover suggests that its gene (MAOA), located on the X chromosome (Xp11.23), is a logical candidate for investigating interindividual differences in vulnerability to psychiatric disorders, especially in males. Studies in both humans and non-human animal models have supported the involvement of MAOA in the etiology of externalizing behaviors, including impulsivity and aggression and several psychiatric disorders in which these behaviors play a role, including antisocial personality disorder (ASPD), conduct disorder (CD), attention deficit hyperactivity disorder (ADHD), and alcoholism [4][5][6][7][8][9][10] In 1993, Brunner et al 4,11 reported a Dutch family in which eight males were affected by a syndrome characterized by borderline mental retardation and impulsive behavior including impulsive aggression, arson, attempted rape, fighting, and exhibitionism The syndrome was due to a stop-codon variant in the eighth exon of MAOA leading to complete and selective deficiency of MAOA activity. This stopcodon variant has not been observed in other study populations; however, subsequent efforts led to the discovery of a common MAOA polymorphism that was shown to affect transcriptional activity [12][13][14] and that is generally assumed to result in a deficiency of MAOA in vivo.…”

“…An excess of low activity alleles has been reported in antisocial alcoholics, 5,7 alcoholics in general, 8 patients with ADHD and CD, 9 and subjects with cluster B personality disorders. 10 Yet several studies have failed to replicate these findings 15 and others have found that genotypes conferring high, rather than low, MAOA activity are associated with ADHD 16 and increased impulsivity, hostility, and aggression.…”

Nature and Nurture Predispose to Violent Behavior: Serotonergic Genes and Adverse Childhood Environment

“…Following the discovery of functional MAOA variants, the impact of these polymorphisms on human aggression and related behaviors was investigated. Initial studies (Samochowiec et al, 1999;Schmidt et al, 2000) argued that antisocial personality disorder in alcoholism was connected to the low-expression genotype, although this was not replicated in two rather small studies (Koller et al, 2003;Lu et al, 2003). Convincing evidence, however, supports the notion that MAOA-uVNTR regulates aggression and impulsivity in a gene-environment-dependent manner.…”