Association of a functional polymorphism of the monoamine oxidase A gene promoter with personality and psychiatric symptoms

Jorm, Anthony F; As, Henderson; Pa, Jacomb; Christensen, Helen; Korten, A. E.; Rodgers, Bryan; Tan, Xiaojie; Easteal, Simon

doi:10.1097/00041444-200010020-00006

Cited by 47 publications

(36 citation statements)

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“…It may therefore be hypothesized that this dysbalance may also be involved in pathogenesis of Cluster B personality disorders. However, there were no associations with anxiety-and depression-related symptoms, with personality traits that predispose to anxiety or with personality traits related to antisocial behavior in a general population sample of 850 Caucasian Australians (Jorm et al, 2000). The allelic variations of MAOA activity did also not have a large impact on the expression of personality characteristics in a Swedish population neither in men nor in women .…”

Section: Discussionmentioning

confidence: 68%

“…While there was a negative association with aggressiveness, impulsivity, and anger-related personality traits in previous studies on diverse clinical, forensic, and nonpatient populations, no significant differences were observed when personality traits were diagnosed by various instruments including the Temperament and Character Inventory, the revised NEO Personality Inventory, and the Karolinska Scales of Personality . MAOA-LPR genotype frequencies did also not differ on measures of the Buss-Durkee Hostility Inventory (hostility), the Behavioral Inhibition System/Behavioral Activation System scales, and the revised Eysenck Personality Questionnaire (Manuck et al, 2000;Jorm et al, 2000).…”

Section: Discussionmentioning

confidence: 83%

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

Jacob

Müller

Schmidt

et al. 2005

Neuropsychopharmacol

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Genetic variants of the monoamine oxidase A (MAOA) have been associated with aggression-, anxiety-, and addiction-related behavior in several nonclinical and clinical populations. Here, we investigated the influence of allelic variation of MAOA activity on aggressionrelated personality traits and disease risk in patients with personality disorders. Personality disorders were diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to cluster A, B, and C. Personality features were assessed by the revised NEO Personality Inventory and the Tridimensional Personality Questionnaire. The genotype of the MAOA gene-linked polymorphic region (MAOA-LPR) was determined in 566 patients with personality disorders and in 281 healthy controls. MAOA genotype was significantly associated with cluster B personality disorders (w 2 ¼ 7.77, p ¼ 0.005, df ¼ 1) but not with cluster C personality disorders. In total, 26.0% of cluster B patients were hemi-or homozygous for the low-activity variant of the MAOA genotype, compared to 16.4% in the control group. Associations between MAOA variants and personality domains related to impulsivity and aggressiveness were inconsistent. Our findings further support the notion that allelic variation of MAOA activity contributes modestly to the balance of hyper-(impulsiveaggressive) and hyporeactive (anxious-depressive) traits.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 83%

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

Jacob

Müller

Schmidt

et al. 2005

Neuropsychopharmacol

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“…Two recent meta-analyses (that included a substantially overlapping set of studies) found evidence of an association between 5-HTTLPR and neuroticism, although less so with other anxiety-related constructs (eg harm avoidance) (Schinka et al, 2004;Sen et al, 2004a). Other genes tested for an association with anxiety-related traits have included monoamine oxidase type A (Eley et al, 2003;Jorm et al, 2000), cytochrome P450 2D6 isoenzyme (Roberts et al, 2004), GABA-A receptor alpha-6 subunit (Sen et al, 2004b) and, in a number of studies, catechol-O-methyltransferase (COMT) (Eley et al, 2003;Enoch et al, 2003;Henderson et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

COMT Polymorphisms and Anxiety-Related Personality Traits

Stein

Fallin

Schork

2005

Neuropsychopharmacol

197

128

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High neuroticism and low extraversion are characteristic of anxiety-prone individuals. A functional variant in the catechol-Omethyltransferase (COMT) gene, the Val158Met ('val/met') polymorphism, has been associated in some prior studies with several phenotypes, including neuroticism. We tested the hypothesis that the val158met polymorphism would be associated with both high neuroticism and low extraversion, making it a plausible candidate locus for anxiety susceptibility. To determine whether val158met is responsible for these effects, we also evaluated the association with haplotypes that included two other SNPs within the COMT gene. We collected a sample of 497 undergraduate college students who were phenotyped on a personality inventory (the NEO-Personality Inventory-Raised (NEO-PI-R)). Subjects were genotyped for three COMT polymorphisms: the well-studied nonsynonymous SNP rs4680 that generates a valine-to-methionine substitution (val158met), rs737865 (near exon #1), and rs165599 (also functional, near the 3 0 -UTR). Together, these three SNPs define a haplotype that is associated with reduced COMT expression in human brain. Logistic regression analyses were used to examine the effects of individual SNPs on extraversion and neuroticism scores. Score tests for association between these traits (quantitatively and dichotomously considered) and haplotypes were also conducted. We evaluated potential for population stratification artifact by genotyping a set of 36 unlinked highly polymorphic markers previously demonstrated to distinguish sufficiently ancestry of major American populations. Two of the SNPs (rs4680 ('val/met') and rs737865) were significantly associated with (low) extraversion and, less consistently, with (high) neuroticism, with effects confined to women. A significant association between COMT haplotype and (low) extraversion and (high) neuroticism was also observed. Formal testing showed that population structure did not explain the findings. These data suggest that involvement of the COMT locus in susceptibility to anxiety-related traits (ie low extraversion and high neuroticism) is unlikely to be wholly accounted for by the well-studied rs4680 ('val/met') polymorphism. Other functional variants may exist that contribute to this relationship. Possible sex-specific effects remain to be further studied and explained.

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“…MAOA is encoded by a gene at Xp11. 23. 6 The functional MAOA-upstream variable number of tandem repeats (MAOA-uVNTR) polymorphism 7,8 in the MAOA gene promoter commonly consists of 3 (3-allele) or 4 (4-allele) copies of a 30-bp sequence, or rarely 2 (2-allele) or 3 copies plus the first 18-bp of the same 30-bp sequence (3a-allele), or 5 copies (5-allele).…”

mentioning

confidence: 99%

Gene-gene interaction between the monoamine oxidase A gene and solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 gene in anorexia nervosa (restrictive subtype)

et al. 2003

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We earlier found an association between anorexia nervosa (AN) restrictive subtype (AN-R) and an inserted sequence within the NETpPR, a polymorphic region located in the promoter of the solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 (SLC6A2) gene. To further examine the noradrenergic system in AN-R we performed an association study with a functional polymorphism (MAOAuVNTR) in the promoter of the monoamine oxidase A (MAOA) gene. Since monoamine oxidase A metabolises noradrenalin, a positive association with the MAOA gene would be biologically plausible. The transmission disequilibrium test and 95 trios/duos (AN-R females þ biological parents) showed the main effect of the longer, more transcriptionally active form of the MAOA-uVNTR (MAOA-L) to be statistically non-significant (McNemar's v 2 ¼ 1.4, df ¼ 1, P ¼ 0.238, odds ratio: 1.4, 95% CI 0.8 -2.7). A case-control approach supported this finding. We then stratified the MAOA-uVNTR TDT data according to the (a) NETpPR genotype of the AN-R females, and (b) NETpPR allele transmitted from NETpPR-S4/L4 heterozygous mothers. In both cases, contingency table analysis revealed previously unreported genegene interaction between the MAOA and SLC6A2 genes (P ¼ 0.019 and 0.019, respectively). Receiving an MAOA-L allele more than doubles the risk for developing AN-R, conditional on an individual also being a NETpPR-L4 homozygote (stratum-specific odds ratio: 2.4, 95% CI 1.1-6.0). These results suggest important involvement of the noradrenergic system in the biological underpinnings of AN-R.

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Association of a functional polymorphism of the monoamine oxidase A gene promoter with personality and psychiatric symptoms

Cited by 47 publications

References 0 publications

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

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

COMT Polymorphisms and Anxiety-Related Personality Traits

Gene-gene interaction between the monoamine oxidase A gene and solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 gene in anorexia nervosa (restrictive subtype)

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