Association studies of MAO-A, COMT, and 5-HTT genes polymorphisms in patients with anxiety disorders of the phobic spectrum

Samochowiec, Jerzy; Hajduk, Anna; Samochowiec, Agnieszka; Horodnicki, J; Stȩpień, Genowefa; Grzywacz, Anna; Kucharska-Mazur, Jolanta

doi:10.1016/j.psychres.2004.05.012

Cited by 123 publications

(74 citation statements)

References 27 publications

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“…We found a similar gender-dependent association with longer allele genotypes in female PD patients with agoraphobia (Maron et al, 2005a). Recently, Samochowiec et al (2004) observed a significant association with longer alleles in females with panic attack phenotypes. Again, this association was absent in males.…”

Section: Mao-a Genesupporting

confidence: 82%

Serotonin Function in Panic Disorder: Important, But Why?

Maron

Shlik

2005

Neuropsychopharmacol

109

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The essential role of serotonin (5-hydroxytryptamine (5-HT)) system in the neurobiology and pharmacotherapy of panic disorder (PD) continues to be a topic of intensive interdisciplinary research. Interest in the involvement of 5-HT in PD has been fuelled by clinical studies demonstrating that medications increasing the synaptic availability of 5-HT, such as selective 5-HT re-uptake inhibitors, are effective in the treatment of PD. Rival theories of 5-HT deficiency vs excess have attempted to explain the impact of 5-HT function in PD. In the past decade, knowledge of the role of 5-HT in the neurobiology of PD has expanded dramatically due to much new research including experimental, treatment, brain-imaging, and genetic studies. The current review attempts to summarize the new data and their implications. The challenge and treatment studies generally confirm the specific inhibitory influence of 5-HT on panicogenesis. The brainimaging studies in PD patients demonstrate functional and clinically relevant alterations in various elements of 5-HT system affecting the neurocircuitry of panic. The findings of genetic association studies suggest that certain 5-HT-related genes may contribute to the susceptibility to PD; however, these data are rather limited and inconsistent. It appears that, even if not the primary etiological factor in PD, the 5-HT function conveys important vulnerability, as well as adaptive factors. A better understanding of these processes may be critical in achieving progress in the treatment of patients suffering from PD.

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Section: Mao-a Genesupporting

confidence: 82%

Serotonin Function in Panic Disorder: Important, But Why?

Maron

Shlik

2005

Neuropsychopharmacol

109

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“…It has also been strongly associated with one anxiety disorder in particularFpanic disorder ( (Ohara et al, 1998;Samochowiec et al, 2004) and, according to a recent meta-analysis, not with obsessive-compulsive disorder (Azzam and Mathews, 2003). There was therefore ample a priori reason to hypothesize that we would find an effect of the val158met polymorphism on neuroticism and extraversion in this study.…”

Section: Discussionmentioning

confidence: 58%

“…In a sample of community subjects selected for either high or low on neuroticism, Eley et al (2003) found weak evidence for association with COMT val158met genotype, when females and males were considered separately. Another recent study of 101 patients with phobic disorders and 202 age-, sex-, and ethnicity-matched control subjects failed to find an association with val158met and phobic disorders (Samochowiec et al, 2004). In a sample of 1234 female nurses, McGrath and colleagues found an association of val158met genotype with phobic anxiety as measured by the Crown-Crisp experimental index, wherein homozygosity for the val allele was associated with a doubling of odds of having high phobic anxiety, compared to met homozygosity (McGrath et al, 2004).…”

Section: Introductionmentioning

confidence: 95%

COMT Polymorphisms and Anxiety-Related Personality Traits

Stein

Fallin

Schork

2005

Neuropsychopharmacol

198

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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“…Following the same direction, Samochowiec et al 19 reported that the frequencies of the 3.5, 4 and 5 repeat alleles of the MAOA polymorphism (encoding the high activity form of the enzyme) were significantly higher in female patients with anxiety disorders, specifically with panic attacks and generalized anxiety disorder. There was also a trend for a higher frequency of the high activity alleles in females with agoraphobia and specific phobia but not with social phobia.…”

Section: Anxiety Disordersmentioning

confidence: 90%

O papel do polimorfismo funcional VNTR da região promotora do gene MAOA nos transtornos psiquiátricos

Nishioka¹,

Perin²,

Sampaio³

et al. 2011

Rev. psiquiatr. clín.

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Introduction: A functional variable number of tandem repeats (VNTR) polymorphism of the promoter region of the monoamine oxidase A (MAOA) gene has been described and many studies have investigated the association of this polymorphism with human behaviors, as well as with several psychiatric disorders. Objective: This study aimed to review the literature on the role of the VNTR functional polymorphism of the promoter region of the MAOA gene on the modulation of human behavior for the development of psychiatric disorders. Method: Searches on the Medline, Embase, Web of Science and PsycInfo databases were performed including works from January 1998 to June 2009. The words used were: "MAOA and human behavior" and "MAOA and psychiatry". Results: Several studies were found (N = 3,873). After the selection process, 109 papers were included in the review. There was found an association of MAOA low activity alleles with antisocial personality disorder, conduct disorder, ADHD, pathological gambling, and substance abuse. High activity alleles were associated with neuroticism, anorexia nervosa and depression and anxiety disorders. There was no association between the MAOA polymorphisms and bipolar disorder and schizophrenia. Discussion: The main findings, summarized in this paper, support a role of MAOA VNTR polymorphism in some psychiatric disorders although some divergences were found due to methodological difficulties in genetic studies. In general, the studies associated the low activity alleles with impulsivity and aggressive behavior ("hyperactive behaviors"), and the high activity alleles of the gene with "hypoactive behaviors", such as depression and anxiety, which demonstrates a modulation of the MAOA enzyme in "hyperactive" and "hypoactive" disorders.

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Association studies of MAO-A, COMT, and 5-HTT genes polymorphisms in patients with anxiety disorders of the phobic spectrum

Cited by 123 publications

References 27 publications

Serotonin Function in Panic Disorder: Important, But Why?

Serotonin Function in Panic Disorder: Important, But Why?

COMT Polymorphisms and Anxiety-Related Personality Traits

O papel do polimorfismo funcional VNTR da região promotora do gene MAOA nos transtornos psiquiátricos

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