Associations between serotonin-related gene polymorphisms and panic disorder

Maron, Eduard; Lang, Aavo; Tasa, Gunnar; Liivlaid, Liivi; Tõru, Innar; Must, Anne; Vasar, Veiko; Shlik, Jakov

doi:10.1017/s1461145704004985

Cited by 74 publications

(44 citation statements)

References 26 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.…”

Section: Mao-a Genesupporting

confidence: 80%

“…As well, neither linkage nor association between 5-HTTLPR and PD was observed in a family-based study; however, a more frequent occurrence of 5-HTTLPR LL genotype was detected in female PD probands (Hamilton et al, 1999). Nevertheless, our group recently found significant differences in the distribution of 5-HTTLPR genotypes and allele frequencies between PD patients and controls, with the LL genotype and L allele variant being more frequent in patients (Maron et al, 2005a). Pertinently, another study found that healthy females with the LL genotype were more sensitive to CCK-4-induced panic attacks than those who are carriers of S allele (Maron et al, 2004b).…”

Section: -Htt Genementioning

confidence: 56%

“…However, the 5-HT-ergic genetic influence seems to be differently related to PD phenotypes and may be genderdependent. Furthermore, the results of several studies (Inada et al, 2003;Rothe et al, 2004a;Maron et al, 2005a) support the notion of Noyes et al (1986) that PD with agoraphobia is a more severe variant of PD with a stronger genetic component.…”

Section: -Ht Receptor Genesmentioning

confidence: 57%

“…Other data showed lack of association between PD phenotypes and several other 5-HTR1A receptor polymorphisms (Inada et al, 2003;Maron et al, 2005b). 5-HT1B receptor gene 861G-C polymorphism did not demonstrate any significant association in patients with PD (Fehr et al, 2000a;Maron et al, 2005a). Furthermore, no associations were found between PD phenotypes and a large number of SNPs in this gene, excluding the major role of the 5-HT1B receptor gene in PD (Maron et al, 2005b).…”

Section: -Ht Receptor Genesmentioning

confidence: 90%

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Serotonin Function in Panic Disorder: Important, But Why?

Maron

Shlik

2005

Neuropsychopharmacol

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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: 80%

Section: -Htt Genementioning

confidence: 56%

Section: -Ht Receptor Genesmentioning

confidence: 57%

Section: -Ht Receptor Genesmentioning

confidence: 90%

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Serotonin Function in Panic Disorder: Important, But Why?

Maron

Shlik

2005

Neuropsychopharmacol

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109

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“…Notably, the serotonin transporter (5-HTT) gene, SLC6A4, probably the most studied candidate gene in psychiatry, is located on 17q11.2. Only one 98 of several case-control association studies in different ethnic groups reported association of PD with the functional length polymorphism in the 5 0 regulatory promoter region (5-HTTLPR) (Supplementary Table 1). A recent meta-analysis, which included data from 10 case (n = 2050)-control (n = 3136) studies (OR = 0.91, P = 0.14), concluded that 5-HTTLPR is not associated with PD.…”

Section: Chromosome 17mentioning

confidence: 99%

Advances in molecular genetics of panic disorder

2010

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The molecular genetic research on panic disorder (PD) has grown tremendously in the past decade. Although the data from twin and family studies suggest an involvement of genetic factors in the familial transmission of PD with the heritability estimate near 40%, the genetic substrate underlying panicogenesis is not yet understood. The linkage studies so far have suggested that chromosomal regions 13q, 14q, 22q, 4q31-q34, and probably 9q31 are associated with the transmission of PD phenotypes. To date, more than 350 candidate genes have been examined in association studies of PD, but most of these results remain inconsistent, negative, or not clearly replicated. Only Val158Met polymorphism of the catechol-O-methyltransferase gene has been implicated in susceptibility to PD by several studies in independent samples and confirmed in a recent meta-analysis. However, the specific role of this genetic variation in PD requires additional analysis considering its genderand ethnicity-dependent effect and putative impact on cognitive functions. The recent advantages in bioinformatics and genotyping technologies, including genome-wide association and gene expression methods, provide the means for far more comprehensive discovery in PD. The progress in clinical and neurobiological concepts of PD may further guide genetic research through the current controversies to more definitive findings.

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Meta‐analysis argues for a female‐specific role of MAOA‐uVNTR in panic disorder in four European populations

Reif

Weber

Domschke

et al. 2012

American J of Med Genetics Pt B

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Panic disorder (PD) is a common mental disorder, ranking highest among the anxiety disorders in terms of disease burden. The pathogenesis of PD is multifactorial with significant heritability, however only a few convincing risk genes have been reported thus far. One of the most promising candidates is the gene encoding monoamine oxidase A (MAOA), due to its key role in monoaminergic neurotransmission, established validity of animal models, and the efficacy of MAO inhibitors in the treatment of PD. A promoter repeat polymorphism in MAOA (MAOA-uVNTR) impacts on gene expression; high-expression alleles have been reported to increase the risk for PD. To further scrutinize the role of this polymorphism, we performed a formal meta-analysis on MAOA-uVNTR and PD using original data from four published European (Estonian, German, Italian, and Polish) samples and genotypes from three hitherto unpublished German PD samples, resulting in the largest (n = 1,115 patients and n = 1,260 controls) genetic study on PD reported to date. In the unpublished samples, evidence for association of MAOA-uVNTR with PD was obtained in one of the three samples. Results of the meta-analysis revealed a significant and female-specific association when calculating an allelic model (OR = 1.23, P = 0.006). This sex-specific effect might be explained by a gene-dose effect causing higher MAOA expression in females. Taken together, our meta-analysis therefore argues that high-expression MAOA-uVNTR alleles significantly increase the risk towards PD in women. However, epigenetic mechanisms might obfuscate the genetic association, calling for ascertainment in larger samples as well as assessment of the MAOA promoter methylation status therein.

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Associations between serotonin-related gene polymorphisms and panic disorder

Cited by 74 publications

References 26 publications

Serotonin Function in Panic Disorder: Important, But Why?

Serotonin Function in Panic Disorder: Important, But Why?

Advances in molecular genetics of panic disorder

Meta‐analysis argues for a female‐specific role of MAOA‐uVNTR in panic disorder in four European populations

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