Association of the functional V158M catechol-O-methyl-transferase polymorphism with panic disorder in women

Domschke, Katharina; Freitag, Christine M.; Kuhlenbäumer, Gregor; Schirmacher, Anja; Sand, Philipp; Nyhuis, Peter; Jacob, Christian; Fritze, Jürgen; Franke, Petra; Rietschel, Marcella; Garritsen, Henk; Fimmers, Rolf; Nöthen, Markus M.; Lesch, Klaus‐Peter; Stögbauer, Florian; Deckert, Jürgen

doi:10.1017/s146114570400416x

Cited by 146 publications

(115 citation statements)

References 23 publications

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“…The fact that the positive result has not only been in the case-controls but also in the family sample is important evidence that population stratification is probably not creating a false positive result. Furthermore, these findings are consistent with two previous studies reporting an association of this more active COMT allele with PD, in particular in women (Domschke et al, 2004;Hamilton et al, 2002). Our findings are in line with a recent study on phobic Association of COMT with panic disorder C Rothe et al anxiety that has been reported to be associated with the valine allele of the functional COMT polymorphism in a sample of 1234 women (McGrath et al, 2004).…”

Section: Discussionsupporting

confidence: 93%

“…Ohara et al (1998) investigated a sample of anxiety disorder patients (n ¼ 108) including a small number of PD patients (n ¼ 29) and found no association. This small sample of PD patients had very low power to detect the COMT effect sizes observed in our study as well as in Domschke et al (2004) and Hamilton et al (2002). Furthermore, it is not clear whether matching of the control subjects concerning gender and age was carried out, since this information was not reported by the authors.…”

Section: Discussionmentioning

confidence: 68%

“…Overall given that the role of COMT Val158Met variant in PD is now reported in four studies, including the present investigation, with sufficient power (Domschke et al, 2004;Hamilton et al, 2002;Woo et al, 2004), further investigations of the COMT gene and nearby markers on chromosome 22 are warranted to increase our understanding of the genetic basis of PD. If COMT is further proven to be involved then new targets for drug development may be uncovered leading to enhanced pharmacological treatment of panic disorder.…”

Section: Discussionmentioning

confidence: 71%

“…In addition, several studies have found an association with PD yet (Domschke et al, 2004;Hamilton et al, 2002;Woo et al, 2002). Therefore, our a priori hypothesis was that this polymorphism is associated with PD.…”

Section: Discussionmentioning

confidence: 97%

“…Recently, two studies reported an association between the high-activity valine allele and PD in Caucasians (Domschke et al, 2004;Hamilton et al, 2002). In contrast, Woo et al (2002) described a significant association (p ¼ 0.005) of the low-activity allele in 51 PD patients of Korean origin.…”

Section: Introductionmentioning

confidence: 99%

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Association of the Val158Met Catechol O-Methyltransferase Genetic Polymorphism with Panic Disorder

Rothe

Koszycki

Bradwejn

et al. 2006

Neuropsychopharmacol

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Genetic as well as clinical data suggest that catechol O-methyltransferase (COMT) is involved in multiple complex psychiatric conditions. Recent studies have described an association between the Val158Met COMT polymorphism and panic disorder. Other recent investigations provide evidence that there are other loci within or nearby the COMT gene that may contribute to the susceptibility to panic disorder. To further evaluate the influence of the Val158Met COMT polymorphism in panic disorder we genotyped this marker in the coding region of the COMT gene and two additional variants (rs737865 and rs165599) in the 5 0 and the 3 0 region, respectively, in two independent Canadian samples: 121 nuclear families, and 89 cases with matched controls. In the nuclear families, significant transmission disequilibrium for the valine allele was observed between the alleles of the Val158Met COMT polymorphism and panic disorder (po0.01). A significant excess of the valine allele was found in analysis of the case-control sample (po0.01). This effect was mainly derived from the subgroup of females. This finding, including the female effect, replicates earlier results in studies of the Val158Met polymorphism in panic disorder. No significant results were found for the other two markers. These results support the hypothesis that the valine allele of the Val158Met COMT polymorphism or a nearby locus is involved in the etiopathogenesis of panic disorder.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Association of the Val158Met Catechol O-Methyltransferase Genetic Polymorphism with Panic Disorder

Rothe

Koszycki

Bradwejn

et al. 2006

Neuropsychopharmacol

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Catechol O-methyltransferase Val158Met Genotype and Neural Mechanisms Related to Affective Arousal and Regulation

Drabant¹,

Hariri²,

Meyer‐Lindenberg³

et al. 2006

Arch Gen Psychiatry

350

280

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Our results indicate that heritable variation in dopamine neurotransmission associated with the met allele of the COMT polymorphism results in heightened reactivity and connectivity in corticolimbic circuits. This may reflect a genetic predisposition for inflexible processing of affective stimuli, a mechanism possibly accounting for aspects of arousal and behavioral control that contribute to emotional dysregulation previously reported in met/met individuals.

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Neurobiology of Anxiety Disorders

2008

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Recent advances in basic and clinical research in the anxiety disorders converge on several areas: (1) critical distinguishing clinical features of these disorders, (2) the neurobiological basis of anxiety disorders in human populations, (3) animal studies that defi ne cause-effect relations between neural function and anxiety or fear behaviors, and (4) studies of etiology that provide an increasingly clear understanding of the developmental trajectories that defi ne vulnerability for anxiety disorders. Additionally, an emerging area of research is studies of behavior, cognitive function, and neural activity in clinical populations to defi ne the clinically relevant effects of pharmacological and psychotherapeutic treatments. This chapter summarizes and synthesizes current research approaches to anxiety disorders and attempts to show the impact of this research on current trends in their diagnosis and treatment. Currently, there is increasing emphasis on relevant clinical dimensions, as opposed to more traditional categorical approaches, and an emerging view of anxiety as a set of cognitive-perceptual disorders that derives from alterations in neural systems critical for attentional processes and emotional regulation. Phillips K , Fulker DW , and Rose RJ ( 1987 ) Path analysis of seven fear factors in adult twin and sibling pairs and their parents . Genetic Epidemiology 4 , 345 -355 .

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Association of the functional V158M catechol-O-methyl-transferase polymorphism with panic disorder in women

Cited by 146 publications

References 23 publications

Association of the Val158Met Catechol O-Methyltransferase Genetic Polymorphism with Panic Disorder

Association of the Val158Met Catechol O-Methyltransferase Genetic Polymorphism with Panic Disorder

Catechol O-methyltransferase Val158Met Genotype and Neural Mechanisms Related to Affective Arousal and Regulation

Neurobiology of Anxiety Disorders

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