Genotype determining low catechol-<i>O</i>-methyltransferase activity as a risk factor for obsessive-compulsive disorder

Karayiorgou, Maria; Altemus, Margaret; Galke, Brandi L.; Goldman, David; Murphy, Dennis L.; Ott, Jürg; Gogos, Joseph A.

doi:10.1073/pnas.94.9.4572

Cited by 288 publications

(206 citation statements)

References 39 publications

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“…On the other hand, this is hard to reconcile with the observation that the association is gender specific. In this regard, it is remarkable that our results are strikingly similar to both reports by Karayiorgou et al (1997Karayiorgou et al ( , 1999, providing further evidence to the previously reported gender-selective association between COMT polymorphism and male patients. It is important to emphasize that in our control sample neither the COMT genotype distribution (v 2 = 4.6, df = 2, p = 0.1), nor the allele frequency (v 2 = 4.6, df = 2, p = 0.1) differed significantly between males and females.…”

Section: Discussionsupporting

confidence: 92%

“…The COMT locus has been reported to be associated with OCD in several previous studies. Karayiorgou et al (1997Karayiorgou et al ( , 1999 found evidence for an association between the lowactivity COMT allele and OCD in male OCD patients, in a case-control study and a family-based study, whereas Alsobrook et al (2002) found evidence pointing to an association between the low-activity COMT allele and OCD in female OCD patients. Niehaus et al (2001) reported a preponderance of COMT high/low heterozygotes in an Afrikaner population of 54 OCD patients, but did not observe gender differences.…”

Section: Discussionmentioning

confidence: 99%

“…The significance of a gender specific association may not be easily explained. Karayiorgou et al (1997Karayiorgou et al ( , 1999 proposed that females have evolved mechanisms to compensate for their lower levels of COMT activity and are therefore less vulnerable to developing OCD in association with a low-activity COMT genotype. On the other hand, as has been noted by Schindler et al (2000), the specific association in males may be a sampling phenomenon, since males typically demonstrate an earlier onset of OCD than females.…”

Section: Discussionmentioning

confidence: 99%

“…Digestion with NlaIII yields either two fragments (13 bp and 83 bp) for the Valallele (COMT H) or three fragments (13 bp, 18 bp and 65 bp) for the Met-allele (COMT L). The fragments were resolved on a 2.5% agarose gel and visualized by ethidium bromide staining (Karayiorgou et al, 1997).…”

Section: Comtmentioning

confidence: 99%

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Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

Denys

Nieuwerburgh

Deforce

et al. 2006

European Neuropsychopharmacology

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Background: Mounting evidence suggests the involvement of the dopamine system in the pathophysiology of obsessive-compulsive disorder. Method: The relationship of the dopamine D 2 receptor (DRD2) TaqI A, and catechol-O-methyltransferase (COMT) NlaIII High/Low activity polymorphism to obsessive-compulsive disorder (OCD) was examined in a sample of 150 patients and 150 controls. Results: OCD patients did not show significant differences in genotype distribution and allele frequency for polymorphisms investigated relative to controls. However, when the sample was stratified by gender, there was a trend to a significant predominance of the DRD2 A2A2 genotype ( p = 0.049), and a higher frequency of the DRD2 A2 allele ( p = 0.020) and low-activity COMT allele ( p = 0.035) in male OCD patients compared to male controls. In addition, we observed an association of the DRD2 A2A2 genotype in patients with an early onset of disease (V15 years) ( p = 0.033). Conclusions: Our findings replicate previous reports and provide support for a potential role of the COMT and DRD2 locus in subgroup of male, early onset patients with OCD.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Comtmentioning

confidence: 99%

See 2 more Smart Citations

Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

Denys

Nieuwerburgh

Deforce

et al. 2006

European Neuropsychopharmacology

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“…The valine allele shows higher COMT activity than the methionine allele (Lachman et al, 1996). The high activity allele has been associated with obsessive compulsive disorder (Karayiorgou et al, 1997) and phobic anxiety (McGrath et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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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Genetic and Environmental Contributions to the Child Behavior ChecklistObsessive-Compulsive Scale

Hudziak

Beijsterveldt

Althoff³

et al. 2004

Arch Gen Psychiatry

129

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The CBCL OCS is influenced by genetic factors (approximately 55%) and unique environmental factors (approximately 45%) in the younger sample, with common environmental influences only at 12 years of age. These effects do not vary with differences in sex or sibling interaction/rater contrast effects. Our data reveal higher genetic influences for obsessive-compulsive behavior and do not demonstrate genetic differences across sex.

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Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder

Cited by 288 publications

References 39 publications

Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

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

Genetic and Environmental Contributions to the Child Behavior ChecklistObsessive-Compulsive Scale

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