Catechol-O-Methyltransferase Gene Polymorphisms in Specific Obsessive–Compulsive Disorder Patients’ Subgroups

Abstract

Pharmacological data and animal models support the hypothesis that the dopaminergic (DA) system is implicated in obsessive-compulsive disorder (OCD). Therefore, this case-control study assessed whether genetics variations in catechol-O-methyltransferase gene (COMT) could influence susceptibility to OCD and OCD features in a Brazilian sample. A sample of 199 patients with OCD and 200 healthy individuals was genotyped for -287A > G (rs2075507) and Val158Met (rs4680) single nucleotide polymorphisms (SNPs) by TaqMan(®) or restriction mapping. We observed a statistically significant predominance of the Met low-activity allele in the male patient group as compared to the male healthy control group. The -287A > G polymorphism's genotypes and alleles were significantly overrepresented among male individuals with ordering and female subjects with washing symptoms. We also found female hoarders to exhibit a significant higher frequency of the low activity Met/Met genotype of Val158Met polymorphism compared to female patients who did not express this dimension. Our data suggest an influence of COMT polymorphisms on OCD and OCD patients' features, such as gender, and ordering, washing, and hoarding symptom dimensions. Further studies to confirm the clinical importance of COMT SNPs in OCD are warranted.

Investigating the role of anticipatory reward and habit strength in obsessive-compulsive disorder

“…29 There are also neurobiological findings to suggest that association between OCD washing and reward anticipation may be linked to brain deficits in reward processing 9 and altered dopaminergic neurotransmission. 30 One study reported that OCD patients were less able than healthy controls to activate the nucleus accumbens bilaterally and the left insula during anticipation of gains in a monetary incentive task. Importantly, this study also found that OCD with contamination/washing dimension symptoms displayed lower activity within these areas when compared with OCD patients with the shamefulchecking symptom dimensions.…”

“…9 Accordingly, we have previously found that one −287A > G catechol-Omethyltransferase polymorphism, which may be related to altered dopaminergic transmission and has been already associated with heroin addiction, was also significantly over-represented among female subjects with washing symptoms and male individuals with symmetry symptoms. 30 We also discovered moderate to high positive correlations between the severity of OCD (including OCI-R total scores and Y-BOCS compulsions scores) and habit strength using the both the SRHI's traditional scoring system (r = 0.46; p < 0.001) and one that excluded items thought to overlap conceptually with compulsivity (ie, "that would require effort not to do it") (r = 0.36; p = 0.001). These findings reinforce the association between OCD's compulsive behaviors and habits.…”

Associations of endocrine stress‐related gene polymorphisms with risk of autism spectrum disorders: Evidence from an integrated meta‐analysis

“…On the other hand, the COMT gene, located on chromosome 22q11.2 [Grossman, Emanuel, & Budarf, ], encodes COMT, which contributes to the inactivation of catecholamines including adrenaline, noradrenaline, and dopamine. The COMT gene val158met polymorphism was found to be related to many physical as well as psychological diseases such as schizophrenia, depressive disorder, bipolar disorder, attention deficit, and hyperactivity and obsessive compulsive disorders [Barnett, Jones, Robbins, & Muller, ; Cao et al, ; Diaz‐Asper et al, ; He et al, ; Jones et al, ; Konishi et al, ; Lachman, Nolan, Mohr, Saito, & Volavka, ; Liu et al, ; Massat et al, ; Melo‐Felippe et al, ; Qian et al, ; Sampaio et al, ; Seok et al, ; Shimada et al, ; Tukel et al, ; Villemonteix et al, ; Wagner et al, ; Watanabe et al, ; Zhang et al, ]. Val158met polymorphism exerts a significant effect on COMT enzyme activity; the Val allele is associated with high enzymatic activity resulting in lower prefrontal dopamine levels in vivo [Lachman et al, ].…”

Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD

“…Other genetic work seems to support these earlier studies, with female hoarders. These people tend to exhibit a greater frequency of the low activity Met/Met genotype of Val158Met polymorphism, compared with females, who did not express this change, suggesting a higher concentration of DA in the synapse ( Melo-Felippe et al., 2016 ).…”