Association between COMT methylation and response to treatment in children with ADHD

Fageera, Weam; Chaumette, Boris; Fortier, Marie-Ève; Grizenko, Natalie; Labbe, Aurélie; Sengupta, Sarojini M.; Joober, Ridha

doi:10.1016/j.jpsychires.2021.01.008

Cited by 14 publications

(8 citation statements)

References 43 publications

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“…The results demonstrated that the COMT rs4818 CC genotype was correlated with a greater overall methylation level and greater methylation degree at COMT CpG51.52 in MAUD patients (Figure 2B, 2C). In contrast, the COMT rs4818 GG genotype was strongly associated with a higher level of methylation in children with ADHD 53 . Although the methylation status of the COMT promoter region did not correlate with the motor impulsivity symptom in MAUD patients (Figure 2C, D), when combined with the COMT rs4818 CC genotype, the decreased methylation level of the COMT promoter region and decreased methylation degree at COMT CpG51.52 unit elevated the motor impulsivity scores (Figure 3E, F).…”

Section: Discussionmentioning

confidence: 73%

Association of single nucleotide polymorphism and methylation of dopamine system-related genes with psychotic symptoms in patients of methamphetamine use disorders

Fang

Liu

et al. 2023

Preprint

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Background: Methamphetamine use disorders (MAUD) can substantially jeopardize public security due to their high-risk social psychology and behavior. Given that the dopamine reward system is intimately associated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of DRD4, COMT genes and paranoid, motor impulsive symptoms in MAUD patients. Methods: A total of 189 MAUD patients participated in our study. Samples of peripheral blood were used to detecte for 3 SNPs and levels of 35 CpG units of methylation in the DRD4 gene’s promoter region, 5 SNPs and 39 CpG units in the COMT gene. Results: MAUD patients with rs1800955 C allele have a lower percentage of paranoid symptom than those with rs1800955 TT. Individuals with paranoid symptom exhibited reduced methylation degree at particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4 CpG2.3 methylation degree resulted in the lower occurrence of the paranoid symptom. Meanwhile, those with COMT rs4818 CC allele have lower motor impulsivity scores in MAUD patients, but greater COMT methylation levels in the promotor region and methylation degree at COMT CpG 51.52 unit. Therefore, based only on COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor impulsivity scores in the MAUD patients. Conclusions: Our results found that the combination of SNP genotyping and methylation status of the DRD4 and COMT genes may serve as biological indicators to evaluate the prevalence of relatively high-risk psychotic symptoms in MAUD patients.

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Section: Discussionmentioning

confidence: 73%

Association of single nucleotide polymorphism and methylation of dopamine system-related genes with psychotic symptoms in patients of methamphetamine use disorders

Fang

Liu

et al. 2023

Preprint

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“…Moreover, we did not assess the type of medications the children were taking, the duration of the illness or of the drug exposure. All these factors can influence DNA methylation, 59 , 60 but it is unlikely that they dysmethylate the same genes as maternal smoking during pregnancy. Future longitudinal studies should consider detailed environmental recording.…”

Section: Discussionmentioning

confidence: 99%

Correlation of the methylomic signature of smoking during pregnancy with clinical traits in ADHD

Chaumette,

Grizenko,

Fageera

et al. 2023

jpn

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Background: Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent childhood disorder. Maternal smoking during pregnancy is a replicated environmental risk factor for this disorder. It is also a robust modifier of gene methylation during the prenatal developmental period. In this study, we sought to identify loci differentially methylated by maternal smoking during pregnancy and relate their methylation levels to various behavioural and physical outcomes relevant to ADHD. Methods: We extracted DNA from blood samples from children diagnosed with ADHD and deeply phenotyped. Genome-wide DNA methylation was assessed using Infinium MethylationEPIC BeadChip. Maternal smoking during pregnancy was self-declared and assessed retrospectively. Results: Our sample included 231 children with ADHD. Statistically significant differences in DNA methylation between children exposed or not to maternal smoking during pregnancy were detected in 3457 CpGs. We kept 30 CpGs with at least 5% of methylation difference between the 2 groups for further analysis. Six genes were associated with varied phenotypes of clinical relevance to ADHD. The levels of DNA methylation in RUNX1 were positively correlated with the CBCL scores, and DNA methylation in MYO1G correlated positively with the score at the Conners rating scale. Methylation level in a CpG located in GFI1 correlated with birthweight, a risk factor for ADHD. Differentially methylated regions were also identified and confirmed the association of RUNX1 methylation levels with the CBCL score. Limitations: The study has several limitations, including the retrospective recall with self-report of maternal smoking during pregnancy as well as the grouping of individuals of varying age and developmental stage and of both males and females. In addition, the correlation design prevents the building of causation models. Conclusion: This study provides evidence for the association between the level of methylation at specific loci and quantitative dimensions highly relevant for ADHD as well as birth weight, a measure that has already been associated with increased risk for ADHD. Our results provide further support to public health educational initiatives to stop maternal smoking during pregnancy.

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“…The results demonstrated that the COMT rs4818CC genotype was correlated with a greater overall methylation level and greater methylation degree at COMTCpG51.52 in MAUD patients (Figure 2b,c). In contrast, the COMT rs4818GG genotype was strongly associated with a higher level of methylation in children with attention deficit hyperactivity disorder (Fageera et al, 2021). Although the methylation status of the COMT promoter region did not correlate with motor‐impulsive symptoms in MAUD patients (Figure 2c,d), when combined with the COMT rs4818 CC genotype, the decreased methylation level of the COMT promoter region and decreased methylation degree at the COMT CpG51.52 unit elevated the motor‐impulsive scores (Figure 2e,f).…”

Section: Discussionmentioning

confidence: 99%

A preliminary study on the association of single nucleotide polymorphisms and methylation of dopamine system‐related genes with psychotic symptoms in patients with methamphetamine use disorder

Fang,

Liu,

Liu

et al. 2023

Eur J of Neuroscience

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Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high‐risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol‐O‐methyltransferase (COMT) genes, and paranoid and motor‐impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor‐impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor‐impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high‐risk psychotic symptoms in MAUD patients.

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Association between COMT methylation and response to treatment in children with ADHD

Cited by 14 publications

References 43 publications

Association of single nucleotide polymorphism and methylation of dopamine system-related genes with psychotic symptoms in patients of methamphetamine use disorders

Association of single nucleotide polymorphism and methylation of dopamine system-related genes with psychotic symptoms in patients of methamphetamine use disorders

Correlation of the methylomic signature of smoking during pregnancy with clinical traits in ADHD

A preliminary study on the association of single nucleotide polymorphisms and methylation of dopamine system‐related genes with psychotic symptoms in patients with methamphetamine use disorder

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