Differential COMT DNA methylation in patients with Borderline Personality Disorder: Genotype matters

Thomas, Mara; Banet, Nora; Wallisch, Annalena; Glowacz, Katarzyna; Becker-Sadzio, Julia; Gundel, Friederike; Nieratschker, Vanessa

doi:10.1016/j.euroneuro.2019.09.011

Cited by 13 publications

(10 citation statements)

References 26 publications

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“…The activity of the COMT enzyme is influenced mainly by a functional single nucleotide polymorphism (rs4680; G to A) in the COMT coding region that causes a Val158Met aminoacid substitution in the corresponding protein, with the Val allele exhibiting a 3- to 4-fold increase in enzyme activity compared to the Met allele [ 29 , 30 ]. Considering that the COMT Val158Met gene is associated with several traits related to NSSI behaviours, including emotion regulation [ 31 , 32 ], borderline personality disorders [ 33 , 34 ] and suicidal behaviours [ 35 , 36 ], we hypothesize that the COMT Val158Met gene might directly moderate the relationship between harsh parenting and NSSI.…”

Section: Introductionmentioning

confidence: 99%

Harsh parenting and non-suicidal self-injury in adolescence: the mediating effect of depressive symptoms and the moderating effect of the COMT Val158Met polymorphism

Liu

Wang

et al. 2021

Child Adolesc Psychiatry Ment Health

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Background Previous studies have suggested that negative parenting environments, especially harsh parenting, are a specific risk factor for non-suicidal self-injury (NSSI). However, the potential mechanism between harsh parenting and NSSI has not been explored. Based on the experiential avoidance model and empirical research, we aimed to examine whether depressive symptoms are a mediator between harsh parenting and NSSI. Moreover, the catechol-O-methyltransferase (COMT) Val158Met polymorphism related to depressive symptoms may also exert a moderating effect on NSSI; thus, the interaction between harsh parenting and COMT was also considered in our study. Methods A total of 373 junior high school students were recruited for the study by using a longitudinal design. The adolescents answered self-report questionnaires and provided saliva samples for DNA genotyping. Results The results revealed that harsh parenting was positively associated with NSSI after 24 months, and this association was mediated by depressive symptoms. Moreover, the moderating role of COMT in the direct and indirect effects of harsh parenting on NSSI was observed only among adolescents with two Val alleles and the relationship was not significant for Met carriers. Conclusions Genetic variations of COMT Val158Met may be a critical candidate in understanding the development of depression and NSSI. We conclude that Val homozygotes of the COMT Val158Met polymorphism play a role in susceptibility to both depressive symptoms and NSSI.

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Section: Introductionmentioning

confidence: 99%

Harsh parenting and non-suicidal self-injury in adolescence: the mediating effect of depressive symptoms and the moderating effect of the COMT Val158Met polymorphism

Liu

Wang

et al. 2021

Child Adolesc Psychiatry Ment Health

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“…Therefore, it is reasonable to assume that personality traits which are likely to be partially regulated by the MB-COMT gene, such as impulsivity (BAS) (Smederevac et al, 2022) and reactive aggression (Fight) as a response to a perceived threat (Reuter et al, 2006), will also be associated with differences in the level of MB-COMT DNAm. Moreover, previous studies have shown evidence that associate MB-COMT DNAm with personality disorders (Dammann et al, 2011;Thomas et al, 2019).…”

Section: Mb-comt Gene and Personality Traitsmentioning

confidence: 95%

Differences in MB-COMT DNA methylation in monozygotic twins on phenotypic indicators of impulsivity

et al. 2023

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Epigenetic modifications of the membrane bound catechol-O-methyltransferase (MB-COMT) gene may affect the enzymatic degradation of dopamine, and consequently, human behavior. This study investigated the association between membrane bound catechol-O-methyltransferase DNA methylation (DNAm) differences in 92 monozygotic (MZ) twins with phenotypic manifestations of cognitive, behavioral, and personality indicators associated with reward-related behaviors and lack of control. We used pyrosequencing to determine DNAm of the regulatory region of membrane bound catechol-O-methyltransferase in saliva DNA. Results of intrapair differences in the percentage of membrane bound catechol-O-methyltransferase DNAm at each of five CpG sites show that there are associations between phenotypic indicators of lack of control and membrane bound catechol-O-methyltransferase DNAm differences on CpG1, CpG2 and CpG4, suggesting the common epigenetic patterns for personality traits, cognitive functions, and risk behaviors.

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“…Um aumento da metilação do promotor PRIMA1 em amostras de sangue periférico e uma diminuição dos níveis de metilação do promotor distal 5´região ETS do rDNA em pacientes TPB foi relatado por Tescher, Gotthardt, Dammann & Dammann (2016). Os genes KCNQ1proteína do canal de potássio controlado por voltagem -MCF2, NINJ2 (proteína induzida por lesão nervosa, NINJURIN2), COMTenvolvido na degradação de catecolaminasapresentaram, respectivamente, aumento da metilação em 1,5, 1,1, 1,2 e 1,07 vezes (Tescher et al, 2013;Thomas et al, 2019).…”

Section: Epigenética E Transtorno De Personalidade Borderline (Tpb)unclassified

“…COMT apresenta duas isoformas, uma ligada a membrana dos tecidos do sistema nervoso central, MB-COMTessa forma no cérebro de pacientes TPB é significativamente hipometiladae outra solúvel nos tecidos periféricos, S-COMT. As análises acerca da metilação são realizadas a partir de fluídos e sangue periférico, portanto, apenas o S-COMT é plausível de análise in vivo, apresentando metilação aumentada nos sítios CpG 1 e CpG 2 (Dammann et al, 2011;Thomas et al, 2019).…”

Section: Epigenética E Transtorno De Personalidade Borderline (Tpb)unclassified

Teorias Etiológicas do Transtorno de Personalidade Borderline: da neurobiologia à epigenética

Honório

Kuwakino

Souza

2021

RSD

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Objetivo: identificar as possíveis anomalias neurobiológicas e epigenéticas, assim como os efeitos do trauma durante a infância na patogênese do Transtorno de Personalidade Borderline (TPB). Metodologia: para a revisão narrativa, utilizou-se a PubMed, Scielo, UpToDate como base de dados, no período entre 2010 e 2020, resultando em 688 artigos, dos quais 26, distintos por critérios de inclusão, serviram de base para este estudo. Resultados: em neurobiologia, anormalidades foram encontradas, entretanto os estudos não conseguiram comprovar se tais modificações originam o transtorno ou são decorrentes da psicopatologia, enquanto na genética metilações aberrantes de genes – candidatos ou por seleção genômica ampla (GWS)- podem estar ligados a etiologia do TPB. Por fim, a análise dos artigos acerca TPB e trauma infantil revelou que uma porcentagem significativa dos indivíduos com o transtorno sofreu abuso ou indiligência na infância. Considerações finais: a teoria que combina a neurobiologia, a epigenética e o ambiente se mostrou a mais plausível para explicar a etiologia do TPB. Dito isso, mais estudos devem ser realizados a fim de compreender tanto se esses achados são patognômicos do transtorno ou consequências dele, quanto as correlações anatômicas e funcionais, genéticas e ambientais para a patogênese do TPB.

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Differential COMT DNA methylation in patients with Borderline Personality Disorder: Genotype matters

Cited by 13 publications

References 26 publications

Harsh parenting and non-suicidal self-injury in adolescence: the mediating effect of depressive symptoms and the moderating effect of the COMT Val158Met polymorphism

Harsh parenting and non-suicidal self-injury in adolescence: the mediating effect of depressive symptoms and the moderating effect of the COMT Val158Met polymorphism

Differences in MB-COMT DNA methylation in monozygotic twins on phenotypic indicators of impulsivity

Teorias Etiológicas do Transtorno de Personalidade Borderline: da neurobiologia à epigenética

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