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

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.

Improvement of hyperadrenergic postural orthostatic tachycardia syndrome (POTS) with methylated B vitamins in the setting of a heterozygous COMT Val158Met polymorphism

A middle-aged woman was diagnosed with postural orthostatic tachycardia syndrome based on her clinical symptoms, elevated norepinephrine levels and positive tilt-table test. The patient was refractory to conventional treatment and improved only after she was treated with methylated B vitamins for her heterozygous catechol-O-methyltransferase Val158Met polymorphism.

The Association between COMT Val158Met Polymorphism and the Post-Traumatic Stress Disorder Risk: A Meta-Analysis

<b><i>Background:</i></b> Genetic factors were suggested to have influence on the development of post-traumatic stress disorder (PTSD). The possible association between catechol-O-methyltransferase (<i>COMT</i>) Val158Met polymorphism and PTSD has been evaluated in several studies. But the results were still controversial. Therefore, we conduct this meta-analysis to address these issues. <b><i>Methods:</i></b> The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched for eligible studies. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to estimate the association between <i>COMT</i> Val158Met polymorphism and PTSD. <b><i>Results:</i></b> Five articles including 6 studies with 893 cases and 968 controls were finally included in the present meta-analysis. The pooled analyses did not demonstrate a significant association between the <i>COMT</i> Val158Met polymorphism and PTSD in any of the selected genetic models: allele model (OR = 1.13, 95% CI: 0.97–1.31), dominant model (OR = 1.17, 95% CI: 0.93–1.46), recessive model (OR = 1.44, 95% CI: 0.78–2.66), and additive model (OR = 1.54, 95% CI: 0.85–2.80). Subgroup analyses suggested that the Hardy-Weinberg equilibrium status of genotype distributions could influence the relationship of <i>COMT</i> Val158Met polymorphism and PTSD. <b><i>Conclusions:</i></b> The present meta-analysis suggested that the <i>COMT</i> Val158Met polymorphism may not be associated with the PTSD risk. Further large-scale and population-representative studies are warranted to evaluate the impact of the <i>COMT</i> Val158Met polymorphism on the risk of PTSD.

Role of COMT V158M Polymorphism in the Development of Dystonia after Administration of Antipsychotic Drugs

Antipsychotics (APDs) represent the main pharmacological strategy in the treatment of schizophrenia; however, their administration often may result in severe adverse effects, such as extrapyramidal symptoms. Typically, dystonic movements are considered the result of impaired function and/or abnormalities of dopaminergic neurotransmission/signaling in the basal ganglia. The catechol O-methyltransferase (COMT) gene is located within the 22q11.2 region, and its product is an enzyme involved in transferring a methyl group from S-adenosylmethionine to catecholamines, including dopamine. Studies showed that COMT Val158Met polymorphism modifies enzymatic activity and, consequently, synaptic dopamine concentration in specific brain areas. We identified a patient with 22q11.2 deletion syndrome presenting with cervical and trunk dystonia after paliperidone administration, which persisted even after drug discontinuation. Given the patient’s genetic condition, we hypothesized that the dopaminergic dysfunction had been aggravated by COMT involvement, thus causing dystonia. In line with this hypothesis, we carried out a study on psychiatric patients in chronic treatment with APD to evaluate the distribution of the COMT Val158Met polymorphism and its role in the onset of adverse extrapyramidal symptoms. The study included four patients with dystonia after administration of APDs compared to 17 patients who never presented adverse drug reactions. Our data suggest that the Val/Val and Met/Met polymorphisms of the COMT gene are associated with a protective effect for the development of collateral extrapyramidal symptoms in patients treated with APDs, while the Val/Met genotype could be considered a risk factor for the development of dystonia after APDs administration.

Examining The Link Between Harsh Parenting And Non-Suicidal Self-Injury In Adolescence: The Role of The COMT Val158Met Polymorphism And Depressive Symptoms

Background: Previous studies have suggested negative parenting environments, especially harsh parenting, is 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 researches, we aimed to examine if 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 were also considered in our study.Method：373 junior high school students were recruited for the study by using a longitudinal design. Adolescents answered self-report questionnaires and provided Saliva samples for DNA genotyping.Result：The results revealed that harsh parenting was positively associated with NSSI after 18 months, and this association was mediated by depressive symptoms. Moreover, the moderating role of COMT in the direct and indirect effect of harsh parenting on NSSI only among adolescents with two Val alleles. However, the relationship was not significant for Met carriers.Conclusion: Genetic variations of COMT Val158Met may be a critical candidate in understanding the development of depression and NSSI. We conclude that the Val homozygotes of the COMT Val158Met polymorphism play a susceptible role both in depressive symptoms and NSSI.

The Effects of Childhood Maltreatment on Non-Suicidal Self-Injury in Male Adolescents: The Moderating Roles of the Monoamine Oxidase A (MAOA) Gene and the Catechol-O-Methyltransferase (COMT) Gene

(1) Background: Numerous studies suggest strong associations between childhood maltreatment and nonsuicidal self-injury (NSSI); this is also true for the roles of dopaminergic genes in the etiology of some psychopathologies related to NSSI. Investigating the interactions of environments and genes is important in order to better understand the etiology of NSSI. (2) Methods: Within a sample of 269 Chinese male adolescents (Mage = 14.72, SD = 0.92), childhood maltreatment and NSSI were evaluated, and saliva samples were collected for MAOA T941G and COMT Val158Met polymorphism analyses. (3) Results: The results revealed no primary effects attributable to MAOA T941G and COMT Val158Met polymorphism on NSSI. However, there was a significant three-way interaction between MAOA, COMT, and child abuse (β = −0.34, p < 0.01) in adolescent NSSI. Except for carriers of the T allele of MAOA and the Met allele of COMT, all studied male adolescents displayed higher NSSI scores when exposed to a higher level of child abuse. A similar three-way interaction was not observed in the case of child neglect. (4) Conclusions: The results indicate that the MAOA gene and COMT gene play moderating roles in the association between child abuse and NSSI of male adolescents and suggest the polygenic underpinnings of NSSI.