Relationship between SIRT1 gene and adolescent depressive disorder with nonsuicidal self-injury behavior

Abstract

Objective: The incidence of non-suicidal self-injury (NSSI) behavior in adolescents is increasing year by year. Patients with a history of both depression and NSSI behavior tend to be at greater risk for suicide. At present, the mechanism of adolescent depressive disorder with NSSI behavior is not clear and still in research and exploration. The expression of the Silent Information Regulator 2 Related Enzyme 1 (SIRT1) gene is closely related to the level of serotonin in molecular mechanisms, and may be closely related to the occurrence and development of depressive disorder. This study aimed to explore the relationship between the SIRT1 gene and NSSI behaviors in adolescents with depressive disorder.Methods: A total of 15 adolescent depressed patients with NSSI behavior and 15 healthy controls were enrolled in the study. Bisulfite Sequencing PCR (BSP) was used to test the methylation level of SIRT1 gene promoter region of the participants. The realtime fluorescent quantitative PCR was conducted to measure the mRNA expression level of SIRT1 gene.Results: Our study found that the methylation level of SIRT1 gene promoter region at cytosine-guanine dinucleotide 5 (CpG5) site in depression group was higher than that of control group. Compared with that of control group, the plasma concentration of Sirt1 protein significantly decreased in depression group. Conclusion:Our study investigated the methylation level and the mRNA expression of SIRT1 gene in adolescent depressive patients with NSSI behavior. The study points towards finding an in vivo molecular marker for those adolescent patients. Abbreviations: 5-HT = 5-hydroxy trptamine, CpG5 = cytosine-guanine dinucleotide5, DSM-5 = 5th edition of the Diagnostic and Statistical Manual of Mental Disorders, MAO-A = Monoamine oxidase A, NSSI = nonsuicidal self-injury, PCR = polymerase chain reaction, SIRT1 = silent information regulator 2 related enzyme 1.

Genetics and epigenetics of self‐injurious thoughts and behaviors: Systematic review of the suicide literature and methodological considerations

“…Only two of the candidate methylation studies focused on adolescents ( POMC , SIRT1 ; Zheng et al, 2020; Wang et al, 2021), and both were focused on self‐injurious behaviors rather than thoughts. There were no candidate methylation studies of SI in youth.…”

Potential mechanisms of non-suicidal self-injury (NSSI) in major depressive disorder: a systematic review

“…85 Furthermore, the brain-derived neurotrophic factor Val66Met polymorphism was found to regulate the relationship between NSSI and childhood emotional environments. 86 Also, by detecting DNA methylation and mRNA expression, 87 Wang et al found a higher methylation level of silent information regulator 2 related enzyme 1 (SIRT1) gene promoter region and a lower expression of Sirt1 protein, related to MDD in some manner, in subjects with MDD+NSSI compared with HCs. However, this study was excluded because of the possibility that the samples were shared with the research of Zheng et al 58 To this point, we have discussed the potential correlation between psychosocial traits, hereditary factors, HPA axis dysfunction, pain perception alteration and NSSI, where childhood trauma might play a role, according to the studies focused on MDD and other disorders.…”

Risk factors, theoretical models, and biological mechanisms of nonsuicidal self-injury: a brief review

“…There is heterogeneity in the candidate gene research, such as variations in the participants' ethnicity. Moreover, those studies lack a control group comprising patients without NSSI [74][75][76]86 . Determining the underlying causes of observed differences in research outcomes between NSSI and related disorders can be challenging, as it remains unclear whether the differences are primarily attributable to NSSI, the presence of concurrent disorders, or the interaction between these factors.…”

“…While it was difficult to differentiate whether the methylation irregularity was a result of depression or NSSI, this implied the possibility of exploring epigenetic markers related to NSSI in this area. Another study reported that in individuals with NSSI, the methylation level at the cytosine-guanine dinucleotide 5 site of the silent information regulator 2 related enzyme 1 gene promoter region was significantly elevated compared with the control group, which may assist in identifying molecular markers in adolescents with NSSI 76 .…”