Epigenetic alterations of the promoter region of the POMC gene in adolescent depressive disorder patients with non-suicidal self-injury behaviors

Doudou Zheng,1,* Xiaojiao Bi,2,* Tianliang Zhang,3 Chao Han,3 Tantan Ma,3 Lina Wang,2 Mengmeng Sun,3 Kaiyan Cui,3 Limin Yang,3 Lanfen Liu3 1Department of Psychiatry, School of Clinical Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Psychology, Shandong Mental Health Center Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China; 3Department of Psychiatry, Shandong Mental Health Center Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lanfen LiuShandong Mental Health Center Affiliated to Shandong University, 49# Wenhua Eastern Road, Jinan, Shandong 250014, People’s Republic of ChinaTel +86 18705317358Email liulf521@163.comPurpose: The incidence of nonsuicidal self-injury (NSSI) behavior among adolescents increases year by year. Patients with a history of both depression and NSSI behaviors tend to have greater risk of suicide. At present, the mechanism of adolescent depressive disorder patients with NSSI behaviors is not clear, epigenetic mechanism may be involved. Proopiomelanocortin (POMC) gene may be associated with depressive disorder. The purpose of this study was to investigate DNA methylation of POMC gene promoter region of adolescent depressive disorder patients with NSSI behaviors.Methods: Bisulfite Sequencing PCR (BSP) was used to test the methylation level of POMC promoter of 15 adolescent depressive disorder patients with NSSI behaviors and 15 healthy controls (HC). Self-made questionnaires were used to collect clinical data of the case group and control group. Hamilton depression scale-24 (HAMD-24), Hamilton anxiety scale (HAMA), Symptom Checklist-90 (SCL-90) were used to evaluate the characteristics and severity of depressive, anxiety and psychotic symptoms. Adolescent self-injury questionnaire was used to assess NSSI behaviors and its severity.Results: BSP analysis found that the POMC methylation level of cytosine-guanine dinucleotide 1 (CpG1) site was higher in the case group than that of HC (P< 0.05). The significance in POMC methylation at CpG1 between case group and HC was gender-independent, and CpG1 methylation level was higher in both male (P< 0.05) and female (P< 0.05) patients than that in HC. The CpG1 methylation level had a little correlation trends with family history of psychosis (P=0.05). We also found that POMC methylation level at CpG17 in female patients was significantly higher than that of the female HC (P< 0.05).Conclusion: There was abnormal methylation in the POMC promoter region of adolescent depressive disorder patients with NSSI behaviors, the methylation of CpG1 may act as epigenetic markers for those adolescents.Keywords: adolescent, depressive disorder, POMC, methylation, nonsuicidal self-injury behavior