Epigenetic Alterations of the Promoter Region of the POMC Gene in Adolescent Depressive Disorder Patients with Nonsuicidal Self-injury Behaviors

Doudou Zheng, Xiaojiao Bi, Tianliang Zhang, Chao Han, Tantan Ma, Lina Wang, Mengmeng Sun, Kaiyan Cui, Limin Yang, Lanfen Liu, Doudou Zheng, Xiaojiao Bi, Tianliang Zhang, Chao Han, Tantan Ma, Lina Wang, Mengmeng Sun, Kaiyan Cui, Limin Yang, Lanfen Liu

Abstract

Purpose: 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: POMC; adolescent; depressive disorder; methylation; nonsuicidal self-injury behavior.

Conflict of interest statement

The authors report no conflicts of interest in this work.

© 2020 Zheng et al.

Figures

Figure 1a
Figure 1a
Continued.
Figure 1b
Figure 1b
Continued.
Figure 1c
Figure 1c
The level of methylation of the POMC gene in different sites.

References

    1. Guerry JD, Prinstein MJ. Longitudinal prediction of adolescent nonsuicidal self-injury: examination of a cognitive vulnerability-stress model. J Clin Child Adolesc Psychol. 2010;39(1):77–89. doi:10.1080/15374410903401195
    1. Benjamin L, Abela, Hankin JRZ, et al. Nonsuicidal self-injury in adolescence: prospective rates and risk factors in a 2½ year longitudinal study. Psychiatry Res. 2011;186(1):65–70. doi:10.1016/j.psychres.2010.07.056
    1. Marshall SK, Tilton-Weaver LC, Stattin H. Non-suicidal self-injury and depressive symptoms during middle adolescence: a longitudinal analysis. J Youth Adolesc. 2013;42(8):1234–1242. doi:10.1007/s10964-013-9919-3
    1. Muehlenkamp JJ, Gutierrez PM. Risk for suicide attempts among adolescents who engage in non-suicidal self-injury. Arch Suicide Res. 2007;11(1):69–82. doi:10.1080/13811110600992902
    1. You J, Leung F. The role of depressive symptoms, family invalidation and behavioral impulsivity in the occurrence and repetition of non-suicidal self-injury in Chinese adolescents: a 2-year follow-up study. J Adolesc. 2012;35(2):389–395. doi:10.1016/j.adolescence.2011.07.020
    1. Jane CE, Erkanli A, Angold A. Is there an epidemic of child or adolescent depression. J Child Psychol Psychiatry. 2006;47:1263–1271.
    1. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Arch Gen Psychiatry. 2005;62(6):593. doi:10.1001/archpsyc.62.6.593
    1. Menke A, Binder EB. Epigenetic alterations in depression and antidepressant treatment. Dialogues Clin Neurosci. 2014;16(3):395–404.
    1. Numata S, Ishii K, Tajima A, et al. Blood diagnostic biomarkers for major depressive disorder using multiplex DNA methylation profiles: discovery and validation. Epigenetics. 2015;10(2):135–141. doi:10.1080/15592294.2014.1003743
    1. Muehlenkamp JJ, Claes L. International prevalence of adolescent non-suicidal self-injury and deliberate self-harm. Child Adolescent psychiatry Mental Health. 2012;6(1):10.
    1. Xiang D, Xiao J, Fu L, et al. DNA methylation of the Tacr2 gene in a CUMS model of depression. Behav Brain Res. 2019;3(365):103–109.
    1. Stonawski V, Frey S, Golub Y, et al. Associations of prenatal depressive symptoms with DNA methylation of HPA axis-related genes and diurnal cortisol profiles in primary school-aged children. Dev Psychopathol. 2019;31(2):419–431. doi:10.1017/S0954579418000056
    1. Li M, D’Arcy C, Li X, Zhang T, Joober R, Meng X. What do DNA methylation studies tell us about depression? A systematic review. Transl Psychiatry. 2019;9:68.
    1. Na KS, Won E, Kang J, Kim A, Ham BJ. Differential effect of COMT gene methylation on the prefrontal connectivity in subjects with depression versus healthy subjects. Neuropharmacology. 2018;137:59–70. doi:10.1016/j.neuropharm.2018.04.030
    1. Jirtle RL, Skinner MK. Environmental epigenomics and disease susceptibility. Nat Rev Genet. 2011;12(7):620–622.
    1. Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Hanson MA. Epigenetic gene promoter methylation at birth is associated with childrens later adiposity. Diabetes. 2011;60(5):1528–1534. doi:10.2337/db10-0979
    1. Robertson GP, Gao X, Wright FA, et al. Aberrant CpG-island methylation has non-random and tumour-type–specific patterns. Nat Genet. 2000;24(2):132–138. doi:10.1038/72785
    1. Lu S, Gao W, Huang M, Li L, Xu Y. In search of the HPA axis activity in unipolar depression patients with childhood trauma: combined cortisol awakening response and dexamethasone suppression test. J Psychiatr Res. 2016;78:24–30. doi:10.1016/j.jpsychires.2016.03.009
    1. Sandman CA, Hetrick W, Talyor D, Marion S, Chicz-DeMet A. Uncoupling of proopiomelanocortin (POMC) fragments is related to self-injury. Peptides. 2000;21(6):785–791. doi:10.1016/S0196-9781(00)00209-6
    1. Chang HS, Won ES, Lee HY, Ham BJ, Kim YG, Lee MS. The association of proopiomelanocortin polymorphisms with the risk of major depressive disorder and the response to antidepressants via interactions with stressful life events. J Neural Transm (Vienna). 2015;122(1):59–68. doi:10.1007/s00702-014-1333-9
    1. Giletta M, Scholte RHJ, Engels RCME, Ciairano S, Prinstein MJ. Adolescent non-suicidal self-injury: a cross-national study of community samples from Italy, the Netherlands and the United States. Psychiatry Res. 2012;197(1–2):66–72. doi:10.1016/j.psychres.2012.02.009
    1. Zielinski MJ, Veilleux JC, Winer ES, Nadorff MR. A short-term longitudinal examination of the relations between depression, anhedonia, and self-injurious thoughts and behaviors in adults with a history of self-injury. Compr Psychiatry. 2017;73:187–195. doi:10.1016/j.comppsych.2016.11.013
    1. Smyth DG. 60 YEARS OF POMC: lipotropin and beta-endorphin: a perspective. J Mol Endocrinol. 2016;56(4):T13–25. doi:10.1530/JME-16-0033
    1. Qu N, He Y, Wang C, et al. A POMC-originated circuit regulates stress-induced hypophagia, depression, and anhedonia. Mol Psychiatry. 2020;25(5):1006–1021. doi:10.1038/s41380-019-0506-1
    1. Groh A, Rhein M, Buchholz V, Burkert A, Walter M. Epigenetic effects of intravenous diacetylmorphine on the methylation of POMC and NR3C1. Neuropsychobiology. 2018;75(4):193–199. doi:10.1159/000486973
    1. Muschler MAN, Lenz B, Hillemacher T, Kraus C, Bleich S. CAGn repeat of the androgen receptor is linked to proopiomelanocortin promoter methylation - Relevance for craving of male alcohol-dependent patients. Psychopharmacology (Berl). 2013;231(10):2059–2066. doi:10.1007/s00213-013-3349-5
    1. Muschler M, Rhein, Ritter A, et al. Epigenetic alterations of the POMC promoter in tobacco dependence. Eur Neuropsychopharmacol. 2018;5(4):924–925.
    1. Yuan N, Kwok, Kwok KHR, et al. Treatment engagement in specific psychological treatment vs. treatment as usual for adolescents with self-harm: systematic review and meta-analysis. Front Psychol. 2019;10:104. doi:10.3389/fpsyg.2019.00104
    1. Knorr AC, Tull MT, Anestis MD, Dixon-Gordon KL, Bennett MF, Gratz KL. The interactive effect of major depression and nonsuicidal self-injury on current suicide risk and lifetime suicide attempts. Arch Suicide Res. 2016;20(4):539–552. doi:10.1080/13811118.2016.1158679
    1. Stanford S, Jones MP, Hudson JL. Appreciating complexity in adolescent self-harm risk factors: psychological profiling in a longitudinal community sample. J Youth Adolesc. 2018;47(5):916–931. doi:10.1007/s10964-017-0721-5
    1. Chen S, Li L. Re-testing reliability, validity and norm applicatility of SCL-90. Chin J Nerv Ment Dis. 2003;29(5):323–327.
    1. Zhao J, Zheng Y. The reliability, validity of HAMD. Chin Ment Health J. 1992;5:214–216.
    1. Wang X, et al. A Handbook On Psychological Hygiene. Chin Ment Health J. 1999;253–254.
    1. Yohn NL, Bartolomei MS, Blendy JA. Multigenerational and transgenerational inheritance of drug exposure: the effects of alcohol, opiates, cocaine, marijuana, and nicotine. Prog Biophys Mol Biol. 2015;118(1–2):21–33. doi:10.1016/j.pbiomolbio.2015.03.002
    1. Sandman CA, Touchette P. beta-Endorphin and ACTH are dissociated after self-injury in adults with developmental disabilities. Am J Ment Retard. 2003;108(6):414–424. doi:10.1352/0895-8017(2003)108<414:EAAADA>;2
    1. Wioletta R, Magdalena L. Deliberate self-injury functions and their clinical correlates among adolescent psychiatric inpatients. Psychiatr Pol. 2017;51(2):303–322. doi:10.12740/PP/63802
    1. Klonsky ED. The functions of deliberate self-injury: a review of the evidence. Clin Psychol Rev. 2007;27(2):226–239. doi:10.1016/j.cpr.2006.08.002
    1. Zetterqvist M, Lundh L, Svedin CG. A cross-sectional study of adolescent non-suicidal self-injury: support for a specific distress-function relationship. Child Adolesc Psychiatry Ment Health. 2014;8(1):23. doi:10.1186/1753-2000-8-23
    1. Plener PL, Fegert JM, Kaess M, et al. Nonsuicidal self-injury in adolescence: a clinical guideline for diagnostics and therapy. Z Kinder Jugend Psychiatr Psychother. 2017;45(6):463–474.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner