PRKCB methylation: a potential biomarker of MDD with childhood chronic stress, a cross-sectional study in drug-naive, first-episode adolescent MDD.

The purpose of this study was to investigate the relationship between childhood chronic stress(CCS), Protein kinase C beta (PRKCB) methylation and adolescent major depressive disorder (MDD). After recruiting 100 adolescents with MDD and 50 healthy controls (HCs), we evaluated the severity of CCS. PRKCB methylation was assessed by pyrosequencing using whole blood-derived DNA. To explore the relationship between CCS, PRKCB and adolescent MDD, we conducted correlation analysis and regression analysis, and constructed multiplicative interaction models and generalized linear models. PRKCB methylation and CCS were both found to be associated with MDD, and CCS was associated with PRKCB methylation. No significant CCS-PRKCB methylation interactions were observed. However, we found the interaction of CCS and MDD on PRKCB methylation. Our results found that PRKCB methylation was influenced by CCS and the disease itself, and PRKCB methylation was significantly positively associated with MDD severity, suggesting that PRKCB methylation may be a potential biomarker for adolescent MDD. This study is a cross-sectional observational study, which cannot draw the conclusion of causality. Prospective cohort studies are needed to further examine the relationship between CCS, adolescent MDD, and PRKCB methylation.

Associations of MSK1 Methylation and Executive Function With Suicidal Ideation in Adolescents With Major Depressive Disorder: A Prospective Cohort Study.

Objective: Adolescent suicide is a major public health problem, and risk of suicide is higher among those with major depressive disorder (MDD), which may be linked to alterations in mitogen- and stress-activated kinase 1 (MSK1) and to defects in executive function. Here, we aimed to investigate the potential impacts of executive function and MSK1 methylation on suicidal ideation in adolescents with MDD.Methods: The study enrolled 66 drug-naive adolescents who were experiencing their first episode of MDD from February 2019 until October 2020. After 6 weeks of receiving antidepressant treatment, 65 participants remained in the study. Suicidal ideation and depressive severity were assessed using the Hamilton Depression Rating Scale, while executive function was evaluated using the Cambridge Neuropsychological Test Automated Battery. MSK1 methylation was measured using bisulfite DNA analysis.Results: Among the 66 adolescents with MDD, 43 (65.15%) reported suicidal ideation, while 23 (34.85%) did not. Individuals with suicidal ideation had worse executive function and higher MSK1 methylation than those without suicidal ideation. The MSK1 methylation percentage may predict suicidal ideation in adolescents with MDD (odds ratio [OR] 1.227, 95% CI [1.031 to 1.461]). Improvement in executive function was significantly associated with reduced suicidal ideation during antidepressant treatment (ß = -0.200, 95% CI [-0.877 to -0.085]).Conclusions: Our results strengthen the evidence for a link among MSK1 methylation, executive function, and suicidal ideation in adolescent MDD.Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2000033402.

Correlation between negative life events and suicide attempts among Yi adolescents with HIV/AIDS in Liangshan Prefecture.

OBJECTIVE: To investigate the incidence of suicide attempts among adolescents with HIV/AIDS in Liangshan Prefecture, Sichuan Province, as well as the correlation between negative life events, sleep, exercise, drug therapy and suicide attempts. METHODS: A total of 180 Yi adolescents aged 11-19 years with HIV/AIDS in a county of Liangshan Prefecture, Sichuan Province, China, were investigated by census. The main outcome indicators included the incidence of suicide attempts and whether negative life events, sleep, exercise, drug therapy and other factors were related to suicide attempts. RESULTS: We found that the incidence rate of suicide attempts among Yi adolescents with HIV/AIDS in Liangshan Prefecture was 13.9%. Negative life events were a risk factor for suicide attempts (OR = 1.047, p < 0.001, 95% CI 1.027-1.067). In the factors of negative life events, adaptation was a risk factor for suicide attempts (OR = 1.203, p = 0.026, 95% CI 1.022-1.416), and academic pressure showed a tendency to be a risk factor for suicide attempts (OR = 1.149, p = 0.077, 95% CI 0.985-1.339). However, the punishment factor, interpersonal stress factor and loss factor had no significant correlation with suicide attempts. There was no significant correlation between sleep, exercise, drug therapy and suicide attempts. CONCLUSION: The proportion of suicide attempts among Yi adolescents with HIV/AIDS in Liangshan Prefecture is high and should be considered. Negative life events are independent risk factors for suicide attempts, and it is necessary to strengthen the screening and early intervention for suicide attempts in HIV/AIDS adolescents with definite negative life events.

Co-expression network of mRNA and DNA methylation in first-episode and drug-naive adolescents with major depressive disorder.

Objective: We explored the DNA methylation and messenger RNA (mRNA) co-expression network and hub genes in first-episode, drug-naive adolescents with major depressive disorder (MDD). To preliminarily explore whether adolescent MDD has unique mechanisms compared with adult MDD. Methods: We compared DNA methylation and mRNA profiles of peripheral blood mononuclear cells from four first-episode and drug-naive adolescents with MDD and five healthy adolescent controls (HCs). We performed differential expression analysis, constructed co-expression network, and screened the hub genes. And enrichment analysis was performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We also downloaded DNA methylation and mRNA datasets of adults with MDD (GSE113725/GSE38206) from the GEO database, and performed differential expression and enrichment analysis. Results: Our clinical data showed that 3034 methylation sites and 4190 mRNAs were differentially expressed in first-episode, drug-naive adolescents MDD patients compared with HCs. 19 hub genes were screened out according to the high degree value in the co-expression network. The results from the GEO database showed that compared with adult HCs, there were 290 methylation sites and 127 mRNAs were differentially expressed in adult MDD patients. Conclusion: Compared with adolescent HCs and adult MDD patients, the DNA methylation and mRNA expression patterns of first-episode, drug-naive adolescent MDD patients were different. The co-expression network of DNA methylation and mRNA and the screened hub genes may play an important role in the pathogenesis of MDD in first-episode, drug-naive adolescents. Compared with adult MDD, adolescent MDD is more enriched in metabolism in terms of function and pathways.

RPS6KA5 methylation predict response to 6-week treatment for adolescent MDD patients.

OBJECTIVE: We aimed to investigate the effect of differentially methylated genes and chronic childhood stress on the development of depressive symptoms in Chinese adolescents, as well as to test whether methylation at baseline can be used as a predictor of remission at follow-up after six weeks of treatment. METHODS: After recruiting 87 MDD patients and 53 healthy controls, we compared demographic and baseline clinical characteristics. The Childhood Chronic Stress Questionnaire was used to assess stress caused by early-life events. MDD patients underwent six weeks of treatment, and response to treatment was assessed using the Beck Depression Inventory-II. In addition, four MDD patients and five controls were randomly chosen for genome-wide methylation analysis. RESULTS: The gene RPS6KA5 showed significant methylation differences between the two groups. Severity of chronic childhood stress was significantly associated with increased risk of depression in adolescents, but not with treatment response. Baseline RPS6KA5 methylation can predict remission after six weeks of treatment. We did not observe any interaction between RPS6KA5 methylation and chronic childhood stress. CONCLUSIONS: Our results suggest that RPS6KA5 methylation can be used as a predictor of response to treatment in adolescent MDD patients. Here we offer new evidence for the role of epigenetics in early response to treatment of depression. TRIAL REGISTRATION: ChiCTR, ChiCTR2000033402, 31/05/2020, http://www.chictr.org.cn/index.aspx.