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.

Interactive effect between sleep and exercise on depressive symptoms in Chinese adolescents.

Objectives: The study aimed to investigate the effects of sleep and exercise, individually and jointly, on depressive symptoms in Chinese adolescents. Methods: Cluster sampling was used to conduct a cross-sectional, electronic survey among 11,563 students from five primary and high schools in Sichuan Province in Western China. The questionnaire contained custom-designed items concerning sleep and exercise, while it used the Center for Epidemiologic Studies Depression Scale to assess depressive symptoms and the Core Self-Evaluations Scale to assess core self-evaluation. Data were analyzed using descriptive statistics and multivariate linear regression. Results: A total of 10,185 valid questionnaires were collected, corresponding to an effective response rate of 88.1%. Among the respondents in the final analysis, 5,555 (54.5%) were boys and 4,630 (45.5%) were girls, and the average age was 15.20 ± 1.72 years (range, 11-18 years). Only less than half of the respondents (4,914, 48.2%) reported insufficient sleep, while the remainder (5,271, 51.8%) had adequate sleep. Nearly one-quarter (2,250, 22.1%) reported insufficient exercise, while the remainder (7,935, 77.9%) reported adequate exercise. More than half of the respondents (5,681, 55.7%) were from vocational high school, 3,368 (33.1%) were from junior high school, 945 (9.3%) were from senior high school, and 191 (1.9%) were from primary school. The prevalence of depressive symptoms among all respondents was 29.5% (95% CI 28.7%-30.4%). When other variables were controlled, the depression score did not vary significantly with gender (B = -0.244, SE = 0.127, P = 0.054), but it decreased by 0.194 points per 1-year increase in age (B = -0.194, SE = 0.037, P < 0.001). Students getting adequate sleep had depression scores 2.614 points lower than those getting insufficient sleep (B = -2.614, SE = 0.577, P < 0.001), while students who engaged in adequate exercise had depression scores 1.779 points lower than those not exercising enough (B = -1.779, SE = 0.461, P < 0.001). The depression score decreased by 0.919 points per 1-point increase in the core self-evaluation score (B = -0.919, SE = 0.008, P < 0.001). In regression controlling for gender, age, and core self-evaluation, sleep and exercise were found to be related significantly to influence depressive symptoms (B = 0.821, SE = 0.315, P = 0.009). Conclusion: Adequate sleep and adequate exercise are individually associated with milder depressive symptoms in Chinese adolescents. Our results further highlight the need for researchers and clinicians to take into account not only the individual but also the joint effects of sleep and exercise on depression in adolescents when conducting research and designing interventions. If sleep or physical exercise has substantially reduced the risk of depressive symptoms, further reductions by improving sleep and exercise become difficult and may even have opposite effects.

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.

Comparing the efficacy of pharmacological and psychological treatment, alone and in combination, in children and adolescents with obsessive-compulsive disorder: A network meta-analysis.

BACKGROUND: Studies have shown that pharmacological and psychological treatments are effective for children and adolescents with obsessive-compulsive disorder (OCD). However, few network meta-analyses have examined whether pharmacological or psychological treatments on their own, or combined, are most effective. METHODS: We conducted a database search and selected randomized controlled trials of pharmacological or psychological treatments, alone or in combination, for children and adolescents with OCD. The primary outcome was change in symptom severity as a result of treatment, as assessed using the Yale-Brown Obsessive Compulsive Scale (YBOCS) or Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). RESULTS: We included 18 studies with 1353 participants and 12 kinds of treatments. In terms of efficacy, all pharmacological and psychotherapy treatments were more effective than placebo. Among the 12 treatments, the efficacy of pharmacological treatment combined with cognitive behavioral therapy (CBT) was more effective than pharmacological treatment alone. When pharmacological treatment was used alone, escitalopram was significantly more effective than clomipramine (CY-BOCS average change 3.42; 95% CI 2.11, 4.65), fluvoxamine (CY-BOCS average change 3.59; 95% CI 1.09, 6.20), paroxetine (CY-BOCS average change 2.80; 95% CI 0.01, 5.64) and sertraline (CY-BOCS average change 3.49; 95% CI 1.53, 5.64). CONCLUSIONS: The available evidence suggests that the combination of pharmacological and psychological treatment is likely to be most effective for children and adolescents with OCD.

Core self-evaluation as mediator between depressive symptoms and suicidal ideation in adolescents.

OBJECTIVES: To explore the role of core self-evaluation in mediating between depressive symptoms and suicidal ideation in Chinese adolescents. METHODS: We used the cluster sampling method to analyze 11,563 students from five primary and secondary schools in China for depressive symptoms, core self-evaluation, and suicidal ideation using the following scoring scales: Core Self-Evaluation Scale (CSES), Center for Epidemiologic Survey Depression Scale (CES-D), the Second Edition of the Beck Depression Inventory (BDI- II), Screen for Child Anxiety Related Emotional Disorders (SCARED), and Adolescent Self-Rating Life Events Checklist (ASLEC). RESULTS: The incidence of depression was 29.7%; anxiety, 34.2%; and suicidal ideation, 28.0%. Core self-evaluation was a protective factor for suicidal ideation [OR 0.947, 95% CI 0.937-0.959, p<0.001]. Conversely, depression as measured by the CSES score was a risk factor for suicidal ideation (OR 1.084, 95% CI 1.073-1.096, p<0.001), as were anxiety as measured by the SCARED score (OR 1.011, 95% CI 1.006-1.016, p<0.001) and adolescent life events according to ASLEC score groups (OR 1.524, 95% CI 1.434-1.621, p<0.001). Core self-evaluation mediated the relationship between depression and suicidal ideation with an effect size of 13.9%. CONCLUSIONS: Better core self-evaluation is a protective factor against suicidal ideation and mediates the relationship between depression and suicidal ideation. We may be able to reduce the risk of suicidal ideation and therefore suicide among adolescents by improving their core self-evaluation.

Associations between childhood chronic stress and dynamic functional connectivity in drug-naïve, first-episode adolescent MDD.

BACKGROUND: We explored the associations between chronic stress and dynamic working patterns of the whole brain using resting state MRI data in drug-naïve, first-episode adolescents with major depressive disorder (MDD). METHODS: We compared dynamic functional connectivity (dyn-FC) and screen out networks with difference in whole brain between 45 healthy controls (HC) and 60 adolescent MDD patients using dynamic independent components analysis. In each of these networks with difference between groups, hub brain regions were selected as functionally connected to more than 30 brain regions at the same time. Then we extracted the dyn-FC coefficients of each hub brain region with other brain regions in each component at different time points and calculated the average value of the entire scan time. Finally, we explored correlations between these average values of the entire scan time and scores on the Childhood Chronic Stress Questionnaire (CCSQ). RESULTS: We found three networks as well as some hub brain regions with different dyn-FC patterns between adolescent MDD and HC. Scores on the CCSQ were found to correlate with dynamic FC between hub brain areas and certain other brain areas in MDD patients. LIMITATIONS: our cross-sectional study design does not allow us to speculate about causality between chronic stress and depression. Prospective cohort studies should explore in detail how the changes in dynamic FC appear and evolve during MDD. CONCLUSIONS: Chronic stress is related with the brain dynamic working patterns in adolescent MDD.

Neurosyphilis with psychotic symptoms and Parkinsonism in a young girl.

A 15-year-old girl with neurosyphilis was misdiagnosed as having viral encephalitis with psychotic symptoms and Parkinsonism. We found that she was experiencing visual hallucinations, persecutory delusions, flattening of affect, poorness of thought, tremors, four-limb rigidity, and restlessness, and she was unable to communicate with others. The Venereal Disease Research Laboratory serum test and further lumbar puncture enabled us to diagnose her with neurosyphilis. After antibiotic treatment, her psychotic symptoms and Parkinsonism were relieved. From this case, we believe that it is important to keep organic psychosis in mind during the diagnostic workup, and we argue that routine syphilis screening is necessary in psychiatry clinical practice.