Sleep problems constitute a risk for depression. However, it is unclear if persistent sleep problems in childhood are associated with enduring depression symptoms in emerging adulthood and the mechanisms underlying this. Data from the Avon Longitudinal Study of Parents and Children birth cohort were used to examine associations between persistent sleep problems across childhood and persistent depression across adolescence and emerging adulthood, and whether inflammation mediates this link. Predictors were parental report of the child’s nighttime sleep duration and midpoint of sleep (MPS), from 6 months to 6–7 years old. Our outcome was self-reported persistent higher depression symptoms, between 13 and 22 years. Latent Class Growth Analysis (LCGA) was used to detect trajectories for sleep duration, MPS, and depression symptoms and used in subsequent logistic regression analyses. Path analyses explored whether C-Reactive Protein [CRP] and Interleukin-6 [IL-6] at age 9 mediated the relationships between exposures and outcome. Data were available on 6,785 participants. Three separate LCGAs revealed distinct trajectories of interest: (a) persistent shorter nighttime sleep, (b) persistent later MPS, and (c) persistent higher depression symptoms. Children with persistent shorter nighttime sleep were at higher risk of persistent higher depression (OR = 1.94, 95
Mental disorders are a major source of disease burden among adolescents and young adults (AYA). A clearer understanding of their long-term temporal trends and variation across sociodemographic settings may help inform more preventive and targeted mental health strategies, consistent with the aims of Predictive, Preventive and Personalized Medicine (PPPM/3PM). We analyzed incidence, prevalence and disability-adjusted life years (DALYs) for mental disorders among individuals aged 15–39 years from 1990 to 2021. Joinpoint regression, age–period–cohort modelling, decomposition analysis and efficiency frontier analysis were applied to identify high-risk populations and key life stages. Future burden (2022–2050) was projected using hybrid regression–ARIMA models under reference and risk-reduction scenarios to explore potential future patterns. Globally, mental disorders accounted for 195.3 million incident cases and 71.0 million DALYs among AYA in 2021. From 1990 to 2021, age-standardized incidence, prevalence, and DALY rates increased significantly, with average annual percentage changes of 0.62, 0.27, and 0.41, respectively. High socio-demographic index (SDI) regions had the highest age-standardized burden and the largest recent increases. Decomposition analysis showed that rising age-specific rates contributed most to increasing burden in high-SDI regions, whereas population growth was the main driver in low-SDI settings. Cohort analysis suggested elevated risks in more recent birth cohorts, with relative risks increasing to approximately 1.20–1.25 among those born after 2000. Under the reference scenario, the future burden among individuals aged 20–29 years was projected to increase substantially by 2050, with DALY rates in the 20–24 age group rising from 2372.9 to 6063.4 per 100,000. Mental disorders remain a substantial and increasing source of disease burden among adolescents and young adults worldwide, with marked variation across sociodemographic settings. These findings highlight the importance of age-specific and context-specific mental health strategies and may help inform more preventive and personalized approaches to AYA mental healthcare.
To date, benzodiazepine tranquilizers are the most widespread drugs, whose therapeutic effect is mediated by their binding with the allosteric binding site of GABA receptors. Despite the relatively high efficiency of benzodiazepines, they have side sedative and myorelaxant effects. Optimization of therapy for anxiety disorders based on use of benzodiazepines remains to be an actual problem. The aim of the present study was to revise in experiment the efficacy and safety of the combined treatment with benzodiazepine tranquilizers and selank, a peptide anxiolytic, registered in the Russian Federation. This study was performed in male Balb/c mice with enhanced basic anxiety. All drugs were injected intraperitoneally. The combined treatment with diazepam or mezapam and selank increased the number of entries and time spent in open arms of the elevated plus maze compared to the animals treated with tranquilizers only. This effect was probably due to the improvement of the anxiolytic effect of tranquilizers by selank or the antisedative effect of the peptide drug. To further clarify the mechanism of this effect, we studied mouse locomotor activity in the non-stressing conditions of a Rat-O-Matic automatic system. Under these conditions, selank prevented a decline of locomotor activity in mice treated with therapeutic doses of diazepam or olanzapine but not of haloperidol. Thus, it has been shown in animal experiments that selank enhances the anxiolytic effect and decreases the sedative and myorelaxant action of benzodiazepine tranquilizers.
Introduction:Evidence on drug-related problem severity and injection-related harm among people using psychoactive substances in Mongolia is limited, particularly in institutional settings. We examined DAST-28 scores, internal consistency, and behavioral correlates in psychiatric and correctional settings. Methods:This multicenter cross-sectional study included 181 participants recruited from the National Center for Mental Health and correctional facilities. The continuous DAST-28 total score was the primary outcome. Internal consistency was evaluated from 28 item responses. A clinically specified seven-covariate linear model with HC3 heteroskedasticity-robust standard errors was primary; ordinal and study-defined DAST-28 ≥ 12 models were supportive analyses. Results:DAST-28 scores were available for 179 participants (median 11.0, interquartile range 6.0-16.0). Among 170 participants with complete item responses, Cronbach's alpha was 0.882 (95% bootstrap confidence interval 0.854-0.902). In the primary model, correctional setting was associated with a 1.82-point lower score (95% CI -3.36 to -0.28), whereas each additional year of use (B = 0.27, 95% CI 0.08-0.45), polysubstance use (B = 2.64, 95% CI 0.79-4.50), and any syringe use (B = 4.43, 95% CI 2.58-6.28) were associated with higher scores. Ordinal and threshold analyses were concordant; variance inflation factors ranged from 1.05 to 1.59. Conclusions:Greater DAST-28 scores were associated with polysubstance use, syringe use, and longer use duration in these institutional samples. The findings may inform comprehensive assessment and harm-reduction linkage but do not establish a diagnostic cutoff, causal relationship, intervention effectiveness, or population prevalence.
BACKGROUND:High-dose lead (Pb) exposure is known to trigger neuroinflammation and glial activation; however, underlying the effects of chronic, low-level Pb exposure affects brain development remain poorly understood. METHODS:In this study, we investigated whether exposure to a sub-threshold concentration of Pb (50 ppm in drinking water), resulting in blood Pb levels (3.6 ± 1.6 ng/dL) well below current international safety standards, can impair neurodevelopment in mice using an integrative multi-omic and morphological approach. RESULTS:Chronic early-life exposure led to significant behavioral abnormalities, including reduced locomotor activity, altered repetitive behaviors, and deficits in working memory. Morphological analyses revealed region-specific dendritic atrophy in hippocampal CA1 neurons, characterized by shortened and less-branched basal dendrites, consistent with impaired hippocampal circuitry. Integrated transcriptomic and epigenomic profiling identified coordinated hypermethylation and downregulation of neurodevelopmental genes such as Rpl26, and Ube2r2. These epigenetic changes converged on suppression of the PI3K/AKT/mTOR signaling axis, as evidenced by the reduced phosphorylation of PI3K, AKT, mTOR, and GSK-3β, alongside reduced expression of essential synaptic proteins (Synapsin I, PSD95, and TrkB). In parallel, the downregulation of NF-κB and COX-2 indicated that these molecular and behavioral abnormalities arose through a non-inflammatory mechanism distinct from classical Pb-induced gliosis. CONCLUSION:Together, our findings demonstrate that even trace Pb exposure can disrupt neurodevelopment through epigenetic repression and signaling dysregulation, resulting in lasting synaptic and cognitive deficits. These results highlight the exceptional vulnerability of the developing brain to environmental Pb levels and underscore the urgent need to re-evaluate current global safety thresholds to ensure neurodevelopmental protection.
