The ubiquitin–proteasome system (UPS) and autophagy are two distinct and interacting proteolytic systems. They play critical roles in cell survival under normal conditions and during stress. An increasing body of evidence indicates that ubiquitinated cargoes are important markers of degradation. p62, a classical receptor of autophagy, is a multifunctional protein located throughout the cell and involved in many signal transduction pathways, including the Keap1–Nrf2 pathway. It is involved in the proteasomal degradation of ubiquitinated proteins. When the cellular p62 level is manipulated, the quantity and location pattern of ubiquitinated proteins change with a considerable impact on cell survival. Altered p62 levels can even lead to some diseases. The proteotoxic stress imposed by proteasome inhibition can activate autophagy through p62 phosphorylation. A deficiency in autophagy may compromise the ubiquitin–proteasome system, since overabundant p62 delays delivery of the proteasomal substrate to the proteasome despite proteasomal catalytic activity being unchanged. In addition, p62 and the proteasome can modulate the activity of HDAC6 deacetylase, thus influencing the autophagic degradation.

Background To date, no national‐scale psychiatric epidemiological survey for children and adolescents has been conducted in China. In order to inform government officials and policymakers and to develop a comprehensive plan for service providers, there was a clear need to conduct an up‐to‐date systematic nationwide psychiatric epidemiological survey. Methods We conducted a two‐stage large‐scale psychiatric point prevalence survey. Multistage cluster stratified random sampling was used as the sampling strategy. Five provinces were selected by comprehensively considering geographical partition, economic development, and rural/urban factors. In Stage 1, the Child Behavior Checklist was used as the screening tool. In Stage 2, Mini‐International Neuropsychiatric Interview for Children and Adolescents and a diagnostic process based on the Diagnostic and Statistical Manual were used to make the diagnoses. Sampling weights and poststratification weights were employed to match the population distributions. Exploratory analyses were also performed using socio‐demographic factors. Prevalence in socio‐demographic factor subgroups and overall were estimated. Rao‐Scott adjusted chi‐square tests were utilized to determine if between‐group differences were present. Factor interactions were checked by logistic regression analyses. Results A total of 73,992 participants aged 6–16 years of age were selected in Stage 1. In Stage 2, 17,524 individuals were screened and diagnosed. The weighted prevalence of any disorder was 17.5% (95% CI: 17.2–18.0). Statistically significant differences in prevalence of any psychiatric disorder were observed between sexes [χ2(1, N = 71,929) = 223.0, p < .001], age groups [χ2(1, N = 71,929) = 18.6, p < .001] and developed vs. developing areas [χ2(1, N = 71,929) = 2,129.6, p < .001], while no difference was found between rural and urban areas [χ2(1, N = 71,929) = 1.4, p = .239]. Male, younger individuals, children, and adolescents from developed areas had higher prevalence of any psychiatric disorder. The prevalence of any psychiatric disorder was found to decrease with the age in the male group, while the female group increased with the age. Individuals diagnosed with attention‐deficit hyperactivity disorder, oppositional defiant disorder, a tic disorder, conduct disorder, and major depression disorder had the highest rates of comorbidity. Conclusions The prevalence of any psychiatric disorder we found is the highest ever reported in China. These results urgently need to be addressed by public mental health service providers and policymakers in order to provide access to the necessary treatments and to reduce the long‐term negative impact of these conditions on families and the society as a whole.

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Psychoeducational family intervention might be still effective in the 14-year follow-up, especially in patients' treatment adherence/compliance and social functioning. Psychoeducational family intervention might be more effective in places where family members frequently participated in patients' care and had a lower level of knowledge on mental illness. Family intervention should be considered when making mental health policy and planning mental health services.

These findings of focal spontaneous hyper- and hypofunction, together with altered brain connectivity in the large-scale resting-state networks, which correlates with executive dysfunction, point to a connectivity-based pathophysiologic process in ADHD.