Reduced NLRP3 inflammasome expression in the brain is associated with stress resilience.

Increased expression of the Nod-like receptor pyrin containing 3 (NLRP3) inflammasome and proinflammatory cytokines is associated with depressive behaviors. This study aimed to explore potential differences in neuroinflammation associated with stress resilience, as well as associated changes in autophagy, in a mouse model of chronic unpredictable mild stress (CUMS). Animals were classified as CUMS resilient or CUMS susceptible based on performance on behavioral tests following the CUMS protocol. Then the expression levels of NLRP3 inflammasome-related proteins, interleukin-1 beta (IL-1ß), and Beclin 1 in stress-related brain regions (e.g., prefrontal cortex and hippocampus) were determined. Results showed that stress exposure triggered significant NLRP3 inflammasome increase in CUMS susceptible mice but not in CUMS resilient mice. These changes were accompanied by altered IL-1ß and Beclin 1 expression levels. These findings indicate that stress resilience is associated with reduced pro-inflammatory signaling and autophagy activation, and suggest that therapeutically targeting these pathways might promote stress resilience.

Contribution of long duration of undiagnosed bipolar disorder to high frequency of relapse: A naturalistic study in China.

BACKGROUND: With attention to misdiagnosis of bipolar disorder (BP), long duration of undiagnosed bipolar disorder (DUBP) had been reported recently in years. This study aims to investigate the contributions of long DUBP to the frequency of relapse in bipolar patients, and explore affect factors of DUBP. METHOD: From 26 hospitals throughout China, 3896 participants diagnosed with BP according to International Classification of Diseases 10th criteria were enrolled in this study. Socio-demographic and clinical data were collected from medical records and specific questionnaires through clinical interviews with patients and their relatives. RESULTS: (1) Our results showed that the mean of DUBP was 40.52months. In total, 779 patients (19.995%) reported DUBP greater than 5years, and 1931 patients (49.564%) reported their DUBP greater than 2years. The number of mood episodes was averaged 5.44, and the frequency ratio of (hypo) mania to depressive episodes was 1.49 (3.27/2.19). (2) Multiple linear regression analysis revealed that DUBP was significantly contributed to the number of relapse (Beta=0.072, p<0.001) after considering the confounding including gender, age at study entry, age of onset, age of first (hypo) manic episodes, age of first depressive episodes, type of first episodes and family history of mental illness. (3) Factors including age at the study entry (Beta=0.526, p<0.001), age of onset (Beta=-1.654, p<0.001), age of first (hypo) manic episode (Beta=0.348, p<0.001), age of first depressive episode (Beta=0.983, p<0.001), depression as the type of first episode (Beta=0.058, p<0.001) and family history of mental illness (Beta=0.029, p<0.05) were significantly contributed to long DUBP. CONCLUSION: It was concluded that long DUBP might lead to high frequent relapse in bipolar patients. The factors correlated with long DUBP include older age, early age of onset, depression as the type of first episode and family history of mental illness. The findings of our study suggest emergency task to early reorganization of bipolar disorder, and improving clinicians' recognition of bipolar disorder from patients with depressive episodes, especially in children and adolescents.