Cognitive Impairment in Nonagenarians: Potential Metabolic Mechanisms Revealed by the Synergy of In Silico Gene Expression Modeling and Pathway Enrichment Analysis.

Previous studies examining the molecular and genetic basis of cognitive impairment, particularly in cohorts of long-living adults, have mainly focused on associations at the genome or transcriptome level. Dozens of significant dementia-associated genes have been identified, including APOE, APOC1, and TOMM40. However, most of these studies did not consider the intergenic interactions and functional gene modules involved in cognitive function, nor did they assess the metabolic changes in individual brain regions. By combining functional analysis with a transcriptome-wide association study, we aimed to address this gap and examine metabolic pathways in different areas of the brain of older adults. The findings from our previous genome-wide association study in 1155 older adults, 179 of whom had cognitive impairment, were used as input for the PrediXcan gene prediction algorithm. Based on the predicted changes in gene expression levels, we conducted a transcriptome-wide association study and functional analysis using the KEGG and HALLMARK databases. For a subsample of long-living adults, we used logistic regression to examine the associations between blood biochemical markers and cognitive impairment. The functional analysis revealed a significant association between cognitive impairment and the expression of NADH oxidoreductase in the cerebral cortex. Significant associations were also detected between cognitive impairment and signaling pathways involved in peroxisome function, apoptosis, and the degradation of lysine and glycan in other brain regions. Our approach combined the strengths of a transcriptome-wide association study with the advantages of functional analysis. It demonstrated that apoptosis and oxidative stress play important roles in cognitive impairment.

Prevalence of burnout among psychiatrists: A systematic review and meta-analysis.

BACKGROUND: Burnout is a consequence of chronic occupational stress exposure. Psychiatrists are prone to burnout due to specific work-related factors. This study examined the burnout prevalence among psychiatrists. METHODS: The study protocol was registered in PROSPERO (CRD42020204615). We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, Web of Science, ClinicalTrials.gov, and OpenGrey for relevant publications. Random-effect meta-analysis was performed. We used subgroup analysis and meta-regression to reveal any association of geographical region, survey year, participants' age, gender, and response rate with burnout. RESULTS: Thirty-six studies involving 5481 participants were included. The prevalence of overall burnout was 25.9% [11.1%-40.7%] as measured by a Maslach Burnout Inventory (MBI) and 50.3% [30.9%-69.8%] as measured by a Copenhagen Burnout Inventory (CBI). The pooled prevalence was 43.5% [27.9%-59%] for high emotional exhaustion (EE), 28.2% [17.5%-38.9%] for high depersonalization (DP), and 32.4% [3.4%-61.3%] for low personal accomplishment (PA). The mean scores of 22-item MBI subscales were 21.51 [18.64%-24.38%] for EE, 6.57 [5.53%-7.62%] for DP, and 31.83 [25.73%-37.94%] for PA. European psychiatrists revealed (p = 0.045) lower EE score (20.82; 95% CI 7.24-24.41) measured by 22-item MBI compared to their non-European colleagues (24.99; 95% CI 23.05-26.94). Other results include mean scores for 16-item MBI-General Survey, burnout rates, and scores in CBI subscales. LIMITATIONS: The main limitation was high heterogeneity in terms of statistics, screening methods, burnout definitions, and cut-off points utilized in included studies. CONCLUSIONS: Burnout is highly prevalent among psychiatrists. Future research should focus on finding consensus on burnout screening, longitudinal evaluation of psychiatrists' burnout predictors, and development of effective intervention strategies.