No abstract

No abstract

Background Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that promotes neurogenesis and neuroprotection. MIF is predominantly expressed in astrocytes in the brain. The serum MIF level and microsatellites/single nucleotide polymorphisms (SNPs) in the MIF gene promoter region are known to be associated with schizophrenia (SCZ). Interestingly, previous studies reported that hypoxia, an environmental risk factor for SCZ, induced MIF expression through binding of the hypoxia inducible factor (HIF)-1 to the hypoxia response element (HRE) in the MIF promoter. Methods We investigated the involvement of MIF in SCZ while focusing on the HIF pathway. First, we conducted an association study of the SNP rs17004038 (C>A) in the HRE of the MIF promoter between 1758 patients with SCZ and 1507 controls. Next, we investigated the effect of hypoxia on MIF expression in primary cultured astrocytes derived from neonatal mice forebrain. Results SNP rs17004038 was significantly associated with SCZ (p = 0.0424, odds ratio = 1.445), indicating that this SNP in the HRE of the MIF promoter was a genetic risk factor for SCZ. Hypoxia induced MIF mRNA expression and MIF protein production and increased HIF-1 binding to the MIF promoter, while the activity of the MIF promoter was suppressed by mutations in the HRE and by deletion of the HRE in astrocytes. Conclusion These results suggest that SNP rs17004038 in the HRE of the MIF promoter was significantly associated with SCZ and may be involved in the pathophysiology of SCZ via suppression of hypoxia and HIF pathway-induced MIF expression.

(1) Background: The COVID-19 pandemic has distressed many populations worldwide, and since its beginning, many institutes have performed cross-sectional studies to assess mental health. We longitudinally examined psychological distress and depressive symptoms among university staff in Japan from 2019 to 2021, before and during the COVID-19 pandemic.; (2) Methods: Participants were teachers and hospital staff working at institutions related to Kobe University, who completed the Brief Job Stress Questionnaire (BJSQ) from 2019 to 2021. This study used the definition recommended by the guideline to identify high-stress. We analyzed the relationship between those who identified as having high-stress before versus during the COVID-19 pandemic using logistic regression analysis (adjusted for age, sex, and occupation).; (3) Results: Results showed that Stress Reaction scores increased slightly in 2020 and significantly in 2021. Time and other factors had a synergistic effect on mental health. The increase in Stress Reaction was significantly associated with females and nurses over the three years. Those with high-stress in 2019 had approximately twenty-fold odds ratios (OR) of having high-stress in 2020 and 2021.; (4) Conclusions: The long-term COVID-19 pandemic may disturb university staff’s mental health. Those who originally experienced high levels of stress were vulnerable to the negative effects of the COVID-19 pandemic.

No abstract