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ObjectiveTo investigate the relationship between single nucleotide polymorphisms (SNPs) related to vitamin D (VitD) metabolism and post-stroke depression (PSD) in patients with ischemic stroke.MethodsA total of 210 patients with ischemic stroke were enrolled at the Department of Neurology in Xiangya Hospital, Central South University, from July 2019 to August 2021. SNPs in the VitD metabolic pathway (VDR, CYP2R1, CYP24A1, and CYP27B1) were genotyped using the SNPscan™ multiplex SNP typing kit. Demographic and clinical data were collected using a standardized questionnaire. Multiple genetic models including dominant, recessive, and over-dominant models were utilized to analyze the associations between SNPs and PSD.ResultsIn the dominant, recessive, and over-dominant models, no significant association was observed between the selected SNPs in the CYP24A1 and CYP2R1 genes and PSD. However, univariate and multivariate logistic regression analysis revealed that the CYP27B1 rs10877012 G/G genotype was associated with a decreased risk of PSD (OR: 0.41, 95% CI: 0.18–0.92, p = 0.030 and OR: 0.42, 95% CI: 0.18–0.98, p = 0.040, respectively). Furthermore, haplotype association analysis indicated that rs11568820-rs1544410-rs2228570-rs7975232-rs731236 CCGAA haplotype in the VDR gene was associated with a reduced risk of PSD (OR: 0.14, 95% CI: 0.03–0.65, p = 0.010), whereas no significant association was observed between haplotypes in the CYP2R1 and CYP24A1 genes and PSD.ConclusionOur findings suggest that the polymorphisms of VitD metabolic pathway genes VDR and CYP27B1 may be associated with PSD in patients with ischemic stroke.

BackgroundThe immune-inflammatory response has been widely considered to be involved in the pathogenesis of post-stroke depression (PSD), but there is ambiguity about the mechanism underlying such association.MethodsAccording to Diagnostic and Statistical Manual of Mental Disorders (5th edition), depressive symptoms were assessed at 2 weeks after stroke onset. 15 single nucleotide polymorphisms (SNPs) in genes of indoleamine 2,3-dioxygenase (IDO, including IDO1 and IDO2) and its inducers (including pro-inflammatory cytokines interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-2 and IL-6) were genotyped using SNPscan™ technology, and serum IDO1 levels were detected by double-antibody sandwich enzyme-linked immune-sorbent assay.ResultsFifty-nine patients (31.72%) were diagnosed with depression at 2 weeks after stroke onset (early-onset PSD). The IDO1 rs9657182 T/T genotype was independently associated with early-onset PSD (adjusted odds ratio [OR] = 3.008, 95% confidence interval [CI] 1.157-7.822, p = 0.024) and the frequency of rs9657182 T allele was significantly higher in patients with PSD than that in patients with non-PSD (χ2 = 4.355, p = 0.037), but these results did not reach the Bonferroni significance threshold (p > 0.003). Serum IDO1 levels were also independently linked to early-onset PSD (adjusted OR = 1.071, 95% CI 1.002-1.145, p = 0.044) and patients with PSD had higher serum IDO1 levels than patients with non-PSD in the presence of the rs9657182 T allele but not homozygous C allele (t = -2.046, p = 0.043). Stroke patients with the TNF-α rs361525 G/G genotype had higher serum IDO1 levels compared to those with the G/A genotype (Z = -2.451, p = 0.014).ConclusionsOur findings provided evidence that IDO1 gene polymorphisms and protein levels were involved in the development of early-onset PSD and TNF-α polymorphism was associated with IDO1 levels, supporting that IDO1 which underlie strongly regulation by cytokines may be a specific pathway for the involvement of immune-inflammatory mechanism in the pathophysiology of PSD.

BackgroundHomocysteine (Hcy) has been indicated to be involved in pathophysiology of post stroke depression (PSD). There is a lack of research to study the relationship between Hcy metabolism genes and PSD. Our study aims to investigate the relationship among Hcy metabolism genes, Hcy, and early-onset PSD.Materials and methodsWe recruited 212 patients with stroke and collected their peripheral blood sample, clinical data, and laboratory test on admission. 12 single nucleotide polymorphisms (SNPs) in methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), and methionine synthase (MTR) genes were genotyped by high-resolution melt analysis. PSD was diagnosed by DSM-V at 2 weeks after stroke. Binary logistic regression and haplotype analysis were used to examine the association between Hcy metabolism genes and PSD. Mediation analysis was performed to clarify whether the SNPs exerted their effect on PSD by affecting the Hcy level.Results81 patients were diagnosed with PSD, and the incidence rate was 38.2%. Hcy level in PSD group was significantly higher than it in non-PSD group (p = 0.019). MTHFR rs1801133 AA genotype an A allele were associated with an elevated risk of PSD after adjustment for some confounding factors (OR = 4.021, 95% CI: 1.459∼11.080, p = 0.007 for AA genotype; OR = 1.808, 95% CI: 1.172∼2.788, p = 0.007 for A allele). Furthermore, the effect of MTHFR rs1801133 AA genotype on PSD was mediated by Hcy (OR = 1.569, 95% CI: 0.013∼3.350, p < 0.05).ConclusionMTHFR rs1801133 and Hcy were associated with PSD, and MTHFR rs1801133 may exert an effect on PSD via mediating Hcy level. This offers a new perspective for treating PSD and understanding the mechanism of PSD.

Evidence accumulation has been the core component in recent development of perceptual and value-based decision-making theories. Most studies have focused on the evaluation of evidence between alternative options. What remains largely unknown is the process that prepares evidence: how may the decision-maker sample different sources of information sequentially, if they can only sample one source at a time? Here we propose a theoretical framework in prescribing how different sources of information should be sampled to facilitate the decision process: beliefs for different noisy sources are updated in a Bayesian manner and participants can proactively allocate resource for sampling (i.e., saccades) among different sources to maximize the information gain in such process. We show that our framework can account for human participants' actual choice and saccade behavior in a two-alternative value-based decision-making task. Moreover, our framework makes novel predictions about the empirical eye movement patterns.

Osteoarthritis (OA) is a common joint disease in the elderly population. Its development has been reported to be associated with cartilage degradation and inflammatory responses. Schisandrin A, a bioactive lignin in Schisandra sphenanthera, has shown its anti-inflammatory potential in various inflammation diseases. However, the effects of Schisandrin A on OA remain to explore. In this study, rat chondrocytes were treated with IL-1β (10 ng/ml) with or without different concentrations of Schisandrin A for 24 h. Cell viability was evaluated by CCK-8 assay. Production of nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Griess reaction and ELISA. The MAPK/NF-κB-related signaling molecules expression and the protein production of inducible nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, MMPs (MMP1, MMP3, MMP13), ADAMTS5, Collagen II, aggrecan, and Sox9 were detected by Western blot. Protein expression of Collagen II, aggrecan, and p65 nuclear translocation was evaluated by immunofluorescence. In vivo, intra-articular injection of 50 μM Schisandrin A or equal volume of vehicle was performed on rat OA models. Severity of cartilage damage was evaluated by HE and Safranin-O-Fast green staining. Our results revealed that Schisandrin A could suppress the IL-1β-induced production of NO and PGE2 in rat chondrocytes. Consistent with these findings, the upregulation of iNOS and Cox2 could also been decreased by Schisandrin A. Additionally, Schisandrin A could inhibit IL-1β-induced cartilage matrix catabolic enzymes including MMPs and ADAMTS5. Moreover, the IL-1β-induced downregulation of Collagen II, aggrecan, and Sox9 could be ameliorated by Schisandrin A. Mechanistically, Schisandrin A functioned by suppressing MAPK and NF-κB signal pathways. In vivo, Schisandrin A prevented cartilage damage in rat OA model. In conclusion, this study elucidates that Schisandrin A inhibits the IL-1β-induced inflammation and cartilage degradation via suppression of MAPK and NF-κB signal pathways, indicating its potential role in OA therapy.