The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression

Autor: Hengshu Chen, Xia Huang, Chang Zeng, Dongren Sun, Fan Liu, Jingyuan Zhang, Qiao Liao, Shihang Luo, Weiye Xu, Yeqing Xiao, Danfeng Zeng, Mingyu Song, Fafa Tian
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Immunology, Vol 14 (2023)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2023.1125634
Popis: 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.
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