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

Abstract

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.

Impact of Baduanjin exercise combined with rational emotive behavior therapy on sleep and mood in patients with poststroke depression: A randomized controlled trial

“…[ 39 ] Moreover, it can upregulate the expression of indolamine 2,3-dioxygenase (IDO enzyme), increase the metabolic consumption of tryptophan, the precursor of 5-HT, and then reduce the synthesis of 5-HT, leading to the occurrence of depression. [ 40 , 41 ] The results of this study suggested that the mechanism of Baduanjin exercise combined with REBT to improve mood and sleep disorders in PSD patients is related to the increase of serum 5-HT and BDNF levels and the decrease of IL-6 levels. In addition, this study found that the MBI scores (Fig.…”

Neuroinflammation and Post-Stroke Depression: Focus on the Microglia and Astrocytes

“…PSD is diagnosed and defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. A person must present at least five out of following nine symptoms: feelings of guilt, a sad mood, decreased energy levels, insomnia, decreased appetite, decreased concentration, changes in psychomotor activity (decreased or increased), and recurrent thoughts of selfharm or suicide and loss of interest in pleasurable activities (anhedonia) that lasts for at least 2 weeks [15]. Nevertheless, DSM-5 is not used for some exceptional cases when diagnosing patients do not exhibit typical psychological symptoms and cannot describe their psychological conditions coherently [16].…”

“…PSD occurs at any time point following stroke. A clinical study about 186 acute stroke patients in hospitals have reported that 31.72% of these patients were identified as suffering from depression within 2 weeks after stroke onset [15]. Mitchell et al have reported in their comprehensive meta-analysis that one-third stroke patients had depressive disorders after a stroke [20].…”

Inflammatory Pathogenesis of Post-stroke Depression

“…Pro-inflammatory cytokines can accelerate Trp metabolism through the activation of IDO, reducing 5-HT synthesis and increasing neurotoxic quinolinic acid (QA) production, thus contributing to PSD [120]. Interestingly, the absence of IDO gene abnormalities prevents depression the onset of even under inflammatory stimuli [121](Shown in Fig. 3).…”