Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Scientific Institute for Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Hospital Duffel - VZW Emmaüs, Duffel, Belgium.
Bipolar Disord. 2020 Feb;22(1):59-69. doi: 10.1111/bdi.12814. Epub 2019 Aug 30.
Cytokines are thought to contribute to the pathogenesis of psychiatric symptoms by kynurenine pathway activation. Kynurenine metabolites affect neurotransmission and can cause neurotoxicity. We measured inflammatory markers in patients with bipolar disorder (BD) and studied their relation to kynurenine metabolites and mood.
Patients with BD suffering from an acute mood episode were assigned to the depressive (n = 35) or (hypo)manic (n = 32) subgroup. Plasma levels of inflammatory markers [cytokines, C-reactive protein] and kynurenine metabolites [tryptophan (TRP), kynurenine (KYN), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), kynurenic acid (KYNA)] were measured on 6 time points during 8 months follow-up. Biological marker levels in patients were compared to controls (n = 35) and correlated to scores on mood scales. Spearman correlations and linear mixed models were used for statistical analysis.
Twenty patients of the manic subgroup, 29 of the depressive subgroup, and 30 controls completed the study. The manic subgroup had a rapid remission of mood symptoms, but in the depressive subgroup subsyndromal symptoms persisted. No differences in inflammation were found between groups. A strong correlation between tumor necrosis factor-α and KYN, KYN/TRP, 3-HK and QA (ρ > 0.60) was specific for the manic group, but only at baseline (during mania). The depressive subgroup had a lower neuroprotective ratio (KYNA/3-HK, P = .0004) and a strong association between interferon-y and kynurenine pathway activation (P < .0001). KYNA was low in both patient groups versus controls throughout the whole follow-up (P = .0008).
Mania and chronic depressive symptoms in BD are accompanied by a strong interaction between inflammation and a potentially neurotoxic kynurenine metabolism.
细胞因子被认为通过犬尿氨酸途径的激活而导致精神症状的发病机制。犬尿氨酸代谢物会影响神经递质传递，并可能导致神经毒性。我们测量了双相情感障碍（BD）患者的炎症标志物，并研究了它们与犬尿氨酸代谢物和情绪的关系。
患有急性情绪发作的 BD 患者被分为抑郁（n=35）或（轻）躁狂亚组（n=32）。在 8 个月的随访期间，我们在 6 个时间点测量了炎症标志物[细胞因子、C 反应蛋白]和犬尿氨酸代谢物[色氨酸（TRP）、犬尿氨酸（KYN）、3-羟基犬尿氨酸（3-HK）、喹啉酸（QA）、犬尿氨酸酸（KYNA）]的水平。将患者的生物标志物水平与对照组（n=35）进行比较，并与情绪量表的评分相关联。使用 Spearman 相关和线性混合模型进行统计分析。
20 名躁狂亚组患者、29 名抑郁亚组患者和 30 名对照组患者完成了研究。躁狂亚组患者的情绪症状迅速缓解，但在抑郁亚组中，亚综合征症状持续存在。各组之间的炎症无差异。肿瘤坏死因子-α与 KYN、KYN/TRP、3-HK 和 QA 之间存在很强的相关性（ρ>0.60），这一相关性仅在躁狂组中具有特异性，但仅在基线时（躁狂期间）存在。抑郁亚组的神经保护比率较低（KYNA/3-HK，P=0.0004），干扰素-y 与犬尿氨酸途径的激活之间存在很强的关联（P<0.0001）。在整个随访过程中，两组患者的 KYNA 均低于对照组（P=0.0008）。
BD 中的躁狂和慢性抑郁症状伴随着炎症和潜在的神经毒性犬尿氨酸代谢之间的强烈相互作用。
