Skorobogatov Katrien, Autier Valérie, Foiselle Marianne, Richard Jean-Romain, Boukouaci Wahid, Wu Ching-Lien, Raynal Sophie, Carbonne Christel, Laukens Kris, Meysman Pieter, Coppens Violette, le Corvoisier Philippe, Barau Caroline, De Picker Livia, Morrens Manuel, Tamouza Ryad, Leboyer Marion
Scientific Initiative for Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Hospital Campus Duffel (UPCD), Duffel, Belgium.
Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium.
Brain Behav Immun Health. 2023 Jan 2;27:100584. doi: 10.1016/j.bbih.2022.100584. eCollection 2023 Feb.
Schizophrenia (SCZ) and bipolar disorder (BD) are associated with immunological dysfunctions that have been hypothesized to lead to clinical symptomatology in particular through kynurenine pathway abnormalities. The aim of this study was thus to investigate the impact of serum kynurenine metabolite levels on diagnosis, clinical state, symptom severity and clinical course in a large French transdiagnostic cohort of SCZ and BD patients. Four patient groups (total n = 507) were included in a cross-sectional observational study: 1) hospitalized acute bipolar patients (n = 205); 2) stable bipolar outpatients (n = 116); 3) hospitalized acute schizophrenia patients (n = 111) and 4) stable schizophrenia outpatients (n = 75), in addition to healthy controls (HC) (n = 185). The quantitative determination of serum kynurenine metabolites was performed using liquid chromatography-tandem mass spectrometry. Kynurenine levels were lower in all patients combined compared to HC while ANCOVA analyses did not reveal inter-diagnostic difference between SCZ and BD. Interestingly, hospitalized patients of both diagnostic groups combined displayed significantly lower kynurenine levels than stabilized outpatients. Psychotic symptoms were associated with lower quinaldic acid (F = 9.18, p=<.001), which is KAT-driven, whereas a longer duration of illness contributed to abnormalities in tryptophan (F = 5.41, p = .023), kynurenine (F = 16.93, p=<.001), xanthurenic acid (F = 9.34, p = .002), quinolinic acid (F = 9.18, p = .003) and picolinic acid (F = 4.15, p = .043), metabolized through the KMO-branch. These data confirm illness state rather than diagnosis to drive KP alterations in SCZ and BD. Lower levels of KP metabolites can thus be viewed as a transdiagnostic feature of SCZ and BD, independently associated with acute symptomatology and a longer duration of illness. Quinaldic acid has seldomly been investigated by previous studies and appears an important state marker in SCZ and BD. As serum samples are used in this study, it is not possible to extrapolate these findings to the brain.
精神分裂症（SCZ）和双相情感障碍（BD）与免疫功能障碍有关，据推测，免疫功能障碍尤其会通过犬尿氨酸途径异常导致临床症状。因此，本研究的目的是调查血清犬尿氨酸代谢物水平对法国一个大型SCZ和BD患者跨诊断队列的诊断、临床状态、症状严重程度和临床病程的影响。一项横断面观察性研究纳入了四组患者（共507例）：1）住院急性双相情感障碍患者（205例）；2）稳定的双相情感障碍门诊患者（116例）；3）住院急性精神分裂症患者（111例）和4）稳定的精神分裂症门诊患者（75例），此外还包括健康对照（HC）（185例）。使用液相色谱 - 串联质谱法对血清犬尿氨酸代谢物进行定量测定。与HC相比，所有患者的犬尿氨酸水平均较低，而协方差分析未显示SCZ和BD之间的诊断差异。有趣的是，两个诊断组的住院患者的犬尿氨酸水平均显著低于稳定的门诊患者。精神病性症状与较低的喹啉酸水平相关（F = 9.18，p = <.001），喹啉酸由犬尿氨酸转氨酶驱动，而病程较长会导致色氨酸（F = 5.41，p = .023）、犬尿氨酸（F = 16.93，p = <.001）、黄尿酸（F = 9.34，p = .002）、喹啉酸（F = 9.18，p = .003）和吡啶酸（F = 4.15，p = .043）异常，这些物质通过犬尿氨酸酶分支代谢。这些数据证实疾病状态而非诊断驱动SCZ和BD中的犬尿氨酸途径改变。因此，较低水平的犬尿氨酸途径代谢物可被视为SCZ和BD的跨诊断特征，与急性症状和较长病程独立相关。先前的研究很少对喹啉酸进行研究，它似乎是SCZ和BD中的一个重要状态标志物。由于本研究使用的是血清样本，无法将这些发现外推至大脑。
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