He Yi, Bo Qijing, Mao Zhen, Yang Jian, Liu Min, Wang Haixia, Kastin Abba J, Pan Weihong, Wang Chuanyue, Sun Zuoli
Beijing Key Laboratory of Mental Disorders, The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
Front Psychiatry. 2022 Mar 9;13:842003. doi: 10.3389/fpsyt.2022.842003. eCollection 2022.
Our previous studies documented that interleukin-15 receptor α (IL-15Rα) knockout (KO) mice exhibited hyperactivity, memory impairment, and desperate behavior, which are core features of schizophrenia and depression. Due to the overlapping symptomology and pathogenesis observed for schizophrenia and depression, the present study attempted to determine whether IL-15Rα was associated with the risk of schizophrenia or depression. One hundred fifty-six participants, including 63 schizophrenia patients, 29 depressive patients, and 64 age-matched healthy controls, were enrolled in the study. We investigated the circulating levels of soluble IL-15Rα and analyzed potential links between the IL-15Rα levels and clinical symptoms present in schizophrenia or depressive patients. We observed reduced serum IL-15Rα levels in schizophrenia patients, but not depressive patients compared with controls. Moreover, a significant negative association was observed between the circulating IL-15Rα levels and excited phenotypes in the schizophrenia patients. The IL-15Rα KO mice displayed pronounced pre-pulse inhibition impairment, which was a typical symptom of schizophrenia. Interestingly, the IL-15Rα KO mice exhibited a remarkable elevation in the startle amplitude in the startle reflex test compared to wild type mice. These results demonstrated that serum levels of soluble IL-15Rα were reduced in schizophrenia and highlighted the relationship of IL-15Rα and the excited phenotype in schizophrenia patients and mice.
我们之前的研究表明,白细胞介素-15受体α(IL-15Rα)基因敲除(KO)小鼠表现出多动、记忆障碍和绝望行为,这些都是精神分裂症和抑郁症的核心特征。由于精神分裂症和抑郁症在症状学和发病机制上存在重叠,本研究试图确定IL-15Rα是否与精神分裂症或抑郁症的风险相关。该研究招募了156名参与者,包括63名精神分裂症患者、29名抑郁症患者和64名年龄匹配的健康对照。我们调查了可溶性IL-15Rα的循环水平,并分析了IL-15Rα水平与精神分裂症或抑郁症患者临床症状之间的潜在联系。我们观察到,与对照组相比,精神分裂症患者血清IL-15Rα水平降低,但抑郁症患者没有。此外,在精神分裂症患者中,循环IL-15Rα水平与兴奋表型之间存在显著的负相关。IL-15Rα基因敲除小鼠表现出明显的前脉冲抑制损伤,这是精神分裂症的典型症状。有趣的是,与野生型小鼠相比,IL-15Rα基因敲除小鼠在惊吓反射测试中的惊吓幅度显著升高。这些结果表明,精神分裂症患者血清可溶性IL-15Rα水平降低,并突出了IL-15Rα与精神分裂症患者及小鼠兴奋表型之间的关系。