From the Department of Psychiatry, Shenzhen Kangning Hospital (Wu); Shenzhen Mental Health Center (Wu). Shenzhen, Guangdong; Yantai Automobile Engineering Professional College (Yu), Yantai; Department of Psychiatry (Wang, Guan), Hebei Province Rong-Jun Hospital, Baoding; Psychiatry Research Center, Beijing HuiLongGuan Hospital, Peking University HuiLongGuan Clinical Medical School (Xiu); and CAS Key Laboratory of Mental Health, Institute of Psychology (Zhang), Chinese Academy of Sciences, Beijing, China.
Psychosom Med. 2021 Jun 1;83(5):485-491. doi: 10.1097/PSY.0000000000000931.
Accumulating evidence has demonstrated that the pathophysiology of schizophrenia is involved in various abnormalities in oxidative stress markers and cytokines closely related to synaptic plasticity. However, the interactive effects among key cytokines, oxidative stress, and executive dysfunction and symptoms of schizophrenia have not been investigated yet.
A total of 189 patients with chronic schizophrenia and 60 controls were recruited in the current study. Tumor necrosis factor α (TNF-α), interleukin (IL)-8, IL-6, and IL-2 levels; catalase, glutathione peroxidase, and superoxide dismutase (SOD) activities; and malondialdehyde (MDA) levels were determined in patients and controls. Executive function was evaluated by the Wisconsin card sorting tests, the verbal fluency tests, and the Stroop word-color test. Clinical symptoms were evaluated by the Positive and Negative Syndrome Scale.
Relative to the controls, the patients had lower activities of SOD and glutathione peroxidase and levels of TNF-α, but higher levels of MDA, IL-8, IL-6, and IL-2 (all p values < .05). A significant negative relationship between SOD activity and IL-8 levels was found only in patients (β = -0.44, p = .008). Furthermore, we found that an interactive effect of low TNF-α level and high MDA level was associated with negative symptoms (β = -0.02, p = .01). Moreover, the interactive effects of IL-8 and MDA or IL-8 and SOD were correlated with executive function only in patients (β = 0.23, p = .02; β = 0.09, p = .03).
Our findings suggest that the interrelationships between oxidative stress markers and cytokines occur in schizophrenia patients, which may be the basis of their pathological mechanisms underlying clinical symptoms and cognitive dysfunction.
越来越多的证据表明，精神分裂症的病理生理学涉及氧化应激标志物和与突触可塑性密切相关的细胞因子的各种异常。然而，关键细胞因子、氧化应激与执行功能障碍以及精神分裂症症状之间的相互作用关系尚未得到研究。
本研究共纳入 189 例慢性精神分裂症患者和 60 名对照者。检测患者和对照者的肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-8、IL-6 和 IL-2 水平、过氧化氢酶、谷胱甘肽过氧化物酶和超氧化物歧化酶（SOD）活性以及丙二醛（MDA）水平。采用威斯康星卡片分类测验、词语流畅性测验和斯特鲁普字-色测验评估执行功能。采用阳性和阴性综合征量表评估临床症状。
与对照组相比，患者的 SOD 和谷胱甘肽过氧化物酶活性以及 TNF-α水平降低，MDA、IL-8、IL-6 和 IL-2 水平升高（均 P 值<0.05）。仅在患者中发现 SOD 活性与 IL-8 水平呈显著负相关（β=-0.44，P=0.008）。此外，我们发现低 TNF-α水平和高 MDA 水平的交互作用与阴性症状相关（β=-0.02，P=0.01）。而且，IL-8 与 MDA 或 IL-8 与 SOD 的交互作用仅在患者中与执行功能相关（β=0.23，P=0.02；β=0.09，P=0.03）。
我们的研究结果表明，氧化应激标志物和细胞因子之间的相互关系存在于精神分裂症患者中，这可能是其临床症状和认知功能障碍病理机制的基础。
