Altered neuroimmune response and oxidative stress have both been implicated in the pathophysiology of schizophrenia. While preclinical studies have proposed several pathways regarding potential interactions between oxidative stress and neuroimmune imbalance in the development of psychosis, the molecular mechanisms underlying this interaction are not yet understood. To date, no study has investigated this link in vivo in the human brain. We conducted the first in vivo study linking translocator protein 18 kDa (TSPO) expression and glutathione (a major brain antioxidant and a marker for redox status) in the medial prefrontal cortex (mPFC) of a relatively large sample of participants (N = 48) including 27 antipsychotic-naïve individuals at clinical high risk for psychosis and 21 matched healthy volunteers using high-resolution PET with TSPO radioligand, [¹⁸F]FEPPA, and 3T proton magnetic resonance spectroscopy (¹H MRS). The omnibus model (including TSPO genotype as covariate) was significant (F_{(4, 43)} = 10.01, p < 0.001), with a significant group interaction (t = -2.10, p = 0.04), suggesting a different relation between [¹⁸F]FEPPA V_T and glutathione in each clinical group. In healthy volunteers, but not in individuals at clinical high risk for psychosis, we found a significant negative association between glutathione levels and [¹⁸F]FEPPA V_T (r = -0.60, p = 0.006). We observed no significant group differences with respect to [¹⁸F]FEPPA V_T or glutathione levels. These findings suggest an abnormal interaction between TSPO expression and redox status in the clinical high risk states for psychosis.

中文翻译：

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TSPO（一种神经免疫标记物）与临床高风险精神病患者氧化还原状态之间的相互作用：一项 PET-MRS 研究。


神经免疫反应的改变和氧化应激都与精神分裂症的病理生理学有关。虽然临床前研究提出了关于精神病发展过程中氧化应激和神经免疫失衡之间潜在相互作用的几种途径，但这种相互作用背后的分子机制尚不清楚。迄今为止，还没有研究在人脑体内调查过这种联系。我们进行了第一项体内研究，将相对较大的参与者样本 (N = 48) 的内侧前额皮质 (mPFC) 中的易位蛋白 18 kDa (TSPO) 表达与谷胱甘肽（一种主要的大脑抗氧化剂和氧化还原状态的标记物）联系起来包括 27 名未接受过抗精神病药物治疗的临床高风险个体和 21 名匹配的健康志愿者，使用高分辨率 PET 与 TSPO 放射性配体、[ ¹⁸ F]FEPPA 和 3T 质子磁共振波谱 ( ¹ H MRS)。综合模型（包括 TSPO 基因型作为协变量）显着（F _{(4, 43)} = 10.01，p < 0.001），具有显着的群体交互作用（t = -2.10，p = 0.04），表明 [ ^18]之间存在不同的关系。每个临床组中的 F]FEPPA V _T和谷胱甘肽。在健康志愿者中，但在临床上精神病高风险个体中，我们发现谷胱甘肽水平与 [ ¹⁸ F]FEPPA V _T之间存在显着负相关（r = -0.60，p = 0.006）。我们观察到 [ ¹⁸ F]FEPPA V _T或谷胱甘肽水平没有显着的组间差异。这些发现表明，在精神病的临床高风险状态下，TSPO 表达与氧化还原状态之间存在异常相互作用。