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：

---

TSPO-一种神经免疫标记物与氧化还原状态在精神病临床高风险中的相互作用：一项PET-MRS研究。

改变的神经免疫反应和氧化应激都与精神分裂症的病理生理有关。尽管临床前研究已经提出了几种有关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途径，但尚不了解这种相互作用的分子机制。迄今为止，还没有研究在人脑中体内研究这种联系。¹⁸ F] FEPPA和3T质子磁共振波谱（¹ H MRS）。总体模型（包括TSPO基因型作为协变量）显着（F _（  4，43 _） = 10.01，p <0.001），组间相互作用显着（t = -2.10，p = 0.04），表明[ ¹⁸每个临床组中的F] FEPPA V _T和谷胱甘肽。在健康志愿者中，但在临床上有精神病高风险的个体中却没有，我们发现谷胱甘肽水平与[ ¹⁸ F] FEPPA V _T之间显着负相关（r = -0.60，p = 0.006）。我们没有观察到关于[ ¹⁸ F] FEPPA V _T的显着分组差异或谷胱甘肽水平。这些发现表明，在精神病的临床高危状态下，TSPO表达与氧化还原状态之间存在异常相互作用。