Several lines of research support immune system dysregulation in psychotic disorders. However, it remains unclear whether the immunological marker alterations are stable and how they associate with brain glial cell function. This longitudinal study aimed at investigating whether peripheral immune functions are altered in the early phases of psychotic disorders, whether the changes are associated with core symptoms, remission, brain glial cell function, and whether they persist in a one-year follow-up. Two independent cohorts comprising in total of 129 first-episode psychosis (FEP) patients and 130 controls were assessed at baseline and at the one-year follow-up. Serum cyto-/chemokines were measured using a 38-plex Luminex assay. The FEP patients showed a marked increase in chemokine CCL22 levels both at baseline (p < 0.0001; Cohen’s d = 0.70) and at the 12-month follow-up (p = 0.0007) compared to controls. The group difference remained significant (p = 0.0019) after accounting for relevant covariates including BMI, smoking, and antipsychotic medication. Elevated serum CCL22 levels were significantly associated with hallucinations (ρ = 0.20) and disorganization (ρ = 0.23), and with worse verbal performance (ρ = −0.23). Brain glial cell activity was indexed with positron emission tomography and the translocator protein radiotracer [¹¹C]PBR28 in subgroups of 15 healthy controls and 14 FEP patients with serum CCL22/CCL17 measurements. The distribution volume (V_T) of [¹¹C]PBR28 was lower in patients compared to controls (p = 0.026; Cohen’s d = 0.94) without regionally specific effects, and was inversely associated with serum CCL22 and CCL17 levels (p = 0.036). Our results do not support the over-active microglia hypothesis of psychosis, but indicate altered CCR4 immune signaling in early psychosis with behavioral correlates possibly mediated through cross-talk between chemokine networks and dysfunctional or a decreased number of glial cells.

几项研究支持精神病患者的免疫系统失调。然而，尚不清楚免疫标志物的改变是否稳定以及它们如何与脑胶质细胞功能相关。这项纵向研究旨在调查外周免疫功能是否在精神病的早期阶段发生改变，这些变化是否与核心症状、缓解、脑胶质细胞功能有关，以及它们是否在一年的随访中持续存在。在基线和一年的随访中评估了两个独立的队列，总共包括 129 名首发精神病 (FEP) 患者和 130 名对照。使用 38-plex Luminex 测定法测量血清细胞/趋化因子。FEP 患者在基线时均显示趋化因子 CCL22 水平显着增加（p < 0.0001；Cohen's d  = 0.70) 和 12 个月的随访 ( p  = 0.0007) 与对照组相比。 在考虑了包括 BMI、吸烟和抗精神病药物在内的相关协变量后，组间差异仍然显着 ( p = 0.0019)。血清 CCL22 水平升高与幻觉 ( ρ  = 0.20) 和混乱 ( ρ  = 0.23) 显着相关，并与较差的语言表现 ( ρ  = -0.23) 显着相关。在 15 名健康对照和 14 名 FEP 患者的血清 CCL22/CCL17 测量亚组中，用正电子发射断层扫描和转运蛋白放射性示踪剂 [ ¹¹ C]PBR28 对脑胶质细胞活性进行索引。分布容积（与对照组相比，[ ¹¹ C]PBR28的V _{T ) 较低 (} p  = 0.026; Cohen's d  = 0.94)，没有区域特异性影响，并且与血清 CCL22 和 CCL17 水平呈负相关 ( p  = 0.036)。我们的结果不支持精神病的过度活跃的小胶质细胞假说，但表明早期精神病中 CCR4 免疫信号的改变与行为相关性可能通过趋化因子网络与功能失调或神经胶质细胞数量减少之间的串扰介导。