Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Schizophr Bull. 2024 Jan 1;50(1):199-209. doi: 10.1093/schbul/sbad114.
Low-grade neural and peripheral inflammation are among the proposed pathophysiological mechanisms of schizophrenia. White matter impairment is one of the more consistent findings in schizophrenia but the underlying mechanism remains obscure. Many cerebral white matter components are sensitive to neuroinflammatory conditions that can result in demyelination, altered oligodendrocyte differentiation, and other changes. We tested the hypothesis that altered immune-inflammatory response system (IRS) and compensatory immune-regulatory reflex system (IRS/CIRS) dynamics are associated with reduced white matter integrity in patients with schizophrenia.
Patients with schizophrenia (SCZ, 70M/50F, age = 40.76 ± 13.10) and healthy controls (HCs, 38M/27F, age = 37.48 ± 12.31) underwent neuroimaging and plasma collection. A panel of cytokines were assessed using enzyme-linked immunosorbent assay. White matter integrity was measured by fractional anisotropy (FA) from diffusion tensor imaging using a 3-T Prisma MRI scanner. The cytokines were used to generate 3 composite scores: IRS, CIRS, and IRS/CIRS ratio.
The IRS/CIRS ratio in SCZ was significantly higher than that in HCs (P = .009). SCZ had a significantly lower whole-brain white matter average FA (P < .001), and genu of corpus callosum (GCC) was the most affected white matter tract and its FA was significantly associated with IRS/CIRS (r = 0.29, P = .002). FA of GCC was negatively associated with negative symptom scores in SCZ (r = -0.23, P = .016). There was no mediation effect taking FA of GCC as mediator, for that IRS/CIRS was not associated with negative symptom score significantly (P = .217) in SCZ.
Elevated IRS/CIRS might partly account for the severity of negative symptoms through targeting the integrity of GCC.
低度神经和外周炎症是精神分裂症发病机制的一种假说。脑白质损伤是精神分裂症的一个较为一致的发现，但潜在的机制尚不清楚。许多脑白质成分对神经炎症条件敏感，可能导致脱髓鞘、少突胶质细胞分化改变等变化。我们检验了以下假说，即改变的免疫炎症反应系统（IRS）和代偿性免疫调节反射系统（IRS/CIRS）动态与精神分裂症患者的脑白质完整性降低有关。
精神分裂症患者（SCZ，70M/50F，年龄=40.76±13.10）和健康对照组（HCs，38M/27F，年龄=37.48±12.31）接受了神经影像学和血浆采集。使用酶联免疫吸附测定法评估了一组细胞因子。使用 3T Prisma MRI 扫描仪通过弥散张量成像测量脑白质完整性，以分数各向异性（FA）表示。使用这些细胞因子生成了 3 个综合评分：IRS、CIRS 和 IRS/CIRS 比值。
SCZ 的 IRS/CIRS 比值明显高于 HCs（P=0.009）。SCZ 的全脑白质平均 FA 明显降低（P<0.001），胼胝体膝部（GCC）是受影响最严重的白质束，其 FA 与 IRS/CIRS 显著相关（r=0.29，P=0.002）。SCZ 患者的 GCC FA 与阴性症状评分呈负相关（r=-0.23，P=0.016）。以 GCC FA 为中介，IRS/CIRS 与阴性症状评分无显著相关性（P=0.217），因此不存在中介效应。
IRS/CIRS 升高可能部分通过靶向 GCC 的完整性来解释阴性症状的严重程度。
