Mäntylä Teemu, Mantere Outi, Raij Tuukka T, Kieseppä Tuula, Laitinen Hanna, Leiviskä Jaana, Torniainen Minna, Tuominen Lauri, Vaarala Outi, Suvisaari Jaana
Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland; Brain Research Unit, O.V. Lounasmaa Laboratory and Advanced Magnetic Imaging Centre, Aalto NeuroImaging, Aalto University School of Science, Espoo, Finland; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
Mental Health Unit, National Institute for Health and Welfare, Helsinki, Finland; Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland; Institute of Clinical Medicine, Department of Psychiatry, Helsinki University, Helsinki, Finland.
PLoS One. 2015 May 13;10(5):e0125112. doi: 10.1371/journal.pone.0125112. eCollection 2015.
First-episode psychosis (FEP) is associated with inflammatory and brain structural changes, but few studies have investigated whether systemic inflammation associates with brain structural changes in FEP. Thirty-seven FEP patients (median 27 days on antipsychotic medication), and 19 matched controls were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular risk markers were measured at baseline and 2 months later. We collected T1- and diffusion-weighted MRIs with a 3 T scanner from the patients at baseline. We analyzed the association of psychosis-related inflammatory markers with gray and white matter (WM) volume using voxel-based morphometry and WM diffusion using tract-based spatial statistics with whole-brain and region-of-interest (ROI) analyses. FEP patients had higher CCL22 and lower TGFα, CXCL1, CCL7, IFN-α2 and ApoA-I than controls. CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls. The association between inflammatory markers and FEP remained significant after adjusting for age, sex, smoking and BMI. We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment. Baseline CCL22 levels correlated negatively with WM volume and positively with mean diffusivity and radial diffusivity bilaterally in the frontal lobes in ROI analyses. Decreased serum level of ApoA-I was associated with smaller volume of the medial temporal WM. In whole-brain analyses, CCL22 correlated positively with mean diffusivity and radial diffusivity, and CXCL1 associated negatively with fractional anisotropy and positively with mean diffusivity and radial diffusivity in several brain regions. This is the first report to demonstrate an association between circulating chemokine levels and WM in FEP patients. Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology. The results suggest that an altered activation of innate immunity may contribute to WM damage in psychotic disorders.
首发精神病（FEP）与炎症和脑结构变化相关，但很少有研究调查全身性炎症是否与FEP中的脑结构变化有关。招募了37例FEP患者（抗精神病药物治疗中位数为27天）和19例匹配的对照。在基线和2个月后测量了38种趋化因子和细胞因子的血清水平以及心血管风险标志物。我们在基线时使用3T扫描仪从患者处收集了T1加权和扩散加权磁共振成像。我们使用基于体素的形态学分析方法分析了与精神病相关的炎症标志物与灰质和白质（WM）体积的关联，并使用基于束的空间统计学方法对WM扩散进行了全脑和感兴趣区域（ROI）分析。FEP患者的CCL22水平高于对照组，而TGFα、CXCL1、CCL7、IFN-α2和ApoA-I水平低于对照组。患者在基线和2个月之间CCL22显著下降，但仍高于对照组。在校正年龄、性别、吸烟和BMI后，炎症标志物与FEP之间的关联仍然显著。我们未观察到炎症标志物与任何症状或抗精神病治疗持续时间之间的相关性。在ROI分析中，基线CCL22水平与额叶双侧WM体积呈负相关，与平均扩散率和径向扩散率呈正相关。血清ApoA-I水平降低与内侧颞叶WM体积较小有关。在全脑分析中，CCL22与平均扩散率和径向扩散率呈正相关，CXCL1在几个脑区与分数各向异性呈负相关，与平均扩散率和径向扩散率呈正相关。这是第一份证明FEP患者循环趋化因子水平与WM之间存在关联的报告。有趣的是，CCL22先前已被认为与与WM病理学相关的自身免疫性疾病有关。结果表明，先天免疫激活的改变可能导致精神障碍中的WM损伤。
