Inflammatory Subtypes in Antipsychotic-Naïve First-Episode Schizophrenia are Associated with Altered Brain Morphology and Topological Organization.
Inflammatory Subtypes in Antipsychotic-Naïve First-Episode Schizophrenia are Associated with Altered Brain Morphology and Topological Organization.
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DOI：
10.1016/j.bbi.2021.11.019
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Lizano P
中科院分区：
文献类型：
--
作者：
Hoang D;Xu Y;Lutz O;Bannai D;Zeng V;Bishop JR;Keshavan M;Lizano P
外周炎症与精神分裂症有关，然而，并非所有个体都表现出炎症改变。最近的研究确定了慢性精神病中的炎症亚型，与低炎症亚型相比，高炎症具有更差的认知表现并显示神经解剖学扩大。目前尚不清楚炎症亚型是否存在于病程的早期，因此，我们的目标是确定抗精神病药物初治首发精神分裂症（FES）的炎症亚型。12外周炎症标志物，临床，认知和神经解剖学指标收集自抗精神病药初治FES患者的自然主义研究。使用无监督主成分分析和分层聚类的组合来根据其细胞因子数据对炎性亚型进行分类（17例FES高，30例FES低和33例健康对照（HC））。线性回归分析用于评估亚型差异。采用部分斯皮尔曼相关性进行神经解剖学与临床和认知测量的相关性。进行图论分析以评估炎症亚型的全局和局部网络特性。高FES组占FES组的36%，并且与低FES组相比，IL 1 β、IL 6、IL 8和TNFα水平显著更高，与HC相比，IL 1 β和IL 8水平更高。与FES低组相比，FES高组的右侧海马旁、尾侧前扣带回和堤岸上级沟厚度更大。与HC相比，FES低显示双侧杏仁核体积和皮质厚度较小。与HC相比，FES高和FES低组表现出较低的拓扑组织效率。个体细胞因子和/或炎症特征与认知和症状测量呈正相关。炎症亚型存在于抗精神病药物初治FES中，并与炎症介导的皮质扩张相关。这些发现支持了我们之前在慢性精神病中的发现，并指出炎症和血脑屏障破坏之间的联系。因此，识别炎症亚型可能为涉及抗炎药物的生物标志物引导治疗提供新的治疗途径。
Peripheral inflammation is implicated in schizophrenia, however, not all individuals demonstrate inflammatory alterations. Recent studies identified inflammatory subtypes in chronic psychosis with high inflammation having worse cognitive performance and displaying neuroanatomical enlargement compared to low inflammation subtypes. It is unclear if inflammatory subtypes exist earlier in the disease course, thus, we aim to identify inflammatory subtypes in antipsychotic naïve First-Episode Schizophrenia (FES). 12 peripheral inflammatory markers, clinical, cognitive, and neuroanatomical measures were collected from a naturalistic study of antipsychotic-naïve FES patients. A combination of unsupervised principal component analysis and hierarchical clustering was used to categorize inflammatory subtypes from their cytokine data (17 FES High, 30 FES Low, and 33 healthy controls (HCs)). Linear regression analysis was used to assess subtype differences. Neuroanatomical correlations with clinical and cognitive measures were performed using partial Spearman correlations. Graph theoretical analyses were performed to assess global and local network properties across inflammatory subtypes. The FES High group made up 36% of the FES group and demonstrated significantly greater levels of IL1β, IL6, IL8, and TNFα compared to FES Low, and higher levels of IL1β and IL8 compared to HCs. FES High had greater right parahippocampal, caudal anterior cingulate, and bank superior sulcus thicknesses compared to FES Low. Compared to HCs, FES Low showed smaller bilateral amygdala volumes and cortical thickness. FES High and FES Low groups demonstrated less efficient topological organization compared to HCs. Individual cytokines and/or inflammatory signatures were positively associated with cognition and symptom measures. Inflammatory subtypes are present in antipsychotic-naïve FES and are associated with inflammation-mediated cortical expansion. These findings support our previous findings in chronic psychosis and point towards a connection between inflammation and blood-brain barrier disruption. Thus, identifying inflammatory subtypes may provide a novel therapeutic avenue for biomarker-guided treatment involving anti-inflammatory medications.
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DOI：
10.1523/jneurosci.1929-08.2008
发表时间：
2008-09-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bassett DS;Bullmore E;Verchinski BA;Mattay VS;Weinberger DR;Meyer-Lindenberg A
通讯作者：
Meyer-Lindenberg A
影响因子：
4.5
作者：
Ellman, Lauren M.;Deicken, Raymond F.;Vinogradov, Sophia;Kremen, William S.;Poole, John H.;Kern, David M.;Tsai, Wei Yann;Schaefer, Catherine A.;Brown, Alan S.
通讯作者：
Brown, Alan S.
影响因子：
11
作者：
Fernandes, B. S.;Steiner, J.;Berk, M.
通讯作者：
Berk, M.
影响因子：
9.3
作者：
Boerrigter D;Weickert TW;Lenroot R;O'Donnell M;Galletly C;Liu D;Burgess M;Cadiz R;Jacomb I;Catts VS;Fillman SG;Weickert CS
通讯作者：
Weickert CS
影响因子：
11.1
作者：
Balusu S;Van Wonterghem E;De Rycke R;Raemdonck K;Stremersch S;Gevaert K;Brkic M;Demeestere D;Vanhooren V;Hendrix A;Libert C;Vandenbroucke RE
通讯作者：
Vandenbroucke RE