Altered neural signaling and immune pathways in peripheral blood mononuclear cells of schizophrenia patients with cognitive impairment: A transcriptome analysis

Wnt信号通路 转录组 信号转导 外周血单个核细胞 精神分裂症(面向对象编程) 小桶 认知功能衰退 生物 免疫学 医学 神经科学 内科学 细胞生物学 基因表达 基因 遗传学 精神科 痴呆 体外 疾病
作者
Jing Qin Wu,Melissa J. Green,Erin Gardiner,Paul A. Tooney,Rodney J. Scott,Vaughan J. Carr,Murray J. Cairns
出处
期刊:Brain Behavior and Immunity [Elsevier BV]
卷期号:53: 194-206 被引量:31
标识
DOI:10.1016/j.bbi.2015.12.010
摘要

Cognitive deficits are a core feature of schizophrenia and contribute significantly to functional disability. We investigated the molecular pathways associated with schizophrenia (SZ; n = 47) cases representing both 'cognitive deficit' (CD; n = 22) and 'cognitively spared' (CS; n = 25) subtypes of schizophrenia (based on latent class analysis of 9 cognitive performance indicators), compared with 49 healthy controls displaying 'normal' cognition. This was accomplished using gene-set analysis of transcriptome data derived from peripheral blood mononuclear cells (PBMCs). We detected 27 significantly altered pathways (19 pathways up-regulated and 8 down-regulated) in the combined SZ group and a further 6 pathways up-regulated in the CS group and 5 altered pathways (4 down-regulated and 1 up-regulated) in the CD group. The transcriptome profiling in SZ and cognitive subtypes were characterized by the up-regulated pathways involved in immune dysfunction (e.g., antigen presentation in SZ), energy metabolism (e.g., oxidative phosphorylation), and down-regulation of the pathways involved in neuronal signaling (e.g., WNT in SZ/CD and ERBB in SZ). When we looked for pathways that differentiated the two cognitive subtypes we found that the WNT signaling was significantly down-regulated (FDR < 0.05) in the CD group in accordance with the combined SZ cohort, whereas it was unaffected in the CS group. This suggested suppression of WNT signaling was a defining feature of cognitive decline in schizophrenia. The WNT pathway plays a role in both the development/function of the central nervous system and peripheral tissues, therefore its alteration in PBMCs may be indicative of an important genomic axis relevant to cognition in the neuropathology of schizophrenia.
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