Is there a role for immune-to-brain communication in schizophrenia?

被引:106
|
作者
Khandaker, Golam M. [1 ]
Dantzer, Robert [2 ]
机构
[1] Univ Cambridge, Dept Psychiat, Box 189,Cambridge Biomed Campus, Cambridge CB2 2QQ, England
[2] Univ Texas Houston, MD Anderson Canc Ctr, Dept Symptom Res, Div Internal Med, 1515 Holcombe Blvd, Houston, TX 77030 USA
基金
英国惠康基金; 美国国家卫生研究院;
关键词
Schizophrenia; Psychotic disorder; Inflammation; Immunity; Immune system; Cytokine; IL-6; CRP; Blood-brain barrier; Endothelial cell; Treatment; Common-cause hypothesis; C-REACTIVE PROTEIN; GENOME-WIDE ASSOCIATION; 1ST EPISODE PSYCHOSIS; HERPES-SIMPLEX VIRUS; KYNURENIC ACID; CEREBROSPINAL-FLUID; DOUBLE-BLIND; CYTOKINE ALTERATIONS; SERUM INTERLEUKIN-6; PRENATAL EXPOSURE;
D O I
10.1007/s00213-015-3975-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Schizophrenia is characterised by hallucinations, delusions, depression-like so-called negative symptoms, cognitive dysfunction, impaired neurodevelopment and neurodegeneration. Epidemiological and genetic studies strongly indicate a role of inflammation and immunity in the pathogenesis of symptoms of schizophrenia. Evidence accrued over the last two decades has demonstrated that there are a number of pathways through which systemic inflammation can exert profound influence on the brain leading to changes in mood, cognition and behaviour. The peripheral immune system-to-brain communication pathways have been studied extensively in the context of depression where inflammatory cytokines are thought to play a key role. In this review, we highlight novel evidence suggesting an important role of peripheral immune-to-brain communication pathways in schizophrenia. We discuss recent population-based longitudinal studies that report an association between elevated levels of circulating inflammatory cytokines and subsequent risk of psychosis. We discuss emerging evidence indicating potentially important role of blood-brain barrier endothelial cells in peripheral immune-to-brain communication, which may be also relevant for schizophrenia. Drawing on clinical and preclinical studies, we discuss whether immune-mediated mechanisms could help to explain some of the clinical and pathophysiological features of schizophrenia. We discuss implication of these findings for approaches to diagnosis, treatment and research in future. Finally, pointing towards links with early-life adversity, we consider whether persistent low-grade activation of the innate immune response, as a result of impaired foetal or childhood development, could be a common mechanism underlying the high comorbidity between certain neuropsychiatric and physical illnesses, such as schizophrenia, depression, heart disease and type-two diabetes.
引用
收藏
页码:1559 / 1573
页数:15
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