Is there a role for immune-to-brain communication in schizophrenia?
Is there a role for immune-to-brain communication in schizophrenia?
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DOI：
10.1007/s00213-015-3975-1
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发表时间：
2016-05
影响因子：
3.4
通讯作者：
Dantzer R
中科院分区：
文献类型：
--
作者：
Khandaker GM;Dantzer R
精神分裂症的特征是幻觉、妄想、抑郁样所谓的阴性症状、认知功能障碍、神经发育受损和神经变性。流行病学和遗传学研究强烈表明炎症和免疫在精神分裂症症状的发病机制中的作用。过去二十年来积累的证据表明，全身性炎症可以通过许多途径对大脑产生深远的影响，导致情绪，认知和行为的变化。外周免疫系统-脑通讯通路在抑郁症的背景下已经被广泛研究，其中炎性细胞因子被认为起着关键作用。在这篇综述中，我们强调了新的证据表明，外周免疫到大脑的通信途径在精神分裂症中的重要作用。我们讨论了最近基于人群的纵向研究，这些研究报告了循环炎性细胞因子水平升高与随后精神病风险之间的相关性。我们讨论了新出现的证据表明血脑屏障内皮细胞在外周免疫脑通讯中可能发挥重要作用，这可能与精神分裂症有关。根据临床和临床前研究，我们讨论了免疫介导的机制是否有助于解释精神分裂症的一些临床和病理生理学特征。我们讨论了这些发现的意义，在未来的诊断方法，治疗和研究。最后，指向与早期生活逆境的联系，我们考虑是否持续的低水平激活的先天免疫反应，由于胎儿或儿童发育受损，可能是一个共同的机制，潜在的高并发症之间的某些神经精神和身体疾病，如精神分裂症，抑郁症，心脏病和2型糖尿病。
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.