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Abstract：
Recent psychoneuroimmunology research has provided new insight into the etiology and pathogenesis of severe mental disorders (SMDs). The mild encephalitis (ME) hypothesis was developed with the example of human Borna disease virus infection years ago and proposed, that a subgroup SMD patients, mainly from the broad schizophrenic and affective spectrum, could suffer from mild neuroinflammation, which remained undetected because hard to diagnose with available diagnostic methods. Recently, in neurology an emerging new subgroup of autoimmune encephalitis (AE) cases suffering from various neurological syndromes was described in context with the discovery of an emerging list of Central Nervous System (CNS) autoantibodies. Similarly in psychiatry, consensus criteria of autoimmune psychosis (AP) were developed for patients presenting with CNS autoantibodies together with isolated psychiatric symptoms and paraclinical findings of (mild) neuroinflammation, which in fact match also the previously proposed ME criteria. Nevertheless, identifying mild neuroinflammation in vivo in the individual SMD case remains still a major clinical challenge and the possibility that further cases of ME remain still under diagnosed appears an plausible possibility. In this paper a critical review of recent developments and remaining challenges in the research and clinical diagnosis of mild neuroinflammation in SMDs and in general and in transdisciplinary perspective to psycho-neuro-immunology and neuropsychiatry is given. Present nosological classifications of neuroinflammatory disorders are reconsidered with regard to findings from experimental and clinical research. A refined grading list of clinical states including \"classical\" encephalitis, AE, AP/ME,and newly proposed terms like parainflammation, stress-induced parainflammation and neuroprogression, and their respective relation to neurodegeneration is presented, which may be useful for further research on the possible causative role of mild neuroinflammation in SMDs. Beyond, an etiology-focused subclassification of ME subtypes, like autoimmune ME or infectious ME, appears to be required for differential diagnosis and individualized treatment. The present status of the clinical diagnosis of mild neuroinflammatory mechanisms involved in SMDs is outlined with the example of actual diagnosis and therapy in AP. Ideas for future research to unravel the contribution of mild neuroinflammation in the causality of SMDs and the difficulties expected to come to novel immune modulatory, anti-infectious or anti-inflammatory therapeutic principles in the sense of precision medicine are discussed.
摘要：
最近的心理神经免疫学研究为严重精神障碍（SMD）的病因和发病机制提供了新的见解。轻度脑炎（ME）假说是几年前以人类博尔纳病病毒感染为例提出的，一组SMD患者，主要来自广泛的精神分裂症和情感谱，可能患有轻度神经炎症，由于可用的诊断方法难以诊断，因此仍未发现。最近,在神经病学中,我们在发现一组新出现的中枢神经系统(CNS)自身抗体的背景下,描述了一个新出现的患有各种神经综合征的自身免疫性脑炎(AE)亚组.同样在精神病学中，自身免疫性精神病（AP）的共识标准是针对出现CNS自身抗体并伴有孤立的精神症状和（轻度）神经炎症的临床旁发现的患者。这实际上也符合先前提出的ME标准。然而，在单个SMD病例中确定体内轻度神经炎症仍然是一个主要的临床挑战，并且进一步的ME病例仍未被诊断的可能性似乎是合理的可能性。在本文中，对SMD中轻度神经炎症的研究和临床诊断以及心理神经免疫学和神经精神病学的一般和跨学科观点进行了严格的回顾。根据实验和临床研究的结果，重新考虑了目前对神经炎症性疾病的疾病分类。包括“经典”脑炎在内的临床状态的精细分级列表，AE,AP/ME,和新提出的术语，如副炎症，应激诱导的副炎症和神经进展，并介绍了它们各自与神经变性的关系，这可能有助于进一步研究SMD中轻度神经炎症的可能致病作用。超越,以病因学为重点的ME亚型分类，如自身免疫性ME或感染性ME，似乎需要鉴别诊断和个体化治疗。以AP的实际诊断和治疗为例，概述了与SMD有关的轻度神经炎症机制的临床诊断现状。未来研究的想法，以揭示轻度神经炎症在SMD因果关系中的贡献，以及预期新的免疫调节的困难，讨论了精准医学意义上的抗感染或抗炎治疗原则。
