Leboyer Marion, Oliveira José, Tamouza Ryad, Groc Laurent
Université Paris-Est, INSERM U955, Laboratoire Psychiatrie Translationnelle, et AP-HP, DHU Pe-PSY, Pole de Psychiatrie et d'addictologie des Hôpitaux Universitaires Henri Mondor, et fondation FondaMental, F-94000, Créteil, France.
Pôle de Psychiatrie, Hôpital Albert Chenevier, 40 rue de Mesly, 94000, Créteil, France.
Psychopharmacology (Berl). 2016 May;233(9):1651-60. doi: 10.1007/s00213-016-4266-1. Epub 2016 Mar 18.
Immune dysregulation is suggested to play an important aetiological role in schizophrenia (SZ) and bipolar disorder (BD) potentially driving neurodevelopmental pathways. Immune dysfunction may precede the onset of psychiatric disorders and parallel the development of multiaxial comorbidity, including suicidal behaviour and metabolic and autoimmune disorders. Depicting the source of the chronic low-grade inflammatory component in SZ and BD is thus a research priority. Strong environmental insults early in life, such as infections, acting on a background of genetic vulnerability, may induce potent and enduring inflammatory responses setting a state of liability to second-hit environmental encounters, namely childhood trauma, drug abuse or additional infectious exposures. The immunogenetic background of susceptibility, suggested to be not only lying within the HLA locus but also implicating inherited deficits of the innate immune system, may amplify the harmful biological effects of infections/psychosocial stress leading to the manifestation of a broad range of psychiatric symptoms.
The present review aims to discuss the following: (i) biological arguments in favour of a chronic low-grade inflammation in SZ and BD and its potential origin in the interaction between the immunogenetic background and environmental infectious insults, and (ii) the consequences of this inflammatory dysfunction by focusing on N-methyl-D-aspartate (NMDA) receptor antibodies and activation of the family of human endogenous retroviruses (HERVs).
Specific therapeutic approaches targeting immune pathways may lead the way to novel personalized medical interventions, improvement of quality of life and average life expectancy of psychiatric patients, if not even prevent mood episodes and psychotic symptoms.
免疫失调被认为在精神分裂症（SZ）和双相情感障碍（BD）的病因学中起着重要作用，可能驱动神经发育途径。免疫功能障碍可能先于精神疾病的发作，并与多轴共病的发展并行，包括自杀行为以及代谢和自身免疫性疾病。因此，描述SZ和BD中慢性低度炎症成分的来源是一项研究重点。生命早期强烈的环境刺激，如感染，作用于遗传易感性背景下，可能诱发强烈且持久的炎症反应，使个体易于遭受二次环境刺激，即童年创伤、药物滥用或额外的感染暴露。易感性的免疫遗传背景，被认为不仅存在于HLA基因座内，还涉及先天免疫系统的遗传缺陷，可能会放大感染/心理社会压力的有害生物学效应，导致广泛的精神症状表现。
本综述旨在讨论以下内容：（i）支持SZ和BD中存在慢性低度炎症及其在免疫遗传背景与环境感染性刺激相互作用中潜在起源的生物学依据，以及（ii）通过关注N-甲基-D-天冬氨酸（NMDA）受体抗体和人类内源性逆转录病毒（HERV）家族的激活来探讨这种炎症功能障碍的后果。
针对免疫途径的特定治疗方法可能会引领新型个性化医疗干预的方向，改善精神科患者的生活质量和平均预期寿命，甚至可能预防情绪发作和精神症状。
