National Institute for Health Research (NIHR) Biomedical Research Centre, South London and Maudsley NHS FoundationTrust and Institute of Psychiatry, King's College London,UK.
Department of Immunobiology,King's College London,UK.
Psychol Med. 2014 Sep;44(12):2475-87. doi: 10.1017/S003329171300295X. Epub 2013 Dec 13.
Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune condition caused by immunoglobulin (Ig)G antibodies directed against the NR1 subunit of the NMDA glutamate receptor. Approximately 65% of cases present with psychiatric symptoms, particularly psychosis. It remains to be established whether anti-NMDA receptor antibodies can cause a 'purely' psychotic illness without overt neurological symptoms.
We conducted a systematic literature search to establish what proportion of patients with schizophrenia and related psychoses have antibodies directed against the NMDA receptor. Studies were included if (a) subjects had a diagnosis of schizophrenia, schizophrenia spectrum disorder or first-episode psychosis (FEP) using standard criteria, (b) serum was analysed for the presence of anti-NMDA receptor antibodies; and (c) the purpose of the study was to look for the presence of anti-NMDA receptor antibodies in patients with a primary psychiatric diagnosis without clinical signs of encephalitis.
Seven studies were included, comprising 1441 patients, of whom 115 [7.98%, 95% confidence interval (CI) 6.69-9.50] were anti-NMDA receptor antibody positive. Of these, 21 (1.46%, 95% CI 0.94-2.23) patients were positive for antibodies of the IgG subclass. Prevalence rates were greater in cases than controls only for IgG antibodies; other subclasses are of less certain aetiological relevance. There was significant heterogeneity in terms of patient characteristics and the antibody assay used.
A minority of patients with psychosis are anti-NMDA receptor antibody positive. It remains to be established whether this subset of patients differs from antibody-negative patients in terms of underlying pathology and response to antipsychotic treatment, and whether immunomodulatory treatments are effective in alleviating psychotic symptoms in this group.
抗 N-甲基-D-天冬氨酸（NMDA）受体脑炎是一种由免疫球蛋白（IgG）抗体针对 NMDA 谷氨酸受体 NR1 亚基引起的自身免疫性疾病。约 65%的病例表现出精神症状，特别是精神病。尚未确定抗 NMDA 受体抗体是否会在没有明显神经症状的情况下导致“纯粹”的精神病。
我们进行了系统的文献检索，以确定有多少精神分裂症和相关精神病患者具有针对 NMDA 受体的抗体。如果符合以下标准，则纳入研究：（a）使用标准标准诊断为精神分裂症、精神分裂症谱系障碍或首发精神病（FEP）；（b）分析血清中是否存在抗 NMDA 受体抗体；（c）研究的目的是在没有脑炎临床迹象的情况下寻找原发性精神病诊断患者中抗 NMDA 受体抗体的存在。
纳入了 7 项研究，共 1441 名患者，其中 115 名（7.98%，95%置信区间[CI]为 6.69-9.50）为抗 NMDA 受体抗体阳性。其中，21 名（1.46%，95%CI 为 0.94-2.23）患者为 IgG 亚类抗体阳性。仅 IgG 抗体在病例中比对照组的阳性率更高；其他亚类的病因相关性不太确定。患者特征和使用的抗体检测方法存在显著异质性。
少数精神病患者抗 NMDA 受体抗体阳性。这部分患者在潜在病理和抗精神病治疗反应方面是否与抗体阴性患者不同，以及免疫调节治疗是否能有效缓解该组患者的精神病症状，仍有待确定。
