Lennox Belinda R, Palmer-Cooper Emma C, Pollak Thomas, Hainsworth Jane, Marks Jacqui, Jacobson Leslie, Lang Bethan, Fox Hannah, Ferry Berne, Scoriels Linda, Crowley Hannah, Jones Peter B, Harrison Paul J, Vincent Angela
Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
Lancet Psychiatry. 2017 Jan;4(1):42-48. doi: 10.1016/S2215-0366(16)30375-3. Epub 2016 Dec 8.
Psychosis is a common presenting feature in antibody-mediated encephalitis, for which prompt recognition and treatment usually leads to remission. We aimed to investigate whether people with circumscribed schizophrenia-like illnesses have such antibodies-especially antibodies against the N-methyl-D-aspartate receptor (NMDAR)-more commonly than do healthy controls.
We recruited patients aged 14-35 years presenting to any of 35 mental health services sites across England with first-episode psychosis, less than 6 weeks of treatment with antipsychotic medication, and a score of 4 or more on at least one selected Positive and Negative Syndrome Scale (PANSS) item. Patients and controls provided venous blood samples. We completed standardised symptom rating scales (PANSS, ACE-III, GAF) at baseline, and tested serum samples for antibodies against NMDAR, LGI1, CASPR2, the GABA receptor, and the AMPA receptor using live cell-based assays. Treating clinicians assessed outcomes of ICD diagnosis and functioning (GAF) at 6 months. We included healthy controls from the general population, recruited as part of another study in Cambridge, UK.
Between Feb 1, 2013, and Aug 31, 2014, we enrolled 228 patients with first-episode psychosis and 105 healthy controls. 20 (9%) of 228 patients had serum antibodies against one or more of the neuronal cell surface antibodies compared with four (4%) of 105 controls (unadjusted odds ratio 2·4, 95% CI 0·8-7·3). These associations remained non-significant when adjusted for current cigarette smoking, alcohol consumption, and illicit drug use. Seven (3%) patients had NMDAR antibodies compared with no controls (p=0·0204). The other antibodies did not differ between groups. Antibody-positive patients had lower PANSS positive, PANSS total, and catatonia scores than did antibody-negative patients. Patients had comparable scores on other PANSS items, ACE-III, and GAF at baseline, with no difference in outcomes at 6 months.
Some patients with first-episode psychosis had antibodies against NMDAR that might be relevant to their illness, but did not differ from patients without NMDAR antibodies in clinical characteristics. Our study suggests that the only way to detect patients with these potentially pathogenic antibodies is to screen all patients with first-episode psychosis at first presentation.
Medical Research Council.
精神病是抗体介导性脑炎常见的临床表现，对此类疾病的迅速识别与治疗通常可使其缓解。我们旨在研究患有局限性精神分裂症样疾病的患者是否比健康对照人群更普遍地存在此类抗体，尤其是抗N-甲基-D-天冬氨酸受体（NMDAR）抗体。
我们招募了年龄在14至35岁之间，在英格兰35个心理健康服务机构中的任何一个就诊的首次发作精神病患者，这些患者接受抗精神病药物治疗少于6周，且在至少一项选定的阳性和阴性症状量表（PANSS）项目上得分达到4分或更高。患者和对照者均提供静脉血样本。我们在基线时完成标准化症状评定量表（PANSS、ACE-III、GAF），并使用基于活细胞的检测方法检测血清样本中抗NMDAR、LGI1、CASPR2、GABA受体和AMPA受体的抗体。治疗医生在6个月时评估ICD诊断结果和功能（GAF）。我们纳入了来自英国剑桥另一项研究的普通人群中的健康对照者。
在2013年2月1日至2014年8月31日期间，我们招募了228例首次发作精神病患者和105名健康对照者。228例患者中有20例（9%）血清中存在针对一种或多种神经元细胞表面抗体，而105名对照者中有4例（4%）存在此类抗体（未调整比值比2.4，95%置信区间0.8 - 7.3）。在对当前吸烟、饮酒和非法药物使用情况进行调整后，这些关联仍无统计学意义。7例（3%）患者存在NMDAR抗体，而对照者中无此情况（p = 0.0204）。其他抗体在两组之间无差异。抗体阳性患者的PANSS阳性、PANSS总分和紧张症得分低于抗体阴性患者。患者在基线时其他PANSS项目、ACE-III和GAF的得分相当，6个月时的结果无差异。
一些首次发作精神病患者存在可能与其疾病相关的抗NMDAR抗体，但在临床特征上与无NMDAR抗体的患者并无差异。我们的研究表明，检测这些潜在致病抗体携带者的唯一方法是在首次就诊时对所有首次发作精神病患者进行筛查。
医学研究理事会
