Background

Antibodies against the N-methyl-D-aspartate receptor (NMDAR) have been described in the serum of people with schizophrenia spectrum disorders (schizophrenia). However, the prevalence and clinical relevance of these antibodies in schizophrenia is unclear. This knowledge gap includes the possibility of such antibodies being associated with a distinct clinical profile, which in turn might warrant a distinct treatment approach. We aimed to assess the seroprevalence of anti-NMDAR antibodies in schizophrenia, and compare symptoms and psychosocial functioning between patients with schizophrenia who were seropositive and seronegative for these antibodies.

Methods

In this case–control comparison, by combining new and existing studies, we included patients diagnosed with schizophrenia from four independent cohorts for whom anti-NMDAR serostatus had been assessed (or could be assessed by us) with live cell-based assays. Included cohorts were from the EULAST study (a trial conducted across 15 European countries and Israel), the OPTiMiSE study (an interventional study in Europe), and the PPiP1 and PPiP2 studies (conducted in the UK). Patients from these cohorts were analysed if they had complete Positive and Negative Syndrome Scale (PANSS) data. No participant had been diagnosed with autoimmune encephalitis or received treatment for this condition. After calculating the prevalence of serum anti-NMDAR antibodies, we examined possible differences in PANSS scores (negative, positive, and general symptom subscales, and total score) between anti-NMDAR-seropositive and anti-NMDAR-seronegative patients. Psychosocial functioning as measured by Personal Social Performance (PSP) score was also compared. All analyses were exploratory and no adjustment was done for multiple testing. People with lived experience were not involved in the conduct of this study.

Findings

We collected individual patient data from 1114 patients with schizophrenia across the four cohorts. The study population had a mean age of 28·6 years (SD 7·6) and comprised 382 (34·3%) women and 732 (65·7%) men, including patients of White (929 [83·4%]), Asian (54 [4·8%]), Black (68 [6·1%]), and other (62 [5·6%]) ethnicities. Overall, 41 (3·7%) participants (range 3·1–4·0% across cohorts) tested positive for serum anti-NMDAR antibodies. Lower symptom severity on the negative symptoms PANSS subscale was observed for anti-NMDAR-seropositive patients (mean score 15·8 [SD 6·4]) than for anti-NMDAR-seronegative patients (18·2 [6·8]; Cohen's d=0·36; p=0·026), as well as on the general symptoms PANSS subscale (32·9 [8·9] vs 36·1 [10·1]; d=0·33; p=0·029) and total PANSS score (65·5 [18·5] vs 72·6 [19·3]; d=0·37; p=0·013). Mean PSP score was better in anti-NMDAR-positive patients (62·0 [17·0]) than in anti-NMDAR-negative patients (53·5 [16·3]; d=0·52; p=0·014).

Interpretation

Serum NMDAR antibodies are present in 3–4% of patients with schizophrenia and are associated with relatively low severity of negative symptoms and relatively good psychosocial functioning. Thus, although the findings await replication in cohorts from other geographical regions, serum anti-NMDAR antibodies might be associated with a different form of psychotic illness. These findings could inform future prognostic and interventional studies examining whether anti-NMDAR antibodies are associated with a specific course of illness or with treatment response.

Funding

None.

中文翻译：

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抗 NMDAR 抗体血清阳性的精神分裂症谱系障碍患者的临床症状和社会心理功能：与检测阴性患者的病例对照比较

 背景

在精神分裂症谱系障碍（精神分裂症）患者的血清中已经描述了针对 N-甲基-D-天冬氨酸受体 （NMDAR） 的抗体。然而，这些抗体在精神分裂症中的患病率和临床相关性尚不清楚。这种知识差距包括此类抗体与不同的临床特征相关的可能性，这反过来可能需要不同的治疗方法。我们旨在评估精神分裂症中抗 NMDAR 抗体的血清阳性率，并比较这些抗体血清阳性和血清阴性的精神分裂症患者的症状和社会心理功能。

 方法

在这个病例对照比较中，通过结合新的和现有的研究，我们纳入了来自四个独立队列的诊断为精神分裂症的患者，这些患者的抗 NMDAR 血清状态已经用基于活细胞的测定进行了评估（或可以由我们评估）。纳入的队列来自 EULAST 研究（在 15 个欧洲国家和以色列进行的试验）、OPTiMiSE 研究（欧洲的一项干预性研究）以及 PPiP1 和 PPiP2 研究（在英国进行）。分析来自这些队列的患者是否具有完整的阳性和阴性症状量表 （PANSS） 数据。没有受试者被诊断出患有自身免疫性脑炎或接受这种疾病的治疗。在计算血清抗 NMDAR 抗体的患病率后，我们检查了抗 NMDAR 血清阳性和抗 NMDAR 血清阴性患者之间 PANSS 评分 （阴性、阳性和一般症状分量表以及总分） 的可能差异。还比较了通过个人社会表现 （PSP） 评分衡量的心理社会功能。所有分析都是探索性的，没有对多次测试进行调整。有生活经验的人没有参与这项研究的进行。

 发现

我们收集了四个队列中 1114 名精神分裂症患者的个体患者数据。研究人群的平均年龄为 28·6 岁 （SD 7·6），包括 382 名 （34·3%） 女性和 732 名 （65·7%） 男性，包括白人 （929 [83·4%]）、亚洲 （54 [4·8%]）、黑人 （68 [6·1%]） 和其他 （62 [5·6%]） 种族的患者。总体而言，41 名 （3·7%） 参与者（队列范围为 3·1–4·0%）血清抗 NMDAR 抗体检测呈阳性。在阴性症状 PANSS 分量表上观察到的症状严重程度低于抗 NMDAR 血清阳性患者 （平均评分 15·8 [SD 6·4]） （18·2 [6·8];科恩的 d=0·36;p=0·026），以及一般症状 PANSS 分量表 （32·9 [8·9] vs 36·1 [10·1];d=0·33;p=0·029）和总 PANSS 评分 （65·5 [18·5] vs 72·6 [19·3];d=0·37;p=0·013）。抗 NMDAR 阳性患者的平均 PSP 评分 （62·0 [17·0]）优于抗 NMDAR 阴性患者 （53·5 [16·3];d=0·52;p=0·014）。

 解释

血清 NMDAR 抗体存在于 3-4% 的精神分裂症患者中，并且与阴性症状的严重程度相对较低和相对良好的心理社会功能有关。因此，尽管这些发现有待在其他地理区域的队列中复制，但血清抗 NMDAR 抗体可能与不同形式的精神病有关。这些发现可以为未来的预后和介入研究提供信息，以检查抗 NMDAR 抗体是否与特定病程或治疗反应相关。

 资金

 没有。