Schizophrenia no longer has clinically defined subsets as they became too difficult to accurately diagnose. In this study, the authors explore a novel and innovative way to use biology to identify subsets of schizophrenia.

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The situation

精神分裂症是一种慢性精神障碍，在青春期表现出来，通常会导致一生的损害和永久残疾。精神分裂症的特征是从幻觉到缺乏动力到缺乏注意力的症状广泛症状。这些不同的疾病进展过程表明精神分裂症的潜在生物学原因的异质性。

问题

尽管经过数十年的科学努力，精神分裂症仍缺乏客观的生物学诊断测试。取而代之的是，精神分裂症的诊断仍然完全依赖于患者和临床精神科医生之间的主观临床访谈。

This creates a problem–how can the underlying biology of schizophrenia be investigated when the investigation begins with an inherently non-biological concept: a subjective clinical diagnosis?

问题is further exacerbated by the method of classification. There are no clinically approved subsets of schizophrenia. Therefore, even if significant biological findings in a small subset of schizophrenia are discovered, they will be diluted, because they are pooled with all clinical cases of the disease.

但是，如果从临床诊断开始过于广泛，并且在生物学上不准确，那么我们如何检测精神分裂症的亚群？

The solution

在our recent study在Translational Psychiatry，我们努力解决由主观和客观的相互作用创建的捕获-22。我们首先设计一种动物模型，该模型表现出类似于精神分裂症患者的症状，即大脑中某些细胞信号通路的破坏。

我们决定专注于一种叫做“中断的蛋白质-in-schizophrenia 1’ (DISC1). DISC1 is a hub protein critical to neuronal development and the maintenance of adult nerve connections (synapses). We genetically engineered a rat model where the DISC1 protein was dysfunctional.

The transgenic rat displayed abnormal behavior, incorrect neuronal connections, and an imbalance of neurotransmitters–all symptoms reminiscent of behavioral disorders like schizophrenia.

通过具有与精神分裂症患者相同异常信号网络的动物模型武装，我们确定了模型中的独特血液标记，因为这些相同的血液标记可能会识别出精神分裂症患者可能会扰乱相似的分子途径的地方。从那里开始，我们将能够对患者进行独立于临床诊断的分层。

我们通过研究差异基因表达细胞，发现它们属于免疫相关基因的较大，失调的网络，从而确定了大鼠模型中的这种血液标记。当我们在两名独立的精神分裂症患者中测试最高标记（称为RGS1和CCL4）时，两个同龄人中它们均同样减少。

在代表失调的免疫网络的这两个标记的帮助下，我们最终可以确定25％的临床定义精神分裂症患者的子集，具有97％的特异性。换句话说，通过使这种免疫相关基因网络失调，我们能够确定定义精神分裂症的子集。

Next steps

Our study presents a unique pairing of an animal model for a subset of schizophrenia and a blood test for identifying the corresponding patient subset. The schizophrenia subset we identified might display similar biological irregularities as the corresponding animal model. If these irregularities correspond, the study of the animal model may allow for the development of causal pharmacotherapies effective in this specific schizophrenia patient subset. Our study illustrates a novel and innovative way to identify subsets of mental illness patients by reverse translation, potentially opening the door to a huge change in the diagnostic culture in clinical psychiatry.

Enjoyed this blog post? Read the full article inTranslational Psychiatry。