Why do not all high schizotypes develop schizophrenia? Protective factors in people with high risk for schizophrenia using machine learning methods

精神分裂症是一种病因不明的严重精神疾病。寻找病因的一个重要步骤是认识到精神分裂症并不代表突然发病的双重表型(存在或不存在)。相反，越来越多的人同意正常人群和患者之间的连续性发挥着重要作用。许多发现指出精神分裂症和分裂型人格特征在现象学、遗传学、认知和神经方面的相似之处。然而，鉴于这种重叠，仍然存在一个重要的问题：为什么大多数分裂类型水平较高的人不会患上精神分裂症？这个问题立即引出了一个相关的问题：高度分裂型但临床未受影响的个体与精神分裂症患者之间在神经和认知方面的差异是什么？换句话说，阻止高分裂类型精神分裂症爆发的神经机制(如韧性)尚不清楚。本研究旨在首次使用机器学习方法系统地研究这些机制。除了表征神经机制外，我们还将评估环境风险因素，并获得精神分裂症的多基因风险评分，以调查这些变量与分裂型和大脑结构和功能的关系。

Schizophrenia is a severe psychiatric illness with unknown aetiology. An important step in the search for aetiological factors has been the realisation that schizophrenia does not represent a binary phenotype (present, absent) with sudden disease onset. Instead, there is growing agreement that continua between normal and patient populations play an important role. Numerous findings point to phenomenological, genetic, cognitive and neural similarity between schizophrenia and the personality trait of schizotypy. Given this overlap there remains, however, an important question: Why do most people with high levels of schizotypy do not develop schizophrenia? This question leads immediately to a related problem: What are the neural and cognitive differences between highly schizotypal but clinically unaffected individuals and patients with schizophrenia? Put differently, the neural mechanisms (e.g. of resilience) that prevent the outbreak of schizophrenia in high schizotypes are unknown. The present study aims to systematically investigate these mechanisms, for the first time, using machine learning methods. In addition to characterising neural mechanisms we will also assess environmental risk factors and we will obtain a polygenic risk score for schizophrenia in order to investigate the association of these variables with schizotypy and brain structure and function.