Linear and non-linear brain changes over the transition to psychosis

在过去的十年里，人们对研究一群患有精神分裂症等精神疾病的超高风险的年轻人产生了极大的兴趣。由于症状和个人或家族史的结合，这些人的风险大大增加，事实上，大约20%的人在被发现后的12个月内发展为精神病。现在很清楚，与没有风险的类似参与者相比，这些风险病例的大脑存在差异，并且这些大脑差异随着精神病的发作而变得更大。我们不知道的是，这些变化是在什么时候发生的。例如，这些变化可能发生在症状增加之前（并以某种方式导致症状增加），这意味着试图阻止这些大脑变化可以预防疾病。在这项研究中，我们试图找出这些大脑变化的确切时间。我们将招募一批精神病风险极高的年轻人作为样本，在一年的时间里，每个月左右扫描他们的大脑。通过比较那些患有精神病的人和那些没有患精神病的人之间大脑变化的轨迹，我们希望能够确定症状进展与大脑结构变化之间的关系。我们还旨在表明，在这段时间内，变化的速度各不相同，并且在从“高危”到首次精神病发作的过渡期间，变化发生得更快。研究人员面临的另一个问题是如何提高对最终发展为精神病的人的预测，因为目前有非常高的假阳性率，他们可能会受到不必要的治疗和耻辱。最近的一种方法是在复杂的统计分析中使用大脑扫描，这将预测从大约20%提高到80%。然而，这只使用了一个时间点。在这项研究中，我们将探讨什么额外的预测能力，可以从包括纵向扫描。这种方法已经用于帮助预测轻度认知障碍患者的痴呆症发作，但尚未应用于有精神病风险的人。

In the past decade there has been great interest in studying a group of young people at ultra high risk for psychotic illnesses such as schizophrenia. These people are at hugely increased risk because of a combination of symptoms and personal or family history, and indeed around 20% of them develop psychosis within 12 months of being identified. It is now clear that there are differences in the brains of these at-risk cases when compared to similar participants not at risk, and that these brain differences get greater with the onset of psychotic illness. What we still do not know is when these changes occur during the progression. For example, it could be that the changes come before (and somehow cause) the increase in symptoms, which would imply that trying to prevent those brain changes could prevent the illness. In this study, we are proposing to try to find out the exact timing of these brain changes. We will do this by recruiting a sample of young people at ultra high risk of psychosis, and scanning their brains every month or so for a year. By comparing the trajectory of brain changes between those who do and those who do not develop psychosis, we hope to be able to determine the relationship between progression of symptoms and alterations in brain structure. We also aim to show that the rate of change varies across this period, and that the changes happen much faster during the period of transition from being 'at-risk' to having a first psychotic episode.A further issue for researchers is how to improve the prediction of who eventually develops psychosis, since there are currently a very high number of false positives who are potentially exposed to unnecessary treatment and stigma. One recent approach has been to use brain scans in complex statistical analyses, and this has improved the prediction from around 20% to 80%. However, this has only used a single time point. In this study we will explore what additional predictive power can be obtained from including longitudinal scans. This approach is already used to help predict the onset of dementia in people with mild cognitive impairment, but has not yet been applied to people at risk for psychosis.