MRI measures of brain structure and function as predictors of medium-term response to psychotherapy in adolescent MDD

青少年重度抑郁症（MDD）是NHS精神卫生服务的一个具有挑战性的优先事项，也是患者及其家人的一个困难经历。建议的治疗方法是心理治疗，如果没有立即的反应，可以结合抗抑郁药。不幸的是，目前还没有办法预测哪些病人最有可能对心理治疗有反应。这种不确定性部分源于我们对抑郁症是如何由对情绪状态及其意识控制很重要的大脑回路功能异常引起的不完全了解。我们想要研究的一个貌似合理的理论是，抑郁症状是由大脑某一部分（边缘系统）对负面事件或刺激的过度反应造成的，而大脑另一个不同但相互联系的区域（额叶皮质）的反应不活跃，无法有效控制抑郁症状。我们预测，在认知行为疗法（一种专注于改善情绪症状的有意识控制的心理疗法）之后，大脑额边缘网络的这种功能失衡可以正常化。我们还期望在治疗开始前测量额边缘脑网络结构和功能异常的程度可以预测患者的预后。一年半后对治疗的反应。为了验证这些预测，我们建议收集120名青少年重度抑郁症患者和40名健康青少年志愿者的大脑结构和功能的磁共振成像（MRI）测量结果。作为一项大型研究的一部分，所有患者将被随机分配到三种不同的心理治疗中，然后进行一次扫描。该研究已获得资助，旨在调查心理治疗对患有抑郁症的年轻人的临床效果。20周后，40名患者（和健康志愿者）也将接受第二次扫描。核磁共振扫描是一种无痛和安全的方法，可以获得关于人类大脑结构和功能的详细信息。本研究的设计和临床管理是通过仔细考虑青少年患者和志愿者的风险和收益来进行的。我们认为，使用现代大脑扫描技术来更好地理解和预测年轻人这种严重精神疾病的病程是及时和重要的，这项研究计划将安全有力地测试关键理论预测，以一种可以改善青少年抑郁症患者未来临床护理的方式。

Major depressive disorder (MDD) in adolescence is a challenging priority for NHS mental health services as well as being a difficult experience for the patient and their family. The recommended treatment is psychotherapy, which can be combined with antidepressants if there is no immediate response. Unfortunately, there is no way currently to predict which patients are most likely to respond to psychotherapy. This uncertainty stems in part from our incomplete knowledge of how depression is caused by abnormal function of brain circuits important for mood states and their conscious control. One plausible theory we want to investigate is that depressive symptoms result from an overactive response to negative events or stimuli in one part of the brain (the limbic system), which is not effectively controlled by an underactive response in a different but interconnected brain region (the frontal cortex). We predict that this functional imbalance in fronto-limbic brain networks can be normalised following cognitive behavioural therapy, a form of psychotherapy focused on improving conscious control of mood symptoms. We also expect that the extent of structural and functional abnormality measured in fronto-limbic brain networks before treatment begins can predict patients? responses to treatment up to one and a half years later.To test these predictions, we are proposing to collect magnetic resonance imaging (MRI) measurements of brain structure and function in 120 adolescent patients with MDD and 40 health adolescent volunteers. All of the patients will be scanned once before they are randomly assigned to one of three different kinds of psychological treatment as part of a larger study, already funded to investigate the clinical effectiveness of psychotherapy for young people with depression. Forty of the patients (and the healthy volunteers) will also be scanned on a second occasion 20 weeks later. MRI scanning is a painless and safe method of obtaining detailed information on the structure and function of the human brain. The design and clinical governance of this study has been informed by a careful consideration of the risks and benefits to adolescent patients and volunteers. We consider that it is timely and important to use modern brain scanning techniques to better understand and predict the course of this serious mental illness in young people and that this research proposal will safely and powerfully test key theoretical predictions in a way that could improve the future clinical care of adolescent patients with major depressive disorder.