Cognitive-Behavioral Therapy & Glutametergic Neurometabolites in Pediatric OCD

描述（由申请人提供）：强迫症（OCD）是一种慢性且经常致残的精神疾病，影响2-4%的儿童和青少年。强迫症最有效的治疗方法之一是认知行为疗法（CBT），但我们并不真正了解CBT在大脑中的作用。这项提议的长期目标是利用神经成像来了解大脑的哪些部分受到CBT的影响，以及大脑的哪些化学系统参与其中。这些知识可以帮助临床医生确定哪些患者更适合药物治疗，哪些更适合CBT治疗。这与美国国立卫生研究院延长健康寿命、减少疾病和残疾负担的使命高度相关。本提案将使用无创神经成像技术磁共振光谱成像（MRSI）。核磁共振成像同时测量大脑多个区域几种神经代谢物的浓度。代谢物谷氨酸和谷氨酰胺（一起测量并缩写为“Glx”）对神经传递和细胞能量需求特别重要，被怀疑在强迫症中受到干扰。这项提议将把重点放在一个被称为“情绪-焦虑-抑郁回路”的大脑结构网络上。在强迫症患者中，该回路的几个结构可能存在功能障碍。在这项建议中，将对30名患有强迫症的儿童或青少年每人进行两次核磁共振成像扫描，一次是在每周12次的CBT课程之前，一次是在之后。他们将与第二组30名未接受治疗的健康儿童和青少年进行比较，这些儿童和青少年在相同的时间间隔前后进行扫描。第三组30名强迫症儿童和青少年将在8周之前和之后接受扫描，他们只是在我们的临床治疗等待名单上等待治疗。8周结束后，他们也将接受认知行为治疗，并在12周疗程结束后进行第三次扫描。所有组在每个时间点还将进行临床和神经认知测试。本提案的具体目的是：1)确定强迫症患者和对照组之间情绪-焦虑-抑郁回路中代谢物Glx的水平是否存在差异；2)确定强迫症患者在CBT后和等待名单后脑回路中Glx水平的变化，以及对照组中Glx水平在一段时间后是否发生变化；3)判断三组患者在CBT前后或单纯等待前后的Glx水平变化与神经认知测试得分变化之间是否存在关系。如果成功，这一建议将确定情绪-焦虑-抑郁回路中的Glx水平是否在未经治疗的强迫症儿童中异常，以及这些水平是否在CBT反应中发生变化。如果后者是真的，那将有助于神经科学家和临床医生确定CBT在大脑的哪个部位起作用。这些数据可能与未来改善强迫症治疗和个体治疗匹配的努力有关。公共卫生相关性：强迫症（OCD）有有效的治疗方法，但即使有最好的治疗方法，大多数患者也只能部分恢复，许多患者根本没有充分的反应。这种不完全和不充分的应对措施在发病率和病人护理费用方面造成了更大的公共卫生成本。本研究旨在更好地了解认知行为治疗（CBT）的脑机制，以开发新的治疗方法并提高现有治疗方法的成功率。

DESCRIPTION (provided by applicant): Obsessive-Compulsive Disorder (OCD) is a chronic and often disabling psychiatric condition, affecting 2-4% of children and adolescents. One of the most effective treatments for OCD is Cognitive-Behavioral Therapy (CBT), yet we do not really know how CBT works in the brain. The long-term objective of this proposal is to use neuroimaging to understand what parts of the brain are affected by CBT and which of the chemical systems of the brain are involved. Such knowledge may help clinicians identify which patients are better to treat with drugs and which with CBT. This is highly relevant to the NIH mission to extend healthy life and reduce the burdens of illness and disability. This proposal will use the noninvasive neuroimaging technique of Magnetic Resonance Spectroscopic Imaging (MRSI). MRSI measures the concentrations of several neurometabolites in multiple brain regions simultaneously. The metabolites glutamate and glutamine (measured together and abbreviated as "Glx") are particularly important for neurotransmission and cell energy requirements and are suspected to be disturbed in OCD. This proposal will focus on a network of brain structures called the "emotion-anxiety depression circuit". In OCD patients, dysfunction is suspected in several structures comprising this circuit. In this proposal, MRSI scans will be performed twice on each of 30 children or adolescents with OCD, once before and once after a course of 12 weekly sessions of CBT. They will be compared to a second group of 30 healthy control children and adolescents who receive no treatment scanned before and after a comparable time interval. A third group of 30 OCD children and adolescents will be scanned before and after 8 weeks while they are simply waiting for treatment on our clinical treatment waitlist. After their 8 weeks are up, they, too, will receive CBT and will be scanned a third time after the 12 weekly sessions are done. All groups will also undergo clinical and neurocognitive testing at each time point. The specific aims of this proposal are: 1) Determine if levels of the metabolite Glx in the emotion-anxiety depression circuit differ between OCD patients and controls; 2) Determine levels of Glx in the circuit change after CBT and after waitlist in the OCD patients and if they change after simple passage of time in the controls; 3) Determine if there is a relationship between changes in scores on neurocognitive testing and changes in Glx levels in the three groups before and after CBT or before and after simply waiting. If successful, this proposal will establish whether Glx levels in the emotion-anxiety depression circuit are abnormal in untreated children with OCD and whether these levels change in response to CBT. If the latter is true, that will help neuroscientists and clinicians determine where in the brain CBT has its effects. Such data may be relevant to future efforts to improve OCD treatment and individual treatment matching. PUBLIC HEALTH RELEVANCE: There are effective treatments for obsessive-compulsive disorder (OCD) but even with the best available treatment most patients enjoy only partial recovery and many patients do not respond adequately at all. Such incomplete and inadequate response contributes to greater public health costs in terms of morbidity and patient care expenses. This proposal aims for a better understanding of the brain mechanisms of cognitive-behavioral therapy (CBT) in order to develop novel therapies and improve the success of existing therapies.