Cognitive-Behavioral Therapy & Glutametergic Neurometabolites in Pediatric OCD

描述(申请人提供)：强迫症(OCD)是一种慢性精神疾病，通常致残，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)，但我们并不真正知道CBT在大脑中是如何发挥作用的。这项提议的长期目标是使用神经成像来了解大脑的哪些部分受到CBT的影响，以及涉及大脑的哪些化学系统。这些知识可能有助于临床医生确定哪些患者更适合使用药物治疗，哪些患者使用CBT治疗更好。这与美国国立卫生研究院延长健康寿命、减轻疾病和残疾负担的使命高度相关。这项提议将使用磁共振光谱成像(MRSI)的非侵入性神经成像技术。核磁共振成像同时测量多个大脑区域中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，缩写为“GLX”)对神经传递和细胞能量需求特别重要，怀疑在强迫症中受到干扰。这项提议将重点放在一个名为“情绪焦虑抑郁回路”的大脑结构网络结构上。在强迫症患者中，怀疑构成这个回路的几个结构存在功能障碍。在这项提议中，将对30名患有强迫症的儿童或青少年每人进行两次MRSI扫描，一次是在CBT之前，一次是在CBT每周12次疗程之后。他们将与第二组30名健康对照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之前和之后没有接受任何治疗。第三组30名强迫症儿童和青少年将在8周前和8周后接受扫描，而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CBT，并将在12周疗程结束后接受第三次扫描。所有小组还将在每个时间点接受临床和神经认知测试。这项建议的具体目的是：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的水平是否不同；2)测定强迫症患者CBT后和等待名单后回路中的GLX水平，以及对照组在简单时间过去后是否发生变化；3)确定三组患者在CBT前后或简单等待前后神经认知测试分数的变化与GLX水平变化之间是否存在关系。如果成功，这项提议将确定未经治疗的强迫症儿童情绪焦虑抑郁回路中的GLX水平是否异常，以及这些水平是否随着CBT的反应而变化。如果后者是真的，这将帮助神经科学家和临床医生确定CBT在大脑中的哪个部位起作用。这些数据可能与未来改善强迫症治疗和个体化治疗匹配的努力相关。与公共卫生相关：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。这种不完整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。这项建议旨在更好地了解认知行为疗法(CBT)的脑机制，以开发新的疗法，并提高现有疗法的成功率。

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.