Cognitive-Behavioral Therapy and Glutamate in Cingulate Gyrus in OCD

描述（由申请人提供）：本研究将描述强迫症（OCD）症状背后重要脑回路的神经化学异常，以及认知行为疗法（CBT）的效果。这些代谢物生物标记物的鉴定将为转化临床研究提供重要的基础，以最大限度地提高CBT减轻症状的能力，并设计针对该疾病核心特征的药物，这对那些对CBT无反应或有机会接受CBT的患者尤其重要。这与NIMH的战略计划有关，该计划旨在促进在大脑中发现精神障碍的原因，并将有助于为开发新的更好的干预措施奠定基础，这些干预措施将精神疾病患者的不同需求和情况结合起来。强迫症是一种经常致残的慢性精神疾病，影响着大约2%的世界人口。大多数患者对目前的治疗反应不完全，许多患者根本没有反应。CBT是一种心理疗法，是治疗强迫症最有效的方法之一，但其作用机制尚不完全清楚。本研究的目的是利用神经影像学来了解神经回路中的神经代谢物异常与强迫症症状的关系，以及CBT如何影响这些症状。在强迫症中，扣带回的几个亚区被怀疑功能障碍，这是一个涉及相关神经回路的大脑区域。该提案将使用磁共振光谱成像（MRSI）来测量大脑代谢物的浓度，包括扣带中的谷氨酸（Glu）。谷氨酸是一种重要的兴奋性神经递质，被怀疑在强迫症中受到干扰。在本研究中，将对25名成年强迫症患者进行为期4周的每日CBT治疗前后的mri扫描。他们将与25名未经治疗的健康对照者进行比较，每隔4周扫描一次。第三组25名强迫症患者将在等待名单上的4周前后接受扫描，然后接受4周的CBT治疗，并在治疗完成后进行第三次扫描。该提案的具体目标是：1)确定强迫症患者和对照组扣带“情感”和“认知”亚区中Glu的水平是否不同；2)确定强迫症患者在CBT或候补名单后Glu是否发生变化，以及对照组在经过一段时间后是否发生变化；3)确定CBT前后Glu与强迫症临床及神经认知症状之间是否存在关系。

DESCRIPTION (provided by applicant): This study will characterize the neurochemical abnormalities in important brain circuits underlying obsessive-compulsive disorder (OCD) symptoms and the effects of cognitive-behavioral therapy (CBT). Identification of such metabolite biomarkers will provide an important foundation for translational clinical studies to maximize the ability of CBT to reduce symptoms and to design medications that target core features of the disease, which is particularly important for those who do not respond to, or have access to, CBT. This is relevant to the NIMH strategic plans to promote discovery in the brain of the causes of mental disorders and will help lay the foundation for the development of new and better interventions that incorporate the diverse needs and circumstances of people with mental illnesses. OCD is an often disabling and chronic psychiatric condition that affects approximately 2% of the world's population. Most patients respond only incompletely to current treatments and many do not respond at all. CBT, a form of psychotherapy, is one of the most effective treatments for OCD, yet its mechanism of action is not fully understood. The objective of this proposed study is to use neuroimaging to understand how neurometabolite abnormalities in neural circuits relate to OCD symptoms, and how these are affected by CBT. In OCD, dysfunction is suspected in several subregions of the cingulate gyrus, a brain region involved in relevant neural circuits. This proposal will use magnetic resonance spectroscopic imaging (MRSI) to measure concentrations of brain metabolites, including glutamate (Glu), in the cingulate. Glu is an important excitatory neurotransmitter that is suspected to be disturbed in OCD. In this proposal, MRSI scans will be performed on 25 adult OCD patients before and after 4 weeks of daily CBT. They will be compared to 25 untreated healthy controls scanned 4 weeks apart. A third group of 25 OCD patients will be scanned before and after 4 weeks while on the waitlist, will then receive 4 weeks of CBT, and will be scanned a third time at its completion. The specific aims of this proposal are: 1) Determine if levels of the Glu in the "emotional" and "cognitive" subregions of the cingulate differ between OCD patients and controls; 2) Determine if Glu changes after CBT or waitlist in the OCD patients and if they change in the controls after simple passage of time; 3) Determine if there are relationships between Glu and clinical and neurocognitive symptoms of OCD before and after CBT.