Multimodal Imaging of the Mesocortical System in Anorexia Nervosa

描述（由申请人提供）：神经性厌食症（AN）是一种严重的疾病，发病率和死亡率在任何精神疾病中都是最高的。疾病通常发生在青春期，目前的治疗方法令人失望，高达50%的患者在出院后一年内需要再次住院。共病率很高，高达66%的人同时患有强迫症（OCD）。我们之前根据已知的强迫症机制提出了AN的神经行为模型，表明皮质纹状体异常，包括中皮层系统（MCS），是AN的高度强迫性特征的基础，而这种特征反过来又介导了僵化、仪式化的饮食行为，从而促进了体重过轻的状态。MCS包括腹侧纹状体（VS）和眶额皮质（OFC）。在初步实验中，我们成功地使用了一种新的静息状态功能连接MRI （rs-fcMRI）方法来证明MCS的功能连接与强迫症患者的强迫症状之间存在反比关系。我们的早期数据在AN中也表明了这一发现。在本提案中，我们正在研究一种以前未应用于AN的多模式策略。我们将检查功能连通性（通过rs-fcMRI）和白质完整性（通过DTI），并探索灌注（通过ASL）。通过结合成像方法，我们将整合功能和结构的连通性。我们建议研究AN急性期和体重恢复后的神经回路，以开始评估这些结果的预后意义和稳定性。具体而言，我们将评估AN患者与健康同龄人相比，是否有腹侧纹状体（VS）和眶额皮质（OFC）之间的功能连通性降低（rs-fcMRI测量），白质完整性降低（以眶额白质分数各向异性（FA）降低为指标），VS和OFC的灌注减少。我们将测量MCS连接是否与强迫症状的程度相关，使用饮食失调特定的强迫测量。我们将纵向研究连通性，在急性治疗前后评估AN患者。此外，我们将收集初步数据，以调查这种潜在的生物标志物与长期病程之间的关系。本研究采用了一种创新的方法来研究an，通过关注MCS，并通过在该领域实施新的神经成像技术。这种方法在整体评估神经回路方面具有显著的优势，从而提高了对神经功能的推断。这项研究将为在大规模R01中使用这些技术奠定基础，这将能够明确地识别神经生物标志物，并将神经影像学与临床结果相结合。因此，这项研究的数据将为AN研究项目提供新的基础，该项目研究神经模型，作为理解和治疗这种毁灭性疾病的基础。

DESCRIPTION (provided by applicant): Anorexia nervosa (AN) is a serious illness associated with substantial morbidity and a mortality rate among the highest of any psychiatric illness. Illness commonly develops in adolescence, and current treatments are disappointing, with up to 50% of patients requiring re-hospitalization within a year of discharge. Comorbidity rates are high, with up to 66% of individuals also suffering from obsessive compulsive disorder (OCD). We have previously proposed a neurobehavioral model of AN, building from known mechanisms of OCD, suggesting that corticostriatal abnormalities, including the mesocortical system (MCS), underlie the highly obsessional characteristic of AN which, in turn, mediates rigid, ritualized eating behaviors that promote the underweight state. The MCS includes the ventral striatum (VS), and the orbitofrontal cortex (OFC). In a preliminary experiment, we successfully used a novel resting state functional connectivity MRI (rs-fcMRI) approach to demonstrate an inverse relationship between functional connectivity in the MCS and obsessional symptoms in individuals with OCD. Our early data suggest this finding in AN, as well. In this proposal, we are investigating a multimodal strategy that has not previously been applied to AN. We will examine functional connectivity (via rs-fcMRI) and white matter integrity (via DTI) and explore perfusion (via ASL). By combining imaging approaches, we will integrate functional and structural connectivity. We propose to study neurocircuitry in the acute phase of AN as well as after weight restoration to begin to evaluate the prognostic significance and stability of these findings. Specifically, we will evaluate whether individuals with AN, as compared with healthy peers, have reduced functional connectivity between the ventral striatum (VS) and orbitofrontal cortex (OFC) as measured by rs-fcMRI, reduced white matter integrity, as indexed by reduced fractional anisotropy (FA), in the orbitofrontal white matter, and reduced perfusion to the VS and OFC. We will measure whether MCS connectivity is associated with degree of obsessional symptoms, using an eating disorder specific obsessive-compulsive measure. We will study connectivity longitudinally, evaluating individuals with AN before and after acute treatment. In addition, we will collect preliminary data to investigate the relationshp between this potential biomarker and longer-term course. The proposed study takes an innovative approach to the study of AN by focusing on the MCS, and by implementing new neuroimaging techniques for the field. This approach has the significant advantage of evaluating the neural circuit as a whole, thereby improving inferences about neural functioning. This study will create a foundation for using these techniques in a large scale R01 that will be able to definitively identify neural biomarkers and integrate neuroimaging with clinical outcome. Thus the data from this study will provide a new foundation for a program of research in AN that investigates neural models as the basis for understanding and treating this devastating illness.