Generalized Anxiety Disorder and Social Anxiety Disorder

在过去的12个月里，我们对广泛性焦虑症(GAD)和广泛性社交恐惧症(GSP)患者的工作中有一项特别突出。 病理性担忧是需求侧管理中GAD的定义特征。因此，了解广泛性焦虑症潜在的神经功能障碍可能是一个重要的治疗目标。然而，人们对焦虑的神经基础或它们如何在GAD患者的治疗过程中发生故障知之甚少。人们对一种可能被视为担忧的对立面的概念有了更多了解：乐观偏见(OB)。OB是大多数健康的人表现出来的，涉及到他们认为与普通人相比，他们不太可能经历负面的生活事件，但更有可能经历积极的生活事件。然而，在之前的行为研究中，我们发现GAD与对未来的OB减少(即现实观点)相关。具体地说，当我们要求参与者指出，与普通人相比，他们认为自己有多大可能经历一些积极的事情(例如，剪个漂亮的头发；中了彩票)或消极的事情(例如，剪得不好的发型；心脏病发作)，GAD患者不太可能乐观。今年的一个目标是使用功能磁共振成像来确定GAD患者这种认知损害的神经基础，并确定这种损害是否特定于GAD而不是GSP。 与之前的工作一致，健康的参与者表现出显著的OB；他们认为自己未来经历负面事件的可能性显著降低，但相对于其他人而言，他们显著更有可能经历未来的积极事件。这在普惠制中也可以看到。然而，广泛性焦虑症患者并未表现出明显的OB。在神经水平上，与GAD组相比，健康组和GSP组的OB与内侧前额叶皮质(RmPFC)的调节显著相关。GAD组与其他两组的不同之处还在于，相对于高影响(例如心脏病发作)事件，GAD组对低影响(例如，发型不好)的神经反应增强。GAD患者的这种神经功能障碍，特别是mPFC内的神经功能障碍，可能代表了这一人群对日常事件的乐观情绪降低和担忧增加的神经基础。此外，更重要的是，GSP患者没有表现出这种功能障碍，这表明了疾病的特异性，并可能代表GAD治疗的一个重要的生物标志物。

Over the last 12 months, one particular strand of our work with patients with Generalized Anxiety Disorder (GAD) and Generalized Social Phobia (GSP) stands out. Pathological worry is the defining feature of GAD in DSM. Understanding the neural dysfunction underlying worry in GAD therefore likely represents an important treatment target. However very little is known about the neural underpinnings of worry or how they may malfunction in patients with GAD complicating treatment progress. More is known about a construct that may be viewed as a counterpoint to worry: optimistic bias (OB). OB is shown by most healthy individuals and involves thinking that compared to the average individual they are less likely to experience negative life events, but more likely to experience positive life events. However, in previous behavioral work we have found that GAD is associated with a reduced OB (i.e., realistic view) about the future. Specifically when we asked participants to indicate how likely they thought they were to experience something positive (e.g., having a great haircut; winning the lottery) or negative (e.g., having a bad haircut; having a heart attack) compared to the average individual, patients with GAD were much less likely to be optimistic. One goal this year was to determine the neural basis of this cognitive impairment in GAD using fMRI and to determine whether such impairment is specific to GAD and not GSP. In line with previous work, healthy participants showed significant OB; they considered themselves significantly less likely to experience future negative but significantly more likely to experience future positive events relative to others. This was also seen in GSP. However, GAD patients showed no significant OB. At the neural level, OB was associated with significantly greater modulation of medial prefrontal cortex (rmPFC) in the healthy and GSP groups compared to the GAD group. The GAD group also differed from the two other groups by showing increased neural responses to low impact (e.g., having a bad haircut) relative to high impact (e.g., having a heart attack) events. This neural dysfunction, particularly within mPFC, in patients with GAD may represent the neural substrate that underlies the reduced optimism and increased worry about everyday events in this population. Further and importantly, patients with GSP did not show such dysfunction, suggesting disorder-specificity and the possibility it could represent an important biomarker for treatment of GAD.