Differential Neuro-Biological Correlates of Emotion- and Stress-Processing in Generalized Anxiety Disorder compared to Major Depression and Social Phobia

广泛性焦虑症（GAD）是一种慢性临床疾病，其特征是过度的，无法控制的担忧和焦虑的期望。广泛性焦虑症的病因和发病机制仍不清楚。神经生物学研究结果尤其稀少和不一致。功能性神经影像学研究指出，与健康对照组相比，广泛性焦虑症受试者的杏仁核和恐惧回路网络的相关神经结构被过度激活。然而，在神经影像学研究中报告了类似的激活模式，这些研究针对的是经常与广泛性焦虑症同时发生的疾病，如抑郁症或其他焦虑症。因此，GAD的神经影像学结果的特异性尚不清楚。关于广泛性焦虑症患者应激系统可能功能障碍的少数研究表明，交感神经反应性升高和下丘脑-垂体-肾上腺轴（HPAA）过度激活，导致皮质醇释放，但也有部分报告内分泌应激反应性降低。这些不同应激系统分离的迹象可能是GAD中重编程HPAA的结果。然而，尚不清楚先前的结果在多大程度上再次被频繁的合并症介导。本基础研究和准实验性比较病例对照研究旨在探讨GAD患者情绪和应激处理的神经、内分泌和自主神经相关性，并确定重度抑郁症（MD）和社交恐惧症（SP）的共同和独特特征。原发性GAD受试者（无共病抑郁或SP），原发性MD（无共病焦虑障碍），原发性SP通过功能性磁共振成像（fMRI）检查无精神病理学的健康对照（无共病抑郁症或GAD）和无精神病理学的健康对照，以揭示神经相关性，同时完成具有注意力状态变化的面部情绪范式，差异恐惧条件范式，以及在预期期间的范式变化确定性和在感知期间的情感刺激的模糊性。此外，与情绪处理和调节相关的大脑区域之间的功能连接正在通过休息状态分析进行评估。基础（头发皮质醇）和急性应激参数（唾液皮质醇，α-淀粉酶，皮肤电导）在心理应激的情况下进行评估。结果预计将有助于改善表征和理解的神经生物学相关性及其相互作用在广泛性焦虑症，并允许分化与MD和SP的诊断，分类和治疗的影响。

Generalized Anxiety Disorder (GAD) is a chronic clinical condition characterized by excessive, uncontrollable worry and anxious expectations. The aetio-pathogenesis of GAD remains poorly understood. Neuro-biological findings are particularly scarce and inconsistent. Functional neuroimaging studies point to exaggerated activation in the amygdala and associated neural structures of the fear circuitry network in subjects with GAD compared to healthy controls. However, similar activation patterns are reported in neuroimaging studies on disorders that frequently co-occur with GAD, such as Depression or other anxiety disorders. Therefore, the specificity of the neuroimaging results for GAD remains unclear. The few available studies on possible dysfunctions of the stress system in GAD suggest an elevated sympathetic reactivity and hyperactivation of the hypothalamic-pituitary-adrenal axis (HPAA), which leads to the release of cortisol, but partly a reduced endocrine stress reactivity has been reported as well. These indications for a dissociation of different stress systems may possibly be a result of a reprogrammed HPAA in GAD. However, it remains unclear in how far previous results are again mediated by frequent comorbidities. This basic research and quasi-experimental comparative case-control-study aims to investigate the neural, endocrine and autonomic correlates of emotion and stress processing in subjects with GAD and to specify common and distinct features with regard to major depression (MD) on the one hand and Social Phobia (SP) on the other hand. Subjects with primary GAD (no comorbid depression or SP), primary MD (no comorbid anxiety disorder), primary SP (no comorbid depression or GAD) and healthy controls without psychopathology are examined via functional magnetic resonance imaging (fMRI) to reveal neural correlates while completing a face-emotion paradigm with variation of attention state, a differential fear conditioning paradigm, and a paradigm varying certainty during anticipation and ambiguity of emotional stimuli during perception. Additionally, functional connectivity between brain areas related to emotional processing and regulation is being assessed by means of a resting-state analysis. Basal (hair cortisol) and acute stress parameters (saliva cortisol, alpha amylase, skin conductance) are assessed in psychological stress situations. Results are expected to contribute to an improved characterization and understanding of the neuro-biologic correlates and their interplay in GAD and to allow differentiation from MD and SP with implications for diagnosis, classification and treatment.