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

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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.