Blunted hypothalamic-pituitary-adrenal axis and increased sympathetic nervous system activity in response to psychosocial stress in Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is characterized by uncontrollable and excessive worries and several somatic symptoms. Biological mechanisms underlying the symptoms of GAD are not fully elucidated, however, results point toward possible abnormalities in hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) activity. Therefore, the present study aimed to investigate HPA axis and SNS response to a stimulus that is characterized by several features pivotally involved in the provocation and experience of anxiety – the Trier Social Stress Test (TSST) – in GAD-patients. 15 patients (13 females, 2 males) with the primary diagnosis of GAD and 14 age-matched healthy subjects (12 females, 2 males) participated in the TSST, a highly standardized laboratory stress test, and provided saliva samples before and after the TSST (–30, –2, +1, +10, +20, +30, +45, +60 minutes) for determination of cortisol and alpha-amylase. GAD-patients showed a blunted cortisol response to the TSST as well as reduced mean cortisol levels during the testing period. In contrast, alpha-amylase secretion in response to the stressor was comparable in both groups, but GAD-patients showed elevated mean alpha-amylase levels during the testing period. The results indicate a dissociation of different stress response systems in GAD. A blunted HPA axis response in GAD might either be a consequence of chronic burden associated with GAD or a vulnerability factor for excessive worrying/anxiety. Further studies are needed to delineate the role of HPA axis functioning in the etiology and maintenance of GAD symptoms.