HPA system in anxiety disorder patients treated with cognitive behavioural therapy: A review

Anxiety disorders (AD) have a complex etiology involving genetic, psychophysiological and environmental factors. Recent biomarker research in AD shows alterations in anatomical, biochemical and physiological pathways as well as endocrinological processes. Perceived stress is one of the factors often reported in relation to the onset and the course of AD, hence, the function of the hypothalamus-pituitary-adrenal (HPA) axis, the endogenous system regulating the stress response homeostasis, may serve as biomarker in disease etiology and response to treatment. Vice versa, successful treatment could have an advantageous effect on the function of the HPA system. In the present review, we summarize findings on HPA-system in relation to AD and first results on their changeability in response to cognitive behavioral therapy (CBT), one of the most efficacious psychotherapeutic treatments for AD. We specifically focus on findings of experimental studies that explored cortisol levels before, during and after exposure-based CBT. A systematic search was conducted in MEDLINE/PubMed, PsycINFO, Web of Science and references of retrieved studies until April 2024. The inclusion criteria were studies enclosing keywords related to the HPA axis, an anxiety disorder and CBT techniques. The results of the summarized studies suggest that cortisol levels have the potential to indicate the AD disease status and serve as possible biomarker in outcome prediction. Global dysfunction of HPA system seems to point to higher symptom burden and less advantageous response to CBT. Furthermore, low cortisol levels elicited in relation to exposure interventions were repeatedly associated with risk for non-response. Additionally, some evidence suggests that successful CBT containing exposure sessions as well as cognitive techniques induce normalization of the HPA system by reducing acute response to fear related stimuli in parallel to normalizing basal cortisol levels. To conclude, cortisol seems to be a promising candidate to depict several aspects of AD-related disease status and CBT effects, however, additional prospective studies are needed to evaluate the mode of applications of this marker in the clinical routine. • The cortisol level may serve as biomarker for psychotherapy effects. • Persistently elevated cortisol levels seem to impede therapy response. • A beneficial effect of cortisol elevation during exposure is supported. • Effective CBT treatment seems to normalize HPA-system abnormalities. • Cognitive processes seem to have an influence on adaptive HPA system functioning.