Influence of the HPA Axis on Anxiety-Related Processes: An RDoC Overview Considering Their Neural Correlates

Through a multidimensional lens, we review the literature on the link between anxiety-related processes, hypothalamic-pituitary-adrenal (HPA) axis functioning (with a particular focus on cortisol), and their neural correlates, using the Research Domain Criteria (RDoC) framework. This approach aims to capture the complexity of these processes by addressing their heterogeneity, multidimensionality, and underlying neurobiological mechanisms. Within the RDoC framework, dysregulated cortisol (whether excessively elevated or blunted) has been linked to disruptions in different processes of the negative valence, positive valence, cognitive, social, arousal, and sensorimotor systems. These effects are associated with distinct neural substrates, including limbic, striatal, and prefrontal control areas. Different processes and neurobiological responses interact in complex, bidirectional ways, and understanding these interdependencies is essential for capturing the full nature of anxiety-related processes. These findings reinforce the value of adopting a multidimensional, RDoC-based framework, which allows for a more integrative and mechanistic understanding of mental health.