Abstract
Both hyper- and hypo-activity of the hypothalamus–pituitary–adrenal (HPA) axis activity are a consistently reported hallmark feature of stress-related disorders, such as major depression and posttraumatic stress disorder (PTSD), respectively. In this manuscript, however, we are summarizing evidence pointing to altered glucocorticoid (GC) sensitivity in relevant target tissues for HPA axis hormones. Specifically, we provide a summary of GC effects on cognitive functions, as an emerging marker for central nervous system GC sensitivity, and of GC effects on peripheral inflammatory responses. With regard to depression and PTSD, evidence thereby points to decreased GC sensitivity of the cognitive and inflammatory systems in depression, and increased GC sensitivity of both systems in PTSD. Taken together, these data support the hypothesis that both psychiatric disorders are characterized by inefficient GC signaling, although through dysregulations at different levels. Potential underlying pathways and implications are discussed.