Glucocorticoids and cognitive function: from physiology to pathophysiology

This paper reviews the literature on the relationship between glucocorticoids and cognitive functioning, including memory and selective attention. The main body of evidence suggests that hypothalamic-pituitary-adrenal (HPA) axis dysfunction or a state of hypercortisolaemia can be correlated with cognitive deficits specific to the medial temporal lobe declarative memory system. These impairments are discussed in relation to patients with HPA abnormalities, as seen in a significant number of patients with major depression or Cushing's syndrome, and also in relation to healthy volunteers after administration of glucocorticoids. It remains to be seen whether there are differential effects on acquisition, consolidation or retrieval processes. However, it would seem that glucocorticoids have a preferential effect on recall of information as opposed to recognition, possibly because recognition is more automatic.Type 2 glucocorticoid receptors (GRs), which are occupied by cortisol in humans in times of stress, are thought to be responsible for the glucocorticoid-induced memory impairment. GRs alter the feedback of the HPA axis, which in turn disrupts hippocampal functioning. While this can be reversible, animal studies suggest that chronic elevation of glucocorticoid levels can lead to the loss of hippocampal neurons and irreversible decline in declarative memory. Copyright 2001 John Wiley & Sons, Ltd.