Understanding the relationships between physiological and psychosocial stress, cortisol and cognition

Abstract

Stress is viewed as a state of real or perceived threat to homeostasis, the management of which involves the endocrine, nervous, and immune systems. These systems work independently and interactively as part of the stress response. The scientific stress literature, which spans both animal and human studies, contains heterogeneous findings about the effects of stress on the brain and the body. This review seeks to summarise and integrate literature on the relationships between these systems, examining particularly the roles of physiological and psychosocial stress, the stress hormone cortisol, as controlled by the hypothalamic-pituitary-adrenal (HPA) axis, and the effects of stress on cognitive functioning. Health conditions related to impaired HPA axis functioning and their associated neuropsychiatric symptoms will also be considered. Lastly, this review will provide suggestions of clinical applicability for endocrinologists who are uniquely placed to measure outcomes related to endocrine, nervous and immune system functioning and identify areas of intervention.

Keywords: cognition; cortisol; endocrinologist; glucocorticoids; hypothalamic - pituitary - adrenal axis; mental health; physiological stress; psychosocial stress.

Figure 1

The negative feedback loop of the HPA axis. CRH = corticotropin-releasing hormone. ACTH = adrenocorticotropic hormone. The body experiences a stressor; this triggers the hypothalamus to release CRH, which stimulates the anterior lobe of the pituitary gland to release ACTH. The adrenal cortex of the adrenal glands responds to stimulation by the ACTH and produces cortisol. High plasma cortisol stimulates the hippocampus (a brain region involved in memory processes, that has an abundance of corticosteroid receptor sites), which also has inhibitory control over the HPA axis to prevent excess cortisol release. When stress is chronic, high levels of circulating cortisol can cause long-term damage to the hippocampus, including hippocampal shrinkage, which can impair the actions of the negative feedback loop. Cortisol also has a negative feedback on the hypothalamus and the pituitary gland, inhibiting CRH and ACTH secretion.