Stress, Cognitive Impairment and Cortisol

Repeated Stress Causes Cognitive Impairment by Suppressing Glutamate Receptor Expression and Function in Prefrontal Cortex

Eunice Y. Yuen, Jing Wei, Wenhua Liu, Ping Zhong, Xiangning Li, and Zhen Yan

(Neuron 73, 962–977, March 8, 2012)

In the Introduction to this important article related to chronic stress and maladaptive changes, the authors clearly outline the relationship between adrenal corticosterone and a number of cognitive and emotional distrubances.


Adrenal corticosterone, the major stress hormone, through the activation of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), can induce long-lasting influences on cognitive and emotional processes. Mounting evidence suggests that inappropriate stress responses act as a trigger for many mental illnesses. For example, depression is associated with hypercortisolaemia (excessive cortisol, whereas posttraumatic stress disorder (PTSD) has been linked to hypocortisolaemia (insufficient cortisol), resulting from an enhanced negative feedback by cortisol (Yehuda, 2002). Thus, corticosteroid hormones are thought to serve as a key controller for adaptation and maintenance of homeostasis in situations of acute stress, as well as maladaptive changes in response to chronic and repeated stress that lead to cognitive and emotional disturbances symptomatic of stress-related neuropsychiatric disorders...

Chronic stress or glucocorticoid treatment has been found to cause structural remodeling and behavioral alterations in the prefrontal cortex (PFC) from adult animals, such as dendritic shortening, spine loss, and neuronal atrophy, as well as impairment in cognitive flexibility and perceptual attention...

Cortisol and Abdominal Obesity

Interesting observation taken from:

The molecular neurobiology of depressionVaishnav Krishnan and Eric J. Nestler


Published in final edited form as:

Nature. 2008 October 16; 455(7215): 894–902. doi:10.1038/nature07455.

Abstract
Unravelling the pathophysiology of depression is a unique challenge. Not only are depressive syndromes heterogeneous and their aetiologies diverse, but symptoms such as guilt and suicidality are impossible to reproduce in animal models. Nevertheless, other symptoms have been accurately modelled, and these, together with clinical data, are providing insight into the neurobiology of depression. Recent studies combining behavioural, molecular and electrophysiological techniques reveal that certain aspects of depression result from maladaptive stress-induced neuroplastic changes in specific neural circuits. They also show that understanding the mechanisms of resilience to stress offers a crucial new dimension for the development of fundamentally novel antidepressant treatments.

Here's the interesting bit related to obesity:

Several metabolic abnormalities that are often associated with depression, such as insulin resistance and abdominal obesity, can be at least partly explained by an increase in glucocorticoids. Hypercortisolaemia in depression is manifested at several levels, including impaired glucocorticoid-receptor-mediated negative feedback, adrenal hyper-responsiveness to circulating adreno-corticotropic hormone (ACTH) and hypersecretion of cortico tropinreleasing factor, the hypothalamic activator of ACTH release from the pituitary. In line with these findings, glucocorticoid and corticotropin-releasing factor receptor antagonists are currently being tested in clinical trials.