Neuroendocrinology of stress
by
Habib KE, Gold PW, Chrousos GP.
Clinical Neuroendocrinology Branch,
National Institute of Mental Health,
National Institutes of Health,
Bethesda, Maryland, USA.
habib@codon.nih.gov
Endocrinol Metab Clin North Am 2001 Sep; 30(3):695-728


ABSTRACT

Comprehending the mechanistics of the stress response and the increasingly serious sequelae of its dysregulation is pivotal to recognize and combat any abnormalities in the stress system. To overcome pathologic hyperactivity of the stress response, it is essential to protect juveniles from trauma and abuse. The more secure the environment, the less likely an individual will experience a stress-related illness. A secondary measure is training stress-prone patients to improve their coping skills, minimizing their reactivity to future stress. In-depth understanding of the neurocircuitry of stress has provided novel tools to manage hyperactivity of the stress system. Hundreds of original articles and numerous laboratories have repeatedly implicated CRH in enhancing the organism's sensitivity to nocuous stimuli and in mobilizing almost the entire cascade of the stress response. By virtue of its broad interactions with the endocrine and autonomic systems, CRH virtually influences every cell in the body. Hyperactivity of CRH is a serious condition that is likely to underlie the pathophysiology of melancholic depression, anxiety, psychosexual disorders, diabetes mellitus, and functional gastrointestinal disorders. One of the most revolutionary progresses in medicine is the introduction of nonpeptide CRH receptor antagonists to target directly the stress system in the brain. Although still in phase 1 trials, preclinical findings from the authors' and others' laboratories strongly indicate the efficacy and low side-effect profile of CRH-R1 antagonists against mental and physical disorders that are exacerbated or precipitated by stress. Such agents are likely to be helpful in treating a wide spectrum of psychiatric disorders, such as melancholic depression, anorexia nervosa, obsessive-compulsive disorder, and withdrawal from certain narcotic agents. Several medical illnesses will probably benefit from such therapies as soon as these prove to be clinically safe and pharmacologically efficacious.
CRF
LHPA
Cytokines
Ketoconazole
Noradrenaline
Corticosteroids
Cushing's syndrome
Stress and aggression
Glucocorticoids and mood
Hippocampal remodelling
Serotonin, stress, and CRH
Stress, depression and anxiety
HPA axis, serotonin and suicide
Depression, opioids and the HPA
Antidepressants and new brain cells
Are antidepressants neuroprotective?
The corticosteroid hypothesis of depression
An overactive immune system and depression
Stress, dynorphin, dysphoria and the kappa opioid system


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