Stress and Disorders of the Stress System

George P. Chrousos

Conclusions

The stress response, which occurs when homeostasis is threatened or perceived to be threatened, is mediated by the stress system. Central effectors (including hypothalamic hormones, such as AVP, CRH and pro-opiomelanocortin-derived peptides and brainstem-derived norepinephrine) and peripheral effectors (including glucocorticoids, norepinephrine and epinephrine) of this system regulate the brain's cognitive, reward and fear systems and wake–sleep centers as well as the growth, reproductive and thyroid hormone axes, and influence the gastrointestinal, cardiorespiratory, metabolic, and immune systems. Malfunction of the stress system might impair growth, development, behavior and metabolism, which potentially lead to various acute and chronic disorders. Our lifestyles and environment in modern societies seem to be particularly permissive for such stress-related disorders.

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Correspondence to
G. P. Chrousos, First Department of Pediatrics, Aghia Sophia Children's Hospital, University of Athens, Thivon and Mikras Asias Streets, Athens 11527, Greece chrousge@med.uoa.gr

Review criteria
The author has been working in the general area of stress for over 30 years. Multiple book sources and articles in MEDLINE and PubMed were employed. All papers selected were English-language, full-text papers. We also searched the reference lists of identified articles for further primary information. The terms "homeostasis", "stress", "glucocorticoids" and "catecholamines" were crossreferenced with terms pertaining to homeostatic functions influenced by stress, such as "arousal", "sleep", "growth", "reproduction", "metabolism" and "immunity", or to pathological conditions related to stress, such as "anxiety", "depression", "obesity" and "metabolic syndrome".

Acknowledgments
This review is partially based on the Geoffrey Harris Memorial Lecture given by the author at the 10^th European Congress of Endocrinology, 3–7 May 2008, Berlin, Germany.

Cite this: Stress and Disorders of the Stress System - Medscape - Jul 01, 2009.

Table 1. Adaptive responses to evolutionary stressors and related diseases in modern human societies ^[68]
Response to survival threat	Selective advantage	Contemporary disease
Combat starvation	Energy conservation	Obesity
		Metabolic syndrome
Combat dehydration	Fluid and electrolyte conservation	Hypertension
Combat injurious agents	Potent immune reaction	Autoimmunity
		Allergy
Anticipate adversaries	Arousal and fear	Anxiety
		Insomnia
Minimize exposure to danger	Social withdrawal	Depression
Prevent tissue strain and damage	Retain tissue integrity	Pain syndromes
		Fatigue syndromes

Box 1. History of stress
The term stress originates from the indo–european root 'str', which has been historically associated with exertion of pressure. Thus, both the Greek 'strangalizein' and its english derivative and synonym 'to strangle', as well as the Latin 'strigere' (to tighten), have their origins in the very distant past. The concept of homeostasis as the general principle of balance or equilibrium of life was first enunciated clearly by the ancient Greek natural philosophers, who called it 'harmony' (Pythagoras) or 'isonomia' (Alkmaeon).^[4,75] The modern synonym 'homeostasis', which means steady state, was coined by the American physiologist walter Cannon in the beginning of the 20th century, whereas the word 'stress' was first used with its current meaning and popularized by the Hungarian Canadian experimentalist Hans selye a few decades later. Both Cannon and selye employed Hooke's law of elasticity to heuristically and creatively extrapolate physical concepts into biology.^[76–81]

Box 2. Central and peripheral functions of the stress response ^[2]
Functions of the central nervous system Facilitation of arousal, alertness, vigilance, cognition, attention and aggression Inhibition of vegetative functions (e.g. reproduction, feeding, growth) Activation of counter-regulatory feedback loops
Peripheral functions Increase of oxygenation Nutrition of brain, heart and skeletal muscles Increase of cardiovascular tone and respiration Increase of metabolism (catabolism, inhibition of reproduction and growth) Increase of detoxification of metabolic products and foreign substances Activation of counter-regulatory feedback loops (includes immunosuppression)

Box 3. Conditions with altered HPA axis activity ^[2]
Increased activity of the HPA axis Cushing syndrome Chronic stress Melancholic depression Anorexia nervosa Obsessive–compulsive disorder Panic disorder Excessive exercise (obligate athleticism) Chronic, active alcoholism Alcohol and narcotic withdrawal Diabetes mellitus Central obesity (metabolic syndrome) Post-traumatic stress disorder in children Hyperthyroidism Pregnancy
Decreased activity of HPA axis Adrenal insufficiency Atypical/seasonal depression Chronic fatigue syndrome Fibromyalgia Premenstrual tension syndrome Climacteric depression Nicotine withdrawal Following cessation of glucocorticoid therapy Following Cushing syndrome cure Following chronic stress Postpartum period Adult post-traumatic stress disorder Hypothyroidism Rheumatoid arthritis Asthma, eczema

Abbreviation: HPA, hypothalamic–pituitary–adrenal.

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