Objective. —This article defines stress and related concepts and reviews their historical development. The notion of a stress system as the effector of the stress syndrome is suggested, and its physiologic and pathophysiologic manifestations are described. A new perspective on human disease states associated with dysregulation of the stress system is provided. Data Sources. —Published original articles from human and animal studies and selected reviews. Literature was surveyed utilizing MEDLINE and the Index Medicus . Study Selection. —Original articles from the basic science and human literature consisted entirely of controlled studies based on verified methodologies and, with the exception of the most recent studies, replicated by more than one laboratory. Many of the basic science and clinical studies had been conducted in our own laboratories and clinical research units. Reviews cited were written by acknowledged leaders in the fields of neurobiology, endocrinology, and behavior. Data Extraction. —Independent extraction and cross-referencing by the authors. Data Synthesis. —Stress and related concepts can be traced as far back as written science and medicine. The stress system coordinates the generalized stress response, which takes place when a stressor of any kind exceeds a threshold. The main components of the stress system are the corticotropin-releasing hormone and locus ceruleus-norepinephrine/autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. There has been an exponential increase in knowledge regarding the interactions among the components of the stress system and between the stress system and other brain elements involved in the regulation of emotion, cognitive function, and behavior, as well as with the axes responsible for reproduction, growth, and immunity. This new knowledge has allowed association of stress system dysfunction, characterized by sustained hyperactivity and/or hypoactivity, to various pathophysiologic states that cut across the traditional boundaries of medical disciplines. These include a range of psychiatric, endocrine, and inflammatory disorders and/or susceptibility to such disorders. Conclusions. —We hope that knowledge from apparently disparate fields of science and medicine integrated into a working theoretical framework will allow generation and testing of new hypotheses on the pathophysiology and diagnosis of, and therapy for, a variety of human illnesses reflecting systematic alterations in the principal effectors of the generalized stress response. We predict that pharmacologic agents capable of altering the central apparatus that governs the stress response will be useful in the treatment of many of these illnesses. ( JAMA . 1992;267:1244-1252)

The Concepts of Stress and Stress System Disorders: Overview of Physical and Behavioral Homeostasis

This article reviews the burgeoning literature on the relationship of mood disorders and heart disease. Major depression and depressive symptoms, although commonly encountered in medical populations, are frequently underdiagnosed and undertreated in patients with cardiovascular disease (CVD). This is of particular importance because several studies have shown depression and its associated symptoms to be a major risk factor for both the development of CVD and death after an index myocardial infarction. This review of the extant literature is derived from MEDLINE searches (1966-1997) using the search terms "major depression," "psychiatry," "cardiovascular disease," and "pathophysiology." Studies investigating pathophysiological alterations related to CVD in depressed patients are reviewed. The few studies on treatment of depression in patients with CVD are also described. Treatment of depression in patients with CVD improves their dysphoria and other signs and symptoms of depression, improves quality of life, and perhaps even increases longevity. Recommendations for future research are proposed.

The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment.

Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendati...

/pdf/revised-american-thyroid-association-guidelines-for-the-2lbm9jji5g.pdf

Revised American thyroid association guidelines for the management of medullary thyroid carcinoma

Stress precipitates depression and alters its natural history Major depression and the stress response share similar phenomena, mediators and circuitries Thus, many of the features of major depression potentially reflect dysregulations of the stress response The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction) Because depression is a heterogeneous illness, we studied two diagnostic subtypes, melancholic and atypical depression In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes Patients with atypical depression present with a syndrome that seems the antithesis of melancholia They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency in atypical depression, and our data show us that these are of central origin Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately In the present paper, we shall first review the mediators and circuitries of the stress system to lay the groundwork for placing in context physiologic and structural alterations in depression that may occur as part of stress system dysfunction

https://www.neurotransmitter.net/Gold.pdf

Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states

Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range.

A sensitive and specific double-isotope dilution method for assaying norepinephrine and epinephrine separately is described. The method is based on enzymatic conversion of these two catecholamines to their respective metanephrines and was applied successfully to measurement of resting plasma concentrations of norepinephrine and epinephrine in normal subjects with the finding that norepinephrine (0.20 ± 0.08 µg/liter) normally constitutes approximately 80% of the plasma catecholamine content and epinephrine (0.05 ± 0.03 µg/liter) 20%.

A sensitive double-isotope derivative assay for norepinephrine and epinephrine. Normal resting human plasma levels.

The total resting plasma catecholamine concentration from 13 drugfree, depressed patients was found to be significantly elevated over concentrations from 47 normal controls. Differential determinations of epinephrine and norepinephrine revealed that both catecholamine components were elevated in the Patients. The literature on norepinephrine concentrations in brain, spinal fluid, and urinary excretion was reviewed and indicated that rather than being decreased, norepinephrine has been found to be either unchanged or increased in depressed patients.

Resting plasma catecholamine concentrations in patients with depression and anxiety.

Marked potentiation of the pressor effects of tyramine hydrochloride, given orally and intravenously, was demonstrated in patients receiving a monoamine oxidase (MAO) inhibitor. Assays of the tyramine content of various foods revealed up to 25μg/ml in wine and 1.4 mg/gm in some cheeses. As little as 20 gm of cheese produced pressor responses which were controllable with phentolamine methane-sulfonate in MAO-inhibited patients. These findings extend previous work on the mechanism of cheese toxicity and emphasize one of the hazards of treatment with MAO inhibitors.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=1163613&pdfFileName=jama_188_13_002.pdf

Monoamine Oxidase Inhibitors, Tyramine, and Cheese

ALTHOUGH the role of 5-hydroxytryptamine (serotonin, 5HT) in the pathophysiology of the carcinoid syndrome, and especially in flush production, has been seriously questioned,2 the fact remains that increased production of serotonin is a hallmark of the condition. If it were possible effectively to inhibit the formation of this pharmacologically potent amine in patients with carcinoid tumors, a likely result would be a better understanding of the clinical significance of serotonin. A possibility of achieving this goal appeared with the studies of Koe and Weissman3 showing that para-chlorophenylalanine (PCP) is a potent and selective depletor of tissue serotonin in animals. It . . .

Inhibition of serotonin synthesis by para-chlorophenylalanine in patients with the carcinoid syndrome.

The enzymatic double-isotope derivative technique has been applied to the measurement of the catecholamines in plasma samples obtained from resting normal subjects and patients with pheochromocytoma or essential hypertension. The plasma catecholamine concentrations in the 18 patients with essential hypertension (0.45 ± 0.16 /xg/L [mean±SD]) were significantly higher (P<0.001) than those in the 32 normal subjects (0.24 ±0.07 fig/L). Values in the patients with pheochromocytomawere all elevated and ranged from 0.54 to 10 μg /L

Karl Engelman

Papers

A sensitive double-isotope derivative assay for norepinephrine and epinephrine. Normal resting human plasma levels.

Resting plasma catecholamine concentrations in patients with depression and anxiety.

Monoamine Oxidase Inhibitors, Tyramine, and Cheese

Inhibition of serotonin synthesis by para-chlorophenylalanine in patients with the carcinoid syndrome.

Catecholamines-cyclic amp-angiotensin receptors. Plasma catecholamine concentrations in patients with hypertension.