EDITORIAL article Front. Syst. Neurosci., 13 August 2019 Volume 13 - 2019 | https://doi.org/10.3389/fnsys.2019.00032

Stress is a universal phenomenon that impacts adversely on most people. This volume provides a readily accessible compendium that explains the phenomenon of stress, the neural, endocrine and molecular mechanisms involved, the clinical effects, and the impact on individuals and society. Clinical attention focuses on disorders of the stress control system (e.g. Cushing's Syndrome: Addison's Disease) and the adverse impact of stress on human physical and mental health. Detailed reviews address disorders such as PTSD, anxiety, major depression, psychoses and related disorders such as combat fatigue and burnout. The work covers interactions between stress and neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, as well as stress-immune-inflammatory interactions in relation to cancer and autoimmune and viral diseases. Emphasis is also placed on the role of stress in obesity, hypertension, diabetes type II and other features of the metabolic syndrome which has now reached epidemic proportions in the USA and other countries. Chapters offer impressive scope with topics addressing animal studies, disaster, diurnal rhythms, drug effects and treatments, cognition and emotion, physical illness, psychopathology, immunology and inflammation, lab studies and tests, and psychological/biochemical/genetic aspects. This book is richly illustrated with over 200 figures, 75 in color. Priced affordably, this compendium of articles appeals to the end user interested in stress research who would not otherwise purchase the larger Encyclopedia of Stress. Articles carefully selected by one of the world's most preeminent stress researchers and contributors represent the most outstanding scholarship in the field, with each chapter providing fully vetted and reliable expert knowledge.

Stress has a different meaning for different people under different conditions. The first and most generic definition of stress was that proposed by Hans Selye: "Stress is the nonspecific response of the body to any demand." Selye's generic definition is applicable to the stress response in all three phylogenetic domains of organisms ranging from bacteria to man. Other definitions have evolved to cater for different situations–for example, cognitive. This article explores the basis for these definitions and their validity, and outlines the neuroendocrine mechanisms that subserve the stress response. The concept of homeostasis, "stability through constancy" as the main mechanism by which the body copes with stress, has given way to allostasis, "stability through change" brought about by central neural regulation of the set points that adjust physiological parameters to meet the stressful challenge. Also reviewed briefly are relatively new stress concepts based on (1) genetic and epigenetic factors that may determine individual susceptibility to stress, and (2) the fact that fetal malnutrition may predispose individuals to the metabolic syndrome (obesity, hypertension, dislipidemia, and diabetes type 2) that has reached epidemic proportions.

In the past, vesicle content release was thought to occur immediately and completely after triggering of exocytosis. However, vesicles may merge with the plasma membrane to form an Ångstrom diameter fusion pore that prevents the exit of secretions from the vesicle lumen. The advantage of such a narrow pore is to minimize the delay between the trigger and the release. Instead of stimulating a sequence of processes, leading to vesicle merger with the plasma membrane and a formation of a fusion pore, the stimulus only widens the pre-established fusion pore. The fusion pore may be stable and may exhibit repetitive opening of the vesicle lumen to the cell exterior accompanied by a content discharge. Such release of vesicle content is partial (subquantal), and depends on fusion pore open time, diameter and the diffusibility of the cargo. Such transient mode of fusion pore opening was not confirmed until the development of the membrane capacitance patch-clamp technique, which enables high-resolution measurement of changes in membrane surface area. It allows millisecond dwell-time measurements of fusion pores with subnanometer diameters. Currently, the soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) proteins are considered to be key entities in end-stage exocytosis, and the SNARE complex assembly/disassembly may regulate the fusion pore. Moreover, lipids or other membrane constituents with anisotropic (non-axisymmetric) geometry may also favour the establishment of stable narrow fusion pores, if positioned in the neck of the fusion pore.

Stress in mammals triggers a neuroendocrine response mediated by the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS). Increased activity of these two systems induces behavioral, cardiovascular, endocrine, and metabolic cascades that enable the individual to fight or flee and cope with stress. Our understanding of stress and stress response mechanisms is generally robust. However, several themes remain uncertain/controversial and perhaps deserve further scrutiny before they achieve canonical status. These themes include perinatal exposure effects on the health of the adult, genetic susceptibility to stress, the neurochemistry of posttraumatic stress disorder (ANS versus the HPA), significance of hippocampal volume for major depressive disorder and other mental disorders, and the role of stress in the etiology of gastroduodenal ulcers. All five themes are of clinical and therapeutic significance, pose fundamental questions about stress mechanisms and offer important areas for future research.

Hans Selye in a note to Nature in 1936 initiated the field of stress research by showing that rats exposed to nocuous stimuli responded by way of a ‘general adaptation syndrome’ (GAS). One of the main features of the GAS was the ‘formation of acute erosions in the digestive tract, particularly in the stomach, small intestine and appendix’. This provided experimental evidence for the view based on clinical data that gastro-duodenal (peptic) ulcers could be caused by stress. This hypothesis was challenged by Marshall and Warren’s Nobel Prize (2005)-winning discovery of a causal association between Helicobacter pylori and peptic ulcers. However, clinical and experimental studies suggest that stress can cause peptic ulceration in the absence of H. pylori . Predictably, the etiological pendulum of gastric and duodenal ulceration has swung from ‘all stress’ to ‘all bacteria’ followed by a sober realization that both factors play a role, separately as well as together. This raises the question as to whether stress and H. pylori interact, and if so, how? Stress has also been implicated in inflammatory bowel disease (IBD) and related disorders; however, there is no proof yet that stress is the primary etiological trigger for IBD. Central dopamine mechanisms seem to be involved in the stress induction of peptic ulceration, whereas activation of the sympathetic nervous system and central and peripheral corticotrophin-releasing factor appears to mediate stress-induced IBD.

The discovery in 1936 that rats respond to various damaging stimuli with a general response that involves alarm, resistance and exhaustion launched the discipline of stress research.

Stress: Concepts, Cognition, Emotion, and Behavior: Handbook in Stress Series, Volume 1, examines stress and its management in the workplace and is targeted at scientific and clinical researchers in biomedicine, psychology, and some aspects of the social sciences. The audience is appropriate faculty and graduate and undergraduate students interested in stress and its consequences. The format allows access to specific self-contained stress subsections without the need to purchase the whole nine volume Stress handbook series. This makes the publication much more affordable than the previously published four volume Encyclopedia of Stress (Elsevier 2007) in which stress subsections were arranged alphabetically and therefore required purchase of the whole work. This feature will be of special significance for individual scientists and clinicians, as well as laboratories. In this first volume of the series, the primary focus will be on general stress concepts as well as the areas of cognition, emotion, and behavior.Offers chapters with impressive scope, covering topics including the interactions between stress, cognition, emotion and behaviourFeatures articles carefully selected by eminent stress researchers and prepared by contributors representing outstanding scholarship in the fieldIncludes rich illustrations with explanatory figures and tablesIncludes boxed call out sections that serve to explain key concepts and methodsAllows access to specific self-contained stress subsections without the need to purchase the whole nine volume Stress handbook series

Copyright: © 2014 Fink G. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Posttraumatic Stress Disorder (PTSD) is a common condition in which a traumatic event is persistently re-experienced in the form of intrusive recollections, dreams or dissociative flashback episodes. Cues to the event lead to distress and are avoided, and there are symptoms of increased arousal. To meet the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (DSM-5), the full symptom picture must be present for more than one month, and the disturbance must cause clinically significant distress or impairment in social, occupational or other areas of functioning [1].

Geoffrey Harris, while still a medical student at Cambridge, was the first researcher (1937) to provide experimental proof for the then tentative view that the anterior pituitary gland was controlled by the CNS. The elegant studies carried out by Harris in the 1940s and early 1950s, alone and in collaboration with John Green and Dora Jacobsohn, established that this control was mediated by a neurohumoral mechanism that involved the transport by hypophysial portal vessel blood of chemical substances from the hypothalamus to the anterior pituitary gland. The neurohumoral control of anterior pituitary secretion was proved by the isolation and characterisation of the 'chemical substances' (mainly neuropeptides) and the finding that these substances were released into hypophysial portal blood in a manner consistent with their physiological functions. The new discipline of neuroendocrinology - the way that the brain controls endocrine glands and vice versa - revolutionised the treatment of endocrine disorders such as growth and pubertal abnormalities, infertility and hormone-dependent tumours, and it underpins our understanding of the sexual differentiation of the brain and key aspects of behaviour and mental disorder. Neuroendocrine principles are illustrated in this Thematic Review by way of Harris' major interest: hypothalamic-pituitary-gonadal control. Attention is focussed on the measurement of GnRH in hypophysial portal blood and the role played by the self-priming effect of GnRH in promoting the onset of puberty and enabling the oestrogen-induced surge or pulses of GnRH to trigger the ovulatory gonadotrophin surge in humans and other spontaneously ovulating mammals.

Neuroendocrinology is the study of how the nervous system controls hormonal secretion and, in turn, how hormones affect neural function and especially the brain. Neural-endocrine interactions occur at several sites in the body. Here, attention is focused on the neural control of the anterior lobe of the pituitary gland (pars distalis). The hormones secreted by the anterior lobe of the pituitary gland control reproduction (through gonadotropin stimulation of sex-steroid secretion, gametogenesis and ovulation), breast development and lactation (by way of prolactin), stress (through adrenocorticotropin stimulation of the adrenal glucocorticoid secretion), body temperature and metabolism (through thyrotropin stimulation of thyroid hormone secretion), and body growth and metabolism (through growth hormone secretion). The neural control of the synthesis and secretion of anterior pituitary hormones is mediated by neurohormones released from hypothalamic nerve terminals into hypophysial portal vessels in the pituitary stalk that transport them to the anterior pituitary gland. All but one (dopamine) of the hypothalamic neurohormones are peptides, ranging in size from the tripeptide thyrotropin-releasing hormone to the 44-amino acid residue growth hormone (GH)-releasing hormone. The function of the hypothalamic-pituitary axis is regulated by the negative feedback action of hormones secreted by the major target organs of the anterior pituitary gland - i.e., the gonads, the thyroid gland, the adrenal glands and adipose tissue. In reproduction, positive feedback also plays a pivotal role in triggering ovulation. Anterior pituitary target hormones, and especially thyroid hormones, sex steroids and the glucocorticoids, play key roles in neurodevelopment, sexual differentiation of the brain, central neurotransmission, behavior and cognition, mood and mental state. Neuroendocrine systems, and the adrenocorticotropin precursor proopiomelanocortin in particular, provided some of the first models for our understanding of gene transcription, translation and post-translational processing in vertebrates. This and other principles related to neurotransmitter/neurohormone synthesis, release, mode of action and control are highlighted as are neuroendocrine findings that have facilitated our understanding, diagnosis and management of disorders in man.

Feedback control systems are fundamental for the normal physiological functioning and homeostasis of the body. There are two types of feedback, negative and positive, of which the former is the more common. Removal of the main pituitary target glands, the adrenal, gonads and thyroid, the most reproducible and reproduced experiment in classical endocrinology, demonstrates that the secretion of pituitary adrenocorticotropin (ACTH), the gonadotropins (luteinizing hormone, LH, and follicle-stimulating hormone, FSH), and thyrotropin (TSH) is controlled by negative feedback exerted by the adrenal corticosteroids, gonadal steroids and thyroid hormones, respectively.Positive feedback, whereby the output of a system increases the output of the stimulator (gain in the system), is far less common than negative feedback, possibly because, taken to its logical conclusion, a positive feedback system, uncontrolled, will eventually self-destruct. Positive feedback is exemplified by (a) estrogen stimulation of gonadotropin secretion, which results in ovulation, and (b) the release of oxytocin induced during parturition by pressure of the fetal head on the uterine cervix. Estrogen stimulation of gonadotropin secretion is reinforced by the servomechanism of the "priming effect" of GnRH, whereby a small pulse of GnRH, by further amplifying pituitary responsiveness to itself, ensures the occurrence of a massive ovulatory gonadotropin surge.Crucial for homeostasis, negative feedback control mechanisms comprise a system in which the output moderates the strength of the controller to a predetermined set-point level. Negative feedback control operates widely throughout the body at the molecular (for example, end-product inhibition of enzyme activity), cellular and whole system/body levels. The mechanisms by which the set point is determined, functionally and anatomically, vary between systems and species.Here, attention will focus on the principles of negative feedback control using the hypothalamic-pituitary-adrenal (HPA) system as example. The HPA system, together with the sympathetic-medullary system, plays a pivotal role in the neuroendocrine response to stress. Homeostasis within the hypothalamic HPA is maintained by a precise negative feedback system by which the adrenal glucocorticoids (afferent limb), cortisol or corticosterone, moderate ACTH synthesis and release (efferent limb). Allostasis - that is, change in HPA activity to cope with increased stress load - is thought to be brought about by change in feedback set-point.

Treatment resistance remains a major obstacle in schizophrenia, with antipsychotic drugs (APDs) being ineffective in about one third of cases. Poor response to standard therapy leaves the APD clozapine as the only effective treatment for many patients. The reason for the superior efficacy of clozapine is unknown, but as we have proposed previously it may involve modulation of neuroplasticity and connectivity through induction of interconnected mitogenic signalling pathways. These include the mitogen-activated protein kinase-extracellular signal regulated kinase (MAPK-ERK) cascade and epidermal growth factor (EGF)/ErbB systems. Clozapine, distinct from other APDs, induced initial inhibition and subsequent activation of the ERK response in prefrontal cortical (PFC) neurons in vitro and in vivo, an action mediated by the EGF receptor (ErbB1). Here we examine additionally the striatum of C57Bl/6 mice to determine if clozapine, olanzapine, and haloperidol differentially regulate the ERK1/2 pathway in a region or time-specific manner conditional on the EGF receptor. Following acute treatment, only clozapine caused delayed striatal ERK phosphorylation through EGF receptor phosphorylation (tyrosine 1068 site) and MEK that paralleled cortical ERK phosphorylation. Olanzapine induced initial pERK1-specific blockade and an elevation 24-h later in PFC but had no effect in the striatum. By contrast, haloperidol significantly stimulated pERK1 in striatum for up to 8 h, but exerted limited effect in PFC. Clozapine but not olanzapine or haloperidol recruited the EGF receptor to signal to ERK. These in-vivo data reinforce our previous findings that clozapine's action may be uniquely linked to the EGF signalling system, potentially contributing to its distinctive clinical profile.