Chronic Stress, the Immune System and Psychiatric Disorders
Abstract
In the last decades, psychoneuroendocrineimmunology research has made relevant contributions to the fields of neuroscience, psychobiology, epigenetics, molecular biology, and clinical research by studying the effect of stress on human health and highlighting the close interrelations between psyche, brain, and bodily systems.
It is now well recognized that chronic stress can alter the physiological cross-talk between brain and biological systems, leading to long-lasting maladaptive effects (allostatic overload) on the nervous, immune, endocrine, and metabolic systems, which compromises stress resiliency and health.
Stressful conditions in early life have been associated with profound alterations in cortical and subcortical brain regions involved in emotion regulation and the salience network, showing relevant overlap with different psychiatric conditions.
This paper provides a summary of the available literature concerning the notable effects of stress on the brain and immune system.
We highlight the role of epigenetics as a mechanistic pathway mediating the influences of the social and physical environment on brain structure and connectivity, the immune system, and psycho-physical health in psychiatric diseases.
We also summarize the evidence regarding the effects of stress management techniques (mainly psychotherapy and meditation practice) on clinical outcomes, brain neurocircuitry, and immune-inflammatory network in major psychiatric diseases.
Val's Note: I always feel weird about Child Abuse and Psychiatric Disorders because it is such an IMPORTANT FACTOR, but I have psychiatric disorders and I wasn't abused as a child.
Further, I think issues such as MATERNAL IMMUNE INFLAMMATION, MATERNAL AUTOIMMUNE DISEASE, and even GRAND-MATERNAL SMOKING can be MAJOR FACTORS.
The Human Immune Response (2019)
Abstract
The human stress response has evolved to maintain homeostasis under conditions of real or perceived stress.
This objective is achieved through autoregulatory neural and hormonal systems in close association with central and peripheral clocks.
The hypothalamic-pituitary-adrenal axis is a key regulatory pathway in the maintenance of these homeostatic processes.
The end product of this pathway - cortisol - is secreted in a pulsatile pattern, with changes in pulse amplitude creating a circadian pattern.
During acute stress, cortisol levels rise and pulsatility is maintained. Although the initial rise in cortisol follows a large surge in adrenocorticotropic hormone levels,
if long-term inflammatory stress occurs, adrenocorticotropic hormone levels return to near basal levels while cortisol levels remain raised as a result of increased adrenal sensitivity.
In chronic stress, hypothalamic activation of the pituitary changes from corticotropin-releasing hormone-dominant to arginine vasopressin-dominant, and cortisol levels remain raised due at least in part to decreased cortisol metabolism.
Acute elevations in cortisol levels are beneficial to promoting survival of the fittest as part of the fight-or-flight response.
However, chronic exposure to stress results in reversal of the beneficial effects, with long-term cortisol exposure becoming maladaptive, which can lead to a broad range of problems including the metabolic syndrome, obesity, cancer, mental health disorders, cardiovascular disease and increased susceptibility to infections.
Neuroimmunoendocrine modulation in disease states and glucocorticoid-based therapeutics are also discussed.
Abstract
The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis.
The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation.
The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling.
After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal.
When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results.
Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis.
The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem.
Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders.
These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis.