Psychoneuroimmunology
Encyclopedia
Psychoneuroimmunology is the study of the interaction between psychological processes and the nervous and immune systems of the human body. PNI takes an interdisciplinary approach, incorporating psychology
, neuroscience
, immunology
, physiology
, pharmacology
, molecular biology
, psychiatry
, behavioral medicine
, infectious diseases, endocrinology
, and rheumatology
.
The main interests of PNI are the interactions between the nervous
and immune systems and the relationships between mental processes and health
. PNI studies, among other things, the physiological
functioning of the neuroimmune system in health and disease; disorders of the neuroimmune system (autoimmune diseases; hypersensitivities
; immune deficiency); and the physical, chemical and physiological characteristics of the components of the neuroimmune system in vitro
, in situ
, and in vivo
.
PNI may also be referred to as psychoendoneuroimmunology (PENI).
Claude Bernard
, a French physiologist of the institute Muséum national d'Histoire naturelle, founded the concept milieu interieur
in the mid 1800s. In 1865, Bernard described the perturbation of this internal state “… there are protective functions of organic elements holding living materials in reserve and maintaining without interruption humidity, heat and other conditions indispensible to vital activity. Sickness and death are only a dislocation or perturbation of that mechanism (Bernard, 1865)". Walter Cannon, a professor of physiology at Harvard University
coined the commonly used term, homeostasis
in his book The Wisdom of the Body,1932, from the Greek word homoios, meaning similar, and stasis, meaning position. In his work with animals Cannon observed that any change of emotional state in the beast, such as anxiety
, distress
, or rage
was accompanied by total cessation of movements of the stomach (Bodily Changes in Pain, Hunger, Fear and Rage, 1915). These studies into the relationship between the effects of emotions and perceptions on the autonomic nervous system, namely the sympathetic and parasympathetic responses that initiated the recognition of the freeze, fight or flight response. His findings were published from time to time in professional journals, then summed up in book form in The Mechanical Factors of Digestion, published in 1911.
Hans Selye
, a student of John's Hopkins University and McGill University
, and a researcher at Université de Montréal
, experimented with animals putting them under different physical and mental adverse conditions and noted that under these conditions the body consistently adapted to heal and recover. Several years of experimentation that formed the empiric foundation of Dr. Selye's concept of the General Adaptation Syndrome. This syndrome consists of an enlargement of the adrenal gland, atrophy of the thymus
, spleen
and other lymphoid
tissue, and gastric ulcerations
.
Selye describes three stages of adaptation, including an initial brief alarm reaction, followed by a prolonged period of resistance and a terminal stage of exhaustion and death. This foundational work led to a rich line of research on the biological functioning of glucocorticoids.
Mid 20th century studies of psychiatric patients reported immune alterations in psychotic patients, including numbers of lymphocytes and poorer antibody
response to pertussis vaccination, compared with nonpsychiatric control subjects. In 1964 George F. Solomon, of The University of California in Los Angeles et all. coined the term "psychoimmunology" and published a landmark paper: "Emotions, immunity, and disease: a speculative theoretical integration."
advanced PNI with their demonstration of classic conditioning of immune function, and coined the term "psychoneuroimmunology". Ader was investigating how long conditioned responses (in the sense of Pavlov
's conditioning of dogs to drool when they heard a bell ring) might last in laboratory rats. To condition the rats, he used a combination of saccharin
-laced water (the conditioned stimulus) and the drug Cytoxan which unconditionally induces nausea and taste aversion and suppression of the immune system. Ader was surprised to discover that after conditioning, just feeding the rats saccharin-laced water was associated with the death of some animals and he proposed that they had been immunosuppressed after receiving the conditioned stimulus. Ader (a psychologist) and Cohen (an immunologist) directly tested this hypothesis by deliberately immunizing conditioned and unconditioned animals, exposing these and other control groups to the conditioned taste stimulus, and then measuring the amount of antibody produced. The highly reproducible results revealed that conditioned rats exposed to the conditioned stimulus were indeed immuno suppressed. In other words, a signal via the nervous system (taste) was affecting immune function. This was one of the first scientific experiments that demonstrated that the nervous system can affect the immune system.
In 1981 David Felten, then working at the Indiana University
of Medicine, discovered a network of nerves leading to blood vessels as well as cells of the immune system. The researchers also found nerves in the thymus
and spleen
terminating near clusters of lymphocyte
s, macrophage
s and mast cell
s, all of which help control immune function. This discovery provided one of the first indications of how neuro-immune interaction occurs.
Ader, Cohen and Felten went on to edit the groundbreaking book Psychoneuroimmunology in 1981, which laid out the underlying premise that the brain and immune system represent a single, integrated system of defense.
In 1985, research by neuropharmacologist Candace Pert
, of the National Institutes of Health
at Georgetown University
revealed that neuropeptide
-specific receptors are present on the cell walls of both the brain and the immune system. The discovery by Pert et al. that neuropeptides and neurotransmitters act directly upon the immune system shows their close association with emotions and suggests mechanisms through which emotions and immunology are deeply interdependent. Showing that the immune and endocrine systems are modulated not only by the brain but also by the central nervous system itself has had an impact on the understanding of emotions, as well as of disease.
Contemporary advances in psychiatry, immunology, neurology and other integrated disciplines of medicine has fostered enormous growth for PNI. The mechanisms underlying behaviorally induced alterations of immune function, and immune alterations inducing behavioral changes, are likely to have clinical and therapeutic implications that will not be fully appreciated until more is known about the extent of these interrelationships in normal and pathophysiological states.
The immune system and the brain talk to each other through signaling pathways. The brain and the immune system are the two major adaptive systems of the body. Two major pathways are involved in this cross-talk: the Hypothalamic-pituitary-adrenal axis
(HPA axis) and the sympathetic nervous system
(SNS). The activation of SNS during an immune response might be aimed to localize the inflammatory response.
The body's primary stress management system is the HPA axis. The HPA axis responds to physical and mental challenge to maintain homeostasis in part by controlling the body's cortisol
level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases. HPA axis activity and cytokines are intrinsically intertwined: inflammatory cytokines stimulate adrenocorticotropic hormone
(ACTH) and cortisol secretion, while, in turn, glucocorticoids suppress the synthesis of proinflammatory cytokines.
Molecules called pro-inflammatory cytokines, which include interleukin-1 (IL-1), Interleukin-2 (IL-2), interleukin-6 (IL-6), Interleukin-12 (IL-12), Interferon-gamma
(IFN-Gamma) and tumor necrosis factor alpha (TNF-alpha) can affect brain growth as well as neuronal function. Circulating immune cells such as macrophages, as well as glial cells (microglia
and astrocytes) secrete these molecules. Cytokine regulation of hypothalamic function is an active area of research for the treatment of anxiety-related disorders.
Cytokines mediate and control immune and inflammatory
responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis
. Like the stress response, the inflammatory reaction is crucial for survival. Systemic inflammatory reaction results in stimulation of four major programs:
These are mediated by the HPA axis and the SNS. Common human diseases such as allergy
, autoimmunity, chronic infections and sepsis
are characterized by a dysregulation of the pro-inflammatory versus anti-inflammatory and T helper (Th1) versus (Th2) cytokine balance.
Recent studies show pro-inflammatory cytokine
processes take place during depression
, mania
and bipolar
disease, in addition to autoimmune hypersensitivity and chronic infections.
Chronic secretion of stress
hormones, glucocorticoids (GCs) and catecholamines (CAs), as a result of disease, may reduce the effect of neurotransmitters, including serotonin
, norepinephrine
and dopamine
, or other receptors in the brain, thereby leading to the dysregulation of neurohormones. Under stimulation, norepinephrine is released from the sympathetic nerve terminals in organs, and the target immune cells express adrenoreceptors. Through stimulation of these receptors, locally released norepinephrine, or circulating catecholamines such as epinephrine
, affect lymphocyte
traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid
cells.
Glucocorticoids also inhibit the further secretion of corticotropin-releasing hormone from the hypothalamus
and ACTH from the pituitary (negative feedback
). Under certain conditions stress hormones may facilitate inflammation through induction of signaling pathways and through activation of the Corticotropin-releasing hormone
.
These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health, developing into a "systemic anti-inflammatory feedback" and/or "hyperactivity" of the local pro-inflammatory factors which may contribute to the pathogenesis of disease.
This systemic or neuro-inflammation and neuroimmune activation have been shown to play a role in the etiology
of a variety of neurodegenerative disorders such as Parkinson's and Alzheimer's disease
, multiple sclerosis
, pain, and AIDS
-associated dementia. However, cytokine
s and chemokine
s also modulate central nervous system (CNS) function in the absence of overt immunological, physiological, or psychological challenges.
and wound
healing have provided the strongest evidence to date, the clinical importance of immunological disregulation is highlighted by increased risks across diverse conditions and diseases.
Stress
is thought to affect immune function through emotional and/or behavioral manifestations such as anxiety
, fear
, tension
, anger
and sadness
and physiological changes such as heart rate
, blood pressure
, and sweating
. Researchers have suggested that these changes are beneficial if they are of limited duration, but when stress is chronic, the system is unable to maintain equilibrium or homeostasis
.
Immune changes in response to very brief stressors have been a central theme in the last decade of PNI research, but older literature also provides early illustrations. In a study published in 1960, subjects were led to believe that they had accidentally caused serious injury to a companion through misuse of explosives.
Two meta-analyses of the literature show a consistent reduction of immune function in healthy people who are experiencing stress.
In the first meta-analysis by Herbert and Cohen in 1993, they examined 38 studies of stressful events and immune function in healthy adults. They included studies of acute laboratory stressors (e.g. a speech task), short-term naturalistic stressors (e.g. medical examinations), and long-term naturalistic stressors (e.g. divorce, bereavement, caregiving, unemployment). They found consistent stress-related increases in numbers of total white blood cells, as well as decreases in the numbers of helper T cells, suppressor T cells, and cytotoxic T cells, B cells, and Natural killer cells (NK). They also reported stress-related decreases in NK and T cell function, and T cell proliferative responses to phytohaemagglutinin
[PHA] and concanavalin A
[Con A]. These effects were consistent for short-term and long-term naturalistic stressors, but not laboratory stressors.
In the second meta-analysis by Zorrilla et al. in 2001, they replicated Herbert and Cohen’s meta-analysis. Using the same study selection procedures, they analyzed 75 studies of stressors and human immunity. Naturalistic stressors were associated with increases in number of circulating neutrophils, decreases in number and percentages of total T cells and helper T cells, and decreases in percentages of Natural killer cell
(NK) cells and cytotoxic T cell
lymphocytes. They also replicated Herbert and Cohen’s finding of stress-related decreases in NKCC and T cell mitogen
proliferation to Phytohaemagglutinin
(PHA) and Concanavalin A
(Con A).
(CRH) from the hypothalamus
is influenced by stress.
Furthermore, stressors that enhance the release of CRH suppress the function of the immune system; conversely, stressors that depress CRH release potentiate immunity.
, catecholamine modulators, ion-channel blockers
, anticonvulsants, GABA agonists
(including opioids and cannabinoids
), COX inhibitors
, acetylcholine modulators
, melatonin
analogs (such as Ramelton), adenosine receptor antagonists
and several miscellaneous drugs (including biologics like Passiflora edulis
) are being studied for their psychoneuroimmunological effects.
For example, SSRI's, SNRI's
and tricyclic
antidepressants acting on serotonin
, norepinephrine
and dopamine
receptors have been shown to be immunomodulatory and anti-inflammatory against pro-inflammatory cytokine processes, specifically on the regulation of IFN-gamma and IL-10, as well as TNF-alpha and IL-6 through a psychoneuroimmunological process. Antidepressants have also been shown to suppress TH1 upregulation.
Tricyclic and dual serotonergic-noradrenergic reuptake inhibition by SNRIs (or SSRI-NRI combinations), have also shown analgesic
properties additionally. According to recent evidences antidepressants also seem to exert beneficial effects in experimental autoimmune neuritis in rats by decreasing Interferon-beta (IFN-beta) release or augmenting NK activity in depressed patients.
These studies warrant investigation for antidepressants for use in both psychiatric and non-psychiatric illness and that a psychoneuroimmunological approach may be required for optimal pharmacotherapy
in many diseases. Future antidepressants may be made to specifically target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.
Extrapolating from the observations that positive emotional experiences boost the immune system, Roberts speculates that intensely positive emotional experiences —sometimes brought about during mystical experiences occasioned by psychedelic medicines—may boost the immune system powerfully. Research on salivary IgA supports this hypothesis, but experimental testing has not been done.
Neuroanatomy
Related Topics
Psychology
Psychology is the study of the mind and behavior. Its immediate goal is to understand individuals and groups by both establishing general principles and researching specific cases. For many, the ultimate goal of psychology is to benefit society...
, neuroscience
Neuroscience
Neuroscience is the scientific study of the nervous system. Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics,...
, immunology
Immunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...
, physiology
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
, pharmacology
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
, molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
, psychiatry
Psychiatry
Psychiatry is the medical specialty devoted to the study and treatment of mental disorders. These mental disorders include various affective, behavioural, cognitive and perceptual abnormalities...
, behavioral medicine
Behavioral medicine
Behavioral medicine is an interdisciplinary field of medicine concerned with the development and integration of knowledge in the biological, behavioral, psychological, and social sciences relevant to health and illness...
, infectious diseases, endocrinology
Endocrinology
Endocrinology is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions called hormones, the integration of developmental events such as proliferation, growth, and differentiation and the coordination of...
, and rheumatology
Rheumatology
Rheumatology is a sub-specialty in internal medicine and pediatrics, devoted to diagnosis and therapy of rheumatic diseases. Clinicians who specialize in rheumatology are called rheumatologists...
.
The main interests of PNI are the interactions between the nervous
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
and immune systems and the relationships between mental processes and health
Health
Health is the level of functional or metabolic efficiency of a living being. In humans, it is the general condition of a person's mind, body and spirit, usually meaning to be free from illness, injury or pain...
. PNI studies, among other things, the physiological
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
functioning of the neuroimmune system in health and disease; disorders of the neuroimmune system (autoimmune diseases; hypersensitivities
Hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
; immune deficiency); and the physical, chemical and physiological characteristics of the components of the neuroimmune system in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
, in situ
In situ
In situ is a Latin phrase which translated literally as 'In position'. It is used in many different contexts.-Aerospace:In the aerospace industry, equipment on board aircraft must be tested in situ, or in place, to confirm everything functions properly as a system. Individually, each piece may...
, and in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
.
PNI may also be referred to as psychoendoneuroimmunology (PENI).
History
Interest in the relationship between psychiatric syndromes or symptoms and immune function has been a consistent theme since the beginning of modern medicine.Claude Bernard
Claude Bernard
Claude Bernard was a French physiologist. He was the first to define the term milieu intérieur . Historian of science I. Bernard Cohen of Harvard University called Bernard "one of the greatest of all men of science"...
, a French physiologist of the institute Muséum national d'Histoire naturelle, founded the concept milieu interieur
Milieu interieur
Milieu intérieur or interior milieu, from the French, milieu intérieur, is a term coined by Claude Bernard to refer to the extra-cellular fluid environment, and its physiological capacity to ensure protective stability for the tissues and organs of multicellular living organisms.-Origin:Claude...
in the mid 1800s. In 1865, Bernard described the perturbation of this internal state “… there are protective functions of organic elements holding living materials in reserve and maintaining without interruption humidity, heat and other conditions indispensible to vital activity. Sickness and death are only a dislocation or perturbation of that mechanism (Bernard, 1865)". Walter Cannon, a professor of physiology at Harvard University
Harvard University
Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...
coined the commonly used term, homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
in his book The Wisdom of the Body,1932, from the Greek word homoios, meaning similar, and stasis, meaning position. In his work with animals Cannon observed that any change of emotional state in the beast, such as anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
, distress
Distress
Distress may refer to:*Distress , occurring when an individual cannot adapt to stress*Suffering*Distress signal, an internationally recognized means for obtaining help...
, or rage
Rage (emotion)
Rage is a feeling of intense anger. It is associated with the Fight-or-flight response and oftentimes activated in response to an external cue, such as the murder of a loved one. The phrase, 'thrown into a fit of rage,' expresses the immediate nature of rage that occurs before deliberation. If left...
was accompanied by total cessation of movements of the stomach (Bodily Changes in Pain, Hunger, Fear and Rage, 1915). These studies into the relationship between the effects of emotions and perceptions on the autonomic nervous system, namely the sympathetic and parasympathetic responses that initiated the recognition of the freeze, fight or flight response. His findings were published from time to time in professional journals, then summed up in book form in The Mechanical Factors of Digestion, published in 1911.
Hans Selye
Hans Selye
Hans Hugo Bruno Selye, CC was a pioneering endocrinologist. Selye did much important scientific work on the hypothetical non-specific response of an organism to stressors. While he did not recognize all of the many aspects of glucocorticoids, Selye was aware of their role in the stress response...
, a student of John's Hopkins University and McGill University
McGill University
Mohammed Fathy is a public research university located in Montreal, Quebec, Canada. The university bears the name of James McGill, a prominent Montreal merchant from Glasgow, Scotland, whose bequest formed the beginning of the university...
, and a researcher at Université de Montréal
Université de Montréal
The Université de Montréal is a public francophone research university in Montreal, Quebec, Canada. It comprises thirteen faculties, more than sixty departments and two affiliated schools: the École Polytechnique and HEC Montréal...
, experimented with animals putting them under different physical and mental adverse conditions and noted that under these conditions the body consistently adapted to heal and recover. Several years of experimentation that formed the empiric foundation of Dr. Selye's concept of the General Adaptation Syndrome. This syndrome consists of an enlargement of the adrenal gland, atrophy of the thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
, spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
and other lymphoid
Lymphoid
Lymphoid is a term used to describe lymph or the lymphatic system.In the context of lymphoid leukemia, it refers specifically to lymphocytes Lymphoid leukemias and lymphomas are now considered to be tumors of the same type of cell lineage. They are called "leukemia" when in the blood or marrow and...
tissue, and gastric ulcerations
Peptic ulcer
A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
.
Selye describes three stages of adaptation, including an initial brief alarm reaction, followed by a prolonged period of resistance and a terminal stage of exhaustion and death. This foundational work led to a rich line of research on the biological functioning of glucocorticoids.
Mid 20th century studies of psychiatric patients reported immune alterations in psychotic patients, including numbers of lymphocytes and poorer antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
response to pertussis vaccination, compared with nonpsychiatric control subjects. In 1964 George F. Solomon, of The University of California in Los Angeles et all. coined the term "psychoimmunology" and published a landmark paper: "Emotions, immunity, and disease: a speculative theoretical integration."
Birth of psychoneuroimmunology
In 1975 Robert Ader and Nicholas Cohen at the University of RochesterUniversity of Rochester
The University of Rochester is a private, nonsectarian, research university in Rochester, New York, United States. The university grants undergraduate and graduate degrees, including doctoral and professional degrees. The university has six schools and various interdisciplinary programs.The...
advanced PNI with their demonstration of classic conditioning of immune function, and coined the term "psychoneuroimmunology". Ader was investigating how long conditioned responses (in the sense of Pavlov
Ivan Pavlov
Ivan Petrovich Pavlov was a famous Russian physiologist. Although he made significant contributions to psychology, he was not in fact a psychologist himself but was a mathematician and actually had strong distaste for the field....
's conditioning of dogs to drool when they heard a bell ring) might last in laboratory rats. To condition the rats, he used a combination of saccharin
Saccharin
Saccharin is an artificial sweetener. The basic substance, benzoic sulfilimine, has effectively no food energy and is much sweeter than sucrose, but has a bitter or metallic aftertaste, especially at high concentrations...
-laced water (the conditioned stimulus) and the drug Cytoxan which unconditionally induces nausea and taste aversion and suppression of the immune system. Ader was surprised to discover that after conditioning, just feeding the rats saccharin-laced water was associated with the death of some animals and he proposed that they had been immunosuppressed after receiving the conditioned stimulus. Ader (a psychologist) and Cohen (an immunologist) directly tested this hypothesis by deliberately immunizing conditioned and unconditioned animals, exposing these and other control groups to the conditioned taste stimulus, and then measuring the amount of antibody produced. The highly reproducible results revealed that conditioned rats exposed to the conditioned stimulus were indeed immuno suppressed. In other words, a signal via the nervous system (taste) was affecting immune function. This was one of the first scientific experiments that demonstrated that the nervous system can affect the immune system.
In 1981 David Felten, then working at the Indiana University
Indiana University
Indiana University is a multi-campus public university system in the state of Indiana, United States. Indiana University has a combined student body of more than 100,000 students, including approximately 42,000 students enrolled at the Indiana University Bloomington campus and approximately 37,000...
of Medicine, discovered a network of nerves leading to blood vessels as well as cells of the immune system. The researchers also found nerves in the thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
and spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
terminating near clusters of lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s, macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s and mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
s, all of which help control immune function. This discovery provided one of the first indications of how neuro-immune interaction occurs.
Ader, Cohen and Felten went on to edit the groundbreaking book Psychoneuroimmunology in 1981, which laid out the underlying premise that the brain and immune system represent a single, integrated system of defense.
In 1985, research by neuropharmacologist Candace Pert
Candace Pert
Candace Beebe Pert is an American neuroscientist and pharmacologist who discovered the opiate receptor, the cellular binding site for endorphins in the brain.-History:...
, of the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
at Georgetown University
Georgetown University
Georgetown University is a private, Jesuit, research university whose main campus is in the Georgetown neighborhood of Washington, D.C. Founded in 1789, it is the oldest Catholic university in the United States...
revealed that neuropeptide
Neuropeptide
Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...
-specific receptors are present on the cell walls of both the brain and the immune system. The discovery by Pert et al. that neuropeptides and neurotransmitters act directly upon the immune system shows their close association with emotions and suggests mechanisms through which emotions and immunology are deeply interdependent. Showing that the immune and endocrine systems are modulated not only by the brain but also by the central nervous system itself has had an impact on the understanding of emotions, as well as of disease.
Contemporary advances in psychiatry, immunology, neurology and other integrated disciplines of medicine has fostered enormous growth for PNI. The mechanisms underlying behaviorally induced alterations of immune function, and immune alterations inducing behavioral changes, are likely to have clinical and therapeutic implications that will not be fully appreciated until more is known about the extent of these interrelationships in normal and pathophysiological states.
The Immune-Brain Loop
PNI research is looking for the exact mechanisms by which specific brainimmunity effects are achieved. Evidence for nervous system–immune system interactions exists at several biological levels.The immune system and the brain talk to each other through signaling pathways. The brain and the immune system are the two major adaptive systems of the body. Two major pathways are involved in this cross-talk: the Hypothalamic-pituitary-adrenal axis
Hypothalamic-pituitary-adrenal axis
The hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland ,...
(HPA axis) and the sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
(SNS). The activation of SNS during an immune response might be aimed to localize the inflammatory response.
The body's primary stress management system is the HPA axis. The HPA axis responds to physical and mental challenge to maintain homeostasis in part by controlling the body's cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases. HPA axis activity and cytokines are intrinsically intertwined: inflammatory cytokines stimulate adrenocorticotropic hormone
Adrenocorticotropic hormone
Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
(ACTH) and cortisol secretion, while, in turn, glucocorticoids suppress the synthesis of proinflammatory cytokines.
Molecules called pro-inflammatory cytokines, which include interleukin-1 (IL-1), Interleukin-2 (IL-2), interleukin-6 (IL-6), Interleukin-12 (IL-12), Interferon-gamma
Interferon-gamma
Interferon-gamma is a dimerized soluble cytokine that is the only member of the type II class of interferons. This interferon was originally called macrophage-activating factor, a term now used to describe a larger family of proteins to which IFN-γ belongs...
(IFN-Gamma) and tumor necrosis factor alpha (TNF-alpha) can affect brain growth as well as neuronal function. Circulating immune cells such as macrophages, as well as glial cells (microglia
Microglia
Microglia are a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system . Microglia constitute 20% of the total glial cell population within the brain...
and astrocytes) secrete these molecules. Cytokine regulation of hypothalamic function is an active area of research for the treatment of anxiety-related disorders.
Cytokines mediate and control immune and inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
. Like the stress response, the inflammatory reaction is crucial for survival. Systemic inflammatory reaction results in stimulation of four major programs:
- the acute-phase reaction
- Sickness behaviorSickness behaviorthumb|350px|right|[[Michael Peter Ancher|Ancher, Michael]], "The Sick Girl", 1882, [[Statens Museum for Kunst]]Sickness behavior is a coordinated set of adaptive behavioral changes that develop in ill individuals during the course of an infection....
- the pain program
- the stress response
These are mediated by the HPA axis and the SNS. Common human diseases such as allergy
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
, autoimmunity, chronic infections and sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
are characterized by a dysregulation of the pro-inflammatory versus anti-inflammatory and T helper (Th1) versus (Th2) cytokine balance.
Recent studies show pro-inflammatory cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
processes take place during depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...
and bipolar
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
disease, in addition to autoimmune hypersensitivity and chronic infections.
Chronic secretion of stress
Stress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
hormones, glucocorticoids (GCs) and catecholamines (CAs), as a result of disease, may reduce the effect of neurotransmitters, including serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, or other receptors in the brain, thereby leading to the dysregulation of neurohormones. Under stimulation, norepinephrine is released from the sympathetic nerve terminals in organs, and the target immune cells express adrenoreceptors. Through stimulation of these receptors, locally released norepinephrine, or circulating catecholamines such as epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
, affect lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid
Lymphoid
Lymphoid is a term used to describe lymph or the lymphatic system.In the context of lymphoid leukemia, it refers specifically to lymphocytes Lymphoid leukemias and lymphomas are now considered to be tumors of the same type of cell lineage. They are called "leukemia" when in the blood or marrow and...
cells.
Glucocorticoids also inhibit the further secretion of corticotropin-releasing hormone from the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
and ACTH from the pituitary (negative feedback
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
). Under certain conditions stress hormones may facilitate inflammation through induction of signaling pathways and through activation of the Corticotropin-releasing hormone
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
.
These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health, developing into a "systemic anti-inflammatory feedback" and/or "hyperactivity" of the local pro-inflammatory factors which may contribute to the pathogenesis of disease.
This systemic or neuro-inflammation and neuroimmune activation have been shown to play a role in the etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
of a variety of neurodegenerative disorders such as Parkinson's and Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
, pain, and AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
-associated dementia. However, cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s and chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
s also modulate central nervous system (CNS) function in the absence of overt immunological, physiological, or psychological challenges.
Psychoneuroimmunological effects
There is now sufficient data to conclude that immune modulation by psychosocial stressors and/or interventions can lead to actual health changes. Although changes related to infectious diseaseInfectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
and wound
Wound
A wound is a type of injury in which skin is torn, cut or punctured , or where blunt force trauma causes a contusion . In pathology, it specifically refers to a sharp injury which damages the dermis of the skin.-Open:...
healing have provided the strongest evidence to date, the clinical importance of immunological disregulation is highlighted by increased risks across diverse conditions and diseases.
Link between stress and disease
Stressors can produce profound health consequences. In one epidemiological study, for example, all-cause mortality increased in the month following a severe stressor – the death of a spouse. Theorists propose that stressful events trigger cognitive and affective responses which, in turn, induce sympathetic nervous system and endocrine changes, and these ultimately impair immune function. Potential health consequences are broad, but include rates of infection HIV progression and cancer incidence and progression.Stress
Stress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
is thought to affect immune function through emotional and/or behavioral manifestations such as anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
, fear
Fear
Fear is a distressing negative sensation induced by a perceived threat. It is a basic survival mechanism occurring in response to a specific stimulus, such as pain or the threat of danger...
, tension
Stress (biology)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
, anger
Anger
Anger is an automatic response to ill treatment. It is the way a person indicates he or she will not tolerate certain types of behaviour. It is a feedback mechanism in which an unpleasant stimulus is met with an unpleasant response....
and sadness
Sadness
Sadness is emotional pain associated with, or characterized by feelings of disadvantage, loss, despair, helplessness, sorrow, and rage. When sad, people often become outspoken, less energetic, and emotional...
and physiological changes such as heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
, blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, and sweating
Sweating
Perspiration is the production of a fluid consisting primarily of water as well as various dissolved solids , that is excreted by the sweat glands in the skin of mammals...
. Researchers have suggested that these changes are beneficial if they are of limited duration, but when stress is chronic, the system is unable to maintain equilibrium or homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
.
Immune changes in response to very brief stressors have been a central theme in the last decade of PNI research, but older literature also provides early illustrations. In a study published in 1960, subjects were led to believe that they had accidentally caused serious injury to a companion through misuse of explosives.
Two meta-analyses of the literature show a consistent reduction of immune function in healthy people who are experiencing stress.
In the first meta-analysis by Herbert and Cohen in 1993, they examined 38 studies of stressful events and immune function in healthy adults. They included studies of acute laboratory stressors (e.g. a speech task), short-term naturalistic stressors (e.g. medical examinations), and long-term naturalistic stressors (e.g. divorce, bereavement, caregiving, unemployment). They found consistent stress-related increases in numbers of total white blood cells, as well as decreases in the numbers of helper T cells, suppressor T cells, and cytotoxic T cells, B cells, and Natural killer cells (NK). They also reported stress-related decreases in NK and T cell function, and T cell proliferative responses to phytohaemagglutinin
Phytohaemagglutinin
Phytohaemagglutinin is a lectin found in plants, especially legumes. PHA actually consists of two closely related proteins, called leucoagglutinin and PHA-E. The letters E and L indicate these proteins agglutinate Erythrocytes and Leukocytes...
[PHA] and concanavalin A
Concanavalin A
Concanavalin A is a lectin originally extracted from the jack-bean, Canavalia ensiformis. It binds specifically to certain structures found in various sugars, glycoproteins, and glycolipids, mainly internal and nonreducing terminal α-D-mannosyl and α-D-glucosyl groups...
[Con A]. These effects were consistent for short-term and long-term naturalistic stressors, but not laboratory stressors.
In the second meta-analysis by Zorrilla et al. in 2001, they replicated Herbert and Cohen’s meta-analysis. Using the same study selection procedures, they analyzed 75 studies of stressors and human immunity. Naturalistic stressors were associated with increases in number of circulating neutrophils, decreases in number and percentages of total T cells and helper T cells, and decreases in percentages of Natural killer cell
Natural killer cell
Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...
(NK) cells and cytotoxic T cell
Cytotoxic T cell
A cytotoxic T cell belongs to a sub-group of T lymphocytes that are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses , or are otherwise damaged or...
lymphocytes. They also replicated Herbert and Cohen’s finding of stress-related decreases in NKCC and T cell mitogen
Mitogen
A mitogen is a chemical substance that encourages a cell to commence cell division, triggering mitosis. A mitogen is usually some form of a protein.Mitogenesis is the induction of mitosis, typically via a mitogen....
proliferation to Phytohaemagglutinin
Phytohaemagglutinin
Phytohaemagglutinin is a lectin found in plants, especially legumes. PHA actually consists of two closely related proteins, called leucoagglutinin and PHA-E. The letters E and L indicate these proteins agglutinate Erythrocytes and Leukocytes...
(PHA) and Concanavalin A
Concanavalin A
Concanavalin A is a lectin originally extracted from the jack-bean, Canavalia ensiformis. It binds specifically to certain structures found in various sugars, glycoproteins, and glycolipids, mainly internal and nonreducing terminal α-D-mannosyl and α-D-glucosyl groups...
(Con A).
Communication between the brain and immune system
- Stimulation of brain sites alters immunity (stressed animals have altered immune systems).
- Immune cells produce cytokines that act on the CNS.
- Immune cells respond to signals from the CNS.
Communication between neuroendocrine and immune system
- Glucocorticoids and catecholamines influence immune cells.
- Endorphins from pituitary & adrenal medullaAdrenal medullaThe adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of cells that secrete epinephrine , norepinephrine , and a small amount of dopamine in response to...
act on immune system. - Activity of the immune system is correlated with neurochemical/neuroendocrine activity of brain cells.
Connections between glucocorticoids and immune system
- Anti-inflammatory hormones that enhance the organisms response to a stressor.
- Prevent the overreaction of the body's own defense system.
- Regulators of the immune system.
- Affect cell growth, proliferation & differentiation.
- Cause immunosuppression.
- Suppress cell adhesionCell adhesionCellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...
, antigenAntigenAn antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
presentation, chemotaxis & cytotoxicity. - Increase apoptosisApoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
.
Corticotropin-releasing hormone (CRH)
Release of corticotropin-releasing hormoneCorticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
(CRH) from the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
is influenced by stress.
- CRH is a major regulator of the HPA axis/stress axis.
- CRH Regulates secretion of Adrenocorticotropic hormoneAdrenocorticotropic hormoneAdrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
(ACTH). - CRH is widely distributed in the brain and periphery
- CRH also regulates the actions of the Autonomic nervous systemAutonomic nervous systemThe autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
ANS and immune system.
Furthermore, stressors that enhance the release of CRH suppress the function of the immune system; conversely, stressors that depress CRH release potentiate immunity.
- Central mediated since peripheral administration of CRH antagonist does not affect immunosuppression.he he he
Pharmaceutical advances
Glutamate agonists, cytokine inhibitors, vanilloid-receptor agonistsTRPV1
The transient receptor potential cation channel subfamily V member 1 ', also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the TRPV1 gene...
, catecholamine modulators, ion-channel blockers
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
, anticonvulsants, GABA agonists
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
(including opioids and cannabinoids
Cannabinoids
Cannabinoids are a class of chemical compounds that include the phytocannabinoids , and chemical compounds that mimic the actions of phytocannabinoids or have a similar structure...
), COX inhibitors
Cyclooxygenase
Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...
, acetylcholine modulators
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
, melatonin
Melatonin
Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...
analogs (such as Ramelton), adenosine receptor antagonists
Adenosine receptor
The adenosine receptors are a class of purinergic receptors, G protein-coupled receptors with adenosine as endogenous ligand.-Pharmacology:...
and several miscellaneous drugs (including biologics like Passiflora edulis
Passiflora edulis
Passiflora edulis is a vine species of passion flower that is native to Paraguay, Brazil and northern Argentina . Its common names include passion fruit and passionfruit...
) are being studied for their psychoneuroimmunological effects.
For example, SSRI's, SNRI's
SNRI
SNRI may refer to:* Serotonin–norepinephrine reuptake inhibitor* Strategic Naval Research Institute...
and tricyclic
Tricyclic
Tricyclics are chemical compounds that contain three interconnected rings of atoms.Many compounds have a tricyclic structure, but in pharmacology, the term has traditionally been reserved to describe heterocyclic drugs...
antidepressants acting on serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
receptors have been shown to be immunomodulatory and anti-inflammatory against pro-inflammatory cytokine processes, specifically on the regulation of IFN-gamma and IL-10, as well as TNF-alpha and IL-6 through a psychoneuroimmunological process. Antidepressants have also been shown to suppress TH1 upregulation.
Tricyclic and dual serotonergic-noradrenergic reuptake inhibition by SNRIs (or SSRI-NRI combinations), have also shown analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
properties additionally. According to recent evidences antidepressants also seem to exert beneficial effects in experimental autoimmune neuritis in rats by decreasing Interferon-beta (IFN-beta) release or augmenting NK activity in depressed patients.
These studies warrant investigation for antidepressants for use in both psychiatric and non-psychiatric illness and that a psychoneuroimmunological approach may be required for optimal pharmacotherapy
Pharmacotherapy
Pharmacotherapy is the treatment of disease through the administration of drugs. As such, it is considered part of the larger category of therapy....
in many diseases. Future antidepressants may be made to specifically target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.
Extrapolating from the observations that positive emotional experiences boost the immune system, Roberts speculates that intensely positive emotional experiences —sometimes brought about during mystical experiences occasioned by psychedelic medicines—may boost the immune system powerfully. Research on salivary IgA supports this hypothesis, but experimental testing has not been done.
See also
Branches of Medicine- Biological psychiatryBiological psychiatryBiological psychiatry, or biopsychiatry is an approach to psychiatry that aims to understand mental disorder in terms of the biological function of the nervous system. It is interdisciplinary in its approach and draws on sciences such as neuroscience, psychopharmacology, biochemistry, genetics and...
- EndocrinologyEndocrinologyEndocrinology is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions called hormones, the integration of developmental events such as proliferation, growth, and differentiation and the coordination of...
- PsychoneuroendocrinologyPsychoneuroendocrinologyPsychoneuroendocrinology is the clinical study of hormone fluctuations and their relationship to human behavior. It may be viewed from the perspective of psychiatry, where in certain mood disorders, there are associated neuroendocrine or hormonal changes affecting the brain...
- ImmunologyImmunologyImmunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...
- NeuroanatomyNeuroanatomyNeuroanatomy is the study of the anatomy and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defined nervous systems, and thus we can begin to speak of...
- Neurobiology
- NeurochemistryNeurochemistryNeurochemistry is the specific study of neurochemicals, which include neurotransmitters and other molecules such as neuro-active drugs that influence neuron function. This principle closely examines the manner in which these neurochemicals influence the network of neural operation...
- NeurologyNeurologyNeurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...
- NeuropharmacologyNeuropharmacologyNeuropharmacology is the study of how drugs affect cellular function in the nervous system. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmacology focuses on the study of how drugs affect human behavior , including the study of how drug dependence...
- PsychiatryPsychiatryPsychiatry is the medical specialty devoted to the study and treatment of mental disorders. These mental disorders include various affective, behavioural, cognitive and perceptual abnormalities...
Neuroanatomy
- Locus ceruleusLocus ceruleusThe locus coeruleus , is a nucleus in the brainstem involved with physiological responses to stress and panic. It was discovered in the 18th century by Félix Vicq-d'Azyr....
- Pedunculopontine nucleusPedunculopontine nucleusThe pedunculopontine nucleus is located in the brainstem, caudal to the substantia nigra and adjacent to the superior cerebellar peduncle. It has two divisions, one containing cholinergic neurons, the pars compacta, and one containing mostly glutamatergic neurons, the pars dissipata...
- Raphe nucleus
- Reticular activating systemReticular activating systemThe reticular activating system is an area of the brain responsible for regulating arousal and sleep-wake transitions.- History and Etymology :...
- Suprachiasmatic nucleusSuprachiasmatic nucleusThe suprachiasmatic nucleus or nuclei, abbreviated SCN, is a tiny region on the brain's midline, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms...
Related Topics
- Allostatic loadAllostatic loadThe term allostatic load, coined by McEwen and Stellar in 1993, is defined as the physiological consequences of chronic exposure to fluctuating or heightened neural or neuroendocrine response that results from repeated or chronic stress....
- Fight-or-flight responseFight-or-flight responseThe fight-or-flight response was first described by Walter Bradford Cannon....
- Healing environmentsHealing environmentsHealing environment, for healthcare buildings describes a physical setting and organizational culture that supports patients and families through the stresses imposed by illness, hospitalization, medical visits, the process of healing, and sometimes, bereavement.The philosophy that guides this...
- Integrative medicineIntegrative medicineIntegrative medicine or integrative health is the combination of the practices and methods of alternative medicine with conventional medicine. The term is relatively recent, and is mainly promoted by proponents of alternative therapies in the west...
- Music therapyMusic therapyMusic therapy is an allied health profession and one of the expressive therapies, consisting of an interpersonal process in which a trained music therapist uses music and all of its facets—physical, emotional, mental, social, aesthetic, and spiritual—to help clients to improve or maintain their...
- Neural top down control of physiologyNeural top down control of physiologyNeural top down control of physiology concerns the direct regulation by the brain of physiological functions...
- Post-traumatic stress disorderPost-traumatic stress disorderPosttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...
- Psychosomatic medicine
- Stress managementStress managementStress management is the alteration of stress and especially chronic stress often for the purpose of improving everyday functioning.Stress produces numerous symptoms which vary according to persons, situations, and severity. These can include physical health decline as well as depression. According...
Recommended Reading
- Berczi and Szentivanyi (2003) NeuroImmune Biology, Elsevier, ISBN 0-444-50851-1 (Written for the highly technical reader)
- Goodkin, Karl, and Adriaan P. Visser, (eds), Psychoneuroimmunology: Stress, Mental Disorders , and Health, American Psychiatric Press, 2000, ISBN 0-88048-171-4, technical.
- Ransohoff, Richard, et al. (eds), Universes in Delicate Balance: Chemokines and the Nervous System, Elsevier, 2002, ISBN 0-444-51002-8
- Robert Ader, David L. Felten, Nicholas Cohen , Psychoneuroimmunology, 4th edition, 2 volumes, Academic Press, (2006), ISBN 0-12-088576-X
- Roberts, Thomas B. (2006). "Do Entheogen-induced Mystical Experiences Boost the Immune System?: Psychedelics, Peak Experiences, and Wellness." Chapter 6 in Psychedelic Horizons. Westport, CT: Praeger/Greenwood.