Psychoneuroimmunology How our brains and bodies are linked

PsychoneuroimmunologyPsychoneuroimmunology

How our brains and bodies are How our brains and bodies are linkedlinked

PsychoneuroimmunologyPsychoneuroimmunology

Study of the interaction between psychological Study of the interaction between psychological processes and the nervous, immune and processes and the nervous, immune and endocrine systems of the bodyendocrine systems of the body

Incorporates psychology, immunology, Incorporates psychology, immunology, physiology, endocrinology, infectious disease, physiology, endocrinology, infectious disease, rheumatology and molecular biology.rheumatology and molecular biology.

Better name: PENI Better name: PENI (psychoendoneuroimmunology(psychoendoneuroimmunology

HistoryHistory

1975, Dr. Robert Adler demonstrated 1975, Dr. Robert Adler demonstrated through classic conditioning experiments: through classic conditioning experiments: Rats were conditioned to associated Rats were conditioned to associated saccharin-laced water with the drug saccharin-laced water with the drug Cytoxan which induces nausea and Cytoxan which induces nausea and suppression of the immune system. suppression of the immune system.

After the conditioning, just feeding the rats After the conditioning, just feeding the rats the saccharin water led to death of some the saccharin water led to death of some by through a compromised IS.by through a compromised IS.

It’s all a circleIt’s all a circle

The immune system can be modulated by The immune system can be modulated by endocrine and neural activityendocrine and neural activity

And it can just as easily influence And it can just as easily influence endocrine and neural activityendocrine and neural activity

The IS and brain talk to each other The IS and brain talk to each other through the hypothalamic-pituitary-adrenal through the hypothalamic-pituitary-adrenal (HPA) axis, other hormonal pathways and (HPA) axis, other hormonal pathways and the sympathetic nervous system (SNS)the sympathetic nervous system (SNS)

In other words:In other words:

We think a thought or experience an We think a thought or experience an emotion, and our body responds either emotion, and our body responds either with health-enhancing or health-inhibiting with health-enhancing or health-inhibiting actionsactions

Physical behaviors (i.e. exercise, diet, etc.) Physical behaviors (i.e. exercise, diet, etc.) can influence our thoughts and emotionscan influence our thoughts and emotions

HPA axisHPA axis

Responds to physical, mental and Responds to physical, mental and emotional challenges by controlling emotional challenges by controlling hormonal and neurotransmittershormonal and neurotransmitters

Many diseases are linked to dis-regulation Many diseases are linked to dis-regulation of this axisof this axis

Review of hormonal termsReview of hormonal terms

HPA axisHPA axis CRHCRH ACTHACTH GlucocorticoidsGlucocorticoids

CorticosteroneCorticosterone CortisolCortisol

CatecholaminesCatecholamines Epinephrine(adrenaline)Epinephrine(adrenaline) Norepinephrine (noradrenalin)Norepinephrine (noradrenalin)

Review of hormonal termsReview of hormonal terms

Endorphins and enkephalinsEndorphins and enkephalins Adrenergic and noradrenergicAdrenergic and noradrenergic Acetylcholine: major neuro-transmitter of Acetylcholine: major neuro-transmitter of

PSNPSN cholinergiccholinergic

Review of IS termsReview of IS terms

Immune cells:Immune cells: Phagocytes: monocytes, macrophagesPhagocytes: monocytes, macrophages Mast cells - trigger inflammatory responseMast cells - trigger inflammatory response LymphocytesLymphocytes

B and T lymphocytesB and T lymphocytes Interferons - anti-viralsInterferons - anti-virals NK cells - anti-viral and cancer cellsNK cells - anti-viral and cancer cells Antibodies/immunoglobulinsAntibodies/immunoglobulins

Cytokines respond to specific antigensCytokines respond to specific antigens Interleukins are types of cytokinesInterleukins are types of cytokines

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These are not separate These are not separate systems!systems!

Immune cells secrete and have receptors Immune cells secrete and have receptors for hormones, neurotransmitters and for hormones, neurotransmitters and neuropeptidesneuropeptides

Neurons have receptors for both Neurons have receptors for both hormones and neurotransmittershormones and neurotransmitters

Many hormones behave like Many hormones behave like neurotransmitters: they are released from neurotransmitters: they are released from endocrine and nervous tissue endocrine and nervous tissue Called neuropeptidesCalled neuropeptides

Not separate systems, cont’dNot separate systems, cont’d

Neuropeptides and classic Neuropeptides and classic neurotransmitters can coexist in the same neurotransmitters can coexist in the same neuronneuron

Neuropeptides found in the brain include Neuropeptides found in the brain include hormones previously thought to reside hormones previously thought to reside only in the GI tract, anterior and posterior only in the GI tract, anterior and posterior pituitary pituitary

““The implications of the nervous and endocrine The implications of the nervous and endocrine systems sharing transmitters are enormous and systems sharing transmitters are enormous and set the stage for significant interactions with the set the stage for significant interactions with the

immune and stress systems. ..The body houses an immune and stress systems. ..The body houses an efficient organization not only for the nervous efficient organization not only for the nervous

system to communicate with the hormones of the system to communicate with the hormones of the endocrine system, or vice versa, but also for the endocrine system, or vice versa, but also for the immune and stress systems to influence and be immune and stress systems to influence and be

influenced by the nervous and endocrine systems.” influenced by the nervous and endocrine systems.” WisneskiWisneski



Communication between Communication between brain and immune systembrain and immune system

Epinephrine and Nor-ep generally suppress the Epinephrine and Nor-ep generally suppress the immune system, but enhance it in the CNS, immune system, but enhance it in the CNS, potentiated by immune cells potentiated by immune cells

Neurons fire more frequently during antibody Neurons fire more frequently during antibody response to an immunization, and nor-ep response to an immunization, and nor-ep decreased decreased

IS sends humoral and neural messages to the IS sends humoral and neural messages to the brain of intruders, which triggers the HPA axis or brain of intruders, which triggers the HPA axis or peripheral cytokinesperipheral cytokines

More Brain/IS communicationMore Brain/IS communication

Activated immune cells are capable of Activated immune cells are capable of permeating the blood brain barrier and permeating the blood brain barrier and secreting cytokines, which can influence secreting cytokines, which can influence peripheral neuroendo functionsperipheral neuroendo functions

Communication between Communication between neuroendocrine and ISneuroendocrine and IS

Immune cells respond to signals from the CNS, Immune cells respond to signals from the CNS, thru the HPA axisthru the HPA axis

Pituitary and adrenal endorphins positively affect Pituitary and adrenal endorphins positively affect the immune systemthe immune system

Cytokines in the brain influence the HPA axisCytokines in the brain influence the HPA axis Cytokines all cause pituitary-like hormones to be Cytokines all cause pituitary-like hormones to be

secreted by Immune cells, modulating pituitary secreted by Immune cells, modulating pituitary hormone secretions (some regulate and some hormone secretions (some regulate and some inhibit normal growth and promote tumor growth)inhibit normal growth and promote tumor growth)

More communication!More communication!

Neuroendo hormones have receptors on and are Neuroendo hormones have receptors on and are produced by immune cells.produced by immune cells.

CRH encourages leukocytes to secrete ACTH CRH encourages leukocytes to secrete ACTH ACTH decreases antibody production, and ACTH decreases antibody production, and

suppresses immune function via glucocorticoid suppresses immune function via glucocorticoid stimulation (why we get sick when stressed)stimulation (why we get sick when stressed)

T lymphocytes have receptors for enkephalins, T lymphocytes have receptors for enkephalins, increasing NK cell activityincreasing NK cell activity



Thymus GlandThymus Gland

Master trainer of immune system: secretes Master trainer of immune system: secretes hormones, is influenced by neurotransmitters, hormones, is influenced by neurotransmitters, and regulates immune systemand regulates immune system

GH, prolactin, ACTH, LH are produced within the GH, prolactin, ACTH, LH are produced within the thymus as well as pituitarythymus as well as pituitary

These hormones regulate immune action and These hormones regulate immune action and influence regulation of the HPA axisinfluence regulation of the HPA axis

Norepinephrine primary thymus hormone: as we Norepinephrine primary thymus hormone: as we age, it increases, reducing immune functionage, it increases, reducing immune function



Pineal GlandPineal Gland

Its sensory receptors are capable of Its sensory receptors are capable of receiving environmental stimuli and receiving environmental stimuli and converting them into action potentials converting them into action potentials capable of communicating with the brain.capable of communicating with the brain. Transforms light-dark perception and Transforms light-dark perception and

transforms it into our circadian rhythm thru transforms it into our circadian rhythm thru production of melatoninproduction of melatonin

Melatonin regulates myriad endocrine and Melatonin regulates myriad endocrine and immune functionsimmune functions

MelatoninMelatonin

Stimulates immune function and reduces Stimulates immune function and reduces the deleterious effects of stressthe deleterious effects of stress

Fits into its own receptor but also into the Fits into its own receptor but also into the benzodiazepine receptorsbenzodiazepine receptors

Immune-boosting effects of melatonin Immune-boosting effects of melatonin appear to come from it stimulating T-appear to come from it stimulating T-lymphocyte helper cells that have already lymphocyte helper cells that have already been stimulated by an antigen.been stimulated by an antigen.





HPA Axis and Immune HPA Axis and Immune SystemSystem

IS is a sensory receptor organ that sends IS is a sensory receptor organ that sends info to CNS through cytokinesinfo to CNS through cytokines

Activated CNS structures (hippocampus, Activated CNS structures (hippocampus, hypothalamus)cause neuroendocrine hypothalamus)cause neuroendocrine immune peripheral effects immune peripheral effects

Immune system stimulates HPA axis, once Immune system stimulates HPA axis, once a certain threshold is met (controlling over-a certain threshold is met (controlling over-responsiveness)responsiveness)

HPA Axis and Immune HPA Axis and Immune System, cont’dSystem, cont’d

Activation of the stress response during Activation of the stress response during injury and illness causes immune injury and illness causes immune suppression , controlling over-expressionsuppression , controlling over-expression

If immune mediators were not checked, If immune mediators were not checked, glucocorticoid secretions would shut down glucocorticoid secretions would shut down immune systemimmune system

Crucial to body’s self-regulationCrucial to body’s self-regulation

Intercellular communication Intercellular communication in the Anterior Pituitaryin the Anterior Pituitary

Novel pituitary-like hormones subtly adjust Novel pituitary-like hormones subtly adjust classic pituitary hormones, thus affecting classic pituitary hormones, thus affecting function and cell growth. function and cell growth.

Overall influence is significant to an Overall influence is significant to an integrated hormonal responseintegrated hormonal response Galanin influences pituitary secretions, which Galanin influences pituitary secretions, which

affect sexual and growth functions, and affect sexual and growth functions, and modulate stress and immune responsemodulate stress and immune response

SummarySummary

Nervous and endocrine systems share Nervous and endocrine systems share neurotransmitters neurotransmitters

Brain receives and responds to chemical Brain receives and responds to chemical and electrical info from ISand electrical info from IS

IS is a sensory organ because it can IS is a sensory organ because it can obtain, process and send info to CNSobtain, process and send info to CNS

Cytokines are principal mediators of Cytokines are principal mediators of communication between neuroendocrine communication between neuroendocrine and ISand IS

Summary, cont’dSummary, cont’d

Lymphocytes have receptors for hormonesLymphocytes have receptors for hormones Thymic hormones influence reg of HPA Thymic hormones influence reg of HPA

axisaxis Bi-directional, afferent-efferent pathway Bi-directional, afferent-efferent pathway

between the IS and neuroendocrine between the IS and neuroendocrine systemssystems

Examples of Integration: New Examples of Integration: New ResearchResearch

Neglect stunts brain development, reducing Neglect stunts brain development, reducing myelin in pre-frontal cortex (Sept. 14 Science)-myelin in pre-frontal cortex (Sept. 14 Science)-neurobiological cause of behavioral changesneurobiological cause of behavioral changes

Signs of depression can be turned on and off in Signs of depression can be turned on and off in mice with laser light - cells which produce mice with laser light - cells which produce dopamine in brain were affected by lightdopamine in brain were affected by light

Daughters whose mom’s had higher stress in Daughters whose mom’s had higher stress in their early life had more cortisol, and 14 years their early life had more cortisol, and 14 years later, there is a reduced connection between later, there is a reduced connection between amygdala and prefrontal cortex amygdala and prefrontal cortex (Science News, 12/15/12, (Science News, 12/15/12, p.10)p.10)

Example: AngiostatinExample: Angiostatin

Peptide which mediates thirstPeptide which mediates thirst Drop of angiostatin in rat’s brain will make rat Drop of angiostatin in rat’s brain will make rat

drinkdrink Drop in LU or KI will also cause them to Drop in LU or KI will also cause them to

conserve water: less water vapor exhaled, less conserve water: less water vapor exhaled, less water in urinewater in urine

All mediated by the emotion/drive state of “thirst”All mediated by the emotion/drive state of “thirst”

More research:More research:

Birth weights are affected by economic Birth weights are affected by economic uncertaintyuncertainty

Poor sleep might be linked to obesity and Poor sleep might be linked to obesity and diabetes: lack of sleep hurts the ability of fat diabetes: lack of sleep hurts the ability of fat cells to respond to insulin efficiently, spilling cells to respond to insulin efficiently, spilling lipids into bloodstream - a state associated with lipids into bloodstream - a state associated with metabolic syndrome, a precursor to Type 2 metabolic syndrome, a precursor to Type 2 diabetesdiabetes

Losing weight reduces inflammatory cells and Losing weight reduces inflammatory cells and proteins in body, a risk factor for many cancersproteins in body, a risk factor for many cancers

Research on PainResearch on Pain

Chronic pain can cause atrophy in areas Chronic pain can cause atrophy in areas of brain involved with emotion, attention of brain involved with emotion, attention and perception of danger. Meditation, and perception of danger. Meditation, thoughts of a loved one, bio-feedback etc thoughts of a loved one, bio-feedback etc caused less activity in somato-sensory caused less activity in somato-sensory cortex, which plays role in perceiving pain cortex, which plays role in perceiving pain (Sean Mackey, pain management, Stanford u)(Sean Mackey, pain management, Stanford u)

Exercise improves immune Exercise improves immune responseresponse

Helps fight off bacterial and viral infectionsHelps fight off bacterial and viral infections Decreases chance of developing heart Decreases chance of developing heart

disease, osteoporosis and cancerdisease, osteoporosis and cancer May help by flushing bacteria out from May help by flushing bacteria out from

lungs, flushing carcinogens out in urine lungs, flushing carcinogens out in urine and sweatand sweat

Exercise send antibodies and wbc thru Exercise send antibodies and wbc thru body at quicker ratebody at quicker rate

Exercise cont’dExercise cont’d

Temporary rise in body temp may prevent Temporary rise in body temp may prevent bacterial growth (similar to fever)bacterial growth (similar to fever)

Slows down release of stress-related Slows down release of stress-related hormoneshormones

Psycho-neuro-endo love Psycho-neuro-endo love connectionconnection

Lust: testosterone and estrogen surgeLust: testosterone and estrogen surge Attraction:Attraction:

Dopamine responsible for feelings of euphoriaDopamine responsible for feelings of euphoria Noradrenaline causes racy hearts and sweaty palmsNoradrenaline causes racy hearts and sweaty palms Seratonin regulates body temp, mood and pain. Low Seratonin regulates body temp, mood and pain. Low

levels lead to obsessive thinkinglevels lead to obsessive thinking Attachment:Attachment:

Oxytocin “love hormone” involved in bondingOxytocin “love hormone” involved in bonding Vasopressin encourages bondingVasopressin encourages bonding



Latest researchLatest research

Three new studies show that lab-produced Three new studies show that lab-produced antibodies that target specific proteins in antibodies that target specific proteins in cells can reduce LDL cholesterol at a rate cells can reduce LDL cholesterol at a rate comparable to statins, without the side comparable to statins, without the side effects effects

““A major conceptual shift in neuroscience has been A major conceptual shift in neuroscience has been wrought by the realization that brain function is modulated wrought by the realization that brain function is modulated

by numerous chemicals in addition to classic by numerous chemicals in addition to classic neurotransmitters. Many of these informational substances neurotransmitters. Many of these informational substances

are neuropeptides, originally studied in other contexts as are neuropeptides, originally studied in other contexts as hormones, gut peptides, or growth factors. …We now hormones, gut peptides, or growth factors. …We now realize that their signal specificity resides in receptors realize that their signal specificity resides in receptors

rather than the close juxtaposition occurring at classical rather than the close juxtaposition occurring at classical synapses…. [we see neuropeptide receptors at brain loci, synapses…. [we see neuropeptide receptors at brain loci, on mobile cells of the immune system]… Neuropeptides on mobile cells of the immune system]… Neuropeptides

and their receptors thus join the brain, glands, and immune and their receptors thus join the brain, glands, and immune system in a network of communication between brain and system in a network of communication between brain and body, probably representing the biochemical substrate of body, probably representing the biochemical substrate of

emotion. emotion. Candace PertCandace Pert

Some additional thoughtsSome additional thoughts

We have been exploring the biological We have been exploring the biological basis for emotions/behaviors, but there basis for emotions/behaviors, but there are many influencing factors:are many influencing factors: Genetic makeupGenetic makeup Environment (pre and post heaven)Environment (pre and post heaven) Choices that we makeChoices that we make

Important that we not think in small boxesImportant that we not think in small boxes

SpeculationsSpeculations

Could the intricate array of electrical and Could the intricate array of electrical and chemical routes of communication of the chemical routes of communication of the immune response lead to a memory of immune response lead to a memory of illness within cells/illness within cells/

Is there a potential for memory in every Is there a potential for memory in every living cell?living cell?

To see a world in a grain of To see a world in a grain of sand, / And a heaven in a sand, / And a heaven in a

wild flower, / Hold infinity in wild flower, / Hold infinity in the palm of your hand, / And the palm of your hand, / And

eternity in an hour.’eternity in an hour.’

William BlakeWilliam Blake



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Psychoneuroimmunology How our brains and bodies are linked