Stress:Stress:Causes, Chemicals, Causes, Chemicals,

ConsequencesConsequences

Just What Exactly Is Just What Exactly Is Stress?Stress?

► Initially identified Initially identified by Selye as by Selye as “noxious agents.”“noxious agents.”

►Became known as Became known as stress syndromestress syndrome..

Source: Source: www.alnoorhospital.com/uploadedfiles/common/stress/jpgwww.alnoorhospital.com/uploadedfiles/common/stress/jpg

Three Stages of StressThree Stages of Stress

► Stage 1Stage 1: The : The alarm reactionalarm reaction in which the body in which the body prepares itself for “fight or flight.”prepares itself for “fight or flight.”

► Stage 2Stage 2: Since the first stage cannot be sustained, : Since the first stage cannot be sustained, there is a general resistance to the stress which is there is a general resistance to the stress which is established.established.

► Stage 3Stage 3: If the stress is continued for a long period of : If the stress is continued for a long period of time, then eventual exhaustion results (the body’s time, then eventual exhaustion results (the body’s response to prolonged “wear and tear”).response to prolonged “wear and tear”).

►Stress includes both internal and external factors.

►Factors involve the “nonspecific response of the body to any demand."

The “Fight or Flight” The “Fight or Flight” ResponseResponse

1.1. Perceive extreme Perceive extreme danger or danger or distressdistress

2.2. Neurons (nerve Neurons (nerve cells) in brain cells) in brain send entire body send entire body into “high gear”into “high gear”

3.3. Responsively Responsively prepare for “fight prepare for “fight or flight”or flight” Source: Source: www.saludparati.com/entres.htmwww.saludparati.com/entres.htm

► Challenged by Challenged by physiological, physiological, psychological, and psychological, and environmental environmental changes (stressors)changes (stressors)

► Failure to Failure to accommodate to accommodate to changes can lead to changes can lead to exhaustionexhaustion

Source: Source: www.bet.com/Health/Archiveswww.bet.com/Health/Archives

Remember Neurons?Remember Neurons?

► specialized cells of which nerve tissue is specialized cells of which nerve tissue is composedcomposed

► have the ability to send “messages” to each have the ability to send “messages” to each other through the release of chemical other through the release of chemical substances called substances called neurotransmittersneurotransmitters

► electrical in nature, maintaining polarity through electrical in nature, maintaining polarity through electrical gradients established by ions on the electrical gradients established by ions on the inside and outside of their cell membranes.inside and outside of their cell membranes.

► send electrical signals (send electrical signals (action potentialsaction potentials) by ) by depolarizing.depolarizing.

Neurons labeled withNeurons labeled with fluorescent proteins fluorescent proteins

Source: Joshua Sanes, Harvard University. Lecture:”Neurons: how they look and what they Source: Joshua Sanes, Harvard University. Lecture:”Neurons: how they look and what they do.7/11/2005do.7/11/2005

How Do Neurons How Do Neurons Communicate?Communicate?

► Neurons do not physically Neurons do not physically touch each other.touch each other.

► Neurons communicate Neurons communicate with one another through with one another through various neurotransmitters various neurotransmitters released from synaptic released from synaptic vesicles at the vesicles at the synaptic synaptic cleftcleft

► The synaptic cleft The synaptic cleft separates one neuron separates one neuron from another.from another.

Source:http://www.miracosta.cc.ca.us/home/sfoster/neurSource:http://www.miracosta.cc.ca.us/home/sfoster/neurons/animation.gif.ons/animation.gif.

Perceptions…Perceptions…

http://www.youtube.com/watch?v=6tLqh1qYvV4

Perception of PainPerception of Pain

Fear/ Helplessness

PAIN

Sleep deprivation Anxiety

““Good” and “Bad” PainGood” and “Bad” Pain“A” Fibers:► Signal “good pain”► Serve as injury warning► Release glutamate

“C” Fibers:► Signal more diffuse, chronic pain► Pain sources include tissue

damage and cancer► Release “substance P”

Source: Source: http://office.microsoft.com/cliparthttp://office.microsoft.com/clipart

A Computer-Brain AnalogyA Computer-Brain Analogy

► Remember when the older computers didn’t have enough memory (RAM) to support more complex programs?

► Continual bombardment of the brain by stress signals results in the inability to process and respond adequately to such signals.

Source: Source: http://office.microsoft.com/cliparthttp://office.microsoft.com/clipart

► Homeostasis, the Homeostasis, the state of internal state of internal constancy or constancy or equilibrium equilibrium necessary to necessary to maintain maintain physiological physiological health is…health is…

► disrupted by disrupted by

stress!stress! Source: Source: http://spwb.com/articles/anti-aging/stress.gifhttp://spwb.com/articles/anti-aging/stress.gif

Disturbance of HomeostasisDisturbance of Homeostasis

► Our bodies react to environmental changes Our bodies react to environmental changes (stressful or otherwise) by producing (stressful or otherwise) by producing hormones and neurotransmitters. hormones and neurotransmitters.

► These chemical substances are the These chemical substances are the messengers and mediators of the nervous messengers and mediators of the nervous system and endocrine system.system and endocrine system.

► Stressful events cause the release of Stressful events cause the release of adrenalin and hormones (e.g., cortisol) from adrenalin and hormones (e.g., cortisol) from the adrenal medulla and cortex, the adrenal medulla and cortex, respectively.respectively.

► Brain integrates Brain integrates and coordinates and coordinates bodily responsesbodily responses

► Physiological and Physiological and behavioral stress behavioral stress responses result in responses result in adaptationadaptation

► Over time “load” Over time “load” accumulates and accumulates and can cause disease, can cause disease, even deatheven death

Source: Source: www.sciencebob.com/lab/bodyzone/brain/htmlwww.sciencebob.com/lab/bodyzone/brain/html

Ex. Psychology and Ex. Psychology and physiology…physiology…

► In a 1977 study published in theIn a 1977 study published in the New England New England Journal of Medicine, Journal of Medicine, researchers showed researchers showed diminished degradation of plasma cortisol and diminished degradation of plasma cortisol and low plasma triiodothyronine (active hormone low plasma triiodothyronine (active hormone controlling metabolic rate) in young women controlling metabolic rate) in young women suffering from anorexia nervosa.suffering from anorexia nervosa.

Population Crowding CausesPopulation Crowding Causes Stress in Deer Stress in Deer

► In the early 1920’s, a pair of In the early 1920’s, a pair of deer was placed on a 150-deer was placed on a 150-acre island in Chesapeake acre island in Chesapeake Bay.Bay.

► The deer population grew The deer population grew until the density reached until the density reached about one deer per acre.about one deer per acre.

► Then the deer began to die Then the deer began to die off (in the absence of known off (in the absence of known predators) despite the predators) despite the presence of adequate food presence of adequate food and water.and water.

Source: Source: www.whiskersinn.com/sale/images/3%20deer.jpwww.whiskersinn.com/sale/images/3%20deer.jpgg

The Post-mortem FindingsThe Post-mortem Findings

► areas of atrophy in the liver tissue, areas of atrophy in the liver tissue, marked decrease in liver glycogen, marked decrease in liver glycogen, and hypoglycemia.and hypoglycemia.

► evidence of small (petechial) brain evidence of small (petechial) brain hemorrhages and both congestion and hemorrhages and both congestion and hemorrhage of the adrenal glands and hemorrhage of the adrenal glands and kidneys.kidneys.

► These findings suggested what later These findings suggested what later was identified as was identified as adrenal stress adrenal stress syndromesyndrome..

Stress in Minnesota Jack RabbitsStress in Minnesota Jack Rabbits

► In a 1939 study also reported in In a 1939 study also reported in The The Bulletin of the Atomic Scientists, Bulletin of the Atomic Scientists, Minnesota Jack Rabbits Minnesota Jack Rabbits demonstrated rise and fall in demonstrated rise and fall in population densities but when death population densities but when death rates and densities were high, they rates and densities were high, they frequently entered into convulsive frequently entered into convulsive seizures or comatose states.seizures or comatose states.

► Liver and adrenal pathology, as Liver and adrenal pathology, as well as hypertension andwell as hypertension andhypoglycemia associated with hypoglycemia associated with adrenal stress syndromeadrenal stress syndrome, , were observed.were observed.

Source: Source: http://homestudy.ibea.com/wildlifeID/043jackrabbit.hthttp://homestudy.ibea.com/wildlifeID/043jackrabbit.htmm

Population Density andPopulation Density and Behavior (Norway Rats) Behavior (Norway Rats)

► In 1962, John In 1962, John Calhoun (of the Calhoun (of the National Institutes of National Institutes of Health) observed Health) observed high mortality rates high mortality rates in confined wild in confined wild Norway rats when Norway rats when population densities population densities were high as a result were high as a result of stress-induced of stress-induced behavioral changes.behavioral changes. Source: http://www.ratbehavior.org/Aggression.htmSource: http://www.ratbehavior.org/Aggression.htm

Population Density andPopulation Density and Behavior (Norway Rats) Behavior (Norway Rats)

► Calhoun conducted Calhoun conducted several experiments several experiments involving both a involving both a quarter-acre enclosure quarter-acre enclosure and 6’ x 6’ and 6’ x 6’ interconnecting pens.interconnecting pens.

► Calhoun made the Calhoun made the following observations:following observations:

Source: Source: http://office.microsoft.com/cliparthttp://office.microsoft.com/clipart

Behavior changes in femalesBehavior changes in females1.1. Pregnancies were often aborted Pregnancies were often aborted

through miscarriage.through miscarriage.

2.2. Considerable disruption of normal Considerable disruption of normal pre- and postpartum maternal pre- and postpartum maternal behavior (i.e., failure to build proper behavior (i.e., failure to build proper nests, nurse offspring and transport nests, nurse offspring and transport litters) occurred.litters) occurred.

3.3. Up to 25% of estrus females were so Up to 25% of estrus females were so vigorously pursued by males that vigorously pursued by males that they did not survivethey did not survive..

Behavior changes in Behavior changes in malesmales

1.1. Some animals became hyperactive, constantly Some animals became hyperactive, constantly fighting.fighting.

2.2. These animals also became hypersexual and These animals also became hypersexual and lost the ability to discriminate among estrus lost the ability to discriminate among estrus and non-estrus females, juveniles, and other and non-estrus females, juveniles, and other males.males.

3.3. Some became cannibalistic.Some became cannibalistic.

4.4. Some became withdrawn, demonstrating no Some became withdrawn, demonstrating no interest in social interaction.interest in social interaction.

Human Population DensityHuman Population Density

►The following slide depicts human The following slide depicts human population growth in Europe from an population growth in Europe from an estimated number of 20 million people estimated number of 20 million people in 400 BC to 728 million in 2000 AD.in 400 BC to 728 million in 2000 AD.

►Note that in the last three centuries or Note that in the last three centuries or so, the growth curve becomes so, the growth curve becomes progressively exponential or progressively exponential or logarithmic.logarithmic.

Source: Source: http://wps.prenhall.comhttp://wps.prenhall.com

Population Density and Population Density and Stress in HumansStress in Humans

► Very few studies directly Very few studies directly correlate stress of correlate stress of crowding with changes in crowding with changes in the human brain.the human brain.

► Compelling evidence now Compelling evidence now available to link available to link neurological changes in neurological changes in human brains to human brains to prolonged exposure to prolonged exposure to general stressgeneral stress..

Source:Source: www.spokane7.com/…/archive/asp? www.spokane7.com/…/archive/asp?mon=Jan2004mon=Jan2004

Stress, Hormones, and the Stress, Hormones, and the BrainBrain

► Once perceived, stress activates the Once perceived, stress activates the hypothalamus hypothalamus of the brain, triggering a cascade of the brain, triggering a cascade of hormones through the of hormones through the hypothalamic-pituitary-hypothalamic-pituitary-adrenal adrenal (HPA)(HPA) axis.axis.

► Trigger of the HPA axis results in the release of Trigger of the HPA axis results in the release of glucocorticoids (e.g., cortisol) from the adrenal glucocorticoids (e.g., cortisol) from the adrenal gland.gland.

Stress, Hormones and Brain: The Stress, Hormones and Brain: The Hypothalamic-Pituitary-Adrenal Hypothalamic-Pituitary-Adrenal

AxisAxis► Some neurons in theSome neurons in the

hypothalamus hypothalamus produce produce corticotropin-releasing factor corticotropin-releasing factor (CRF).(CRF).

► The synapses of these cells The synapses of these cells make contact with blood make contact with blood vessels, sending CRF to the vessels, sending CRF to the adenohypophysis adenohypophysis (anterior (anterior pituitary)pituitary)

► The pituitary then secretes The pituitary then secretes adrenocorticotrophic hormone adrenocorticotrophic hormone (ACTH) causing glucocorticoid (ACTH) causing glucocorticoid release by the adrenal cortex.release by the adrenal cortex.

► At the same time the adrenal At the same time the adrenal medulla produces adrenalinmedulla produces adrenalin..

Source:Source:www.aafp.org/afp/20000901/1119_f2.gif.www.aafp.org/afp/20000901/1119_f2.gif. (The American Academy of Family Physicians)(The American Academy of Family Physicians)

What do glucocorticoids What do glucocorticoids (such as cortisol) do? (such as cortisol) do?

► increase blood glucose for the “fight or flight” reaction and increase blood glucose for the “fight or flight” reaction and thus have short-term benefits. thus have short-term benefits.

► Over time, frequent release of these glucocorticoids Over time, frequent release of these glucocorticoids adversely affects the hippocampus of the brain (the center of adversely affects the hippocampus of the brain (the center of numerous glucocorticoid receptors). numerous glucocorticoid receptors).

Normal levels maintain normal neuronal function in the Normal levels maintain normal neuronal function in the hippocampushippocampus

High levels adversely affect synaptic transmission and actually High levels adversely affect synaptic transmission and actually interfere with glucose uptake by neurons. interfere with glucose uptake by neurons.

► Resultant reduction of neural connections may responsively Resultant reduction of neural connections may responsively induce memory loss (Seckl, 2005).induce memory loss (Seckl, 2005).

Daily changes in cortisolDaily changes in cortisol in depressed patients in depressed patients

Source: Neuroscience Presentation by Paul Arfydio, Harvard University. July 14, 2005

Jonathan Seckl’s ConclusionsJonathan Seckl’s Conclusions

► Both animals and humans may gradually develop a Both animals and humans may gradually develop a stress-related syndrome involving:stress-related syndrome involving:

1.1. Excess levels of glucocorticoidsExcess levels of glucocorticoids

2.2. Pathological changes in the structure and function of Pathological changes in the structure and function of hippocampal cellshippocampal cells

3.3. Neuronal death (sometimes)Neuronal death (sometimes)

4.4. Increased numbers of hippocampal glucocorticoid Increased numbers of hippocampal glucocorticoid receptors, making the brain more sensitive to negative receptors, making the brain more sensitive to negative feedback control.feedback control.

► This may be one mechanism of action for certain This may be one mechanism of action for certain antidepressant drugs.antidepressant drugs.

ReferencesReferences► Boyer, R.M.,Boyer, R.M.,et al. et al. Cortisol secretion and metabolism in Cortisol secretion and metabolism in

anorexia nervosa.anorexia nervosa.NEJM, 294 (NEJM, 294 (4),1977.4),1977.

► Brooks, Crystal. Overcrowding and violence in federal Brooks, Crystal. Overcrowding and violence in federal correctional institutions:An empirical analysis. Retrieved from correctional institutions:An empirical analysis. Retrieved from http://dspace.library.drexel.edu.http://dspace.library.drexel.edu.

► Bresler, Jack B., ed. Bresler, Jack B., ed. Human Ecology. Human Ecology. Reading,MA. Addison-Wesley.1966.

► Calhoun, John. Population density and social pathology. Scientific American. Feb.,1962.

References (continued)References (continued)

► Cox, Thomas. Black Hills State University. Learning and Cox, Thomas. Black Hills State University. Learning and Conditioning Laboratory. PSYC305L. Fall, 2004. Retrieved Conditioning Laboratory. PSYC305L. Fall, 2004. Retrieved from http://www.bhsu.edu.from http://www.bhsu.edu.

► Duane, Mary, Duane, Mary, et al. et al. Inquiry in science using an animal Inquiry in science using an animal behavior model. Retrieved from behavior model. Retrieved from http://www.woodrowwilson.org/teachers/bi/1998/planariahttp://www.woodrowwilson.org/teachers/bi/1998/planaria/index.htm/index.htm..

► Hoagland, Hudson. Cybernetics of population control. Hoagland, Hudson. Cybernetics of population control. Bulletin of the Atomic ScientistsBulletin of the Atomic Scientists. Feb.,1964.. Feb.,1964.

► Marieb, Elaine N. Marieb, Elaine N. Essentials of Human Anatomy and Essentials of Human Anatomy and Physiology.Physiology. San Francisco. Addison-Wesley-Longman. San Francisco. Addison-Wesley-Longman. 2000.2000.

References (continued)References (continued)

► Massachusetts Department of Education. Massachusetts Department of Education. Massachusetts Massachusetts Curriculum Frameworks. Curriculum Frameworks. Retrieved fromRetrieved from http://www.doe.mass.edu/frameworks.http://www.doe.mass.edu/frameworks.

► Mayer, Emeran A. The neurobiology of stress and emotions. Mayer, Emeran A. The neurobiology of stress and emotions. Participate/Digestive Health Matters.Participate/Digestive Health Matters.Winter, 2001.Winter, 2001.

► McEwen, Bruce and Teresa Seeman. Allostatic load and McEwen, Bruce and Teresa Seeman. Allostatic load and allostasis. Retrieved fromallostasis. Retrieved fromhttp://www.macses.uscf.edu/Research/allostatic/notebook/http://www.macses.uscf.edu/Research/allostatic/notebook/allostatic. allostatic. August, 1999. August, 1999.

► National Institute of Child Health and Human Development. National Institute of Child Health and Human Development. NIH Backgrounder. http://www.nichd.nih.gov. Sept. 9, 2002.NIH Backgrounder. http://www.nichd.nih.gov. Sept. 9, 2002.

References (continued)References (continued)► National Research Council and National Academy of Sciences. National Research Council and National Academy of Sciences.

National Sciences Education Standards. Retrieved from National Sciences Education Standards. Retrieved from http://www.nap.edu/readingroom/books/nses/html/index.html.http://www.nap.edu/readingroom/books/nses/html/index.html.

► Regoeczi, Wendy C. The impact of density: The importance on Regoeczi, Wendy C. The impact of density: The importance on nonlinearity and selection on flight and fight response. nonlinearity and selection on flight and fight response. Social ForcesSocial Forces. . 81, 2002. Retrieved from81, 2002. Retrieved fromhttp://www.ncsociology.org/sociationtoday/v22/crowding.htm.http://www.ncsociology.org/sociationtoday/v22/crowding.htm.

► Seckl, Jonathan R. Glucocorticoids, aging, and nerve cell damage. Seckl, Jonathan R. Glucocorticoids, aging, and nerve cell damage. Retrieved from Retrieved from http://neuroendo.org.uk/index/php/content/view/18/11. June, 2005.http://neuroendo.org.uk/index/php/content/view/18/11. June, 2005.

► Society for Neuroscience. Society for Neuroscience. Brain Facts, a Primer on the Brain and Brain Facts, a Primer on the Brain and Nervous System.Nervous System. Washington. Society for Neuroscience. Washington. Society for Neuroscience.

References (continued)References (continued)

► Spedding, M. and P. Lestage. Synaptic plasticity and Spedding, M. and P. Lestage. Synaptic plasticity and neuropathology: New approaches in drug discovery. neuropathology: New approaches in drug discovery. MedSciMedSci (Paris). 21:1. Jan., 2005. (Paris). 21:1. Jan., 2005.

► United States Dept. of Agriculture. Agricultural United States Dept. of Agriculture. Agricultural Research Service. Detecting stress in animals. Research Service. Detecting stress in animals. Agricultural ResearchAgricultural Research. Jan.,2002.. Jan.,2002.

► University of Scranton Neuroscience program. University of Scranton Neuroscience program. “Welcome to the Sheep brain Dissection Guide.” “Welcome to the Sheep brain Dissection Guide.” Retrieved from http://www.humboldt.edu.Retrieved from http://www.humboldt.edu.