Transcript Social Inequality, Psychology, and Health: Biological Mechanisms

Justin Thielman
EPI 6181
April 1st, 2011
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Starting point: Connection between socioeconomic status
(SES) and health
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Possible reasons for this association
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Increased stress levels and poorer emotional states among lower
SES groups due to poorer working conditions; greater
unemployment; less adequate nutrition weakens resiliency; less
control over work and life in general.
Fewer resources to deal with stress among low SES
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Gradient: increasing SES associated with better health.
poorer coping mechanisms, decreased social capital, less effective
social support.
How exactly do these psychosocial factors affect health
outcomes?
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Indirect effect
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Negative emotional states may result in maladaptive health
behaviours that have a negative effect on health.
 Ex: Increased stress levels can make problem drinking more likely
which can cause liver damage. Often specific effects (cirrhosis, or MVC).
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Direct effect
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Negative emotional states may affect hormone levels or immunity.
 Ex: Increased stress levels may decrease immunity and make the body
more susceptible to infections (catching a cold when you’re overworked
and worn out). Often non-specific effects.
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Focus of presentation: biological mechanisms of DIRECT
effect.
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Genetics
Immune System
Nervous System
Endocrine System
Genotype: Individual’s genetic composition
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Ex: Two recessive genes that code for blue eyes
Ex: Two recessive genes that code for sickle cell
anaemia
Phenotype: Individual’s physical expression of a
specific trait
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Ex: Blue eyes
Ex: Sickle cell anaemia
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Genetic information stored in deoxyribonucleic acid (DNA)
DNA organized into chromosomes found in nucleus of most
cells
Normal humans have 23 pairs of chromosomes
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22 pairs of autosomes + one pair of sex chromosomes
Sperm fertilizes ovum and meiosis begins
Chromosome pairs split up. Offspring receives 23
individual chromosomes from mother + 23 from father = 23
new pairs [1]
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Dominant (ex: brown hair)
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Recessive (ex: blue eyes)
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One chromosome from gene pair determines phenotype
Need gene from only ONE parent for trait to be expressed
Both chromosomes from gene pair needed to determine phenotype
Need genes from BOTH parents for trait to be expressed
Sex-linked (ex: male-pattern baldness)
Men: one X chromosome (from mother) + one Y chromosome
(from father)
 Women: two X chromosomes (one from father + one from the
mother)
 Y chromosome much smaller than X, so most traits determined by
X chromosome
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Transcription
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Translation
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Portion of DNA unravels
Messenger RNA (mRNA) created from part of DNA
mRNA exits nucleus into cytoplasm
Transfer RNA (tRNA) uses mRNA’s information to
create proteins
Proteins used in most structures and functions
throughout the body
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Environment plays major role in determining
whether phenotype is expressed by genotype
People are predisposed to conditions by their
genotypes, but behaviours and environment
interact with genes to determine many
conditions.
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Some people are genetically predisposed to diabetes,
but can avoid this illness with a healthy diet and
physical activity. Others are not predisposed and
will not develop diabetes no matter what their diet
and activity level is.
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Genes may directly affect health
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Certain genotypes predispose people to a range of diseases from
diabetes to heart disease to cancer.
Does psychosocial environment affect genetic expression?
Environment cannot alter a person’s genotype (short of a genetic
mutation), but phenotype is heavily influenced by environment
 Ex: a woman with a genetic predisposition to breast cancer may or
may not develop this cancer depending on environmental factors
such as reproduction and hormone exposure.
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Epigenetics: Modification of activation and expression of
genes by factors other than genetic sequence
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i.e. changes in phenotype that are not due to changes in genotype
Epigenetics has become a central field of interest in understanding
environment-gene interactions. It is no longer ‘nature versus
nurture’, but ‘nature via nurture’.
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Immune response elicited when foreign substance
enters body
Two types:
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Innate or Non-specific:
 Called non-specific because the same response occurs
regardless of the foreign material that enter the body
 Characterized by inflammation reaction
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Acquired or specific:
 Tailored to specific pathogens that enter the body.
 Characterized by antibodies, T-cells (T-lymphocytes), and
B-cells (B-lymphocytes)
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Bacteria (or other foreign material) enters body through wound
(or other route)
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Platelets released from bloodstream to clot blood at wound site
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Pain, redness, swelling
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Neutrophils migrate to site and kill bacteria by phagocytosis (Link
to YouTube video and another)
Macrophages remove pathogens by phagocytosis and release
hormones called CYTOKINES
Cytokines attract T-cells and B-cells to site and activate these cells
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Pathogens such as bacteria and viruses have unique proteins
on their surfaces called antigens (mnemonic: ‘antibody
generating’ proteins)
After entering the body, the bacteria (or other pathogen) is
phagocytosed by macrophages which signal T-cells and Bcells using cytokines
Cytotoxic T-cells bind to infected cells and release chemicals
that kill the pathogen
Suppressor T-cells inhibit immune response when no longer
needed
Helper T-cells assist in B-cell growth
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B-cells develop into either antibody-producing cells or
memory cells.
Antibodies are matched specifically to the pathogenic
antigen. They kill the pathogenic cells in a variety of ways.
Secondary immune response: Memory cells remain in the
body after the pathogen is eliminated. If a pathogen
presenting the same antigen enters the body again, the
immune response will be much faster and stronger than it
was the first time.
Vaccines work by introducing an inactivated virus into the
body that elicits an immune response and causes memory
cells to develop for that virus.
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Cytokines are hormones released by macrophages to attract
and activate other immune cells.
Pro-inflammatory cytokines such as interleukin-6 (IL-6)
promote inflammation.
Anti-inflammatory cytokines such as IL-10 decrease the
immune response.
Anxious and depressed moods increase the production of
pro-inflammatory cytokines [2], [3].
IL-6 promotes the production of C-reactive protein, which is
a risk factor for myocardial infarction [4].
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Systematic Review found that cytokines promote tumour progression:
“A number of studies have suggested that several proinflammatory and
anti-inflammatory cytokines promote tumor progression through the
direct activation of nuclear factor-κB (NF-κB) and the upregulation of
angiogenesis and adhesion molecules. Furthermore, these processes
suppress host antitumor immunity, leading to tumor progression and
metastasis. ” [5].
Study using animal models found that social stress alters bacteria in the
gut: “stressor exposure decreased the relative abundance of bacteria in
the genus Bacteroides, while increasing the relative abundance of bacteria
in the genus Clostridium. The stressor also increased circulating levels of
IL-6 and MCP-1, which were significantly correlated with stressorinduced changes to three bacterial genera “ [6].
Review looked at a link between the cytokine IL-18 and Alzheimer’s:
“Emerging data indicate that the cytokine Interleukin (IL)-18, one of the
key mediator of inflammation and immune response, has relevance in the
physiopathological processes of the brain, by ultimately influencing the
integrity of neurons and putatively contributing to AD.” [7].
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Nervous System:
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Endocrine System:
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Brain, spinal cord, nerves and neurons throughout the body.
Information travels via electrical impulses along neurons and
neurotransmitters between neurons.
Examples of neurotransmitters: acetylcholine, serotonin.
Glands (pituitary, thyroid, adrenal, etc.) and other organs such as gonads,
pancreas, etc.
Information travels via endocrine hormones that travel through the
bloodstream.
Information signals are slower and act more globally than in the nervous
system
Examples of endocrine hormones: cortisol, testosterone.
Some body chemicals (ex: epinephrine aka adrenaline) act as both
neurotransmitters and hormones.
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Structures in the brain: cingulate gyrus, fornix,
thalamus, hypothalamus, hippocampus,
amygdala, mamillary bodies, olfactory bulb
Key role in emotional state
“Fight or flight” response experienced during
dangerous or otherwise highly stressful
situations
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Regulates reactions to stress, emotions, immune
system, other bodily processes
Corticotropin-releasing hormone (CRH) secreted
from hypothalamus
CRH travels to pituitary, stimulates release of
adrenocorticotropic hormone (ACTH)
ACTH transported to adrenal cortex, stimulates
production and release of corticosteroids such as
cortisol
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Stress increases sympathetic nervous system
(SNS) activity
SNS stimulates adrenal medulla to release
epinephrine
Epinephrine causes increased heart rate,
increased rate of respiration, inhibition of
digestive system, release of glucose, increased
alertness, etc.
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Stress activates the HPA system, causing elevated
levels of cortisol [8].
Cortisol suppresses immune function, increasing
susceptibility to disease if prolonged [9].
Stress affects the SAM axis, causing epinephrine to
be released from the adrenal gland [10].
Epinephrine increases heart rate and blood
pressure, which can cause cardiovascular problems
if prolonged.
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Systematic review of studies of people with
severe community-acquired pneumonia found
that increased cortisol levels were associated
with increased mortality [11].
Glucocorticoids such as cortisol reduce the
action of Natural Killer Cells (another type of
immune system cell) [12].
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The nervous system, endocrine system, and immune
system all affect each other.
The HPA and SAM axes are examples of the nervous
and endocrine systems working together (hence
‘neuroendocrine’).
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Hypothalamus (nervous), Pituitary (endocrine), Adrenal Cortex
(endocrine).
Sympathetic (nervous), Adrenal Medulla (endocrine)
Cortisol and epinephrine inhibit the immune system.
The cytokine IL-6 stimulates corticotropin-releasing
hormone production which heightens HPA activity [2].
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Study by Chapman, Tuckett, and Song refers to the
interrelated responses of nervous, endocrine, and
immune systems as a “supersystem” response to pain
and stress. “Individuals vary and are vulnerable to
dysregulation and dysfunction in particular organ
systems due to the unique interactions of genetic,
epigenetic and environmental factors, as well as the
past experiences that characterize each person.” [13].
“The interaction between intracellular signals elicited
by cytokines and the activated glucocorticoid receptor
(GR) results in the induction or repression of gene
transcription coordinating an effective immune
response, and then its resolution avoiding excessive
deleterious reactions. “ [14].
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How do we identify the exact causes of health
disparities?
Psychological
State
Health
Psychological
State
Immune
System
Health
Social
Environment
Physical
Environment
Psychological
State
Immune
System
HEALTH
Genetics
Behaviour
Endocrine
System
Nervous
System
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[1] Burton, P., Tobin, M., Hopper, J. (2005). Key concepts in genetic epidemiology. The
Lancet. 366:941-51.
[2] Dentino, A.N., Pieper, C.F., Rao, K.M.K., Currie, M.S., Harris, T., Blazer, D.G., Cohen,
H.J. (1999). Association of interleukin-6 and other biologic variables with depression in
older people living in the community. Journal of the American Geriatrics Society, 47(1):611
[3] Leventhal, H., Patrick-Miller, L., Leventhal, E.A., Burns, E.A. (1998). Does stressemotion cause illness in elderly people? Annual Review of Gerontology and Geriatric.
17:138-184
[4] Papanicolaou, D.A., Wilder, R.L., Manolagas, S.C., Chrousos, G.P. (1998). The
pathophysiologic roles of interleukin-6 in human disease. Annals of Internal Medicine.
128(2):127-137
[5] Tsujimoto, H., Ono, S., Ichikura, T., Matsumoto, Y., Yamamoto, J., Hase, K. (2010).
Roles of inflammatory cytokines in the progression of gastric cancer: Friends or foes?
Gastric Cancer. 13(4):212-221
[6] Bailey, M.T., Dowd, S.E., Galley, J.D., Hufnagle, A.R., Allen, R.G., Lyte, M. (2011).
Exposure to a social stressor alters the structure of the intestinal microbiota: Implications
for stressor-induced immunomodulation. Brain, Behavior, and Immunity. 25(3):397-407
[7] Bossù, P., Ciaramella, A., Salani, F., Vanni, D., Palladino, I., Caltagirone, C.,
Scapigliati, G. (2011). Interleukin-18, from neuroinflammation to alzheimer's disease.
Current Pharmaceutical Design. 16(38):4213-4224
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[8] Miller, A.H. (1998). Neuroendocrine and immune system interactions in stress and
depression.
Psychiatric Clinics of North America. 21(2):443-463
[9] Rabin, B.S. (1999). Stress, Immune Function, and Health: The Connection.
[10] Malarkey, W.B., Wu, H., Cacioppo, J.T., Malarkey, K.L., Poehlmann, K.M., Glaser,
R., Kiecolt-Glaser, J.K. (1996). Chronic stress down-regulates growth hormone gene
epression in peripheral bood mononuclear cells of older adults. Endocrine. 5(1):33-39
[11] Salluh, J.I.F., Shinotsuka, C.R., Soares, M., Bozza, F.A., Lapa e Silva, J.R., Tura, B.R.,
Bozza, P.T., Vidal, C.G. (2010). Cortisol levels and adrenal response in severe
community-acquired pneumonia: A systematic review of the literature. Journal of Critical
Care. 25(3):541.e1-541.e8
[12] Krukowski, K., Eddy, J., Kosik, K.L., Konley, T., Janusek, L.W., Mathews, H.L.
(2011). Glucocorticoid dysregulation of natural killer cell function through epigenetic
modification. Brain, Behavior, and Immunity. 25(2):239-249
[13] Chapman, C.R., Tuckett, R.P., Song, C.W. (2008). Pain and Stress in a Systems
Perspective: Reciprocal Neural, Endocrine, and Immune Interactions. Journal of Pain.
9(2):122-145
[14] Liberman, A.C., Castro, C.N., Noguerol, M.A., Tabarrozzi, A.E.B., Druker, J., Perone,
M.J., Arzt, E. (2010). Molecular mechanisms of glucocorticoids action: From basic
research to clinical implications. Current Immunology Reviews. 6(4):371-380
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[1]http://www.nature.com/ng/journal/v37/n7/fig_tab/n
g0705-662_F1.html
[2] http://www.webbooks.com/eLibrary/Medicine/Appendix/Inheritance.htm
[3]http://mariakonovalenko.wordpress.com/2010/10/07/
gene-expression-defined/
[4]http://www.uic.edu/classes/bios/bios100/lecturesf04a
m/lect23.htm
[5] http://theogler.blogspot.com/2010_07_01_archive.html
[6] http://www.neurosciencerus.org/NeuroBrainEn.html
[7]http://www.becomehealthynow.com/popups/sympth_
parasympth.htm
[8] http://andrewknaup.com/persistence
[9] http://intmed.exblog.jp/7312852/