Hserv 534

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Hserv 534 12Biology of Population Health
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Summary so far?
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Summary so far

• Health and hierarchy are strongly related,
  effects are stronger than any other factor(s)
• Rules governing reciprocal behavior in society
  have the greatest impact on a population's health
• US health has declined in health relative to
  other nations consistent with trends in the lack
  of reciprocation (SLR disorder)
• Health care a polemic, highly desired,
• not very effective

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Summary so far?
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Epistemology Research Process

• ?
• hard wired
• how raised
• views of parents, associates
• teaching
• Experience
• Ultimately most things are simple and can be
  explained simply

? POLICIES / OUTCOMES ?
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Epistemology Research Process

• -Multi-factorial, complex
• -Ask simplified question
• -Answer that question soon
• -Work to get it published
• Discussion always requests more research
• -More research on another simplified question
• -Get academic promotions
• -Avoid controversy, generalizations, overviews
• -Retire

• ?
• hard wired
• how raised
• views of parents, associates
• teaching
• Experience
• Ultimately most things are simple and can be
  explained simply

? POLICIES / OUTCOMES ?
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Meaning of biology?
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Meaning of biology?

• What would it take for you to believe there was a
  biological explanation behind any health-related
  idea?

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BIOLOGY Population health

• Organelles
• genetic material
• mitochondria
• cell wall
• Cells
• Organs
• Individuals
• Families
• Communities
• (States, provinces, districts)
• Nations GLOBE

• Gaia hypothesis
• James Lovelock, Lynn Margulis
• Super-organism, Supra-being
• Howard Bloom

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BIOLOGY Population health

• Causal inferences?

• Epidemiology approaches
• multiple studies
• dose-response
• direction of causation
• biological plausibility
• Austin Bradford-Hill 1956
• Surgeon General's Report Smoking and health 1964

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Agenda

• INDIVIDUAL BIOLOGY
• Human stress response
• Caring and sharing/calm connection stress
  response
• Parasympathetic/sympathetic stress response
• SUPERORGANISM BIOLOGY
• Biology of nations, communities
• GLOBAL BIOLOGY

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Vital Signs of Health
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Vital Signs of Health
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Socio-Economic-Politico GLOBAL Gradient
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• study of life what level of organization?
• cell
• organ
• individual
• population or aggregate of individuals

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EACH level FRAME for concepts of life

• Cell ---gtto organ (lining of coronary artery
  cytomologous monkey)
• Organ and cholesterol level
• Individual
• current weight, blood pressure
• - maternal grandmother circumstances
• - early childhood (parental attachment)
• responses to stressor, control in life
• influence of behaviors
• diet, exercise, smoking or other substance use

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biological mechanisms

• - DNA, genotypes, phenotypes, non-DNA-based
  (epigenetics)
• - cell wall release of neurotransmitters,
  receptors
• - organ brain and neuron sculpting
• human
• population

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Population Frames

• Political changes or circumstances
• (FSU and increasing inequality)
• (Japan and decreasing inequality)
• USA decreasing taxes on the rich, not increasing
  minimum wage cf. maximum wage
• early childhood (US, Papua New Guinea and
  Swaziland)
• Canada increasing income share going to richest
  0.1
• Social changes or circumstances
• FSU and drug labs in abandoned buildings
• USA glorifying consumption
• Japan and CEO's managers take pay cuts
• Finland speeding fines tied to income

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Population level biology

• Gap between rich and poor and relation to
  violence, teen births, IMR, life expectancy
• promoters/inhibitors of population health
• Saturday night specials, hand guns
• local ordinances for setting thermostats for hot
  water heaters to not scald babies
• seat belt laws
• ?

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Individual Human

• Disease orientated biology
• immune system
• cortisol and stress response
• toxins (methyl mercury, asbestos)
• Health oriented biology
• parasympathetic/sympathetic tone
• oxytocin,
• serotonin
• dopamine
• agonic or hedonic or eudiamonic mode

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How does the Socio-Economic-Political
environment get under the skin?SEPSSocio-Econom
ic-Political Status
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How does the Socio-Economic-Political environment
get under the skin?Early Life

• Intergenerational aspects (maternal gm)
• Small for Gestational Age at risk of DMII, HTN,
  CAD, developmental risk
• some impact of early childhood on this
• (LBW children in high SEPS may have developmental
  advantage over nl BW low SEPS)
• attachment and critical early window when infant
  is pre-wired to require input

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How does the Socio-Economic-Political environment
get under the skin?Biological Embedding

• children spend years for human brain development
  in socioeconomic, political, psychosocial and
  developmental environments of very differing
  qualities, leading to systematic differences in
  brain structure and function
• closely associated with systematic differences in
  function of HAP, SAM, and PNI (immune function,
  and blood clotting factors)
• SAM, HPA, PNI axes have "life" within individuals
  in society, that in turn has empirically
  demonstrable role in producing SEPS gradients
  over life course
• Case study Meaney and handling rats, licking
  and grooming
• see HPA differences, and intergenerational effects

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How does the Socio-Economic-Political environment
get under the skin?Biological Embedding

• SEPS, psychosocial, political and developmental
  environments across life course influence
• objective degree of stressfulness of
  circumstances of daily life
• degree to which given circumstances are
  experienced as stressful
• cognitive, social and emotional coping skills
  people bring with them into adulthood
• physiological pattern of host response to
  stresses of daily living
• individual's biological responses to
  circumstances and experiences of daily life
• function of organ systems,
• create systematic differentials in morbidity and
  mortality that cut across variety of disease
  processes

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How does the Socio-Economic-Political environment
get under the skin?Mid Life

• Sympatho-adrenal-medullary (SAM) response to
  threatening/challenging circumstances,
  transformed in low SEPS circumstances to "learned
  helplessness"
• cannot solve problems of daily living and convert
  physiological responses to learned helplessness,
  ie switch SAM response to HPA defeat reaction
  with increased cortisol secretion (Lundberg
  hypothesis)

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How does the Socio-Economic-Political environment
get under the skin?Mid Life

• Kristensen's 50 year old healthy men (Sweden and
  Lithuania) may demonstrate effect of biological
  embedding
• associated with low self-esteem, increased
  reported job strain, decreased decision latitude
  in jobs, increased depression

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How does the Socio-Economic-Political environment
get under the skin?Late life

• allostatic load (spring model)
• daily homeostasis changes (tensing spring)
  affects aging differently in those with different
  set points
• spring's shape at rest reflects loss of
  elasticity, and if physiological set point
  influenced by earlier life experiences, could
  merge biological embedding with allostatic load
  based on aging , and see how individual's
  allostatic load set where it is in midlife

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Allostatic Load

• Allostasis homeostasis through change
• compensation that organism engages in to maintain
  homeostasis successfully in face of a consistent
  moderate stressor (price paid by body for being
  forced to adapt)
• ALLOSTATIC LOAD is wear and tear experienced by
  body by repeated allostasis cycles
• e.g. Kiecolt-Glaser looked at wound healing in
  those who were spouse-caregivers of Alzheimer's
  patients, , related to IL-8 and IL-1 levels
  (cytokines when not inhibited by chronic stress
  bring about healing)

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Geronimus 2006
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Geronimus 2006
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INDIVIDUAL BIOLOGY
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Biologic Mechanisms

• INDIVIDUAL
• Great Leveller
• Baboon studies in the field (Sapolsky)
• Cynomologous monkeys in captivity (Shively)
• Allostasis
• Human Population Studies (LiVcordia)

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Biological Mechanisms

• Primate data
• Baboons
• Higher basal cortisol levels in low ranking
  animals
• Increased feedback inhibition at hippocampus
• Cynomolgus monkeys
• Coronary artery disease in low ranking females
• Human population studies LiVicordia Study
• Vilnius, Lithuania and Linköping, Sweden

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Sympathetic Nervous System
Parasympathetic Nervous System
Uvnäs Moberg 2003
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gt sympathomimetics
Response to Stressor
Yehuda NEJM 2002
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Other such studies (attenuated cortisol response)

• Chronic stress in high school teachers
  (attenuated cortisol response and absence of
  cardiovascular responsiveness)
• High baseline cortisol, attenuated cortisol
  response seen in extremely trained athletes,
  male addicts with symptomatic HIV infection
• Women with metastatic breast cancer
• Rats under chronic stress (elevated basal
  cortisol)
• Subordinate monkeys (high basal levels)

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Cardiovascular effects

• Cardiovascular allostasis
• Catecholamines affect HR BP

• Cardiovascular allostatic load
• Hypertension
• Atherosclerosis
• Type II diabetes
• Abdominal obesity
• Blood pressure declines during sleep,
  hypertensive person has higher levels, see some
  decline during sleep
• When allostatic load elevated, get prolonged
  stress response

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Brain Effects

• Allostasis
• Via HPA axis and neurotransmitters
• Memories of emotionally charged events

• Allostatic Load
• Cognitive dysfunction through mechanisms
  involving
• reduced neuronal excitability
• neuronal atrophy
• death of cells in hippocampus

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Mental modes Hedonic

• Appeasement transformed to reassuring,conciliatory
  gestures between mutually dependent individuals
• Absence of fear of punishment characterizes
  relationship between individuals
• Extensively studied in children in playgroups
  where (hedonic) leader type children do not
  escalate threat into aggression, but initiate
  play and cooperation contrast with agonistic AND
  HAVE LOWER URINARY CORTISOL EXCRETION

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Immune System Effects

• Allostasis Adrenal steroids
• help move immune competent cells to areas where
  they are needed to fight infections
• Modulate expression of cytokines and chemokines
  (hormones of immune system)

• Allostatic Load
• Immuno-suppression when mediators secreted
  chronically

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Biobehavioral responses to stress in females,
partlyoxytocin-induced

• Men fight or flight
• Women
• tend and befriend (Taylor)
• calm and connection (Uvnäs Moberg)

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Uvnäs Moberg 2003
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Uvnäs Moberg 2003
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Uvnäs Moberg 2003
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Paraympathatic nervous system activity a
mechanism at population level

• Oxytocin production triggered by pleasant
  experiences that include eating, warm baths,
  gentle vibration and sex.
• acts through the parasympathetic nervous system,
  one half of the mammalian autonomic nervous
  system that regulates unconscious processes such
  as breathing and heart rate.
• Sympathetic nervous system (SAM) adrenaline to
  activate "fight or flight" .
• Parasympathetic system, generates "rest and
  digest" response, signaling things are safe and
  that stress hormones can subside.
• oxytocin brings about a psychological response
  in humans "lust and trust".
• higher SEPS people more parasympathetic tone

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Sympathetic Nervous System
Parasympathetic Nervous System
fight or flight
rest and digest lust and trust
Sapolsky 2004
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Sympathetic Nervous System
Parasympathetic Nervous System
Uvnäs Moberg 2003
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Heart Rate Variability SEPS

• Sinus arrhythmia
• RRV HF, LF
• SES
• Parasympathetic nervous system may be mechanism
  linking low SEPS to mortality morbility
• Sloan, R. P., M.-H. Huang, et al. (2005).
  Socioeconomic status and health is
  parasympathetic nervous system activity an
  intervening mechanism? Int. J. Epidemiol. 34(2)
  309-315.

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Evolution, Trust and Oxytocin

• Neuroeconomics
• fish sex neuropeptide vasotocin, oxytocin in
  mammals allows recognition and pair-bonding,
• Attachment monogamous promiscuous mammals
• Cooperation (queue outside restaurants)
• Hippocampus amygdala only areas known to
  produce new brain cells in adult humans

• Oxtocin
• Increased with trust (social guidance system)
• Brain scans, oxytocin measurements
• KNOCKOUT MICE

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Oxytocin knockout mice

• Female rat avoids baby rats until she has had her
  own and then oxytocin surges produce supermoms
• Knockout mice (bred missing oxytocin gene) don't
  recognize cage-mates with whom were raised
• injecting oxytocin into amygdala restores social
  recognitions

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POPULATION (SUPERORGANISM) BIOLOGY
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Livcordia Study

• Lithuania CV mort 4x Sweden, not explained by
  standard risk factors
• Pop based random samples of 50 year old men in
  Vilnius, Lithuania, Linköping Sweden
• Vilnius men had higher job strain, lower social
  support than Linköping men
• Men with inc. BP, MI, Stroke, angina, DM excluded
• Measured salivary serum cortisol and
  cardiovascular reactivity to a standardized
  laboratory stress test
• Anger recall
• Mental arithmetic
• Cold pressor test (ice water hand immersion)
• Measured BP, pulse

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Livcordia Study

• Baseline blood pressures higher in Lithuanian
  than Swedish men (plt.01)
• Substantial increases in Systolic Blood Pressure,
  Diastolic Blood Pressure and Heart Rate seen
• Higher increases in Lithuanian men than Swedish,
  but difference not significant

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Livcordia StudyCortisol Measurements

• Baseline Cortisol levels were higher in Vilnius
  than Linköping (plt.0001)
• Cortisol rise with stress was four times higher
  for Linköping than Vilnius men (plt.001)

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TRUST Olympics
percentage of respondents, by country, to surveys
who responded affirmatively to the the question
Generally speaking, would you say that most
people can be trusted, or that you cannot be too
careful in dealing with people? The surveys
were done in person in 1996 using the native
language, and the questions correspond to
impressions of the respondents own countries.
Strikingly, the data vary by an order of
magnitude while only 3 of those surveyed in
Brazil and 5 in Peru say their compatriots are
trustworthy, 65 of Norwegians and 60 of Swedes
believe this to be so. The United States comes in
at 36, down from 50 in 1990 the U.K. has been
holding steady at 44 for the past decade. Zak
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