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HS 482 # 13 Biology of Population Health

HS 482 # 13 Biology of Population Health. Meaning of biology?. What do you know about human biology What is the basis of that knowledge?. 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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HS 482 # 13 Biology of Population Health

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  1. HS 482 # 13Biology of Population Health

  2. Meaning of biology? • What do you know about human biology • What is the basis of that knowledge?

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

  4. 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

  5. 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

  6. Agenda • INDIVIDUAL BIOLOGY • Human stress response • Inflammation and stress, ses • Caring and sharing/calm & connection stress response • Parasympathetic/sympathetic stress response • SUPERORGANISM BIOLOGY • Biology of nations, communities • GLOBAL BIOLOGY

  7. study of life what level of organization? cell organ individual population or aggregate of individuals

  8. Vital Signs of Health

  9. Vital Signs of Health

  10. Peripheral Blood Mono-Nuclear Cells Telomerase: a protein component and an RNA primer sequence which acts to protect the terminal ends of chromosomes Telomere: region of repetitive DNA at the end of chromosomes which protects the end of the chromosome from destruction Sapolsky 2004 Epel et. al. 2004

  11. EACH level: FRAME for concepts of life • DNA telemerase lower in lower ses • Cell--->to 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

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

  13. Individual Human • Disease orientated biology • immune system • cortisol and stress response • Inflammatory response, IL-6 • toxins (methyl mercury, asbestos) • Health oriented biology • parasympathetic/sympathetic tone • oxytocin, • serotonin • dopamine • agonic or hedonic or eudiamonic mode

  14. Socio-Economic-PoliticoGLOBAL Gradient

  15. How does the Socio-Economic-Political environment get under the skin?SEPSSocio-Economic-Political Status

  16. How does the Socio-Economic-Political environment get under the skin?Early Life • Intergenerational aspects (maternal gm) • Small for Gestational Age (IUGR) at risk of DMII, HTN, CAD, + developmental risk • some impact of early life 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

  17. 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 PsychoNeuroImmune (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

  18. 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

  19. 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) • EVOLUTIONARY BASIS FOR DEPRESSION

  20. 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

  21. 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

  22. 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)

  23. Geronimus 2006

  24. INDIVIDUAL BIOLOGY

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

  26. Sympathetic Nervous System Parasympathetic Nervous System Uvnäs Moberg 2003

  27. > sympathomimetics Response to Stressor Yehuda NEJM 2002

  28. Other studies (attenuated cortisol response) • Chronic stress in high school teachers (attenuated cortisol response and absence of cardiovascular responsiveness) • Healthy parents of cancer-children can't mount cortisol response to suppress pro-inflammatory IL-6 • High baseline cortisol, attenuated cortisol response seen in: extremely trained athletes, male addicts with symptomatic HIV infection • Women with metastatic breast cancer • ACS patients(most after thrombolysis or PCTA), studied 12-14 wks after cardiac event with stress test, • Rats under chronic stress (elevated basal cortisol) • Subordinate monkeys (high basal levels)

  29. 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

  30. 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

  31. INFLAMMATION

  32. A: Leukocyte recruitment to early atherosclerotic site Cytokines are chemotactic For intimal migration Monocytes engulf lipids and become atherosclerotic foam cells T lymphocytes secrete cytokines and growth of smooth muscle cells increases C: T lymphocytes secrete cytokines, inhibit production of collagen by smooth muscle cells, & stimulate production of macrophages to express collagen-degrading enzymes. Weakens fibrous cap that protects blood from thrombogenic lipid core of plaque. When plaque ruptures, thrombus forms.

  33. MESA US Cohort Ranjit et. al. 2007

  34. MESA US Cohort Ranjit et. al. 2007

  35. Hegewald et. al. 2007

  36. Hegewald et. al. 2007

  37. Adverse Behaviors & Health • Vulnerability • US data from 1990 National Health Interview Survey (41,104 aged ≥18) • Higher status reduces harm of smoking for morbidity and SAH even when controlling for other lifestyle influences Pampel & Rogers 2004 Physical exercise, stress, BMI, alcohol

  38. Adverse Behaviors & Health • Conclusions: • can't generalize to other time periods or countries with different levels of inequality • Prevention Paradox • Prevention (lifestyle changes) may benefit population with little contribution to individual (Rose, Sick Societies) Pampel & Rogers 2004 TACIT ASSUMPTION Rich and poor have same biology

  39. 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

  40. Biobehavioral responses to stress in females, partlyoxytocin-induced • Men: fight or flight • Women: • tend and befriend (Taylor) • calm and connection (Uvnäs Moberg)

  41. Uvnäs Moberg 2003

  42. Uvnäs Moberg 2003

  43. Uvnäs Moberg 2003

  44. 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

  45. Sympathetic Nervous System Parasympathetic Nervous System fight or flight rest and digest lust and trust Sapolsky 2004

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