Social Determinants of Mental and Physical Health MAPP Annual Meeting April 29, 2011

1. Social Determinants of Mental and Physical HealthMAPP Annual MeetingApril 29, 2011 Edward Pontius, MD, DFAPA Medical Director / ACCESS Team Portland, Maine Maine Medical Center Dept of Psychiatry Grand Rounds, 12/07/10 Maine Medical Association Public Affairs Committee, 02/09/11 University of New England Department of Social Work, 02/16/11 Maine Housing, 03/04/11 (followup) Maine Medical Center Dept of Psychiatry Grand Rounds, 03/22/11 Brunswick Housing Authority, 04/08/11

2. Social Determinants of Mental Health Outcome INTRODUCTION What can explain increasing prevalence and severity of mental and physical illness? How can we understand the connection between social factors and health? What difference does it make? Next Steps- what we can do to address SDOH-related suffering, disability, mortality and social cost Conclusion

4. It’s About Fairness…

5. US Income Inequality:Gini Coefficient by State in 2007

6. When Did Awareness of Fairness Develop? • Social primates developed acute awareness of relative social advantage in competitive and cooperative circumstances- likely 30 million years ago. • Failure to develop and maintain strong social support is a dangerous condition. • Food source insecurity, predation, and aggression from within and outside the social group are issues • Social primates can implement an emergency phenotypic adaptation in response to uncertain social support

8. Nature 425, 297-299 (18 September 2003)  Monkeys reject unequal pay Sarah F. Brosnan1 & Frans B. M. de Waal1 Living Links, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA

14. Deliberate cut marks on a 9,000-year-old human bone excavated in a west country cave more than a century ago suggest that prehistoric Devonians may have been cannibals. Scientists at Oxford University have examined a fragment of human bone from Kents Cavern, near Torquay in Devon, after a curator spotted it in a mass of animal bone in a museum store. They concluded that it was part of the forearm of a human adult, and that the seven cut marks were deliberately made with a stone tool around the time of death.

16. Anxiety in US College Students Male, Female 1952-1993

19. (Whitaker, Anatomy of an Epidemic, 2010)

20. Life is uncertain…Eat dessert first!

21. It’s about safety…

22. Adverse Childhood Experiences Study Robert Anda, MD CDC Vincent Filetti, MD Department of Preventative Medicine Kaiser Permante Medical Center, San Diego V

23. The 10 Categories of Adverse Childhood Experience • Childhood abuse before age 18 Emotional Abuse Physical Abuse Sexual Abuse • Neglect Emotional Physical • Growing up in a seriously dysfunctional household as evidenced by: -Witnessing domestic violence -Alcohol or other substance abuse in the home - Mentally ill or suicidal household members - Parental marital discord (as evidenced by separation or divorce) - Crime in the home (as evidenced by having a household member imprisoned)

27. Central Dogma of Molecular Biology:DNA => RNA => Protein BROKEN GENES => BROKEN BRAINS Frances Crick

28. Central Dogma of Molecular Biology:DNA => RNA => Protein • BROKEN GENES => BROKEN BRAINS • Few genes found that explain major mental illness Frances Crick

29. Central Dogma of Molecular Biology:DNA => RNA => Protein • BROKEN GENES => BROKEN BRAINS • Few genes found that explain major mental illness • Difficult to explain persistence of illnessgiven low reproductive fitness associated with some highly-heritable illness (Uher, 2010) Frances Crick

30. Why Heritability Must Be Non-Genetic

31. Central Dogma of Molecular Biology:DNA => RNA => Protein • BROKEN GENES => BROKEN BRAINS • Few genes found that explain major mental illness • Difficult to explain persistence of illnessgiven low reproductive fitness associated with some highly-heritable illness (Uher, 2010) • New non-genetic mechanisms found that could explain persistent and heritable illnesses with current low reproductive fitness- Epigenetic mechanisms Frances Crick

32. Epigenetic Mechanisms- Modulating Gene Expression

33. Hongerwinter Dutch Hunger Winter 1944-1945 A food blockade lead to famine that caused 18,000 deaths Six decades later children exposed to the famine during the first 10 weeks after conception had less DNA methylation of the imprinted IGF2 gene than their unexposed same-sex siblings

34. Hongerwinter Dutch Hunger Winter 1944-1945 A food blockade lead to famine that caused 18,000 deaths Six decades later children exposed to the famine during the first 10 weeks after conception had less DNA methylation of the imprinted IGF2 gene than their unexposed same-sex siblings Youths and adults also suffered life-long impact. At 14 years old, Audrey Hepburn suffered the Hongerwinter...  Audrey Hepburn

35. Hongerwinter Dutch Hunger Winter 1944-1945 A food blockade lead to famine that caused 18,000 deaths Six decades later children exposed to the famine during the first 10 weeks after conception had less DNA methylation of the imprinted IGF2 gene than their unexposed same-sex siblings Youths and adults also suffered life-long impact. At 14 years old, Audrey Hepburn suffered the Hongerwinter...  Which may explain her life-long devotion to humanitarian causes- particularly the suffering of children... Audrey Hepburn

36. Hongerwinter Dutch Hunger Winter 1944-1945 A food blockade lead to famine that caused 18,000 deaths Six decades later children exposed to the famine during the first 10 weeks after conception had less DNA methylation of the imprinted IGF2 gene than their unexposed same-sex siblings Youths and adults also suffered life-long impact. At 14 years old, Audrey Hepburn suffered the Hongerwinter...  Which may explain her life-long devotion to humanitarian causes- particularly the suffering of children... Many believe that the Hongerwinter caused her chronic illnesses, including depression and 3 pack/day smoking by 1960... Audrey Hepburn

37. Hongerwinter Dutch Hunger Winter 1944-1945 A food blockade lead to famine that caused 18,000 deaths Six decades later children exposed to the famine during the first 10 weeks after conception had less DNA methylation of the imprinted IGF2 gene than their unexposed same-sex siblings Youths and adults also suffered life-long impact. At 14 years old, Audrey Hepburn suffered the Hongerwinter...  Which may explain her life-long devotion to humanitarian causes- particularly the suffering of children... Many believe that the Hongerwinter caused her chronic illnesses, including depression and 3 pack/day smoking by 1960... Audrey Hepburn

38. Hongerwinter Dutch Hunger Winter 1944-1945 A food blockade lead to famine that caused 18,000 deaths Six decades later children exposed to the famine during the first 10 weeks after conception had less DNA methylation of the imprinted IGF2 gene than their unexposed same-sex siblings Youths and adults also suffered life-long impact. At 14 years old, Audrey Hepburn suffered the Hongerwinter...  Which may explain her life-long devotion to humanitarian causes- particularly the suffering of children... Many believe that the Hongerwinter caused her chronic illnesses, including depression and 3 pack/day smoking by 1960...contributing to her death by cancer at age 63... Audrey Hepburn

39. Mechanisms for Adaptation to Stressful, Unpredictable Environments

40. The hypothalamic–pituitary–adrenal axis has been the focus of extensive research with regard to the phenotypic plasticity this system shows in response to environmental influences on mammalian development. This review proposes that the mesolimbic dopamine system is similarly reactive to indicators of environmental adversity during development. Physical, physiological, and toxicological stressors encountered during perinatal development have been routinely demonstrated to affect dopamine neurophysiology, most likely through consequent exposure to maternal glucocorticoids or a reduction in oxygen supply. However, findings remain inconsistent with regard to the nature of impact these events have on the dopamine system. Both hyper- and hypo-dopaminergic changes have been noted. This review argues that the directionality of change is a function of chronicity and severity of the insult, and that both resultant phenotypes are adaptive developmental responses, despite their potential for conferring vulnerability for psychopathology in humans. Mechanisms for Adaptation to Stressful, Unpredictable Environments

42. Marshmallow Test Click on screen for Marshmallow Test Video

43. Exponential vs Hyperbolic Discounting… MEDICAL HYPOTHESES Volume 69, Issue 1, Pages 195-198 (2007) Hyperbolic discounting may be reduced to electrical coupling in dopaminergic neural circuits Taiki Takahashi Received 22 October 2006; accepted 24 October 2006. published online 02 January 2007. Summary  Loss of self-control in drug addicts (e.g. cocaine and amphetamine dependent patients) has been associated with hyperbolic discounting of delayed rewards (i.e., inconsistency in intertemporal choice). Neurobiophysical mechanisms underlying hyperbolic discounting are still unknown in spite of recent extensive work in neuroeconomics. Understanding of neuronal mechanisms of hyperbolic discounting is important for establishing neuropharmacological treatment of addiction. At the cognitive level, previous studies have indicated that psychophysics of time-estimation (i.e., Weber–Fechner law and Steven’s power law of time-perception) may explain inconsistency in intertemporal choice. Regarding neuronal substrates of time-estimation, drugs of abuse dramatically change time-estimation, indicating that dopaminergic activities may mediate time-estimation. With respect to neuronal changes induced by drugs of abuse, recent studies have revealed that gap junction proteins (e.g., connexin 36) in dopamine neurons are increased by an self-administration of dopaminergic drugs such as cocaine and amphetamine. However, it has been yet to be examined how the enhanced electrical coupling due to substance administration induces addiction. Furthermore, a recent biophysical modelling study has demonstrated that the effect of the psychophysical laws are potentiated by non-synaptic electrical coupling between neurons via gap junctions.

44. HYPERBOLIC vs. EXPONENTIAL Discounting… In HYPERBOLIC DISCOUNTING, valuations fall very rapidly for small delay periods, but then fall slowly for longer delay periods. This contrasts with EXPONENTIAL DISCOUNTING, in which valuation falls by a constant factor per unit delay, regardless of the total length of the delay. The standard experiment used to reveal a test subject's hyperbolic discounting curve is to compare short-term preferences with long-term preferences. For instance: "Would you prefer a dollar today or three dollars tomorrow?" or "Would you prefer a dollar in one year or three dollars in one year and one day?" For certain range of offerings, a significant fraction of subjects will take the lesser amount today, but will gladly wait one extra day in a year in order to receive the higher amount instead. Individuals with such preferences are described as "present-biased". Individuals using hyperbolic discounting reveal a strong tendency to make choices that are inconsistent over time—they make choices today that their future self would prefer not to make, despite using the same reasoning. This dynamic inconsistency happens because hyperbolic discounts value future rewards much more than exponential discounting.

45. What Is the Value of the Future?Hyperbolic vs. Exponential Discounting…

46. Homo Sapiens 1.0 • Plan B – Precocial Shift • Insecure Social Environment • Best Bet Is For Short-Term Payoffs • Social Systems Support Development Valuing Immediate Goals • Future Generations Gain Benefit of Continued Survival • Price of Vulnerability to Stress-Related Chronic Illness Plan A – Altricial Investment Long Term Stable Social Environment Investments in Long-Term Goals Have Likely Payoff Social Systems Support Development Valuing Long-Term Goals Future Generations Gain Benefit of Complex Cultural Meme Transmission

47. Adverse Childhood Experience

48. Social Determinants of Mental Health

49. Social Determinants of Mental Health Outcome Introduction How are we doing with mental health outcome? What can explain increasing prevalence and severity of mental illness? HOW CAN WE UNDERSTAND THE CONNECTION BETWEEN SOCIAL FACTORS AND MENTAL ILLNESS? What difference does it make? Next Steps- what we can do to address SDOH-related suffering, disability, mortality and social cost Conclusion

50. Whitehall StudiesSir Michael Marmot, MDUniversity College London