gene environment interplay and the biology of misfortune
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Gene-environment interplay and the biology of misfortune The Jill - PowerPoint PPT Presentation

Gene-environment interplay and the biology of misfortune The Jill Joseph Lecture Childrens National Medical Center W. Thomas Boyce Departments of Pediatrics and Psychiatry University of California, San Francisco A life of almost


  1. Bush, Adler & Boyce, 2012 BDNF Val66Met polymorphism 0.9 BDNF Met carrier Cortisol Level (Std) Fall Chronic Daily 0.6 BDNF Val/Val 0.3 0.0 -0.3 -0.6 -1 SD +1 SD Family Income

  2. Bush, Adler & Boyce, 2012 BDNF Val66Met polymorphism 0.9 BDNF Met carrier Cortisol Level (Std) Fall Chronic Daily 0.6 BDNF Val/Val 0.3 0.0 -0.3 -0.6 -1 SD +1 SD Family Income

  3. Ellis, Essex & Boyce, 2011 Low warmth, low SNS reactivity High warmth, low SNS reactivity Low warmth, high SNS reactivity High warmth, high SNS reactivity 5 4 Tanner Stage 3 2 1 -3 -1.5 0 1.5 3 Age in Years, Centered on 12.5

  4. Ellis, Essex & Boyce, 2011 Low warmth, low SNS reactivity High warmth, low SNS reactivity Low warmth, high SNS reactivity High warmth, high SNS reactivity 5 4 Tanner Stage 3 2 1 -3 -1.5 0 1.5 3 Age in Years, Centered on 12.5

  5. Ellis, Essex & Boyce, 2011 Low warmth, low SNS reactivity High warmth, low SNS reactivity Low warmth, high SNS reactivity High warmth, high SNS reactivity 5 4 Tanner Stage 3 2 1 -3 -1.5 0 1.5 3 Age in Years, Centered on 12.5

  6. Ellis, Essex & Boyce, 2011 Low warmth, low SNS reactivity High warmth, low SNS reactivity Low warmth, high SNS reactivity High warmth, high SNS reactivity 5 4 Tanner Stage 3 2 1 -3 -1.5 0 1.5 3 Age in Years, Centered on 12.5

  7. Ellis, Essex & Boyce, 2011 Low warmth, low SNS reactivity High warmth, low SNS reactivity Low warmth, high SNS reactivity High warmth, high SNS reactivity 5 4 Tanner Stage 3 2 1 -3 -1.5 0 1.5 3 Age in Years, Centered on 12.5

  8. DIFFERENTIAL NEUROBIOLOGICAL SUSCEPTIBILITY TO SOCIAL CONTEXT

  9. Society Behavior DIFFERENTIAL NEUROBIOLOGICAL Brain SUSCEPTIBILITY TO SOCIAL CONTEXT Circuitry/ synapse Genome/ epigenome

  10. SES, stress and oral health Dental caries = single most • common chronic disease of childhood Strong SES and racial disparities • Known etiologic factors: lead • exposure, tobacco smoke, diet, and access to fluoridated water Oral bacteria Strep mutans and • Lactobacillus acidophilus Leading account of disparities: • neglect of children’s dental hygiene by low SES parents

  11. T 1 T 2 T 3

  12. T 1 T 2 T 3

  13. T 1 T 2 T 3

  14. T 1 T 2 T 3

  15. T 1 T 2 T 3 Deciduous teeth as a stress biomarker in young children?

  16. enamel crown dentin pulp chamber gum root canal root supporting ligament accessory canal root end opening T 1 T 2 T 3 Deciduous teeth as a stress biomarker in young children?

  17. enamel crown dentin pulp chamber gum root canal root supporting ligament accessory canal root end opening T 1 T 2 T 3 Deciduous teeth as a stress biomarker in young children?

  18. Sociobiological effects on childhood dental caries (Boyce et al, 2010) Dental SES caries

  19. Sociobiological effects on childhood dental caries (Boyce et al, 2010) Cariogenic bacteria Dental SES caries

  20. Sociobiological effects on childhood dental caries (Boyce et al, 2010) Cariogenic bacteria Dental SES caries ∆ Dental Financial HPA microanatomy stress activation

  21. Sociobiological effects on childhood dental caries (Boyce et al, 2010) Cariogenic bacteria Dental SES Bacteria x Cortisol caries ∆ Dental Financial HPA microanatomy stress activation

  22. Sociobiological effects on childhood dental caries (Boyce et al, 2010) Oral health disparities related to two interacting pathways: Cariogenic • Earlier and more intensive exposure to an agent of bacteria Dental disease among low SES children SES Bacteria x Cortisol caries • More family adversity resulting in greater HPA activation, ∆ Dental Financial HPA cortisol secretion, and microanatomic vulnerability microanatomy stress activation

  23. Beyond the visible, surface forces driving socioeconomic health disparities…

  24. • Toxins Beyond the visible, • Diet surface forces driving • Health care socioeconomic health • Housing disparities… • Violence • Parenting • Adversity and stress

  25. • Toxins Beyond the visible, • Diet surface forces driving • Health care socioeconomic health • Housing disparities… • Violence • Parenting • Adversity and stress Might there be deeper, less visible currents of social inequality?

  26. African cichlid fish maintain severe hierarchical • organization in which only dominant males have reproductive access to females

  27. African cichlid fish maintain severe hierarchical • organization in which only dominant males have reproductive access to females Rats in subordination paradigm show pro- • inflammatory shifts in cytokine signaling pathways

  28. African cichlid fish maintain severe hierarchical • organization in which only dominant males have reproductive access to females Rats in subordination paradigm show pro- • inflammatory shifts in cytokine signaling pathways Primate species form stable, linearly transitive social • hierarchies Subordinate positions: upregulated adrenocortical • function, impaired immune competence, decreased resistance to disease

  29. African cichlid fish maintain severe hierarchical • organization in which only dominant males have reproductive access to females Rats in subordination paradigm show pro- • inflammatory shifts in cytokine signaling pathways Primate species form stable, linearly transitive social • hierarchies Subordinate positions: upregulated adrenocortical • function, impaired immune competence, decreased resistance to disease Young children form social orders within weeks of • entering new social groups Are subordinate positions in early peer hierarchies • associated with greater stress, exaggerated reactivity, and excessive, stress-related morbidity?

  30. Naturalistic measures of dominance/ subordination behavior

  31. Naturalistic measures of dominance/ subordination behavior • Social dominance: a pattern of repeated encounters in which the outcome consistently favors the same dyad member

  32. Naturalistic measures of dominance/ subordination behavior • Social dominance: a pattern of repeated encounters in which the outcome consistently favors the same dyad member • Dominance observations: critical event and scan sampling over 3-5 weeks

  33. Naturalistic measures of dominance/ subordination behavior • Social dominance: a pattern of repeated encounters in which the outcome consistently favors the same dyad member • Dominance observations: critical event and scan sampling over 3-5 weeks • Behaviors: physical attack, imitation, directing, threat, relational aggression

  34. Naturalistic measures of dominance/ subordination behavior 1 2 3 4 5 6 7 8 9 10 11 • Social dominance: a pattern of 12 13 repeated encounters in which the 14 outcome consistently favors the same 15 = dyad member 16 • Dominance observations: critical event = and scan sampling over 3-5 weeks • Behaviors: physical attack, imitation, directing, threat, relational aggression

  35. 338 kindergarten children; 29 public school classrooms

  36. Depression,8Ina5en6on,8Peer8rela6onships,8Academic8competence Boys Girls .5 0 !.5 2 1 0 !1 !2 2 1 0 !1 !2 Social8Posi6on8(Low8to8High) 338 kindergarten children; Depression Ina5en6on Peer8rela6onships Academic8competence 29 public school classrooms

  37. • Subordinate children sustain higher rates of depression and inattention, poorer peer relationships and academic competence • Boys > girls Depression,8Ina5en6on,8Peer8rela6onships,8Academic8competence Boys Girls .5 0 !.5 2 1 0 !1 !2 2 1 0 !1 !2 Social8Posi6on8(Low8to8High) 338 kindergarten children; Depression Ina5en6on Peer8rela6onships Academic8competence 29 public school classrooms

  38. • Subordinate children sustain higher rates of depression and inattention, poorer peer relationships and academic competence • Boys > girls Depression,8Ina5en6on,8Peer8rela6onships,8Academic8competence Boys Girls .5 0 !.5 2 1 0 !1 !2 2 1 0 !1 !2 Social8Posi6on8(Low8to8High) 338 kindergarten children; Depression Ina5en6on Peer8rela6onships Academic8competence 29 public school classrooms

  39. Powerful, stress-related effects of social subordination and Powerful, stress-related effects of social subordination and marginality, at both the societal and small group level. marginality, at both the societal and small group level.

  40. Powerful, stress-related effects of social subordination and Powerful, stress-related effects of social subordination and marginality, at both the societal and small group level. marginality, at both the societal and small group level. Effects that can be mitigated by more egalitarian, empathic policies and practices.

  41. Developmental calibration of neurobiological circuitry: How does it happen?

  42. Developmental calibration of neurobiological circuitry: How does it happen? • Same species of buckeye butterfly • Polyphenism driven by temperature and length of daylight • A conditional adaptation involving differential epigenetic regulation of genes determining wing coloration and pattern

  43. Environmental exposures

  44. Environmental exposures

  45. Environmental exposures Epigenetic marks as the physical nexus between genes and environments

  46. Wisconsin Study of Families and Work N = 109 N = 570 Infancy Preschool Parental stressors Epigenetic profiling of buccal epithelial cells

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