1. Note: Clicker Q’s @ end

2. Nuts & Bolts Plan for Today Lecture – Focus on the BI phenotype and its association with mental health, especially social anxiety disorder (SAD) Take-home critical thinking questions

3. PSYC 612: How does N/NE contribute to emotional disorders? Part 2 of 3 Focus on Behavioral Inhibition (BI) and Social Anxiety Disorder AJ Shackman 15 October 2014

4. Today’s Conceptual Roadmap What is behavioral inhibition (BI)? How is BI related to other models of T&P, such as N/NE or Gray’s BIS? Implications for thinking about childhood temperament vs. adult personality? Individual differences in BI predict anxiety and other psychiatric disorders? Why? How? Is BI a viable intermediate phenotype?

5. Today’s Conceptual Roadmap What is behavioral inhibition (BI)? How is BI related to other models of T&P, such as N/NE or Gray’s BIS? Implications for thinking about childhood temperament vs. adult personality? Individual differences in BI predict anxiety and other psychiatric disorders? Why? How? Is BI a viable intermediate phenotype?

6. Today’s Conceptual Roadmap What is behavioral inhibition (BI)? How is BI related to other models of T&P, such as N/NE or Gray’s BIS? Implications for thinking about childhood temperament vs. adult personality? Individual differences in BI predict anxiety and other psychiatric disorders? Why? How? Is BI a viable intermediate phenotype?

7. Jerry Kagan (Harvard)

8. Nathan Fox (UMD) Jenni Blackford (Vanderbilt)Danny Pine (NIMH)

9. What is BI? Intuitive Feel NA Fox et al ARP 2005

10. Marked Individual Differences in BI http://www.abc.net.au/tv/life/video/LIFEAT1.htm

11. BI in Toddlers Passive Avoidance / Freezing Avoid unfamiliar events, objects (‘robot’) and people (‘intruder’) When faced with such challenges, children with high levels of BI cease their play, become quiet, and withdraw to the proximity of their caregivers NA Fox et al ARP 2005

12. BI in Toddlers Passive Avoidance / Freezing Avoid unfamiliar events, objects (‘robot’) and people (‘intruder’) When faced with such challenges, children with high levels of BI cease their play, become quiet, and withdraw to the proximity of their caregivers NA Fox et al ARP 2005

13. What About Grown Ups?

14. Retrospectively Assessing BI in Adults Reznick and colleagues’ RSRI Were you afraid of unfamiliar animals, such as those you encountered on the street or at someone else’s home? Did it upset you when your parents left you with a new, unfamiliar baby-sitter? Did you ever pretend to be sick in order to avoid going to school or to other social events? Did you enjoy meeting new children your age?

15. Retrospectively Assessing BI in Adults Reznick and colleagues’ RSRI Were you afraid of unfamiliar animals, such as those you encountered on the street or at someone else’s home? Did it upset you when your parents left you with a new, unfamiliar baby-sitter? Did you ever pretend to be sick in order to avoid going to school or to other social events? Did you enjoy meeting new children your age?

16. Retrospectively Assessing BI in Adults Reznick and colleagues’ RSRI Were you afraid of unfamiliar animals, such as those you encountered on the street or at someone else’s home? Did it upset you when your parents left you with a new, unfamiliar baby-sitter? Did you ever pretend to be sick in order to avoid going to school or to other social events? Did you enjoy meeting new children your age? Students: Why would you want to assess BI in this way? (Clue: Longitudinal Studies)

17. Retrospectively Assessing BI in Adults Reznick and colleagues’ RSRI Were you afraid of unfamiliar animals, such as those you encountered on the street or at someone else’s home? Did it upset you when your parents left you with a new, unfamiliar baby-sitter? Did you ever pretend to be sick in order to avoid going to school or to other social events? Did you enjoy meeting new children your age? Usual Caveats About Self- Report Measures Apply

18. How is BI Related to Other Models and Other Kinds of Data That We Have Discussed in Class?

19. BI in Toddlers Passive Avoidance / Freezing They remain vigilant (orient toward source of potential threat) May show high levels of distress (‘reactive’) or show elevated levels of the stress hormone cortisol Parallels with AT in monkeys (freezing/cortisol) and BIS (passive avoidance) in adults

20. BI in Toddlers Parallels with AT in monkeys (freezing/cortisol) and BIS (passive avoidance) in adults

21. BI in Toddlers Sustained emotional reaction: Do not recover or return to baseline very quickly Per Richie Davidson

22. BI in Toddlers Right >> Left frontal EEG asymmetry Parallels with work in anxious, inhibited adults and monkeys

23. BI is a Facet of N/NE Zentner et al. 2012; cf. Caspi et al 2005 Caspi’s Hierarchical Model of T&P

24. How stable is BI? Students – What is your intuition, Do High-BI Toddlers Grow Up to be High-BI Adults? NA Fox et al ARP 2005

25. BI Shows Modest Continuity Stability estimates for BI typically fall in the low to moderate range E.g. 4.5 to 7 years of age (R = 0.24; ~6% variance) (Stevenson-Hinde & Shouldice, 1995) ~50% of infants in the High-BI group were classified as High at 2 years; only ~33% at 4 years; 2/3 changed (Fox et al. 2001) NA Fox et al ARP 2005

26. BI Shows Modest Continuity Stability estimates for BI typically fall in the low to moderate range E.g. 4.5 to 7 years of age (R = 0.24; ~6% variance) (Stevenson-Hinde & Shouldice, 1995) ~50% of infants in the High-BI group were classified as High at 2 years; only ~33% at 4 years; 2/3 changed (Fox et al. 2001) NA Fox et al ARP 2005

27. BI Shows Modest Continuity Stability estimates for BI typically fall in the low to moderate range E.g. 4.5 to 7 years of age (R = 0.24; ~6% variance) (Stevenson-Hinde & Shouldice, 1995) ~50% of infants in the High-BI group were classified as High at 2 years; only ~33% at 4 years; 2/3 changed (Fox et al. 2001) NA Fox et al ARP 2005

28. BI Shows Modest Continuity Relatively high proportion of children switch from inhibited to noninhibited classifications (e.g., Perez- Edgar & Fox, 2005; Kagan & Snidman, 1999) Put simply, many to most kids grow out of extreme early-life BI As Kagan says, there is no need to be fatalistic if you are the parent of a high-BI child; considerable plasticity and room for optimism NA Fox et al ARP 2005

29. BI Shows Modest Continuity Relatively high proportion of children switch from inhibited to noninhibited classifications (e.g., Perez- Edgar & Fox, 2005; Kagan & Snidman, 1999) Put simply, many to most kids grow out of extreme early-life BI As Kagan says, there is no need to be fatalistic if you are the parent of a high-BI child; considerable plasticity and room for optimism NA Fox et al ARP 2005

30. BI Shows Modest Continuity Suggests that the environment / nurture plays an important role in determining continuity (Rubin et al 2002) e.g., stress/adversity e.g., derisive parenting associated with increased continuity; NA Fox et al ARP 2005

31. BI Shows Modest Continuity Suggests that the environment / nurture plays an important role in determining continuity (Rubin et al 2002) e.g., stress/adversity e.g., derisive parenting associated with increased continuity; NA Fox et al ARP 2005

32. Students—Why Isn’t BI More Stable? Might this reflect a mixture of Age-Appropriate Fears vs. More Extreme Dispositions? Blackford & Pine

33. Students—Why Isn’t BI More Stable? Might this reflect a mixture of Age-Appropriate Fears vs. More Extreme Dispositions? Blackford & Pine

34. Students— Show of hands, how many of you had some kind of strong fear or anxiety when you were little that you ‘grew out of’ (e.g., strangers, losing your parents, getting lost, monsters, etc.) Blackford & Pine

35. Students— Why Might Fear & Anxiety Be a Normative, Adaptive Part of Early Childhood? Blackford & Pine

37. Modest Continuity Reflects Normative Developmental Milestones Fear and anxiety are adaptive in the face of danger Intense fear and anxiety are a normal part of childhood – Most infants experience stranger anxiety @ ~8-12 months – Most toddlers experience separation anxiety @ ~10-18 mo Blackford & Pine

38. Modest Continuity Reflects Normative Developmental Milestones Fear and anxiety are adaptive in the face of danger Intense fear and anxiety are a normal part of childhood – Most infants experience stranger anxiety @ ~8-12 months – Most toddlers experience separation anxiety @ ~10-18 mo Blackford & Pine

39. Modest Continuity Reflects Normative Developmental Milestones Fear and anxiety are adaptive in the face of danger Intense fear and anxiety are a normal part of childhood – Most infants experience stranger anxiety @ ~8-12 months – Most toddlers experience separation anxiety @ ~10-18 mo Blackford & Pine

40. Modest Continuity Reflects Heterogeneity Fears are thought to be protective, preventing the child from encountering harm during periods marked by the onset of walking and increased exploration For most kids, the normative fears vanish by 2-3 years

41. Modest Continuity Reflects Heterogeneity Fears are thought to be protective, preventing the child from encountering harm during periods marked by the onset of walking and increased exploration For most kids, the normative fears vanish by 2-3 years

42. Modest Continuity Reflects Heterogeneity But for some kids, childhood is marked by the persistence of these fears and the development of new fears, which we would deem non-normative or age-inappropriate (i.e., clinically significant)

43. Modest Continuity Reflects Heterogeneity But for some kids, childhood is marked by the persistence of these fears and the development of new fears, which we would deem non-normative or age-inappropriate (i.e., clinically significant) Modest continuity of BI partially reflects heterogeneity in the functional significance of early-life anxiety and inhibition; for some kids, normal part of growing up; for others, harbinger of life-long challenges

44. Modest Continuity Reflects Heterogeneity But for some kids, childhood is marked by the persistence of these fears and the development of new fears, which we would deem non-normative or age-inappropriate (i.e., clinically significant) Modest continuity of BI partially reflects heterogeneity in the functional significance of early-life anxiety and inhibition; for some kids, normal part of growing up; for others, harbinger of life-long challenges It also reflects the emergence/maturation of emotion regulation

45. Given this heterogeneity We’re going to focus on the subset of children who are characterized by stable AND high levels of BI

46. Stable, High BI Confers Risk Kids who consistently show heightened BI across repeated laboratory assessments are at risk for developing Anxiety Disorders Major Depressive Disorder (MDD) Substance Use Disorders (SUDs) Hirshfeld-Becker NDCAD 2010

47. Stable, High BI Confers Risk Kids who consistently show heightened BI across repeated laboratory assessments are at risk for developing Anxiety Disorders Major Depressive Disorder (MDD) Substance Use Disorders (SUDs) Hirshfeld-Becker NDCAD 2010

48. Extreme behavioral inhibition (BI) confers liability for Social Anxiety Disorder (SAD)

49. What exactly is SAD? Students?

50. MTV Perspective…

51. http://www.mtv.com/videos/true-life-i-have-social-anxiety/1706675/playlist.jhtml

52. NIMH Perspective

53. Social Anxiety Disorder / Social Phobia http://www.nimh.nih.gov/health/topics/social-phobia-social-anxiety-disorder/index.shtml

54. Social Anxiety Disorder / Social Phobia http://www.nimh.nih.gov/health/topics/social-phobia-social-anxiety-disorder/index.shtml

55. Social Anxiety Disorder / Social Phobia http://www.nimh.nih.gov/health/topics/social-phobia-social-anxiety-disorder/index.shtml

56. Social Anxiety Disorder / Social Phobia http://www.nimh.nih.gov/health/topics/social-phobia-social-anxiety-disorder/index.shtml

57. Social Anxiety Disorder / Social Phobia http://www.nimh.nih.gov/health/topics/social-phobia-social-anxiety-disorder/index.shtml

58. Social Anxiety Disorder / Social Phobia http://www.nimh.nih.gov/health/topics/social-phobia-social-anxiety-disorder/index.shtml

59. Social Anxiety Disorder / Social Phobia http://www.nimh.nih.gov/health/topics/social-phobia-social-anxiety-disorder/index.shtml

60. Social Anxiety Disorder / Social Phobia http://www.nimh.nih.gov/health/topics/social-phobia-social-anxiety-disorder/index.shtml

61. Bottom Line: Convergence between the social reticence of extreme BI and SAD

62. Students? What might explain this trajectory? That is, how does BI ‘become’ adult dysfunction?

63. BI Influences Social Skill Acquisition BI Promotes Problematic Social Behaviors Behaviorally inhibited children interact with others in less effective ways (e.g., nonassertive strategies during peer interactions) BI Predicts Worse Social Outcomes More likely to have their requests refused Leads to poorer quality peer relationships Makes it more and more challenging for BI kids to - learn social skills - forge strong social relationships with new people (develop new social networks among peers, friends, schoolmates and ultimately dorm-mates, colleagues, and co-workers) These kinds of social exchange / social interaction mechanisms may underlie the association between BI and psychopathology Extreme BI  Aberrant Social Skills/Peer Relations  Psychopathology

64. BI Influences Social Skill Acquisition BI Promotes Problematic Social Behaviors Behaviorally inhibited children interact with others in less effective ways (e.g., nonassertive strategies during peer interactions) BI Predicts Worse Social Outcomes More likely to have their requests refused Leads to poorer quality peer relationships Makes it more and more challenging for BI kids to - learn social skills - forge strong social relationships with new people (develop new social networks among peers, friends, schoolmates and ultimately dorm-mates, colleagues, and co-workers) These kinds of social exchange / social interaction mechanisms may underlie the association between BI and psychopathology Extreme BI  Aberrant Social Skills/Peer Relations  Psychopathology

65. BI Influences Social Skill Acquisition BI Promotes Problematic Social Behaviors Behaviorally inhibited children interact with others in less effective ways (e.g., nonassertive strategies during peer interactions) BI Predicts Worse Social Outcomes More likely to have their requests refused Leads to poorer quality peer relationships Makes it more and more challenging for BI kids to - learn social skills - forge strong social relationships with new people (develop new social networks among peers, friends, schoolmates and ultimately dorm-mates, colleagues, and co-workers) These kinds of social exchange / social interaction mechanisms may underlie the association between BI and psychopathology Extreme BI  Aberrant Social Skills/Peer Relations  Psychopathology

66. BI Influences Social Skill Acquisition BI Promotes Problematic Social Behaviors Behaviorally inhibited children interact with others in less effective ways (e.g., nonassertive strategies during peer interactions) BI Predicts Worse Social Outcomes More likely to have their requests refused Leads to poorer quality peer relationships Makes it more and more challenging for BI kids to - learn social skills and confidence - forge strong social relationships with new people (develop new social networks among peers, friends, schoolmates and ultimately dorm-mates, colleagues, and co-workers) These kinds of social exchange / social interaction mechanisms may underlie the association between BI and psychopathology Extreme BI  Aberrant Social Skills/Peer Relations  Psychopathology

67. BI Influences Social Skill Acquisition BI Promotes Problematic Social Behaviors Behaviorally inhibited children interact with others in less effective ways (e.g., nonassertive strategies during peer interactions) BI Predicts Worse Social Outcomes More likely to have their requests refused Leads to poorer quality peer relationships Makes it more and more challenging for BI kids to - learn social skills and confidence - forge strong social relationships with new people (develop new social networks among peers, friends, schoolmates and ultimately dorm-mates, colleagues, and co-workers) These kinds of social exchange / social interaction mechanisms may underlie the association between BI and psychopathology Extreme BI  Aberrant Social Skills/Peer Relations  Psychopathology

68. BI Influences Social Skill Acquisition Social Behaviors & Outcomes Over time, the experience of social failure may teach BI children to interpret ambiguous social situations as threatening and believe that poor social outcomes are a result of internal causes; socially anxious

69. Collectively, these data raise the possibility that BI represents an intermediate phenotype or even an endophentype for SAD …

70. Quick Recap

71. 2 Kinds of Intermediate Phenotypes Miller & Rockstroh Ann Rev Clin Psychol 2013 Intermediate Phenotype: Nonheritable cause of the trait Stable, high levels of BI  SAD Endophenotype: Special Case I.P. that is causal and heritable Could BI be an Endophenotype for SAD?

72. 2 Kinds of Intermediate Phenotypes Miller & Rockstroh Ann Rev Clin Psychol 2013 Intermediate Phenotype: Nonheritable cause of the trait Stable, high levels of BI  SAD Endophenotype: Special Case I.P. that is causal and heritable Could BI be an Endophenotype for SAD?

73. 2 Kinds of Intermediate Phenotypes Miller & Rockstroh Ann Rev Clin Psychol 2013 Intermediate Phenotype: Nonheritable cause of the trait Stable, high levels of BI  SAD Endophenotype: Special Case I.P. that is causal and heritable Could BI be an Endophenotype for SAD?

74. 2 Kinds of Intermediate Phenotypes Miller & Rockstroh Ann Rev Clin Psychol 2013 Intermediate Phenotype: Nonheritable cause of the trait Stable, high levels of BI  SAD Endophenotype: Special Case I.P. that is causal and heritable Could BI be an Endophenotype for SAD?

75. Yes! Modest Heritability Heritability estimates in toddlerhood range from.41–.64 (DiLalla et al., 1994; Emde et al., 1992; Matheny, 1989; Robinson et al., 1992) BI is elevated among preschoolers of parents with panic disorder Parents of kids with elevated BI themselves are more likely to have a diagnosable anxiety disorder (Rosenbaum et al., 1991)

76. Yes! Modest Heritability Heritability estimates in toddlerhood range from.41–.64 (DiLalla et al., 1994; Emde et al., 1992; Matheny, 1989; Robinson et al., 1992) BI is elevated among preschoolers of parents with panic disorder Parents of kids with elevated BI themselves are more likely to have a diagnosable anxiety disorder (Rosenbaum et al., 1991)

77. Yes! Modest Heritability Heritability estimates in toddlerhood range from.41–.64 (DiLalla et al., 1994; Emde et al., 1992; Matheny, 1989; Robinson et al., 1992) BI is elevated among preschoolers of parents with panic disorder Parents of kids with elevated BI themselves are more likely to have a diagnosable anxiety disorder (Rosenbaum et al., 1991) Work to establish whether BI is causal is on-going (Childhood Intervention Study in Australia)

78. Today’s Take Home Points What is behavioral inhibition (BI)? How is BI related to other models of T&P, such as N/NE or Gray’s BIS? Implications for thinking about childhood temperament vs. adult personality? Individual differences in BI predict anxiety and other psychiatric disorders? Why? How? Is BI a viable intermediate phenotype?

79. Today’s Take Home Points What is behavioral inhibition (BI)? How is BI related to other models of T&P, such as N/NE or Gray’s BIS? Implications for thinking about childhood temperament vs. adult personality? Individual differences in BI predict anxiety and other psychiatric disorders? Why? How? Is BI a viable intermediate phenotype?

80. Today’s Take Home Points What is behavioral inhibition (BI)? How is BI related to other models of T&P, such as N/NE or Gray’s BIS? Implications for thinking about childhood temperament vs. adult personality? Individual differences in BI predict anxiety and other psychiatric disorders? Why? How? Is BI a viable intermediate phenotype?

81. Critical Thinking Questions (pick 2)

82. 1.What are some loose ends with this simplified account? What are the most important challenges for future research?

83. Critical Thinking Questions (pick 2) 2.Watch the complete episode of MTV’s True Life: Social Anxiety Disorder (http://www.mtv.com/videos/true-life-i- have-social-anxiety/1706675/playlist.jhtml).http://www.mtv.com/videos/true-life-i- have-social-anxiety/1706675/playlist.jhtml Briefly describe how this popular media perspective on SAD jibes with the NIMH’s perspective

84. Critical Thinking Questions (pick 2) 2.Watch the complete episode of MTV’s True Life: Social Anxiety Disorder (http://www.mtv.com/videos/true-life-i- have-social-anxiety/1706675/playlist.jhtml).http://www.mtv.com/videos/true-life-i- have-social-anxiety/1706675/playlist.jhtml Briefly describe how this popular media perspective on SAD jibes with the NIMH’s perspective (http://www.nimh.nih.gov/health/topics/social- phobia-social-anxiety-disorder/index.shtml).http://www.nimh.nih.gov/health/topics/social- phobia-social-anxiety-disorder/index.shtml

85. Critical Thinking Questions (pick 2) 3. What are the implications of the material we discussed today for intervention? Should we screen and target high-risk children for interventions aimed at reducing childhood BI and preventing the subsequent development of psychopathology. Why or why not?

86. Which is true? A.There is one anxiety disorder B.There is a whole family of anxiety disorders

87. The most common family of psychiatric disorders is A.Anxiety B.Depression C.Schizophrenia D.Somatoform

88. Anxiety disorders tend to onset A.Late in life B.Mid life C.Early in life

89. Depression tends to onset A.Early in life B.Mid life C.Late in life

90. The most burdensome disorder (disability, illnes, death) in the US is A.Depression B.Heart Disease C.COPD D.Cancer E.Alzheimers

91. Elevated N/NE is a risk factor for A.Anxiety disorders B.Depressive disorders C.Both

92. Anxiety and depression symptoms A.Form a coherent, factor (internalizing) B.Are categorically distinct C.Should be thought of as natural kinds, discrete entities that exist in nature waiting to be discovered

93. Anxiety and depression A.Are highly co- morbid B.Rarely co-occur in the same individual

94. Treatments targeting one emotional disorder A.Ameliorate (decrease) the symptoms of other emotional disorders B.Decrease ratings of N/NE C.Both, suggesting a common cause

95. Negative life events & psychological pathogens such as stress tend to A.Cause individuals to cross the diagnostic boundary and experience a frank depressive disorder B.Increase the risk of developing a diagnosable anxiety disorder C.Increase N/NE D.All of the above

96. Anxiety disorders, depression, and N/NE A.Reflect completely separate genes B.Are inherited together (shared inheritance), suggesting a common genetic underpinning

97. Recent meta-analyses demonstrate that A.A variety of anxiety disorders, like N/NE, are associated with heightened amygdala activation to potential threat B.Depression, like N/NE, is associated with increased amygdala reactivity to aversive cues C.Both, providing evidence for a common biology

98. Barlow argues that the development of a particular Dx (‘diagnostic specificity’) reflects A.N/NE and a disorder-specific learned vulnerability (e.g., fear dogs) B.N/NE and an innate vulnerability C.N/NE and other non-specific risk factors

99. N/NE is a A.Cause of emotional disorders B.Symptom of emotional disorders C.Identical to or synonymous with the emotional disorders D.A symptom of too much anxiety

100. The End

101. Extra Slides

102. Social Anxiety Disorder / Social Phobia Strong fear of being judged by others and of being embarrassed, criticized, or “found out.” Can be so strong that it gets in the way of going to work or school or doing other everyday things Everyone has felt anxious or embarrassed at one time or another. For example, meeting new people or giving a public speech can make anyone nervous But people with social phobia worry about these and other things for weeks before they happen http://www.nimh.nih.gov/health/topics/social-phobia-social-anxiety-disorder/index.shtml

103. Social Anxiety Disorder / Social Phobia Afraid of doing common things in front of other people e.g., signing a check in front of a cashier at the grocery store eating or drinking in front of other people using a public restroom http://www.nimh.nih.gov/health/topics/social-phobia-social-anxiety-disorder/index.shtml

104. Intermediate Phenotypes are a Bridge Symptomatic Disorders (Phenotype) Genome (Genotype)

105. Endophenotypes: 6 Criteria Miller & Rockstroh Ann Rev Clin Psychol 2013 6. Can be measured reliably *

106. Social Anxiety Disorder / Social Phobia People with SAD know that they shouldn't be as afraid as they are, but have trouble regulating their fears Maladaptive Active Avoidance Behaviors May end up staying away from places or events (e.g., party or other gatherings) where they think they might have to do something that could embarrass them http://www.nimh.nih.gov/health/topics/social-phobia-social-anxiety-disorder/index.shtml

107. Social Anxiety Disorder / Social Phobia People with SAD know that they shouldn't be as afraid as they are, but have trouble regulating their fears Maladaptive Active Avoidance Behaviors May end up staying away from places or events (e.g., party or other gatherings) where they think they might have to do something that could embarrass them http://www.nimh.nih.gov/health/topics/social-phobia-social-anxiety-disorder/index.shtml