1. Plan for Today Clicker Questions from Last Time Lecture Part 1/2 – Focus on the BI phenotype and its association with mental health today; next time focus on the neurobiology – Session ID = 855564 Take-home critical thinking questions

2. PSYC 210: How does T&P contribute to emotional disorders? Focus on Childhood Behavioral Inhibition (BI) and Social Anxiety Disorder, Part 1 AJ Shackman 10 March 2014

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

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

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

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

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

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

9. 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

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

11. 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

12. 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

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

14. 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

15. 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

16. 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

17. 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?

18. Jerry Kagan (Harvard)

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

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

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

22. 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

23. What About Grown Ups?

24. 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?

25. 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)

26. 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

27. How is BI Related to Other Models and Other Kinds of Data?

28. 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

29. 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

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

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

32. BI is a Facet of N/NE Zentner et al. 2012; cf. Caspi et al 2005

33. 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

34. 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

35. 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

36. 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

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

38. 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

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

41. 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

42. 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

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)

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

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

48. What exactly is SAD? Intuitive Feel via MTV

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

50. NIMH Perspective

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

52. 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

53. In sum, Convergence between the social reticence of extreme BI and SAD

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

55. 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

56. 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

57. 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

58. 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

59. Collectively, these data suggest that BI represents an intermediate phenotype for SAD

60. Quick Recap

61. Deleterious Outcome / Dx: Complex Antisocial Behaviors and Substance Abuse Simpler Intermediate Cause: Elevated Risk Taking on the BART Complex, Multidimensional Traits: C/SC Psychological & Biological Substrates: e.g., Altered Activity in the Risk Aversion Network Genotype (DNA) Intermediate Phenotypes are Bridges I.P.’s are a Bridge to Discovery

62. 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?

63. 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?

64. 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?

65. 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?

66. 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)

67. 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)

68. 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?

69. Critical Thinking Questions (pick 2) 1.What are some loose ends with this simplified account? What are the most important challenges for future research? 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). 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.mtv.com/videos/true-life-i-have-social- anxiety/1706675/playlist.jhtmlhttp://www.nimh.nih.gov/health/topics/social-phobia-social- anxiety-disorder/index.shtml 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?

70. The End

71. Extra Slides

72. 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

73. 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

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

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