Nuts Bolts Plan for Today Shorter meeting today

Nuts & Bolts Plan for Today Shorter meeting today – No clicker review Lecture (Lahey, Barlow, and Ormel papers) – Emotional disorders: symptoms & burden – Informed citizens and taxpayers Take-home critical thinking questions

PSYC 612: How does T&P contribute to emotional disorders? Part 1 of 3 Focus on N/NE AJ Shackman 15 October 2014

Take Care of Yourself & One Another

Today’s Conceptual Roadmap • What are the emotional disorders? Why are they a big deal? • Why is N/NE a risk factor for multiple diagnoses? – What does this mean for our understanding of the emotional disorders? – For the DSM (the ‘Bible’ of psychiatric diagnoses)? • What is the ‘common denominator’ shared by N/NE and the emotional disorders? – Shared biology? – Other kinds of core features

Section 1: What is N/NE and how is it related to emotional disorders

Students: What are key features of N/NE?

Neuroticism / Negative Emotionality (N/NE) Caspi et al. ARP 2005; Barlow et al. CPS 2013

N/NE: Boiling It Down Emotion • susceptibility to negative moods Appraisal • experience the world as distressing or threatening Motivation • aversive / defensive; tendency to work hard to avoid punishment Caspi et al. ARP 2005; Barlow et al. CPS 2013

N/NE: Boiling It Down Emotion • susceptibility to negative moods Appraisal • experience the world as distressing or threatening Motivation • aversive / defensive; tendency to work hard to avoid punishment Lumper! Like Caspi, David Barlow emphasizes the similarities between different models and measures of Negative Emotionality (NE) • Neuroticism • Behavioral Inhibition System (BIS) • (Childhood) Behavioral Inhibition (BI) • Negative Affectivity (NA) • Trait Anxiety (STAI) • Harm Avoidance (HA) Caspi et al. ARP 2005; Barlow et al. CPS 2013

Students: What is the significance?

Lahey Amer Psychol 2009

For comparison purposes, a Cohen’s d of 1. 04 is equivalent to R =. 46 (21% shared variance) ~1 SD difference Lahey Amer Psychol 2009

Section 2: Crash course in emotional disorders (I do not expect you to retain the specifics of the next few slides, just the gist)

Emotional Dx are a Big Deal

Emotional Dx are a Big Deal Emotional Dx Are a Big Deal - tremendous suffering - tremendous economic burden - aggravate other problems and disorders

Anxiety Dx: Signs http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Anxiety Dx: Signs Students – What are the key features of the anxiety disorders? http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Anxiety Dx: Signs http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Anxiety Dx: Signs Family of Disorders • Generalized Anxiety (GAD)) • Panic • Post-Traumatic Stress (PTSD) • Social Anxiety / Social Phobia • Other Specific Phobias General About attacks About trauma cues About social interactions e. g. , dogs, spiders http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Anxiety Dx: Very Common http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Anxiety Dx: Very Common Anxiety disorders are the most common family of mental Illnesses, affecting 40 M U. S. adults http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Anxiety Dx: Snares Many Teens http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Anxiety Dx: Snares Many Teens Anxiety disorders affect 1 in 4 teens Teens with untreated anxiety disorders are at higher risk for performing poorly in school, missing out on important social experiences with peers and others, and substance abuse http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Anxiety Dx: Under-Treated http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Anxiety Dx: Expensive http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Anxiety Dx: Expensive Cost the U. S. >$42 B/yr, one-third of the country's $148 billion total mental health bill All in all, ~10% of Medicaid funding pays for mental health care and ~20% of state/local health programs pay for mental health care http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Major Depressive Disorder (MDD)

MDD: Signs Students – What are the key features of depression? http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

MDD: Signs http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

MDD: Dx Criteria http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

MDD: Common http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Burden: MDD is the leading disorder DALY = disability-adjusted life-year http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Mood Disorders: Under-Treated http: //www. adaa. org/about-adaa/press-room/facts-statistics & http: //www. nimh. nih. gov/Statistics/index. shtml

Bottom Line: N/NE Confers Substantial Risk for Emotional Disorders and Emotional Disorders are a Big Deal Lahey Amer Psychol 2009; cf. Kotov et al Psych Bull 2010; Watson &Naragon-Gainey CPS 2014

Bottom Line: N/NE Confers Substantial Risk for Emotional Disorders N/NE is … • The strongest predictor of categorical emotional disorder diagnoses (Kotov et al. , 2010) • The strongest predictor of continuous symptoms (self-report and clinical ratings) that cut across disorders • Especially strongly linked to general distress/negative affectivity (e. g. , depressed mood, anxious mood, worry), which lies at the core of the emotional disorders • Remains predictive of anxiety and depression symptoms even after eliminating overlapping content (Uliaszek et al. , 2009) • I feel depressed (DSM) vs. I feel blue (N/NE) Lahey Amer Psychol 2009; cf. Kotov et al Psych Bull 2010; Watson &Naragon-Gainey CPS 2014

Bottom Line: N/NE Confers Substantial Risk for Emotional Disorders N/NE is … • The strongest predictor of categorical emotional disorder diagnoses (Kotov et al. , 2010) • The strongest predictor of continuous symptoms (self-report and clinical ratings) that cut across disorders • Especially strongly linked to general distress/negative affectivity (e. g. , depressed mood, anxious mood, worry), that lies at the core of the emotional disorders • Remains predictive of anxiety and depression symptoms even after eliminating overlapping content (Uliaszek et al. , 2009) • I feel depressed (DSM) vs. I feel blue (N/NE) Lahey Amer Psychol 2009; cf. Kotov et al Psych Bull 2010; Watson &Naragon-Gainey CPS 2014

Why? ? ? ? Risk

Why does N/NE confer risk for multiple disorders? Multiple Disorders ? ? ? Risk MDD

Section 3. Why is N/NE a ‘Transdiagnostic Risk Factor’ ?

David Barlow (BU) Among the most prominent living anxiety researchers Key member of the team that wrote DSM-IV

Barlow Argues that N/NE and Emotion Disorders Reflect a Common Transdiagnostic Cause For convergent evidence, see Ormel et al CPR 2013

Barlow Argues that N/NE and Emotion Disorders Reflect a Common Transdiagnostic Cause A common cause gives rise to features that are shared hallmarks of anxiety, depression, and N/NE This would explain why N/NE confers liability for multiple emotional disorders They are not categorically different entities For convergent evidence, see Ormel et al CPR 2013 ANX N/NE DEP Internalizing Spectrum Of Disorders (a. k. a. Emotional Dx’es)

Barlow Argues that N/NE and Emotion Disorders Reflect a Common Transdiagnostic Cause A common cause gives rise to features that are shared hallmarks of anxiety, depression, and N/NE This would explain why N/NE confers liability for multiple emotional disorders Because they are not categorically different entities For convergent evidence, see Ormel et al CPR 2013 ANX N/NE DEP Internalizing Spectrum Of Disorders (a. k. a. Emotional Dx’es)

Barlow offers 6 lines of evidence

#1: Disorders are not categorically distinct Factor analyses indicate broad spectra, not discrete diagnoses • Dump in the symptoms (‘diagnostic criteria’) that are used by the DSM to define all of the emotional disorders • Do you get factors corresponding to the DSM diagnoses? • E. g. , MDD vs. GAD vs. PTSD etc. • No! You get broad spectra of ‘internalizing’ symptoms NO! YES!

#1: Disorders are not categorically distinct

#1: Disorders are not categorically distinct 0000

#1: Disorders are not categorically distinct Third and last example

#1: Disorders are not categorically distinct Can re-represent each of the categorical diagnoses as “scores” on two correlated dimensions (Distress and Fear) The “scores” do a better job predicting deleterious future outcomes than the diagnoses Bottom Lines #1. DSM diagnoses are not real natural kinds, they are clinically convenient short-hand descriptions of symptom clusters #2. Evidence suggests that the symptoms that define the disorders reflect 2 highly correlated factors (‘latent’ dimensions), which helps to explain why, for example, MDD and GAD Frequentlyco-occur

#1: Disorders are not categorically distinct Can re-represent each of the categorical diagnoses as “scores” on two correlated dimensions (Distress and Fear) The “scores” do a better job predicting deleterious future outcomes than the diagnoses 2 Bottom Lines #1. DSM diagnoses are not real natural kinds, they are clinically convenient short-hand descriptions of symptom clusters #2. Evidence suggests that the symptoms that define the disorders reflect 2 highly correlated factors (Distress & Fear = Internalizing), which helps to explain why, for example, MDD and GAD often co-occur and why N/NE predicts both

Not just the symptoms that ‘hang together’

#2: Emotional Dx’es are Highly Comorbid Consistent with the factor analysis of symptoms, • Individuals diagnosed with one emotional disorder often meet diagnostic criteria for one or more other emotional disorders • Tend to hang together in nature • Suggests that they reflect different manifestations of one or a limited number of aberrant mechanisms • Which helps to explain why N/NE predicts multiple emotional disorders

#2: Emotional Dx’es are Highly Comorbid Consistent with the factor analysis of symptoms, • Individuals diagnosed with one emotional disorder often meet diagnostic criteria for one or more other emotional disorders e. g. , Nearly 50% of those Dx’ed with depression are also diagnosed with an anxiety disorder • Like the symptoms, the disorders tend to hang together in the clinic • Suggests that they reflect different manifestations of one or a limited number of aberrant mechanisms • Common mechanism(s) helps to explain why N/NE predicts multiple emotional disorders

#2: Emotional Dx’es are Highly Comorbid Consistent with the factor analysis of symptoms, • Individuals diagnosed with one emotional disorder often meet diagnostic criteria for one or more other emotional disorders e. g. , Nearly 50% of those Dx’ed with depression are also diagnosed with an anxiety disorder • Like the symptoms, the disorders tend to hang together in the clinic • Suggests that they reflect different manifestations of one or a limited number of aberrant mechanisms. Common mechanism(s) helps to explain why N/NE predicts multiple emotional disorders

#3. Things that Alter One Disorder Tend to Alter the Others (and N/NE) in a Similar Way

#3: Overlapping Treatment Effects Treatments targeting one emotional disorder often improve other, non-targeted symptoms as well as N/NE • Cognitive-behavioral therapy for generalized anxiety disorder can produce improvements in depressive symptoms • Pharmacological treatments for MDD reduce N/NE • Treatment effects and T&P hang together, suggesting that • The disorders reflect a limited number of underlying mechanisms • One of which appears to be N/NE • Helps to explain why N/NE is a risk factor for multiple emotional disorders

#3: Overlapping Treatment Effects Treatments targeting one emotional disorder often improve other, non-targeted symptoms as well as N/NE • Cognitive-behavioral therapy for generalized anxiety disorder can produce improvements in depressive symptoms • Pharmacological treatments for MDD reduce N/NE • Treatment effects and T&P hang together, suggesting that • The disorders reflect a limited number of underlying mechanisms • Which we can conceptualize as N/NE or a common cause • Helps to explain why N/NE is a risk factor for multiple emotional disorders

The opposite effect is also true Bad things increase depression, anxiety, and N/NE in tandem

#4: Shared Environmental ‘Pathogens’ Mirroring the treatment evidence, negative events that increase the risk for developing one emotional disorder tend to increase the risk of developing the others • E. g. , stress, early adversity, conflict, unemployment, abuse/maltreatment • All increase the risk of developing a diagnosable emotional disorder There is some evidence that they can also elevate N/NE This is consistent with a shared/common biological vulnerability and can explain why N/NE predicts multiple emotional disorders

#4: Shared Environmental ‘Pathogens’ Mirroring the treatment evidence, negative events that increase the risk for developing one emotional disorder tend to increase the risk of developing the others • E. g. , stress, early adversity, conflict, unemployment, abuse/maltreatment • All increase the risk of developing a diagnosable emotional disorder There is evidence that they also elevate N/NE This is consistent with a shared/common biological vulnerability and can explain why N/NE predicts multiple emotional disorders

#5: Shared Genes (Heritability) The emotional disorders are somewhat heritable N/NE is somewhat heritable The variation in emotional disorders that is heritable is shared across multiple disorders AND N/NE Familial aggregation and segregation • Families (pedigrees) tend to have higher or lower levels of emotional disorders AND N/NE • Individuals within families with higher levels of one tend to have higher levels of the others • Common inheritance • Shared genetic underpinnings Common genetic substrate would help to explain why N/NE is a risk factor for multiple emotional disorders

#5: Shared Genes (Heritability) The emotional disorders are somewhat heritable N/NE is somewhat heritable The variation in emotional disorders that is heritable is shared among multiple disorders AND N/NE Familial aggregation and segregation • Families (pedigrees) tend to have higher or lower levels of emotional disorders AND N/NE • Individuals within families with higher levels of one (e. g. , anxiety) tend to have higher levels of the others (depression, N/NE) • Common inheritance • Shared genetic underpinnings Common genetic substrate, one shared by multiple DX’es and N/NE, would help to explain why N/NE is a risk factor for multiple emotional disorders

#6: Common Neural Circuit Across DX’es The emotional disorders (and N/NE) are consistently associated with heightened activation in a core brain circuit centered on the amygdala and anterior insula Shared biological substrates can explain why N/NE is a risk factor for multiple emotional disorders

#6: Common Neural Circuit Across DX’es The emotional disorders (and N/NE) are consistently associated with heightened activation in a core brain circuit centered on the amygdala and anterior insula Shared biological substrates can explain why N/NE is a risk factor for multiple emotional disorders Across Anxiety Disorders

#6: Common Neural Circuit Across DX’es The emotional disorders (and N/NE) are consistently associated with heightened activation in a core brain circuit centered on the amygdala and anterior insula Shared biological substrates can explain why N/NE is a risk factor for multiple emotional disorders Depression, too

Interim Summary 1. N/NE predicts the emotional disorders (non-specific risk) 2. Symptoms hang together (internalizing spectrum) 3. Disorders hang together (co-morbidity) 1 -3 suggest that the disorders and N/NE reflect a common cause(s) 4. Treatments cause parallel, non-specific decreases 5. Environmental pathogens like stress cause parallel, non-specific increases 4 -5 provide more mechanistic evidence that T&P (N/NE) and psychopathology (emotional disorders) reflect a common substrate 6. Shared heritability, suggesting shared genes 7. Shared brain circuitry 6 -7 begin to address the make-up of the common cause

What explains who develops which disorder (diagnostic specificity)?

The development of a particular emotional disorder reflects… 1. Non-specific common cause: Elevated N/NE 2. Disorder specific, learned vulnerability e. g. , Why a specific phobia of dogs?

Is N/NE a cause, a symptom, or simply ‘the same as’ the emotional disorders?

N is a Cause, Not a Symptom CMD = Common Mental Disorder; Ormel et al CPR 2013

N is a Cause, Not a Symptom Yes Yes CMD = Common Mental Disorder; Ormel et al CPR 2013

Common Cause Does Not Mean ‘The Same As’ Some individuals with high levels of N/NE never meet diagnostic criteria for an emotional disorder Not altogether clear what this means - e. g. , able to cope with or regulate N/NE to maintain sufficient function (hence do not meet DSM criteria)? Perhaps Dx requires N/NE AND poor coping skills - e. g. , disorder requires N/NE + another - e. g. , lower intensity of N/NE (threshold effect) - e. g. , N/NE reflects a vulnerability (‘diathesis’); by chance, some never experience sufficient stress or the like to trigger fullblown disorder

Common Cause Does Not Mean ‘The Same As’ Some individuals with high levels of N/NE never meet diagnostic criteria for an emotional disorder Not altogether clear what this means - e. g. , able to cope with or regulate N/NE to maintain sufficient function (hence do not meet DSM criteria)? Perhaps Dx requires N/NE AND poor coping skills - e. g. , disorder requires N/NE + another cause, such as stress - e. g. , lower intensity of N/NE (threshold effect) - e. g. , N/NE reflects a vulnerability (‘diathesis’); by chance, some never experience sufficient stress or the like to trigger fullblown disorder

Take Home Points 1. There are substantial similarities and co-morbidity between the anxiety and depressive disorders. Spectra, not fundamentally different natural kinds 2. Manipulations that decrease (treatment) or increase (negative events) one Dx, tend to have similar effects on the others as well as N/NE suggesting a common substrate 3. Elevated levels of N/NE are a common/shared feature of the emotional disorders (anxiety, depression) 4. This shared phenotype (symptoms or traits) reflects a common biological substrate (genes, brain circuits) 5. Specificity: Why do some individuals develop particular disorders, such as specific phobia of dogs? This reflects learning and experience (exposure to aggressive dog) interacting with the core vulnerability (e. g. , hyper-reactive amygdala) 6. All in all, this evidence suggests that individual differences in N/NE and Emotional Disorders are not fundamentally different, but instead reflect a common cause

Take Home Points 1. There are substantial similarities and co-morbidity between the anxiety and depressive disorders. Spectra, not fundamentally different natural kinds 2. Manipulations that decrease (treatment) or increase (negative events) one Dx, tend to have similar effects on the others as well as N/NE suggesting a common substrate 3. Elevated levels of N/NE are a common/shared feature of the emotional disorders (anxiety, depression) 4. This shared phenotype (symptoms or traits) reflects a common biological substrate (genes, brain circuits) 5. Specificity: Why do some individuals develop particular disorders, such as specific phobia of dogs? This reflects learning and experience (exposure to aggressive dog) interacting with the core vulnerability (e. g. , hyper-reactive amygdala) 6. All in all, this evidence suggests that N/NE and Emotional Disorders are not fundamentally different, but instead reflect a common cause

Critical Thinking Questions (Pick 2)

Critical Thinking Questions (Pick 2) 1. Briefly discuss the implications of what we discussed today for a loved one or celebrity (living or dead) suffering from an emotional disorder 2. Briefly discuss the most important challenges or limitations of Barlow’s account and how future research could address them (see the extra slides for hints). 3. Choose your own adventure: We talked about many facets of mental illness and personality today. Write a nano-essay on whatever facet was most interesting to you (e. g. , societal impact of mental illness, implications for public healthcare, etc. )

The End

Things to Consider Tweaking for Spring 2014

N = Neuroticism; E = Extraversion; D = Disinhibition; C = Conscientiousness Distress = GAD + MDD; Fear = Panic and Phobias

Alex – these next few slides actually make the point that MDD and SAD are really similar, which belongs in one of the earlier ppt’s the ‘fun-seeking’ data are kind of disturbing…suggest that MDD is more about PE than appetitive motivation

Regarding Weak MDD-E Relations

Regarding Weak MDD-E Relations Low PE is supposed to be the facet that distinguishes depression from the anxiety disorders Low E/PE High N/NE Tripartite Model: Clark & Watson JAP 1991; Watson et al JAP 1995 a, b

Regarding Weak MDD-E/PE Relations Low PE is supposed to be the facet that distinguishes depression from the anxiety disorders Low PE High N/NE Tripartite Model: Clark & Watson JAP 1991; Watson et al JAP 1995 a, b

Regarding Weak MDD-E Relations Weak relations may reflect the use of a broadband measure of Extraversion, rather than a more specific measure of Positive Emotionality

Regarding Weak MDD-E Relations Weak relations may reflect the use of a broadband measure of Extraversion, rather than a more specific measure of Positive Emotionality Collected multiple measures of each facet of E/PE Results revealed that 1) E/PE = 4 Facets = Sociability, PE, Exhibitionism/Dominance, and Fun-Seeking 2) Depression, but not anxiety, was strongly and selectively related to low PE

Extra Slides

Future Challenges 1. Need to understand the mechanisms that convey risk (N/NE Dx) * What exactly is that arrow? ? * What are the proximal mechanisms mediating the assoc. between T&P and Dx * Increased reactivity, biased attention, neg appraisals, stress generation, maladaptive coping, etc? 2. Another way to think about this is, We need to dissect N/NE into its constituents * Mood/Feelings, Cognition, Peripheral Physiol, Behavior, Learning * May be helpful to adopt an endophenotype-type simplication strategy 3. Adjudicating between causal models * Manipulations targeting N/NE would let you pick vulnerability vs. common cause * No studies have tested whether Tx-induced reductions in N/NE are separable from changes in Dx; if so, evidence favoring vulnerability 4. N/NE is a transdiagnostic risk factor. We also need to understand the mechanisms that determine diagnostic divergence. * e. g. , why do some develop SAD vs. MDD vs. PD? * Can be environmental (severe childhood teasing vs. loss of loved one) or biological (sensitivity to interoceptive cues) 013/in press; Caspi CPS 2013/in press; Ormel et al CPR 2013; Nolen-Hoeksema & Watkins PPS 2011

Neuroticism / Negative Emotionality (N/NE) Israel et al JPSP 2014

Differences in N/NE in turn reflect - A disorder-nonspecific biological vulnerability (e. g. , hyperreactive amygdala) - That promotes a disorder nonspecific psychological vulnerability

Shared, trans-diagnostic phenotype, common to N/NE and the Dxes Characterized by – More frequent/intense negative emotions – Reduced emotional clarity and acceptance of emotional experiences – Tendency to experience negative emotions as more unpleasant or to have heightened apprehension about the prospect of feeling distressed or anxious in the future (elevated “anxiety sensitivity”; anx about being anxious)

Another Hallmark of the Core Phenotype

Another Hallmark of the Core Phenotype Tendency to rely on strategies aimed at reducing negative emotions that paradoxically serve to increase and maintain negative emotions – Attentional avoidance – Other Escape / Avoidance Strategies * overt situational avoidance (social anxiety disorder/SAD, specific phobias, PTSD, depression, agoraphobia, PD) * worrisome thoughts / ruminations / compulsions that serve to avoid or control distress (GAD, OCD, MDD) * Avoid eye contact, stand further from others, safety behaviors (SAD, PD)