Nuts & Bolts Plan for Today Exam – Grades uploaded to Canvas in the next 48 hours – Item #51 will be dropped – Reminder: 4point extra credit opportunity (see syllabus for details) Lecture: Lahey, Barlow, and [opMonal] Ormel papers – EmoMonal disorders: symptoms & burden – Informed ciMzens and taxpayers Takehome criMcal thinking quesMons No class on Thursday (SAS meeMng in SF / ADAA meeMng in Miami)
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Nuts & Bolts Plan for Today Exam – Grades uploaded to Canvas in the next 48 hours – Item #51 will be dropped – Reminder: 4-‐point extra credit opportunity (see syllabus for details)
Lecture: Lahey, Barlow, and [opMonal] Ormel papers – EmoMonal disorders: symptoms & burden – Informed ciMzens and taxpayers
Take-‐home criMcal thinking quesMons No class on Thursday (SAS meeMng in SF / ADAA meeMng in Miami)
PSYC 210:
How does T&P contribute to emoMonal disorders?
Part 1 of 3
Focus on N/NE
AJ Shackman 7 April 2015
Take Care of Yourself & One Another
Today’s Conceptual Roadmap • What are the emoMonal disorders? Why are they a big deal?
• Why is N/NE a risk factor for mulMple diagnoses? – What does this mean for our understanding of the emo6onal disorders?
– For the DSM (the ‘Bible’ of psychiatric diagnoses)?
• What is the ‘common denominator’ shared by N/NE and the emoMonal disorders? – Shared biology? – Other kinds of core features
Today’s Conceptual Roadmap • What are the emoMonal disorders? Why are they a big deal?
• Why is N/NE a risk factor for mulMple diagnoses? – What does this mean for our understanding of the emo6onal disorders?
– For the DSM (the ‘Bible’ of psychiatric diagnoses)?
• What is the ‘common denominator’ shared by N/NE and the emoMonal disorders? – Shared biology? – Other kinds of core features
Today’s Conceptual Roadmap • What are the emoMonal disorders? Why are they a big deal?
• Why is N/NE a risk factor for mulMple diagnoses? – What does this mean for our understanding of the emo6onal disorders?
– For the DSM (the ‘Bible’ of psychiatric diagnoses)?
• What is the ‘common denominator’ shared by N/NE and the emoMonal disorders? – Shared biology? – Other kinds of core features
Today’s Conceptual Roadmap • What are the emoMonal disorders? Why are they a big deal?
• Why is N/NE a risk factor for mulMple diagnoses? – What does this mean for our understanding of the emo6onal disorders?
– For the DSM (the ‘Bible’ of psychiatric diagnoses)?
• What is the ‘common denominator’ shared by N/NE and the emoMonal disorders? – Shared biology? – Other kinds of core features
Today’s Conceptual Roadmap • What are the emoMonal disorders? Why are they a big deal?
• Why is N/NE a risk factor for mulMple diagnoses? – What does this mean for our understanding of the emo6onal disorders?
– For the DSM (the ‘Bible’ of psychiatric diagnoses)?
• What is the ‘common denominator’ shared by N/NE and the emoMonal disorders? – Shared biology? – Other kinds of core features?
SecMon 1: What is N/NE and how is it related to emoMonal disorders
Students: What are key features of N/NE?
NeuroMcism / NegaMve EmoMonality (N/NE)
Caspi et al. ARP 2005; Barlow et al. CPS 2013
N/NE: Boiling It Down
Caspi et al. ARP 2005; Barlow et al. CPS 2013
EmoMon • suscepAbility to negaAve moods
Appraisal
• experience the world as distressing or threatening MoMvaMon
• aversive / defensive; tendency to work hard to avoid punishment
N/NE: Boiling It Down
Caspi et al. ARP 2005; Barlow et al. CPS 2013
EmoMon • suscepAbility to negaAve moods
Appraisal
• experience the world as distressing or threatening MoMvaMon
• aversive / defensive; tendency to work hard to avoid punishment
N/NE: Boiling It Down
Caspi et al. ARP 2005; Barlow et al. CPS 2013
EmoMon • suscepAbility to negaAve moods
Appraisal
• experience the world as distressing or threatening MoMvaMon
• aversive / defensive; tendency to work hard to avoid punishment
N/NE: Boiling It Down EmoMon
• suscepAbility to negaAve moods Appraisal
• experience the world as distressing or threatening MoMvaMon
• aversive / defensive; tendency to work hard to avoid punishment
Like Caspi, David Barlow emphasizes the similariMes between different models and measures of NegaMve EmoMonality (NE)
Family of Disorders • Generalized Anxiety (GAD)) General • Panic About aJacks • Post-‐TraumaAc Stress (PTSD) About trauma cues • Social Anxiety / Social Phobia About social interacLons • Other Specific Phobias e.g., dogs, spiders
Family of Disorders • Generalized Anxiety (GAD)) General • Panic About aJacks • Post-‐TraumaAc Stress (PTSD) About trauma cues • Social Anxiety / Social Phobia About social interacLons • Other Specific Phobias e.g., dogs, spiders
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
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
Cost the U.S. >$42B/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
Boeom Line— N/NE confers substan6al risk for emo6onal disorders and emo6onal disorders are a big deal Whadya mean ‘risk’?
Boeom Line— N/NE confers substan6al risk for emo6onal disorders and emo6onal disorders are a big deal Whadya mean ‘risk’?
N/NE is … • The strongest predictor of categorical emoAonal disorder diagnoses
(Kotov et al., 2010)
• The strongest predictor of conLnuous symptoms (self-‐report and clinical raAngs) that cut across disorders
• Especially strongly linked to general distress/negaAve affecAvity (e.g., depressed mood, anxious mood, worry), which lies at the core of the emoAonal disorders
• Remains predicAve of anxiety and depression symptoms even aler eliminaAng 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
N/NE is … • The strongest predictor of categorical emoAonal disorder diagnoses
(Kotov et al., 2010)
• The strongest predictor of conLnuous symptoms (self-‐report and clinical raAngs) that cut across disorders
• Especially strongly linked to general distress/negaAve affecAvity (e.g., depressed mood, anxious mood, worry), which lies at the core of the emoAonal disorders
• Remains predicAve of anxiety and depression symptoms even aler eliminaAng 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
N/NE is … • The strongest predictor of categorical emoAonal disorder diagnoses
(Kotov et al., 2010)
• The strongest predictor of conLnuous symptoms (self-‐report and clinical raAngs) that cut across disorders
• Especially strongly linked to general distress/negaAve affecAvity (e.g., depressed mood, anxious mood, worry), that lies at the core of the emoAonal disorders
• Remains predicAve of anxiety and depression symptoms even aler eliminaAng 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
N/NE is … • The strongest predictor of categorical emoAonal disorder diagnoses
(Kotov et al., 2010)
• The strongest predictor of conLnuous symptoms (self-‐report and clinical raAngs) that cut across disorders
• Especially strongly linked to general distress/negaAve affecAvity (e.g., depressed mood, anxious mood, worry), that lies at the core of the emoAonal disorders
• Remains predicAve of anxiety and depression symptoms even aler eliminaAng 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
???
MDD
MulMple Disorders
Why does N/NE confer risk for mulMple disorders?
Risk
SecMon 3. Why is N/NE a ‘TransdiagnosMc 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 EmoMon Disorders Reflect a Common
TransdiagnosMc Cause
For convergent evidence, see Ormel et al CPR 2013
ANX DEP N/NE
Barlow Argues that N/NE and EmoMon Disorders Reflect a Common
TransdiagnosMc 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 mulAple emoAonal disorders They are not categorically different enAAes
ANX DEP N/NE
For convergent evidence, see Ormel et al CPR 2013
Barlow Argues that N/NE and EmoMon Disorders Reflect a Common
TransdiagnosMc 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 mulAple emoAonal disorders Because they are not categorically different enAAes
ANX DEP N/NE
Internalizing Spectrum Of Disorders
(a.k.a. EmoMonal Dx’es)
For convergent evidence, see Ormel et al CPR 2013
Barlow offers 6 lines of evidence
#1: Disorders are not categorically disMnct Factor analyses indicate broad spectra, not discrete diagnoses
• Dump in the symptoms (‘diagnosMc criteria’) that are used by the DSM to define all of the emoMonal 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 disMnct Factor analyses indicate broad spectra, not discrete diagnoses
• Dump in the symptoms (‘diagnosMc criteria’) that are used by the DSM to define all of the emoMonal 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 disMnct Factor analyses indicate broad spectra, not discrete diagnoses
• Dump in the symptoms (‘diagnosMc criteria’) that are used by the DSM to define all of the emoMonal 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!
What does a spectrum look like to a psychiatric sta6s6cian?
#1: Disorders are not categorically disMnct
#1: Disorders are not categorically disMnct
0000
#1: Disorders are not categorically disMnct Third and last example
#1: Disorders are not categorically disMnct Can re-‐represent each of the categorical diagnoses as “scores” on two correlated dimensions (Distress and Fear) The “scores” do a beeer job predicMng deleterious future outcomes than the diagnoses Boeom Lines #1. DSM diagnoses are not real natural kinds, they are clinically convenient short-‐hand descripMons 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 disMnct Can re-‐represent each of the categorical diagnoses as “scores” on two correlated dimensions (Distress and Fear) The “scores” do a beeer job predicMng deleterious future outcomes than the diagnoses 2 Boeom Lines #1. DSM diagnoses are not real natural kinds, they are clinically convenient short-‐hand descripMons 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 open co-‐occur and why N/NE predicts both
#1: Disorders are not categorically disMnct Can re-‐represent each of the categorical diagnoses as “scores” on two correlated dimensions (Distress and Fear) The “scores” do a beeer job predicMng deleterious future outcomes than the diagnoses 2 Boeom Lines #1. DSM diagnoses are not real natural kinds, they are clinically convenient short-‐hand descripMons of symptom clusters (sound familiar?) #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 open co-‐occur and why N/NE predicts both
#1: Disorders are not categorically disMnct Can re-‐represent each of the categorical diagnoses as “scores” on two correlated dimensions (Distress and Fear) The “scores” do a beeer job predicMng deleterious future outcomes than the diagnoses 2 Boeom Lines #1. DSM diagnoses are not real natural kinds, they are clinically convenient short-‐hand descripMons of symptom clusters (sound familiar?) #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 open co-‐occur and why N/NE predicts both
Not just the symptoms that ‘hang together’
#2: EmoMonal Dx’es are Highly Comorbid Consistent with the factor analysis of symptoms,
• Individuals diagnosed with one emoAonal disorder olen meet diagnosAc criteria for one or more other emoAonal disorders
• Tend to hang together in nature
• Suggests that they reflect different manifestaAons of one or a limited number of aberrant mechanisms
• Which helps to explain why N/NE predicts mulAple emoAonal disorders
#2: EmoMonal Dx’es are Highly Comorbid Consistent with the factor analysis of symptoms,
• Individuals diagnosed with one emoAonal disorder olen meet diagnosAc criteria for one or more other emoAonal 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 manifestaAons of one or a limited number of aberrant mechanisms
• Common mechanism(s) helps to explain why N/NE predicts mulAple emoAonal disorders
#2: EmoMonal Dx’es are Highly Comorbid Consistent with the factor analysis of symptoms,
• Individuals diagnosed with one emoAonal disorder olen meet diagnosAc criteria for one or more other emoAonal 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 manifestaAons of one or a limited number of aberrant mechanisms
• Common mechanism(s) helps to explain why N/NE predicts mulAple emoAonal disorders
#2: EmoMonal Dx’es are Highly Comorbid Consistent with the factor analysis of symptoms,
• Individuals diagnosed with one emoAonal disorder olen meet diagnosAc criteria for one or more other emoAonal 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 manifestaAons of one or a limited number of aberrant mechanisms. Common mechanism(s) helps to explain why N/NE predicts mulAple emoAonal disorders
#3. Things that Alter One Disorder Tend to Alter the Others
(and N/NE) in a Similar Way
#3: Overlapping Treatment Effects Treatments targeMng one emoMonal disorder open improve other, non-‐targeted symptoms as well as N/NE
• CogniAve-‐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, suggesAng 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 mulAple emoAonal disorders
#3: Overlapping Treatment Effects Treatments targeMng one emoMonal disorder open improve other, non-‐targeted symptoms as well as N/NE
• CogniAve-‐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, suggesAng 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 mulAple emoAonal disorders
#3: Overlapping Treatment Effects Treatments targeMng one emoMonal disorder open improve other, non-‐targeted symptoms as well as N/NE
• CogniAve-‐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, suggesAng 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 mulAple emoAonal disorders
#3: Overlapping Treatment Effects Treatments targeMng one emoMonal disorder open improve other, non-‐targeted symptoms as well as N/NE
• CogniAve-‐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, suggesAng 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 mulAple emoAonal 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, negaMve events that increase the risk for developing one emoMonal 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 emoAonal 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 mulMple emoMonal disorders
#4: Shared Environmental ‘Pathogens’ Mirroring the treatment evidence, negaMve events that increase the risk for developing one emoMonal 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 emoAonal 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 mulMple emoMonal disorders
#4: Shared Environmental ‘Pathogens’ Mirroring the treatment evidence, negaMve events that increase the risk for developing one emoMonal 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 emoAonal 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 mulMple emoMonal disorders
#4: Shared Environmental ‘Pathogens’ Mirroring the treatment evidence, negaMve events that increase the risk for developing one emoMonal 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 emoAonal 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 mulMple emoMonal disorders
Bateson Can J Psychiatry 2011
Bateson Can J Psychiatry 2011
#4: Shared Environmental ‘Pathogens’ Mirroring the treatment evidence, negaMve events that increase the risk for developing one emoMonal 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 emoAonal 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 mulMple emoMonal disorders
#5: Shared Genes (Heritability) The emoMonal disorders are somewhat heritable N/NE is somewhat heritable The variaMon in emoMonal disorders that is heritable is shared across mulMple disorders AND N/NE Familial aggregaMon and segregaMon
• Families (pedigrees) tend to have higher or lower levels of emoAonal disorders AND N/NE
• Individuals within families with higher levels of one tend to have higher levels of the others
• Common inheritance • Shared geneAc underpinnings
Common geneMc substrate would help to explain why N/NE is a risk factor for mulMple emoMonal disorders
#5: Shared Genes (Heritability) The emoMonal disorders are somewhat heritable N/NE is somewhat heritable The variaMon in emoMonal disorders that is heritable is shared among mulMple disorders AND N/NE Familial aggregaMon and segregaMon
• Families (pedigrees) tend to have higher or lower levels of emoAonal 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 geneAc underpinnings
Common geneMc substrate, one shared by mulMple DX’es and N/NE, would help to explain why N/NE is a risk factor for mulMple emoMonal disorders
#5: Shared Genes (Heritability) The emoMonal disorders are somewhat heritable N/NE is somewhat heritable The variaMon in emoMonal disorders that is heritable is shared among mulMple disorders AND N/NE (jargon term: geneMcally correlated) Familial aggregaMon and segregaMon
• Families (pedigrees) tend to have higher or lower levels of emoAonal 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 geneAc underpinnings
Common geneMc substrate, one shared by mulMple DX’es and N/NE, would help to explain why N/NE is a risk factor for mulMple emoMonal disorders
#5: Shared Genes (Heritability) The emoMonal disorders are somewhat heritable N/NE is somewhat heritable The variaMon in emoMonal disorders that is heritable is shared among mulMple disorders AND N/NE (jargon term: geneMcally correlated) Familial aggregaMon and segregaMon
• Families (pedigrees) tend to have higher or lower levels of emoAonal 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 geneAc underpinnings
Common geneMc substrate, one shared by mulMple DX’es and N/NE, would help to explain why N/NE is a risk factor for mulMple emoMonal disorders
#5: Shared Genes (Heritability) The emoMonal disorders are somewhat heritable N/NE is somewhat heritable The variaMon in emoMonal disorders that is heritable is shared among mulMple disorders AND N/NE (jargon term: geneMcally correlated) Familial aggregaMon and segregaMon
• Families (pedigrees) tend to have higher or lower levels of emoAonal 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 geneAc underpinnings
Common geneMc substrate, one shared by mulMple DX’es and N/NE, would help to explain why N/NE is a risk factor for mulMple emoMonal disorders
#6: Common Neural Circuit Across DX’es The emoMonal disorders (and N/NE) are consistently associated with heightened acMvaMon 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 mulMple emoMonal disorders
#6: Common Neural Circuit Across DX’es The emoMonal disorders (and N/NE) are consistently associated with heightened acMvaMon 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 mulMple emoMonal disorders
#6: Common Neural Circuit Across DX’es The emoMonal disorders (and N/NE) are consistently associated with heightened acMvaMon 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 mulMple emoMonal disorders
Across Anxiety Disorders
#6: Common Neural Circuit Across DX’es The emoMonal disorders (and N/NE) are consistently associated with heightened acMvaMon 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 mulMple emoMonal disorders
Depression, too!
#6: Common Neural Circuit Across DX’es The emoMonal disorders (and N/NE) are consistently associated with heightened acMvaMon 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 mulMple emoMonal disorders
Depression, too
Interim Summary 1. N/NE predicts the emoMonal 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 mechanis6c evidence that T&P (N/NE) and psychopathology (emo6onal disorders) reflect a common substrate
6-‐7 begin to address the make-‐up of the common cause
Interim Summary 1. N/NE predicts the emoMonal 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 mechanis6c evidence that T&P (N/NE) and psychopathology (emo6onal disorders) reflect a common substrate
6-‐7 begin to address the make-‐up of the common cause
Interim Summary 1. N/NE predicts the emoMonal 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 mechanis6c evidence that T&P (N/NE) and psychopathology (emo6onal disorders) reflect a common substrate
6-‐7 begin to address the make-‐up of the common cause
Interim Summary 1. N/NE predicts the emoMonal 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 mechanis6c evidence that T&P (N/NE) and psychopathology (emo6onal disorders) reflect a common substrate
6-‐7 begin to address the make-‐up of the common cause
Interim Summary 1. N/NE predicts the emoMonal 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 mechanis6c evidence that T&P (N/NE) and psychopathology (emo6onal disorders) reflect a common substrate
6-‐7 begin to address the make-‐up of the common cause
Interim Summary 1. N/NE predicts the emoMonal 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 mechanis6c evidence that T&P (N/NE) and psychopathology (emo6onal disorders) reflect a common substrate
6-‐7 begin to address the make-‐up of the common cause
Interim Summary 1. N/NE predicts the emoMonal 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 mechanis6c evidence that T&P (N/NE) and psychopathology (emo6onal disorders) reflect a common substrate
Is N/NE a cause, a symptom, or simply ‘the same as’ the emo6onal disorders?
N is a Cause, Not a Symptom
CMD = Common Mental Disorder; Ormel et al CPR 2013
N is a Cause, Not a Symptom
CMD = Common Mental Disorder; Ormel et al CPR 2013
Yes
Yes
Yes
Yes
Yes
N/NE precedes disorder onset
Common Cause Does Not Mean ‘The Same As’
Some individuals with high levels of N/NE never meet diagnosAc criteria for an emoAonal disorder Not altogether clear what this means
-‐ e.g., able to cope with or regulate N/NE to maintain sufficient funcAon (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 full-‐ blown disorder
Common Cause Does Not Mean ‘The Same As’
Some individuals with high levels of N/NE never meet diagnosAc criteria for an emoAonal disorder Not altogether clear what this means
-‐ e.g., able to cope with or regulate N/NE to maintain sufficient funcAon (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 full-‐ blown disorder
Common Cause Does Not Mean ‘The Same As’
Some individuals with high levels of N/NE never meet diagnosAc criteria for an emoAonal disorder Not altogether clear what this means
-‐ e.g., able to cope with or regulate N/NE to maintain sufficient funcAon (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 full-‐ blown disorder
Common Cause Does Not Mean ‘The Same As’
Some individuals with high levels of N/NE never meet diagnosAc criteria for an emoAonal disorder Not altogether clear what this means
-‐ e.g., able to cope with or regulate N/NE to maintain sufficient funcAon (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 full-‐ blown disorder
Common Cause Does Not Mean ‘The Same As’
Some individuals with high levels of N/NE never meet diagnosAc criteria for an emoAonal disorder Not altogether clear what this means
-‐ e.g., able to cope with or regulate N/NE to maintain sufficient funcAon (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 full-‐ blown disorder
Take Home Points 1. There are substanMal similariMes and co-‐morbidity between the anxiety and
depressive disorders. Spectra, not fundamentally different natural kinds
2. ManipulaMons that decrease (treatment) or increase (negaMve events) one Dx, tend to have similar effects on the others as well as N/NE suggesMng a common substrate
3. Elevated levels of N/NE are a common/shared feature of the emoMonal 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 parMcular disorders, such as specific phobia of dogs?
This reflects learning and experience (exposure to aggressive dog) interacMng with the core vulnerability (e.g., hyper-‐reacMve amygdala)
6. All in all, this evidence suggests that individual differences in N/NE and
EmoMonal Disorders are not fundamentally different, but instead reflect a common cause
Take Home Points 1. There are substanMal similariMes and co-‐morbidity between the anxiety and
depressive disorders. Spectra, not fundamentally different natural kinds
2. ManipulaMons that decrease (treatment) or increase (negaMve events) one Dx, tend to have similar effects on the others as well as N/NE suggesMng a common substrate
3. Elevated levels of N/NE are a common/shared feature of the emoMonal 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 parMcular disorders, such as specific phobia of dogs?
This reflects learning and experience (exposure to aggressive dog) interacMng with the core vulnerability (e.g., hyper-‐reacMve amygdala)
6. All in all, this evidence suggests that individual differences in N/NE and
EmoMonal Disorders are not fundamentally different, but instead reflect a common cause
Take Home Points 1. There are substanMal similariMes and co-‐morbidity between the anxiety and
depressive disorders. Spectra, not fundamentally different natural kinds
2. ManipulaMons that decrease (treatment) or increase (negaMve events) one Dx, tend to have similar effects on the others as well as N/NE suggesMng a common substrate
3. Elevated levels of N/NE are a common/shared feature of the emoMonal 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 parMcular disorders, such as specific phobia of dogs?
This reflects learning and experience (exposure to aggressive dog) interacMng with the core vulnerability (e.g., hyper-‐reacMve amygdala)
6. All in all, this evidence suggests that individual differences in N/NE and
EmoMonal Disorders are not fundamentally different, but instead reflect a common cause
Take Home Points 1. There are substanMal similariMes and co-‐morbidity between the anxiety and
depressive disorders. Spectra, not fundamentally different natural kinds
2. ManipulaMons that decrease (treatment) or increase (negaMve events) one Dx, tend to have similar effects on the others as well as N/NE suggesMng a common substrate
3. Elevated levels of N/NE are a common/shared feature of the emoMonal disorders (anxiety, depression). EmoMonal disorders are a Really Big Deal
4. This shared phenotype (symptoms or traits) reflects a common biological substrate (genes, brain circuits)
5. Specificity: Why do some individuals develop parMcular disorders, such as specific phobia of dogs?
This reflects learning and experience (exposure to aggressive dog) interacMng with the core vulnerability (e.g., hyper-‐reacMve amygdala)
6. All in all, this evidence suggests that individual differences in N/NE and
EmoMonal Disorders are not fundamentally different, but instead reflect a common cause
Take Home Points 1. There are substanMal similariMes and co-‐morbidity between the anxiety and
depressive disorders. Spectra, not fundamentally different natural kinds
2. ManipulaMons that decrease (treatment) or increase (negaMve events) one Dx, tend to have similar effects on the others as well as N/NE suggesMng a common substrate
3. Elevated levels of N/NE are a common/shared feature of the emoMonal disorders (anxiety, depression). EmoMonal disorders are a Really Big Deal
4. This shared phenotype (symptoms or traits) reflects a common biological substrate (genes, brain circuits)
5. Specificity: Why do some individuals develop parMcular disorders, such as specific phobia of dogs?
This reflects learning and experience (exposure to aggressive dog) interacMng with the core vulnerability (e.g., hyper-‐reacMve amygdala)
6. All in all, this evidence suggests that individual differences in N/NE and
EmoMonal Disorders are not fundamentally different, but instead reflect a common cause
Take Home Points 1. There are substanMal similariMes and co-‐morbidity between the anxiety and
depressive disorders. Spectra, not fundamentally different natural kinds
2. ManipulaMons that decrease (treatment) or increase (negaMve events) one Dx, tend to have similar effects on the others as well as N/NE suggesMng a common substrate
3. Elevated levels of N/NE are a common/shared feature of the emoMonal disorders (anxiety, depression). EmoMonal disorders are a Really Big Deal
4. This shared phenotype (symptoms or traits) reflects a common biological substrate (genes, brain circuits)
5. Specificity: Why do some individuals develop parMcular disorders, such as specific phobia of dogs?
This reflects learning and experience (exposure to aggressive dog) interacMng with the core vulnerability (e.g., hyper-‐reacMve amygdala)
6. All in all, this evidence suggests that individual differences in N/NE and
EmoMonal Disorders are not fundamentally different, but instead reflect a common cause
Take Home Points 1. There are substanMal similariMes and co-‐morbidity between the anxiety and
depressive disorders. Spectra, not fundamentally different natural kinds
2. ManipulaMons that decrease (treatment) or increase (negaMve events) one Dx, tend to have similar effects on the others as well as N/NE suggesMng a common substrate
3. Elevated levels of N/NE are a common/shared feature of the emoMonal disorders (anxiety, depression). EmoMonal disorders are a Really Big Deal
4. This shared phenotype (symptoms or traits) reflects a common biological substrate (genes, brain circuits)
5. Specificity: Why do some individuals develop parMcular disorders, such as specific phobia of dogs?
This reflects learning and experience (exposure to aggressive dog) interacMng with the core vulnerability (e.g., hyper-‐reacMve amygdala)
6. All in all, this evidence suggests that N/NE and EmoMonal Disorders are not
fundamentally different, but instead reflect a common cause
CriMcal Thinking QuesMons (Pick 2)
CriMcal Thinking QuesMons (Pick 2) 1. Briefly discuss the implicaAons of what we discussed
today for a loved one or celebrity (living or dead) suffering from an emoAonal disorder e.g. Robin Williams
2. Briefly discuss the most important challenges or limitaAons 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 interesAng to you (e.g., societal impact of mental illness, implicaAons for public healthcare, etc.)
CriMcal Thinking QuesMons (Pick 2) 1. Briefly discuss the implicaAons of what we discussed
today for a loved one or celebrity (living or dead) suffering from an emoAonal disorder e.g. Robin Williams
2. Briefly discuss the most important challenges or limitaAons 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 interesAng to you (e.g., societal impact of mental illness, implicaAons for public healthcare, etc.)
CriMcal Thinking QuesMons (Pick 2) 1. Briefly discuss the implicaAons of what we discussed
today for a loved one or celebrity (living or dead) suffering from an emoAonal disorder e.g. Robin Williams
2. Briefly discuss the most important challenges or limitaAons of Barlow’s account and how future research could address them.
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 interesAng to you (e.g., societal impact of mental illness, implicaAons for public healthcare, sAgma, etc.)
ConLnued on next slide
CriMcal Thinking QuesMons (Pick 2) 4. There’s growing evidence that the microfauna in our intesAnes influence our state of mind. The gut-‐brain axis seems to be bidirecAonal—the brain acts on gastrointesAnal and immune funcAons that shape the gut’s microbial makeup, and gut microbes make neurotransmiSers and metabolites that act on the brain. e.g. ScienAsts colonized the intesAnes of one strain of mice with bacteria taken from the intesAnes of another mouse strain, the recipient animals would take on aspects of the donor’s personality. Naturally Amid mice would become more exploratory, whereas more daring mice would become apprehensive and shy. What do you think? Briefly describe the potenAal implicaAons of this work (e.g. for our understanding of T&P, for psychopathology, for the development of ‘neutriceuAcals’ (ProbioAcs for your Brain, etc.)
Schmidt Nature 2015; Cryan & Dinan Nature Rev Neuro 2012; Collins et al Nature Rev Microbio 2012
CriMcal Thinking QuesMons (Pick 2) 4. There’s growing evidence that the microfauna in our intesAnes influence our state of mind. The gut-‐brain axis seems to be bidirecAonal—the brain acts on gastrointesAnal and immune funcAons that shape the gut’s microbial makeup, and gut microbes make neurotransmiSers and metabolites that act on the brain. e.g. ScienAsts colonized the intesAnes of one strain of mice with bacteria taken from the intesAnes of another mouse strain, the recipient animals would take on aspects of the donor’s personality. Timid mice became exploratory, whereas daring mice became apprehensive and shy. What do you think? Briefly describe the potenAal implicaAons of this work (e.g. for our understanding of T&P, for psychopathology, for the development of ‘neutriceuAcals’ (ProbioAcs for your Brain, etc.)
Schmidt Nature 2015; Cryan & Dinan Nature Rev Neuro 2012; Collins et al Nature Rev Microbio 2012
CriMcal Thinking QuesMons (Pick 2) 4. There’s growing evidence that the microfauna in our intesAnes influence our state of mind. The gut-‐brain axis seems to be bidirecAonal—the brain acts on gastrointesAnal and immune funcAons that shape the gut’s microbial makeup, and gut microbes make neurotransmiSers and metabolites that act on the brain. e.g. ScienAsts colonized the intesAnes of one strain of mice with bacteria taken from the intesAnes of another mouse strain, the recipient animals would take on aspects of the donor’s personality. Timid mice became exploratory, whereas daring mice became apprehensive and shy. What do you think? Briefly describe the potenAal implicaAons of this work (e.g. for our understanding of T&P, for psychopathology, and for the development of ‘neutriceuAcals’ (ProbioAcs for your Brain, etc.))
Schmidt Nature 2015; Cryan & Dinan Nature Rev Neuro 2012; Collins et al Nature Rev Microbio 2012
CriMcal Thinking QuesMons (Pick 2) 5. The Anxiety & Depression AssociaAon of America (ADAA) distributes a number of compelling video clips and other kinds of informaAon on what it’s like to live with an anxiety disorder: • Stossel Interview Re Anxiety hSp://www.adaa.org/about-‐adaa/press-‐room/mulAmedia/stossel
What do you think? Watch one of the video clips or read the M&M webpage and then briefly comment on what you found most interesAng, informaAve, or counter-‐intuiAve. Briefly comment on how you might make use of this informaAon or other facts about mental illness that we covered in class in your own daily life (with friends, family members, or co-‐workers).
CriMcal Thinking QuesMons (Pick 2) 5. The Anxiety & Depression AssociaAon of America (ADAA) distributes a number of compelling video clips and other kinds of informaAon on what it’s like to live with an anxiety disorder: • Stossel Interview Re Anxiety hSp://www.adaa.org/about-‐adaa/press-‐room/mulAmedia/stossel
What do you think? Watch one of the video clips or read the M&M webpage and then briefly comment on what you found most interesAng, informaAve, or counter-‐intuiAve. Briefly comment on how you might make use of this informaAon or other facts about mental illness that we covered in class in your own daily life (with friends, family members, or co-‐workers).
The End (No Review QuesMons)
Things to Consider Tweaking for Spring 2014
N = NeuroAcism; E = Extraversion; D = DisinhibiAon; C = ConscienAousness Distress = GAD + MDD; Fear = Panic and Phobias
Alex – these next few slides actually make the point that MDD and SAD are really 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 appeAAve moAvaAon
Regarding Weak MDD-‐E RelaMons
Regarding Weak MDD-‐E RelaMons Low PE is supposed to be the facet that disMnguishes depression from the anxiety disorders
TriparMte Model: Clark & Watson JAP 1991; Watson et al JAP 1995a, b
High N/NE
Low E/PE
Regarding Weak MDD-‐E/PE RelaMons Low PE is supposed to be the facet that disMnguishes depression from the anxiety disorders
TriparMte Model: Clark & Watson JAP 1991; Watson et al JAP 1995a, b
High N/NE
Low PE
Regarding Weak MDD-‐E RelaMons Weak relaMons may reflect the use of a broadband measure of Extraversion, rather than a more specific measure of PosiMve EmoMonality
Regarding Weak MDD-‐E RelaMons Weak relaMons may reflect the use of a broadband measure of Extraversion, rather than a more specific measure of PosiMve EmoMonality
Collected mulMple measures of each facet of E/PE
Results revealed that 1) E/PE = 4 Facets = Sociability, PE, ExhibiAonism/Dominance, and Fun-‐Seeking 2) Depression, but not anxiety, was strongly and selecAvely related to low PE
Extra Slides
1. Need to understand the mechanisms that convey risk (N/NE à Dx) * What exactly is that arrow?? * What are the proximal mechanisms mediaAng the assoc. between T&P and Dx * Increased reacAvity, biased aSenAon, neg appraisals, stress generaAon, maladapAve coping, etc?
2. Another way to think about this is, We need to dissect N/NE into its consMtuents
* Mood/Feelings, CogniAon, Peripheral Physiol, Behavior, Learning * May be helpful to adopt an endophenotype-‐type simplicaAon strategy
3. AdjudicaMng between causal models
* ManipulaAons targeAng N/NE would let you pick vulnerability vs. common cause * No studies have tested whether Tx-‐induced reducAons in N/NE are separable from changes in Dx; if so, evidence favoring vulnerability
4. N/NE is a transdiagnosMc risk factor. We also need to understand the mechanisms that
determine diagnosMc 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 (sensiAvity to interocepAve cues)
Future Challenges
Barlow CPS 2013/in press; Caspi CPS 2013/in press; Ormel et al CPR 2013; Nolen-‐Hoeksema & Watkins PPS 2011
NeuroMcism / NegaMve EmoMonality (N/NE)
Israel et al JPSP 2014
Differences in N/NE in turn reflect
-‐ A disorder-‐nonspecific biological vulnerability (e.g., hyper-‐reacAve amygdala)
-‐ That promotes a disorder nonspecific psychological vulnerability
Shared, trans-‐diagnosMc phenotype, common to N/NE and the Dxes
Characterized by – More frequent/intense negaAve emoAons
– Reduced emoAonal clarity and acceptance of emoAonal experiences
– Tendency to experience negaAve emoAons as more unpleasant or to have heightened apprehension about the prospect of feeling distressed or anxious in the future (elevated “anxiety sensiAvity”; anx about being anxious)
Another Hallmark of the Core Phenotype
Another Hallmark of the Core Phenotype Tendency to rely on strategies aimed at reducing negaMve emoMons that paradoxically serve to increase and maintain negaMve emoMons
– ASenAonal avoidance – Other Escape / Avoidance Strategies