Novel Cognitive Target for Treating Irritability and Anxiety in Youth

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A Novel Cognitive Target for the
Treatment of Co-occurring
Irritability and Anxiety in Youth
 
Analyse DeSousa
1,2
, Simona Haller PhD
3
, Ellen Leibenluft MD
3
,
Melissa Brotman PhD
3
, Matt Jones PhD
4
, 
Joel Stoddard MD
1,2
1Pediatric Mental Health Institute, Children’s Hospital Colorado; 2School of Medicine,
University of Colorado (Anschutz); 3Emotion and Development, NIMH; 4Institute of
Cognitive Science, University of Colorado (Boulder)
 
14 August, 2017
Irritability
 
 
Debilitating symptom that spans mental disorders
BP, anxiety, DMDD, etc
Few evidence based treatments
One promising target for treatment development is
the Hostile Interpretation Bias
 
 
Hostile
Interpretation
Bias (HIB)
 
Tendency to judge ambiguous social information as
being threatening
HIB persists in irritable youth, even when they receive
feedback that social information is benign
1
 
 
1. Stoddard, J., et al. (2016).
Hostile
Interpretation
Bias (HIB)
 
Tendency to judge ambiguous social information as
being threatening
HIB persists in irritable youth, even when they receive
feedback that social information is benign
1
Two hypothesis may explain why HIB persists:
-Irritable youth 
may not detect 
subtle social cues
-Irritable youth 
may be slow to learn 
benign associations
 
 
1. Stoddard, J., et al. (2016).
Interpretation Bias Training
Baseline balance point
 
Feedback threshold
Angry judgments
Happy judgments
 
X
 
Computational Learning Model
 
Computational Learning Model
Remember: Prior work suggested two hypothesis
 
n=9 DMDD; n=15 HV
 
may not detect 
subtle social cues
 
may be slow to learn 
benign associations
 
Study Population
 
48 youth (8-21 yo); %F=41.67
8 youth were excluded for
accuracy <75%
 
 
 
 
Data Analysis
 
Mixed effects model:
  
ARI + SCARED =
 
σ
ε
 
(
may not detect 
subtle social cues)
 
(
may be slow to learn 
benign associations)
 
Adjusting for age, gender, and IQ
Subject as random factor
Results
 
Generalization (σ):
We found no significant associations between σ
and any of the clinical variables (p values>0.08)
Learning Rate (ε):
Significant interactive effect of ARI by SCARED
across ε, β(SE)=0.01(0.005), t(27)=2.11, p=0.04
All other associations with ε were non-significant
(p values>0.18)
 
Results
 
Generalization (σ):
We found no significant associations between σ
and any of the clinical variables (p values>0.08)
Learning Rate (ε):
Significant interactive effect 
of ARI by SCARED
across ε, β(SE)=0.01(0.005), t(27)=2.11, p=0.04
All other associations with ε were non-significant
(p values>0.18)
 
Irritability by
Anxiety on
Learning Rate
Key Findings
 
Irritable youth 
may not detect 
subtle social cues
Irritable youth 
may be slow to learn 
benign
associations
The significant effect we found was 
opposite 
our
expectations
Post hoc 
analysis:
Quick to learn
 
angry
 
associations
Instead of 
slow to learn 
benign associations
 
 
Key Findings
 
Irritable youth 
may not detect 
subtle social cues
Irritable youth 
may be slow to learn 
benign
associations
The significant effect we found was 
opposite 
our
expectations
Post hoc 
analysis:
Quick to learn
 
angry
 
associations
Instead of 
slow to learn 
benign associations
 
Future
Directions
 
Irritability and anxiety should be considered
together in further development
Investigate the 
rapid reinforcement of hostile
judgements 
as a potential training target
 
References
 
1. Stoddard, J., Sharif-Askary, B., Harkins, E.A., Frank,
H.R., Brotman, M.A., Penton-Voak, I.S., Maoz, K., Bar-
Haim, Y., Munafo, M., Pine, D.S., Liebenluft, E. (2016). An
open pilot study of training hostile interpretation bias to
treat disruptive mood disorder. Journal of Child and
Adolescent Psychopharmacology, 26, 49-57. doi:
10.1089/cap.2015.0100
undefined
 
Acknowledgment
 
 
All participants and their families
Slide Note

[Today I am going to talk to you about a new target for the development of treatment of youth who are both irritable and anxious.]

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Research explores Hostile Interpretation Bias as a potential target for treating co-occurring irritability and anxiety in youth. The study investigates why this bias persists in irritable individuals and proposes Interpretation Bias Training as a treatment approach. Computational learning models are utilized to understand face stimuli judgments and learning processes.


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  1. 14 August, 2017 A Novel Cognitive Target for the Treatment of Co-occurring Irritability and Anxiety in Youth Analyse DeSousa1,2, Simona Haller PhD3, Ellen Leibenluft MD3, Melissa Brotman PhD3, Matt Jones PhD4, Joel Stoddard MD1,2 1Pediatric Mental Health Institute, Children s Hospital Colorado; 2School of Medicine, University of Colorado (Anschutz); 3Emotion and Development, NIMH; 4Institute of Cognitive Science, University of Colorado (Boulder)

  2. Irritability Debilitating symptom that spans mental disorders BP, anxiety, DMDD, etc Few evidence based treatments One promising target for treatment development is the Hostile Interpretation Bias

  3. Tendency to judge ambiguous social information as being threatening Hostile Interpretation Bias (HIB) HIB persists in irritable youth, even when they receive feedback that social information is benign1 1. Stoddard, J., et al. (2016).

  4. Tendency to judge ambiguous social information as being threatening Hostile Interpretation Bias (HIB) HIB persists in irritable youth, even when they receive feedback that social information is benign1 Two hypothesis may explain why HIB persists: -Irritable youth may not detect subtle social cues -Irritable youth may be slow to learn benign associations 1. Stoddard, J., et al. (2016).

  5. Fixation (1500-2500 ms) Face (200 ms) Mask (20 ms) Remained until happy or angry response made

  6. Interpretation Bias Training Training Blocks Assess Train x 6 Angry judgments X Happy judgments Assess Baseline balance point Feedback threshold

  7. Computational Learning Model V= ( V) Face Stimuli Judgement H A

  8. Computational Learning Model V= ( V) Parameter Measures Face Stimuli Generalization Judgement H Learning Rate A Reliability

  9. Remember: Prior work suggested two hypothesis may not detect subtle social cues may be slow to learn benign associations Generalization Learning Rate Group Group n=9 DMDD; n=15 HV

  10. Study Population Characteristics M (SD) 48 youth (8-21 yo); %F=41.67 Age 14.1 (3.0) 8 youth were excluded for accuracy <75% IQ 115.3 (11.4) ARI (Irritability) 1.4 (1.8) SCARED (Anxiety) 12.7 (11.3) CDI (Depression) 15.1 (10.0) CONNERS (ADHD)54.5 (15.0)

  11. Data Analysis Mixed effects model: (may not detect subtle social cues) ARI + SCARED = (may be slow to learn benign associations) Adjusting for age, gender, and IQ Subject as random factor

  12. Generalization (): Results We found no significant associations between and any of the clinical variables (p values>0.08) Learning Rate ( ): Significant interactive effect of ARI by SCARED across , (SE)=0.01(0.005), t(27)=2.11, p=0.04 All other associations with were non-significant (p values>0.18)

  13. Generalization (): Results We found no significant associations between and any of the clinical variables (p values>0.08) Learning Rate ( ): Significant interactive effect of ARI by SCARED across , (SE)=0.01(0.005), t(27)=2.11, p=0.04 All other associations with were non-significant (p values>0.18)

  14. Irritability by Anxiety on Learning Rate

  15. Irritable youth may not detect subtle social cues Key Findings Irritable youth may be slow to learn benign associations The significant effect we found was opposite our expectations Post hoc analysis: Quick to learnangryassociations Instead of slow to learn benign associations

  16. Irritable youth may not detect subtle social cues Key Findings Irritable youth may be slow to learn benign associations The significant effect we found was opposite our expectations Post hoc analysis: Quick to learnangryassociations Instead of slow to learn benign associations Limitations Low level irritability in sample Depression and ADHD may be confounds

  17. Irritability and anxiety should be considered together in further development Future Directions Investigate the rapid reinforcement of hostile judgements as a potential training target

  18. References 1. Stoddard, J., Sharif-Askary, B., Harkins, E.A., Frank, H.R., Brotman, M.A., Penton-Voak, I.S., Maoz, K., Bar- Haim, Y., Munafo, M., Pine, D.S., Liebenluft, E. (2016). An open pilot study of training hostile interpretation bias to treat disruptive mood disorder. Journal of Child and Adolescent Psychopharmacology, 26, 49-57. doi: 10.1089/cap.2015.0100

  19. Acknowledgment All participants and their families Our lab team: Joel Stoddard, MD Anne Penner, MD Robert Evans Our Collaborators: Simona Haller, PhD Ellen Leibenluft, MD Melissa Brotman, PhD Matt Jones, PhD PMHI Summer Research Program: Merlin Ariefdjohan, PhD, MPH Emmaly Owens, MA Marisa Deguzman Funding NIMH Intramural Research Program Department of Psychiatry, School of Medicine, University of Colorado Dr. Dominique Martinez, CCTSI, Office of Diversity and Inclusion, University of Colorado Dr. Douglas Novins and Dr. Jennifer Hagman, PMHI, Department of Psychiatry, School of Medicine, University of Colorado

  20. C o r r e l a t i o n o f C l i n i c a l V a r i a b l e s ( r ) A g e 0 . 0 2 0 . 1 7 0 . 0 6 - 0 . 0 3 0 . 1 7 I Q 0 . 0 2 0 . 1 4 - 0 . 0 3 0 . 0 5 - 0 . 1 4 0 . 2 5 A R I 0 . 1 7 0 . 1 4 0 . 4 7 0 . 1 5 0 . 4 8 S C A R E D 0 . 0 6 - 0 . 0 3 0 . 4 7 0 . 1 1 0 . 3 1 C D I - 0 . 0 3 0 . 0 5 0 . 1 5 0 . 1 1 0 . 0 9 0 C O N N E R S 0 . 1 7 - 0 . 1 4 0 . 4 8 0 . 3 1 0 . 0 9 C D I A R I A g e C O N N E R S I Q S C A R E D

  21. Clinical Diagnosis N (%) DMDD 6 (12.5%) ADHD 15 (31.3%) Anxiety 5 (10.4%) Relatives of BD 6 (12.5%) BD 2 (4.2%) HV 14 (12.2%)

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