Understanding brain mechanisms of cognitive behavioral therapy for

depression in obesity

Jun Ma, MD, PhD, FAHA, FABMR Professor of Medicine

Director, Center for Health Behavior Research University of Illinois at Chicago

Financial disclosures: None

Background

• Integrated therapy for comorbid depression and obesity is lacking • Neural mechanisms are understudied

CDC, 2015

Prevalence of obesity

CDC, 2014

Depression and obesity

NIH, 2017

Major depression

Outline

•Design overview of two linked studies •Depression treatment outcomes

•Mediating effects of neural circuit functions on

changes in theory-based constructs for Problem-Solving Therapy for depression

RAINBOW: Research Aimed at Improving Both Mood and Weight

Study design (R01 HL119453)

6-Month 12-Month 18-Month 24-Month

✔ ✔ (Primary)

In progress In progress

• Recruit

• Screen

• Baseline Rand

omize

(n

=409

) Intervention

Usual care control

Program to Encourage Active and Rewarding Lives (PEARLS)

Evidence-Based Programs

Group Lifestyle Balance (GLB) program

• Collaborative stepped care • Problem-Solving Therapy/PST (first-line) • As-needed antidepressant medications • Developed by Univ. of Washington

• Adapted from Diabetes Prevention Program • Healthy eating, active living, and behavioral

self-management • Developed by Univ. of Pittsburgh

I-CARE Intervention 12-month Health Coach-Led Team-Based Care

• Active intervention: 9 in-person sessions & 12 home videos over 6 months • Maintenance: 6 monthly phone sessions • Technology-enhanced, collaborative care

I-CARE: Integrated Coaching for Better Mood and Weight intervention

GLB references: Ma et al. 2012 JAMA intern Med Kramer et al. 2009 Am J Prev Med

PEARLS references: Ciechanowski et al. 2004 JAMA Chaytor et al. 2011 Epilepsy & behavior : E&B Ciechanowski et al. 2010 Epilepsy & behavior : E&B Katon et al. 2010 Contemp Clin Trials ; 2010 NEJM

PEARLS program for depression

GLB program for obesity

I-CARE Intervention for comorbid depression and obesity

Primary • Depression severity • BMI Secondary • CVRFs (waist, BP) • Anxiety, sleep • Disability • Quality of life

• Problem-solving skill training

• Goal setting • Self-monitoring • Action planning • Social support

Intervention Techniques Outcomes

• Heathy eating • Physical activity • Problem-solving

abilities & attitudes Problem

orientation Problem-solving

skills

Cognition/Behavior

Understanding Effectiveness

ENGAGE Project (UH2 HL132368): Engaging self-regulation targets to understand the mechanisms

of behavior change and improve mood and weight outcomes

Jun Ma and Leanne Williams

PEARLS program for depression

GLB program for obesity

I-CARE Intervention for comorbid depression and obesity

Primary • Depression severity • BMI Secondary • CVRFs (waist, BP) • Anxiety, sleep • Disability • Quality of life

• Problem-solving skill training

• Goal setting • Self-monitoring • Action planning • Social support

Intervention Techniques Outcomes

• Heathy eating • Physical activity • Problem-solving

abilities & attitudes Problem

orientation Problem-solving

skills

Cognition/Behavior Self-Regulation Targets

Regulation of emotion

Regulation of cognition

Regulation of self-focused reflection

Understanding Mechanisms: Self-Regulation

ENGAGE Testing Flow

Baseline 2-Month 6-Month 12-Month 18-Month 24-Month

✔ ✔

N/A ✔

✔ ✔

✔ ✔

In progress N/A

In progress In progress

x 4 visits

RAINBOW (n=409)

ENGAGE (n=108)

Intervention Usual care control

Baseline characteristics Mean ± SD, % Age, years 51.0 ± 12.1 Female 70 Race/Ethnicity

Non-Hispanic White 71 Asian/Pacific Islander 10

Hispanic 14 Education

Some college 24 College graduate and beyond 70

Body mass index (BMI), kg/m2 36.7 ± 6.4 Patient Health Questionnaire (PHQ9) 13.8 ± 3.1 Depression Symptom Checklist (SCL20) 1.5 ± 0.5 Prior depression per EHR* 70 Treated with antidepressant medications 41 General Anxiety Disorder (GAD7) 8.4 ± 5.1 *EHR, electronic

health records

Depression Severity

Depression Response and Remission

SCL20 Change and PST Theoretical Constructs

Overall Problem Solving Ability r=-0.25 p<0.001

Positive Problem Orientation r=-0.05 p=0.44

Negative Problem Orientation r=0.25 p<0.001

Rational Problem Solving r=0.06 p=0.33

Impulsive/Careless Style r=0.14 p=0.01

Avoidant Style r=0.28 p<0.001

Taxonomy of Neural Circuit Dysfunctions Self-reflection Emotion regulation Cognitive control

Brain circuits

Default Mode Negative Affect Sadness

Negative Affect Threat Positive Affect Cognitive Control

Quantify circuit dys-

functions

Rumination Negative Bias Threat Dysregulation Anhedonia Cognitive

Dyscontrol

(CD1,D2 + CD1,D3 + CD1,D4 + CD2,D4 +

CD3,D4)/5

(AN1 + AN2 + AN3 + AN4 + AN5 - CN1,N2 -CN1,N3 +

CN1,N4 + CN1,N5)/9

(-AT1 + AT2 + AT3 -CT1,T2 - CT1,T3)/5

(AP1-AP2-AP3)/3

(-AC1-AC2-AC3-CC1,C2 - CC2,C3)/5

Williams, 2016 Lancet Psychiatry

Brain Circuit Dysfunctions at 2 Months

Low dysfunction High dysfunction

Intervention Control

Brain Circuit Dysfunctions at 2 Months

Impu

lsiv

e/Ca

rele

ss Negative Affect - Threat Cognitive Control Circuit

Avoi

dant

Mal

adap

tive

Prob

lem

-Sol

ving

Sty

les

Cognitive Control Circuit Negative Affect - Sadness

Low dysfunction High dysfunction

Intervention Control

Conclusions

• Brain functions for the regulation of cognition and emotion may bear important implications for improving the potency and efficiency of cognitive behavioral therapy

Acknowledgements

R01HL119453 UH2HL132368

Jeremy Bailenson, PhD, Stanford

Jun Ma, MD PhD Univ Illinois Chicago

Lisa Goldman Rosas, PhD MPH, PAMFRI

Mark Snowden, MD MPH, Univ Washington

Elizabeth Venditti, PhD, Univ Pitts

Megan Lewis, PhD RTI

Philip Lavori, PhD Stanford

Lan Xiao, PhD PAMFRI

Olivier Gevaert, PhD, Stanford

Leanne Williams, PhD Stanford

Joshua Smyth, PhD Penn State Univ

Paul Dagum, MD PhD, Mindstrong

Trisha Suppes, MD PhD, Stanford

Brian Wandell, PhD, Stanford

Walter Greenleaf, PhD, Stanford

Catherine Stoney, PhD, NHLBI

Susan Czajkowski, PhD, NCI

Janine Simmons, MD PhD, NHLBI

Jeremy Goldhaber-Fiebert, PhD, Stanford

RAINBOW and ENGAGE study participants and staff

Brain Circuit Dysfunctions at Baseline Predict

Low dysfunction High dysfunction

Intervention Control

Cognitive dyscontrol Negative bias Rumination

Chan

ge in

Fru

it/Ve

geta

ble

Inta

ke

Chan

ge in

Phy

sica

l Act

ivity

Participants who did NOT benefit from the intervention if at baseline they had: - LOW cognitive dyscontrol - HIGH negative bias - HIGH rumination

Not Engaged (30%)

Somewhat Engaged (11%)

Engaged (59%)

Sessions attended*** 4.5 ± 2.6 a 12.0 ± 4.1 b 14.8 ± 1.0 c Weeks with self-monitoring:

Weight*** 2.1 ± 3.3 a 4.3 ± 4.8 a 17.5 ± 11.1 b Activity minutes*** 1.4 ± 2.2 a 5.5 ± 5.5 a 17.7 ± 11.7 b

Pedometer steps*** 8.0 ± 8.4 a 21.4 ± 16.0 b 33.3 ± 14.6 c

Intervention Engagement

***P < 0.0001. abc Different letters denote significant pairwise differences. Values are mean ± SD unless otherwise noted.

Intervention Response: PHQ9 Trajectories

β1 = Linear coefficient, β2 = Quadratic coefficient *Includes intervention participants (70%) with PHQ9 data in at least 3 quarters during the yearlong intervention

Pred

icte

d PH

Q9

scor

es*

Weeks since intervention session 1

Cluster 2-Moderate symptoms with treatment response: 10% Intercept = 12.90350, P<.0001; β1 = -0.41714, P<.0001; β2 = 0.00551, P<.0001

Cluster 1-Moderate symptoms without treatment response: 20% Intercept = 11.04656, P<.0001 β1 = -0.11193, P=0.0034; β2 = 0.00195, P=0.0146

Cluster 3-Milder symptoms with treatment response: 40% Intercept = 7.40531; P<.0001; β1 = -0.23414, P<.0001; β2 = 0.00336, P<.0001

Intervention Response: % Weight Change Trajectories

Pre

dict

ed %

wei

ght c

hang

e fr

om b

asel

ine*

Weeks since baseline

β1 = Linear coefficient, β2 = Quadratic coefficient *Includes intervention participants (60%) with self-monitored weight data in at least 3 quarters during the yearlong intervention

Cluster 1-Minimal weight loss: 25% β1 = -0.06399, P<.0001; β2 = 0.00126, P<.0001

Cluster 2-Moderate weight loss: 30% β1 = -0.28481, P<.0001; β2 = 0.00242, P<.0001 Cluster 3-Most weight loss: 6%

β1 = -0.52924, P<.0001; β2 = 0.00484, P<.0001

Baseline Characteristics Intervention Engagement

PHQ9 Response

Behavioral Problem-solving abilities

Positive problem orientation

Negative problem orientation

Clinical Prior depression per EHR

Systolic blood pressure

Depression severity (SCL20)

Obesity and depression severity

Anxiety (GAD7)

Post-traumatic stress disorder

Hospitalizations last year

Baseline Characteristics Intervention Engagement

PHQ9 Response

Sociodemographic Female

Education

Family annual income

Married/living with a partner

Psychosocial Problems with pain/discomfort

Problems with anxiety/depression

Obesity-related problems

Sheehan Disability Scale scores

SF8 mental health scores

Better intervention engagement and PHQ9 response associated with…

Positive association. Inverse association.

SCL20 Change and PST Theoretical Constructs