Efficacy of Interpretation Bias Modification in Depressed Adolescents

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Efficacy of Interpretation Bias Modification in Depressed Adolescents Jamie A. Micco, Ph.D. Department of Psychiatry Massachusetts General Hospital/ Harvard Medical School Boston, Massachusetts, USA

Disclosures Dr. Micco has nothing to disclose.

Acknowledgements Collaborators Dina R. Hirshfeld-Becker, PhD Aude Henin, PhD Funding NIMH: F-32 MH088065 Research Assistants Janet Caruso, B.A. Allison Clarke, B.A. Charlotte Henesy Maura Millette, B.A. Allie Megna, B.A. Nicholas Morrison, B.A. Special Thanks Bethany Teachman, PhD

Introduction 20% of adolescents meet criteria for lifetime major depression by age 18 Approximately 30% do not respond to SSRI medication, CBT, or both types of treatment (March et al, 2004) Innovative or enhanced treatments for this population are needed

Cognitive Bias Modification (CBM) Mathews and Mackintosh (2000) developed a computerized paradigm for inducing positive or negative interpretations of ambiguous social situations in non-clinical subjects Interpretation bias has been modified with CBM programs in adults who score highly on measures of social anxiety (Beard & Amir, 2008), specific phobia (Teachman & Addison, 2008), and GAD (Hirsch et al, 2009) Few studies of CBM with non-clinical or anxious children or adolescents (Vassilopoulos et al, 2009; Muris et al, 2008), which have shown promising results; no studies to date of CBM for depression

CBM for Depressed Youth Depressed adolescents display negative interpretation biases (e.g., Timbremont et al., 2008; Dalgleish et al, 1997) o Negative interpretations of neutral and ambiguous information o Selective attention to negative information Interpretive biases associated with social phobia and depression are similar (e.g., Micco & Ehrenreich, 2009) Will a computerized interpretation bias modification program also be effective for depression, using scenarios relevant to potential loss, rejection, and failure, and developmentally tailored to adolescents?

Participants 48 adolescents and young adults, ages 14-21 years, recruited through fliers, Internet, and clinics at MGH 3 enrolled, but dropped after first visit (included in mixed-effects analyses) 3 not included in analyses (BDI score by first visit<14 [n=2], manic episode by post-tx [n=1]) Inclusion/Exclusion Criteria: o BDI-II score = 14+ at phone screen o Working command of English o No medication/therapy changes within 2 weeks o No active psychosis or mania, previous diagnosis of Autism Disorder, mental retardation, or severe dyslexia

Participants Intervention Control Sig. N 23 (16 female) 22 (17 female) NS Age 17.70±1.94 years Ethnicity 74% Caucasian 17% Biracial 9% Other 18.86±1.81 years 68% Caucasian 14% Biracial 18% Other t=2.09 p<.05 NS BDI-Pre 27.59±10.64 28.00±10.86 NS

Depression Characteristics Intervention Control Current MDD Full: 65% Sub-threshold: 30% None: 5% Full: 59% Sub-threshold: 36% None: 5% Severity Mild: 27% Moderate: 55% Severe: 18% Mild: 38% Moderate: 33% Severe: 29% Treatment History None: 9% Therapy only: 13% Meds only: 9% Therapy+Meds: 43% Hospital: 26% None: 14% Therapy only: 14% Meds only: 10% Therapy+Meds: 38% Hospital: 24%

Design: Pilot RCT Attention Control Group Intervention Group Baseline Assessment Four sessions over two weeks of exposure to neutral scenarios Post-Tx Assessment Two-week FU Baseline Assessment Four sessions over two weeks of positive interpretation training Post-Tx Assessment Two-week FU

Modification Paradigm Intervention Group: 100 three-line scenarios per session (randomly drawn from a pool of 200) o 66 scenarios that are relevant to potential loss, rejection, or failure; ambiguous until the final word (which forces a positive interpretation of the scenario), followed by a comprehension question o 24 filler (neutral) scenarios Attention Control Group: also receive 100 scenarios a session, but all are filler scenarios

Modification Paradigm Example Training Scenario: You have to give an oral presentation in history class this morning. You stand up in front of your class with your notes in your hand. Partway through, people think your presentation is g-od. Does the class like your presentation? Y/N

Modification Paradigm Example Training Scenario: Your older cousin has had trouble finishing school and cannot hold down a job. You wonder if you will end up like him. You realize that your life will turn out bet_er. Will things turn out badly for you? Y/N

Modification Paradigm Example Filler Scenario: You take your dog outside for a walk. While walking, he picks up a big stick and brings it to you. You throw the stick for him to go and f-tch. Does your dog run after the stick? Y/N

Hypotheses Compared to adolescents in the attention control group, adolescents receiving the positive interpretation training will show: 1) Greater reduction in negative interpretation bias over time; and, 2) Greater reduction in scores on measures of depression, anxiety, and negative affect at post-tx and follow-up.

Outcome Measures Primary Outcome: Interpretation Bias 1. Test of Interpretation Bias (Recognition Task) 2. Dysfunctional Attitudes Scale (DAS) 3. Affective Go/No Go Task (CANTAB) Secondary Outcomes: Depression/Anxiety 1. SCID-IV or K-SAD, mood modules 2. BDI-II 3. STAI-Trait/State 4. PANAS 5. Subjective Units of Depression (SUDS)

Test of Interpretation Bias (TIB) 10 completely ambiguous scenarios Participants rate (1-4) how similar each of four interpretations is to what they read Example: The Movies You are on your way to meet a friend at the movie theater. You are supposed to meet him near the ticket booth. When you arrive, your friend is not wa_ting.

Test of Interpretation Bias How similar is each statement below to the scenario you just read on a scale from 1 (not at all similar) to 4 (very similar)? 1. When you arrive, your friend is running late for the movie. [Positive Target] 2. When you arrive, your friend has stood you up. [Negative Target] 3. When you arrive, you realize you have money for popcorn. [Positive Foil] 4. When you arrive, you realize that the movie is sold out. [Negative Foil]

Test of Interpretation Bias Negative and Positive Target scores each range from 10-40 Bias score = Positive Target/Negative Target, with higher ratios indicative of a more positive interpretation bias

Change in Bias Scores 1.4 1.3 1.2 1.1 1 0.9 Treatment Control 0.8 0.7 0.6 BL Mid Post FU Mixed Effects Model (REML): Main effect for time (at post-tx), β=.214, p<.05, no Group x Time Interaction

Bias Change: Negative BL Bias Only 1.2 1.1 1 0.9 0.8 Treatment Control N=26 0.7 0.6 BL Mid Post FU Mixed Effects Model (REML): Main effect for time (at post-tx), β=.212, p<.05, Group x Time Interaction (at mid-tx and post-tx), β=.330, p<.05 andβ=.263, p=.07

DAS 165 160 155 150 145 140 135 130 125 120 BL Post FU Treatment Control N=37 Mixed Effects Model (REML): Group x Time Interaction (at post-tx and FU), β=- 15.37, p<.05 and β=-26.29, p=.001

BDI-II Scores 29 27 25 23 21 Treatment Control 19 17 15 BL Mid Post FU Mixed Effects Model (REML): Main effect for time:β=-5.82, p<.01 (mid-tx), β=- 5.73, p<.01 (post-tx), β=-7.35, p<.001 (FU); no Group x Time interaction

STAI-Trait Scores 60 58 56 54 52 Treatment Control 50 48 BL Mid Post FU Mixed Effects Model (REML): Main effect for time:β=-4.14, p<.05 (post-tx), β=-7.86, p<.01 (FU); no Group x Time interaction

Summary No significant differences between intervention and control groups in interpretation bias change When restricting sample to adolescents with initial negative bias, then intervention group shows significantly greater improvement in interpretation bias at mid- and post-treatment Greater change in dysfunctional cognitions (DAS) in intervention versus control group at post-treatment and follow-up No differences between groups in depression or anxiety symptom improvement

Future Considerations How much dose is enough? Must negative mood be induced before training? Should CBM for depression be considered an adjunct to CBT, or a stand-alone treatment?