While there are as of yet no FDA-approved medications for cocaine dependence, behavioral therapies such as cognitive-behavioral therapy (CBT) have strong empirical support as well as durability of effects. Evaluation of neurobiological factors is a promising strategy for evaluating mechanisms of empirically supported therapies, as well as for identifying potentially novel targets for treatment development. We propose to add three imaging sessions (pre-treatment, post-treatment, and 6-month follow-up) to a recently initiated randomized clinical trial evaluating two forms of CBT (therapist- and computer-delivered) versus manual-guided standard counseling for 96 cocaine-dependent individuals drawn from the parent trial. Using hypotheses derived from preliminary data using the proposed tasks (Stroop Color-Word Interference and Monetary Incentive Delay Tasks) and measures (white matter integrity, regional brain volumes and resting state brain function), we will: 1) investigate the extent to which the baseline measures of the imaging tasks predict treatment outcomes; 2) evaluate changes in fMRI measures from pre- to post-treatment (baseline to 12 weeks) and by treatment condition (CBT versus standard counseling); 3) examine the relationship of within- treatment change in brain activation to 6-month follow-up outcomes (with an emphasis on understanding CBT's durability and sleeper effect); and 4) investigate the relationships between brain activations and CBT dosing (CBT sessions and homework completed). This project leverages a rare opportunity to evaluate neural mechanisms of action associated with addiction treatment in general and CBT in particular, as well as a unique opportunity to examining neural factors related to the durability of effects (sleeper effects) in CBT. Demonstration of durable changes in brain activation paralleling CBT-related improvements in cognitive control would represent an important step in elucidating and strengthening treatment effects, as well as understanding CBT's mechanisms of action, enabling clinicians to target specific skills and strategies to the individuals most likely to beneit from them.

Public Health Relevance

This project proposes to leverage yield from an existing clinical trial comparing efficacy of a novel computer- delivered cognitive-behavioral therapy with demonstrated efficacy to clinician-delivered CBT and a manualized drug treatment control by adding multiple neuroimaging assessments at pre-treatment, post-treatment and follow-up. The goal of this project is to identify neurobiological correlates of treatment outcome and response, and to extend our understanding of CBT's mechanism of action and durability, with the long-range aim of maximizing the effectiveness of this form of treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA035058-03
Application #
8914560
Study Section
Risk, Prevention and Intervention for Addictions Study Section (RPIA)
Program Officer
Aklin, Will
Project Start
2013-08-01
Project End
2016-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
3
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
Yip, Sarah W; Worhunsky, Patrick D; Xu, Jiansong et al. (2018) Gray-matter relationships to diagnostic and transdiagnostic features of drug and behavioral addictions. Addict Biol 23:394-402
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Carroll, Kathleen M; Kiluk, Brian D (2017) Cognitive behavioral interventions for alcohol and drug use disorders: Through the stage model and back again. Psychol Addict Behav 31:847-861
Fauth-Bühler, Mira; Mann, Karl; Potenza, Marc N (2017) Pathological gambling: a review of the neurobiological evidence relevant for its classification as an addictive disorder. Addict Biol 22:885-897
Yip, Sarah W; Morie, Kristen P; Xu, Jiansong et al. (2017) Shared microstructural features of behavioral and substance addictions revealed in areas of crossing fibers. Biol Psychiatry Cogn Neurosci Neuroimaging 2:188-195

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