Neurocognitive and Neurobehavioral Mechanisms of Change Following Psychological Treatment for Alcohol Use Disorder (ABQTREAT)

Neurocognitive and Neurobehavioral Mechanisms of Change Following Psychological Treatment for Alcohol Use Disorder

Alcohol Use Disorder (AUD) is a significant public health problem, with prevalence rates of 13.9% for current and 29.1% for lifetime diagnosis (Grant et al., 2015). AUD creates harm at the individual, familial, and societal level, with an estimated societal cost of $249 billion (Sacks et al., 2015) per year. The course of AUD typically is characterized by periods of relapse to problematic drinking (Maisto et al., 2014), signaling a need for better treatments and understanding of mechanisms of behavior change. The goal of this research is to conduct a randomized clinical trial with 140 participants who have an Alcohol Use Disorder (AUD). Each participant will complete behavioral assessments, self-report surveys and brain imaging before and after receiving psychotherapy treatment to change their drinking behaviors. Various aspects of behavior change will be looked at to better understand changes in brain function and emotional reactivity when someone changes their patterns of alcohol use. The two treatment used in this study have been found to be helpful in reducing alcohol use. Participants will be randomly assigned to either Mindfulness-Based Relapse Prevention (MBRP) or Cognitive Behavior Therapy (CBT) that will be completed in 12 weekly therapy sessions. It is anticipated that there will be numerous changes in brain function that are found when someone reduces or stops their alcohol use after the completion of 12 weeks of treatment.

Although pharmacological and psychosocial treatments for alcohol use disorders (AUDs) exist that improve outcomes over natural recovery (Finney et al., 2013), outcomes are still modest. Identifying mechanisms of behavior change (MOBCs) that lead to successful outcomes may be critical for efforts to improve existing treatments or to better match patients with particular treatments. The goal of the proposed research is to conduct a randomized clinical trial to systematically examine pretreatment neurocognitive and behavioral characteristics and changes in brain function over time during two empirically supported treatments for AUD. One hundred forty treatment-seeking individuals with an AUD will be randomized to receive either 8 weeks of Cognitive Behavioral Treatment (CBT) or Mindfulness Based Treatment (MBT) after receiving 4 weeks of a platform treatment that focuses on enhancing motivation to change. Neurocognitive and behavioral characteristics will be measured using neuroimaging, comprehensive behavioral assessments, and patient self-reports. To establish the temporal relationship between changes in drinking and changes in these MOBCs, patients will be assessed at: (a) baseline; (b) four weeks into treatment; (c) immediately post-treatment; and (d) 9- and 15-months post-baseline. Self-report measures and behavioral tasks will be administered at monthly intervals during treatment; and fMRI will be collected at baseline, and at 3, and 9-months post baseline. The primary aim of the study is to examine the effects of the treatments on three hypothesized mechanisms: craving/regulation of craving, cognitive and behavioral control, and regulation of affect/arousal. The secondary aim will identify neurocognitive and behavioral baseline characteristics predictive of reductions in drinking over time and differential patterns of response to CBT or MBT.

The CBT condition will include 8 weekly, 60-minute sessions, and will be delivered according to the Epstein & McCrady (2009) cognitive-behavioral treatment manual, excluding material provided in the platform treatment. The treatment manual and accompanying client workbook provide detailed therapist instructions for each session, client exercises, worksheets, and homework assignments. The treatment focuses on cognitive and behavioral coping skills training, and emphasizes problem-solving as an overall approach to dealing with drinking.

The MBT condition will be adapted from the 8-week version of the mindfulness-based relapse prevention (MBRP) manual (Bowen et al., 2011; Witkiewitz et al., 2005). The main adaptation will be to eliminate the relapse prevention/CBT components and focus attention on mindfulness practices. The mindfulness practices in MBT are designed to increase awareness of triggers and decrease reactivity to distress or discomfort in the presence of triggers (Witkiewitz & Bowen, 2010). The relevant worksheets and homework assignments focusing on mindfulness tools will be maintained from the MBRP manual.

The CBT condition will include 8 weekly, 60-minute sessions, and will be delivered according to the Epstein & McCrady (2009) cognitive-behavioral treatment manual, excluding material provided in the platform treatment. The treatment manual and accompanying client workbook provide detailed therapist instructions for each session, client exercises, worksheets, and homework assignments. The treatment focuses on cognitive and behavioral coping skills training, and emphasizes problem-solving as an overall approach to dealing with drinking. Treatment sessions may be audio-recorded for supervision and to ensure that the treatment is being delivered as intended.

The MBT condition will be adapted from the 8-week version of the mindfulness-based relapse prevention (MBRP) manual (Bowen et al., 2011; Witkiewitz et al., 2005). The main adaptation will be to eliminate the relapse prevention/CBT components and focus attention on mindfulness practices. The mindfulness practices in MBT are designed to increase awareness of triggers and decrease reactivity to distress or discomfort in the presence of triggers (Witkiewitz & Bowen, 2010). The relevant worksheets and homework assignments focusing on mindfulness tools will be maintained from the MBRP manual. Treatment sessions may be audio-recorded for supervision and to ensure that the treatment is being delivered as intended.

Penn Alcohol Craving Scale will be used to examine changes in craving that occur during and after treatment.

The difference in percent signal change during alcohol vs. neutral picture cues in ventral striatum will be assessed using a cue task while participants are scanned using functional magnetic resonance imaging

The UPPS-P Impulsivity Questionnaire will be used to examine changes in impulsivity that occur during and after treatment.

The Monetary Choice Questionnaire will be used to determine the degree to which impulsive choice changes during and after treatment. A discounting rate (k) will be computed for each administration.

The difference in percent signal change during successful inhibition of responses vs. successful non-inhibition trials in right inferior frontal cortex will be assessed using a stop signal task while participants are scanned using functional magnetic resonance imaging.

The difference in percent signal change during unsuccessful inhibition of responses vs. successful non-inhibition trials in dorsal anterior cingulate cortex will be assessed using a stop signal task while participants are scanned using functional magnetic resonance imaging.

The difference in percent signal change during negative vs. neutral picture cues in amygdala will be assessed using a cue task while participants are scanned using functional magnetic resonance imaging.

The Negative Affect Summary score from the NIH toolbox will be used to assess overall negative affect changes during and after treatment.

Baseline, 4-week within treatment visit, 8-week within treatment visit, and 3-month follow-up, 9-month follow-up, and 15-month follow-up

The Form 90 will be used to derive estimates of the outcome: drinks (standard drink=14 grams of pure alcohol) per drinking day.

Baseline, 4-week within treatment visit, 8-week within treatment visit, and 3-month follow-up, 9-month follow-up, and 15-month follow-up

The Form 90 will be used to derive estimates of the outcome: percent heavy drinking days, where heavy drinking is defined as 4+ drinks per occasion for women and 5+ drinks per occasion for men.

Baseline, 4-week within treatment visit, 8-week within treatment visit, and 3-month follow-up, 9-month follow-up, and 15-month follow-up

Inclusion Criteria: Age 22-85 years Self-identify as a heavy/binge/weekly drinker Engage in "hazardous and harmful alcohol use" (Babor et al., 2001) based on an AUDIT score > 8 for men and > 7 for women Breath alcohol level of 0.00 at in-person screening Right handed Explicitly be seeking help for their drinking Alcohol use during the past 30 days Exclusion Criteria: History of brain injury or neurological diagnoses Evidence of current psychosis Past-year substance dependence other than nicotine or marijuana Evidence of recent illicit drug (other than marijuana) use on a urine screen Contraindications for MRI (e.g., medical devices in the body) Female participants who think they may be pregnant must pass a urine pregnancy screen prior to each MRI scanning session Estimated IQ < 80 Unable to read or speak English fluently History of major alcohol withdrawal Currently in treatment for alcohol use (or within the past 6 months)

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