Catehol-o-methyltransferase gene Val158met polymorphism as a potential predictor of response to computer-assisted delivery of cognitive-behavioral therapy among cocaine-dependent individuals: Preliminary findings from a randomized controlled trial.

Background: Findings from uncontrolled studies suggest that the COMT Val108/158Met polymorphism may affect response to cognitive behavioral therapy (CBT) in some populations. Using data from a randomized controlled trial evaluating computerized CBT (CBT4CBT), we evaluated treatment response by COMT genotype, with the a priori hypothesis that Val carriers would have improved response to computerized delivery of CBT.

Methods: 101 cocaine-dependent individuals, of whom 81 contributed analyzable genetic samples, were randomized to standard methadone maintenance treatment plus CBT4CBT or standard treatment alone in an 8 week trial.

Results: There was a significant genotype by time effect on frequency of cocaine use from baseline to the end of the 6 month follow-up, suggesting greater reductions over time for Val carriers relative to individuals with the Met/Met genotype. There was a significant treatment condition by genotype interactions for rates of participants attaining 21 or more days of continuous abstinence as well as self-reported percent days of abstinence, suggesting less cocaine use among Val carriers when assigned to CBT compared to standard treatment. Exploration of possible mechanisms using measures of attentional biased also pointed to greater change over time in these measures among the Val carriers assigned to CBT.

Conclusion: These are the first data from a randomized controlled trial indicating significant interactions of COMT polymorphism and behavioral therapy condition on treatment outcome, where Val carriers appeared to respond particularly well to computerized CBT. These preliminary data point to a potential biomarker of response to CBT linked to its putative mechanism of action, enhanced cognitive control.