Using neuroimaging to predict relapse to smoking: role of possible moderators and mediators

Background and aims: Preclinical animal studies have established stressors, substance use associated cues, and priming as distinct triggers of relapse in substance dependence. These triggers seem to induce relapse by activating distinct brain pathways. In order to test these findings in humans, it is necessary to establish new human research paradigms. Neuroimaging may help to study brain regions involved in mediating the effects of these distinct triggers of relapse and to further delineate mediators of these pathways. In order to understand individual differences it is crucial to assess the impact of moderators on these pathways to relapse. Methods: Paradigms to study distinct relapse triggers are currently being set up for tobacco dependence. It is practically impossible to study human relapse and specifically its neurobiological pathways in the natural surrounding. Instead we aim to establish vulnerability patterns in a laboratory environment, applying functional magnetic resonance imaging (fMRI) assessments during trigger exposure. Brain activation determined by fMRI may constitute a sensitive measure to assess responses to cues, stress, and priming. Establishing these paradigms will then allow to further delineate the role of possible mediators (e.g. attention, inhibition) and moderators (e.g. sex, genetic factors) underlying relapse to smoking. Results: Initial results are encouraging, but this approach needs further studies to proof its usefulness. Conclusions: We outline an approach to study nicotine relapse within a laboratory environment, using fMRI assessments during trigger exposure. The long term goal is rational treatment development. To reach this goal it is crucial to identify, include and investigate critical moderators and mediators of relapse within this approach. Copyright © 2008 John Wiley & Sons, Ltd.