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With respect to unseen cues - a possible relapse predictor?

Posted by teresafr on 27 Feb 2008 at 15:05 GMT

First, i should introduce myself as a co-author on the paper, 'Prelude to Passion...' I have worked with Dr. Childress for several years examining the brain and behavioral correlates of drug addiction, specifically with respect to cocaine and cigarette addiction. One dilemma we have encountered is the inability of some of our patients to label the craving state and yet relapse is just as prevalent in these individuals. The ability of 'unseen' cues (unaware of their craving) to activate similar brain regions as those activated by 'seen' cues may be one of the underlying mechanisms leading to relapse in such individuals. The fact that frontal regions involved in inhibitory behavior are not drawn into the picture are supportive. How can this be tested in the real world of drug addiction? Following addicts out into the real world is difficult. Often the world of a drug addict is a chaotic place. Many of our patients never return to our treatment center.....
Secondly, this inability to label craving may be a genetic predisposition or a consequence of repeated assault on the brain by the corrosive action of these psychoactive substances, or as many researchers in the field believe, a combination of the two. Recently, we have been able to show that cue reactivity IS at least partially genetically mediated and our laboratory will continue to study this and other relapse predictors. The ultimate goal is to establish a brain/behavioral/genetic endophenotype, such that treatments for addiction can be structured to meet individual needs to reduce relapse rates.

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RE: With respect to unseen cues - a possible relapse predictor?

childress_a replied to teresafr on 29 Feb 2008 at 06:06 GMT

Dear Dr. Franklin -- Thanks so much for both comments...

1) With regard to testing the ability of the brain response to (visible or "unseen") drug cues to predict substance use vulnerability --

This can be approached in a number of ways -- each with advantages and disadvantages.

As examples: a) the brain response to drug cues can be correlated with retrospective, self-reported history of drug use/relapse -- this approach has all the downsides of self-report, but is inexpensive; 2) the brain response can be used to predict prospective, objective drug use outcomes (with quantitative toxicologies) -- As you point out, these kinds of clinical outcome data are expensive to obtain and are often plagued by attrition and non-random data loss; 3) For a strong proof-of-concept approach, the brain response to drug cues can be correlated with latency or magnitude of actual drug use in a controlled laboratory setting, , e.g., smokers with the larger brain response to ("seen" or "unseen") cigarette cues may later light up more quickly and/or smoke more cigarettes in a setting where cigarette cues are presesnt. I think you are exploring the potential of this latter paradigm -- a good choice.

2) Indeed, the brain response to drug cues shows a great deal of individual variation. As we have collaboratively demonstrated that dopamine release occurs to cocaine cues, it seems very likely that genetic differences in dopamine (DA) transmission will account for some of the individual differences in the brain response to cocaine cues. Your recent imaging and genetics findings in smokers are consistent with this general hypothesis, and are very intriguing. Combining neurogenetic and neuroimaging approaches will hopefully offer us (not only) better predictors for relapse, but -- eventually -- better screening of candidate medications for those with the best clinical potential.

Thanks again for your good thoughts,

ARChildress

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