Abstract
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.
Keywords: moderators, mediators, functional magnetic resonance imaging (fMRI), neuroimaging, smoking
Full Text
The Full Text of this article is available as a PDF (167.3 KB).
REFERENCES
- Anthony JC, Warner LA, Kessler RC. Comparative epidemiology of dependence on tobacco, alcohol, controlled substances and inhalants: basic findings from the National Comorbidity Survey. Exp Clin Psychopharmacol 1994; 2: 244–68. [Google Scholar]
- Birmingham K. What is translational medicine. Nat Med 2002; 8(7): 647. DOI: 10.1038/nm0702‐647 [DOI] [PubMed] [Google Scholar]
- Dani JA, Harris RA. Nicotine addiction and comorbidity with alcohol abuse and mental illness. Nat Neurosci 2005; 8: 1465–70. DOI: 10.1038/nn1580 [DOI] [PubMed] [Google Scholar]
- DiFranza JR, Rigotti NA, McNeill AD. Initial symptoms of nicotine dependence in adolescents. Tob Control 2000; 9: 313–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Epstein DH, Preston KL. The reinstatement model and relapse prevention: a clinical perspective. Psychopharmacology 2003; 168(1–2): 31–41. DOI: 10.1007/s00213‐003‐1470‐6 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003; 160(4): 636–45. [DOI] [PubMed] [Google Scholar]
- Grant BF, Hasin DS, Chou SP, Stinson FS, Dawson DA. Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry 2004; 61: 1107–15. [DOI] [PubMed] [Google Scholar]
- Landsberg MW, Scheef L, Daamen MM, Bludau J, Schildberg F, Bopp B, Johanson CE, Schütz CG. Cue‐induced brain activation and relapse in smokers participating in a six months smoking cessation treatment program. A functional MRI study. Submitted for publication.
- Miller NS, Gold MS. Dissociation of “conscious desire” (craving) from and relapse in alcohol and cocaine dependence. Ann Clin Psychiatry 1994; 6(2): 99–106. [DOI] [PubMed] [Google Scholar]
- O'Brien CP. A range of research‐based pharmacotherapies for addiction. Science 1997; 278(5335): 66–70. DOI: 10.1126/science.278.5335.66 [DOI] [PubMed] [Google Scholar]
- O'Brien CP, Gardner EL. Critical assessment of how to study addiction and its treatment: human and non‐human animal models. Pharmacol Ther 2005; 108(1): 18–58. DOI: 10.1016/j.pharmthera.2005.06.018 [DOI] [PubMed] [Google Scholar]
- Kraemer HC, Stice E, Kazdin A, Offord D, Kupfer D. How do risk factors work together? Mediators, moderators, and independent, overlapping, and proxy risk factors. Am J Psychiatry 2001; 158(6): 848–56. [DOI] [PubMed] [Google Scholar]
- McKay JR, Franklin TR, Patapis N, Lynch KG. Conceptual, methodological, and analytical issues in the study of relapse. Clin Psychol Rev 2006; 26(2): 109–27. DOI: 10.1016/j.cpr.2005.11.002 [DOI] [PubMed] [Google Scholar]
- Schütz CG, Landsberg MW, Daamen M, Scheef L. Cue and stress induced brain activity changes and relapse in smokers. CPDD, Scottsdale AZ 17–22.06 2006. (abstract).
- Shaham Y, Hope BT. The role of neuroadaptations in relapse to drug seeking. Nat Neurosci 2005; 8(11): 1437–9. DOI: 10.1038/nn1105‐1437 [DOI] [PubMed] [Google Scholar]
- Stewart J. Pathways to relapse: factors controlling the reinitiation of drug seeking after abstinence. Nebr Symp Motiv 2004; 50: 197–234. [PubMed] [Google Scholar]
- Storr CL, Zhou H, Liang KY, Anthony JC. Empirically derived latent classes of tobacco dependence syndromes observed in recent‐onset tobacco smokers: epidemiological evidence from a national probability sample survey. Nicotine Tob Res 2004; 6: 533–45. DOI: 10.1080/14622200410001696493 [DOI] [PubMed] [Google Scholar]
- Vocci FJ, Acri J, Elkashef A. Medication development for addictive disorders: the state of the science. Am J Psychiatry 2005; 162(8): 1432–40. [DOI] [PubMed] [Google Scholar]
- World Health Organization (WHO) . Tobacco or Health: A Global Status Report. Geneva: WHO, 1997. [Google Scholar]