New Findings on Biological Factors Predicting Addiction Relapse Vulnerability
- 2.2k Downloads
Relapse is a highly prevalent phenomenon in addiction. This paper examines the new research on identifying biological factors that contribute to addiction relapse risk. Prospective studies examining relapse risk are reviewed, and clinical, biological, and neural factors that predict relapse risk are identified. Clinical factors, patient-related factors, and subjective and behavioral measures such as depressive symptoms, stress, and drug craving all predict future relapse risk. Among biological measures, endocrine measures such as cortisol and cortisol/corticotropin (ACTH) ratio as a measure of adrenal sensitivity and serum brain-derived neurotrophic factor were also predictive of future relapse risk. Among neural measures, brain atrophy in the medial frontal regions and hyperreactivity of the anterior cingulate during withdrawal were identified as important in drug withdrawal and relapse risk. Caveats pertaining to specific drug abuse type and phase of addiction are discussed. Finally, significant implications of these findings for clinical practice are presented, with a specific focus on determining biological markers of relapse risk that may be used to identify those individuals who are most at risk of relapse in the clinic. Such markers may then be used to assess treatment response and develop specific treatments that will normalize these neural and biological sequelae so as to significantly improve relapse outcomes.
KeywordsAddiction relapse Stress dysregulation Drug craving Cortisol Cortisol/ACTH ratio Serum BDNF Anterior cingulate Biomarkers Human studies Biological factors Vulnerability
Preparation of this review was supported by grants from the National Institutes of Health (P50-DA165556, R01-AA13892, R01-DA27230, UL1-DE019589, PL1-DA024859).
No potential conflict of interest relevant to this article was reported.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 4.• Hyman SM, Paliwal P, Chaplin TM, et al. Severity of childhood trauma is predictive of cocaine relapse outcomes in women but not men. Drug Alcohol Depend. 2008;92:208–16. This paper is the first to show sex differences in the association of severity of childhood trauma and cocaine relapse outcomes.PubMedCrossRefGoogle Scholar
- 18.•• Sinha R, Fox HC, Hong KI, et al. Effects of adrenal sensitivity, stress- and cue-induced craving, and anxiety on subsequent alcohol relapse and treatment outcomes. Arch Gen Psychiatr. 2011, (epub online). This is the first study to show that provoked alcohol craving and adrenal sensitivity are predictive of subsequent alcohol relapse.Google Scholar
- 20.McRae-Clark A, Carter R, Price K, et al. Stress and cue-elicited craving and reactivity in marijuana-dependent individuals. Psychopharmacology (Berl). 2011.Google Scholar
- 30.•• Epstein DH, Willner-Reid J, Vahabzadeh M, et al. Real-time electronic diary reports of cue exposure and mood in the hours before cocaine and heroin craving and use. Arch Gen Psychiatr. 2009;66:88–94. This is the first study to use EMA to demonstrate the effects of real world cue and stress exposure on subsequent drug use.PubMedCrossRefGoogle Scholar
- 31.• Preston KL, Epstein DH. Stress in the daily lives of cocaine and heroin users: relationship to mood, craving, relapse triggers, and cocaine use. Psychopharmacology. 2011, (in press). This is an excellent paper illustrating of the use of recent methodologic advances with monitoring drug use daily in the real world and demonstrating how stress is associated with drug use.Google Scholar
- 41.• Lubman DI, Yucel M, Kettle JW, et al. Responsiveness to drug cues and natural rewards in opiate addiction: associations with later heroin use. Arch Gen Psychiatr. 2009;66:205–12. This is the first study to show that reduced positive affect to drug cues and natural rewards is associated with later drug use.PubMedCrossRefGoogle Scholar
- 56.Fatseas M, Denis C, Massida Z, et al. Cue-induced reactivity, cortisol response and substance use outcome in treated heroin dependent individuals. Biol Psychiatr. 2011, Jul 7 (Epub ahead of print).Google Scholar
- 59.•• D’Sa C, Fox HC, Hong K, et al. Increased serum brain-derived neurotrophic factor (BDNF) is predictive of cocaine relapse outcomes: a prospective study. Biological Psychiatr. 2011 (in press). This is the first study to identify a biomarker in the basal state that is significantly higher during early recovery from cocaine, and also to predict time to cocaine relapse.Google Scholar
- 75.Seo D, Jia Z, Lacadie CM, et al. Sex differences in neural responses to stress and alcohol context cues. Hum Brain Mapp. 2010.Google Scholar
- 79.Wrase J, Grusser S, Klein S, et al. Development of alcohol-associated cues and cue-induced brain activation in alcoholics. Biol Psych. 2002;17:287–91.Google Scholar
- 92.• Azizian A, Nestor LJ, Payer D, et al. Smoking reduces conflict-related anterior cingulate activity in abstinent cigarette smokers performing a Stroop task. Neuropsychopharmacology. 2010;35:775–82. This paper identified the specific effect of nicotine withdrawal and smoking on anterior cingulate function.PubMedCrossRefGoogle Scholar
- 94.Sinha R, Shaham Y, Heilig M. Translational and reverse translational research on the role of stress in drug craving and relapse. Psychopharmacology (Berl). 2011.Google Scholar