New Findings on Biological Factors Predicting Addiction Relapse Vulnerability

Abstract

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.

This is a preview of subscription content, access via your institution.

Fig. 1

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    Brownell KD, Marlatt GA, Lichtenstein E, Wilson GT. Understanding and preventing relapse. Am Psychol. 1986;41:765–82.

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Brandon TH, Vidrine JI, Litvin EB. Relapse and relapse prevention. Annu Rev Clin Psychol. 2007;3:257–84.

    PubMed  Article  Google Scholar 

  3. 3.

    Paliwal P, Hyman SM, Sinha R. Craving predicts time to cocaine relapse: further validation of the now and brief versions of the cocaine craving questionnaire. Drug Alcohol Depend. 2008;93:252–9.

    PubMed  Article  CAS  Google Scholar 

  4. 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.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Sinha R, Garcia M, Paliwal P, et al. Stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses are predictive of cocaine relapse outcomes. Arch Gen Psychiatr. 2006;63:324–31.

    PubMed  Article  Google Scholar 

  6. 6.

    Dodge R, Sindelar J, Sinha R. The role of depressive symptoms in predicting drug abstinence in outpatient substance abuse treatment. J Subst Abus Treat. 2005;28:189–96.

    Article  Google Scholar 

  7. 7.

    Sinha R. How does stress increase risk of drug abuse and relapse? Psychopharmacology (Berl). 2001;158:343–59.

    Article  CAS  Google Scholar 

  8. 8.

    Shaham Y, Shalev U, Lu L, et al. The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology. 2003;168:3–20.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    McKay JR, Rutherford MJ, Alterman AI, et al. An examination of the cocaine relapse process. Drug Alcohol Depend. 1995;38:35–43.

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Sinha R. Chronic stress, drug use, and vulnerability to addiction. Ann N Y Acad Sci. 2008;1141:105–30.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    • Enoch MA. The role of early life stress as a predictor for alcohol and drug dependence. Psychopharmacology (Berl). 2011;214:17–31. This is an excellent recent review documenting high rates of early trauma in addictive disorders.

    Article  CAS  Google Scholar 

  12. 12.

    Koob GF, Le Moal M. Drug abuse: hedonic homeostatic dysregulation. Science. 1997;278:52–8.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Koob GF, Ahmed SH, Boutrel B, et al. Neurobiological mechanisms in the transition from drug use to drug dependence. Neurosci Biobehav Rev. 2004;27:739–49.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Volkow ND, Fowler JS. Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cerebral Cortex. 2000;10:318–25.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Kalivas PW, Volkow ND. The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatr. 2005;162:1403–13.

    PubMed  Article  Google Scholar 

  16. 16.

    Robinson TE, Berridge KC. The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction. 2000;95 Suppl 2:S91–S117.

    PubMed  Google Scholar 

  17. 17.

    Sinha R. Modeling stress and drug craving in the laboratory: implications for addiction treatment development. Addict Biol. 2009;14:84–98.

    PubMed  Article  Google Scholar 

  18. 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.

  19. 19.

    •• McKee S, Sinha R, Weinberger AH, et al. Stress decreases the ability to resist smoking and potentiates smoking intensity and reward. J Psychopharmacol. 2011;25(4):490–502. This is the first laboratory demonstration of stress-induced nicotine relapse.

    PubMed  Article  Google Scholar 

  20. 20.

    McRae-Clark A, Carter R, Price K, et al. Stress and cue-elicited craving and reactivity in marijuana-dependent individuals. Psychopharmacology (Berl). 2011.

  21. 21.

    Fox HC, Hong KI, Siedlarz K, Sinha R. Enhanced sensitivity to stress and drug/alcohol craving in abstinent cocaine-dependent individuals compared to social drinkers. Neuropsychopharmacology. 2008;33:796–805.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Sinha R, Fox HC, Hong KA, et al. Enhanced negative emotion and alcohol craving, and altered physiological responses following stress and cue exposure in alcohol dependent individuals. Neuropsychopharmacology. 2009;34:1198–208.

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Field M, Wiers RW, Christiansen P, et al. Acute alcohol effects on inhibitory control and implicit cognition: implications for loss of control over drinking. Alcohol Clin Exp Res. 2010;34(8):1346–52.

    PubMed  CAS  Google Scholar 

  24. 24.

    Constantinou N, Morgan CJ, Battistella S, et al. Attentional bias, inhibitory control and acute stress in current and former opiate addicts. Drug Alcohol Depend. 2010;109:220–5.

    PubMed  Article  Google Scholar 

  25. 25.

    Baker TB, Piper ME, McCarthy DE, et al. Addiction motivation reformulated: an affective processing model of negative reinforcement. Psychol Rev. 2004;111:33–51.

    PubMed  Article  Google Scholar 

  26. 26.

    Brown SA, Vik PW, McQuaid JR, et al. Severity of psychosocial stress and outcome of alcoholism treatment. J Abnorm Psychol. 1990;99:344–8.

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Brown SA, Vik PW, Patterson TL, et al. Stress, vulnerability and adult alcohol relapse. J Stud Alcohol. 1995;56:538–45.

    PubMed  CAS  Google Scholar 

  28. 28.

    Greenfield SF, Kolodziej ME, Sugarman DE, et al. History of abuse and drinking outcomes following inpatient alcohol treatment: a prospective study. Drug Alcohol Depend. 2002;67:227–34.

    PubMed  Article  Google Scholar 

  29. 29.

    Epstein DH, Marrone GF, Heishman SJ, et al. Tobacco, cocaine, and heroin: craving and use during daily life. Addict Behav. 2009;35:318–24.

    PubMed  Article  Google Scholar 

  30. 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.

    PubMed  Article  Google Scholar 

  31. 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.

  32. 32.

    Shiffman S. Dynamic influences on smoking relapse process. J Personal. 2005;73:1–34.

    Article  Google Scholar 

  33. 33.

    Hall SM, Havassy BE, Wassermann DA. Commitment to abstinence and acute stress in relapse to alcohol, opiates and nicotine. J Counsel Clin Psychol. 1990;58:175–81.

    Article  CAS  Google Scholar 

  34. 34.

    Greenfield SF, Weiss RD, Muenz LR, et al. The effect of depression on return to drinking: a prospective study. Arch Gen Psychiatr. 1998;55:259–65.

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Kirschbaum C, Pirke KM, Hellhammer DH. The ‘Trier Social Stress Test’—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology. 1993;28:76–81.

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Back SE, Hartwell K, DeSantis SM, et al. Reactivity to laboratory stress provocation predicts relapse to cocaine. Drug Alcohol Depend. 2010;106:21–7.

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Coffey SF, Saladin ME, Drobes DJ, et al. Trauma and substance cue reactivity in individuals with comorbid posttraumatic stress disorder and cocaine or alcohol dependence. Drug Alcohol Depend. 2002;65:115–27.

    PubMed  Article  Google Scholar 

  38. 38.

    Sinha R, Catapano D, O’Mally S. Stress-induced craving and stress responses in cocaine dependent individuals. Psychopharmacology. 1999;142:343–51.

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Cooney NL, Litt MD, Morse PA, et al. Alcohol cue reactivity, negative-mood reactivity, and relapse in treated alcoholic men. J Abnorm Psychol. 1997;106:243–50.

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Breese GR, Chu K, Dayas CV, et al. Stress enhancement of craving during sobriety and the risk of relapse. Alcohol Clin Exp Res. 2005;29(2):185–95.

    PubMed  Article  Google Scholar 

  41. 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.

    PubMed  Article  Google Scholar 

  42. 42.

    Shiffman S, Paty JA, Gnys M, et al. First lapses to smoking: within-subjects analysis of real-time reports. J Consult Clin Psychol. 1996;64:366–79.

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Kreek MJ, Koob GF. Drug dependence: stress and dysregulation of brain reward pathways. Drug Alcohol Depend. 1998;51:23–47.

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Contoreggi C, Herning RI, Na P, et al. Stress hormone responses to corticotropin-releasing hormone in substance abusers without severe comorbid psychiatric disease. Biol Psych. 2003;54:873–8.

    Article  CAS  Google Scholar 

  45. 45.

    Al’absi M, Hatsukami DK, Davis G. Attenuated adrenocorticotropic responses to psychological stress are associated with early smoking relapse. Psychopharmacology (Berlin). 2005;181:107–17.

    Article  Google Scholar 

  46. 46.

    Adinoff B, Junghanns K, Kiefer F, Krishnan-Sarin S. Suppression of the HPA axis stress-response: implications for relapse. Alcohol Clin Exp Res. 2005;29:1351–5.

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Sinha R, Talih M, Malison R, et al. Hypothalamic-pituitary-adrenal axis and sympatho-adreno-medullary responses during stress-induced and drug cue-induced cocaine craving states. Psychopharmacology (Berl). 2003;170:62–72.

    Article  CAS  Google Scholar 

  48. 48.

    Fox HC, Hong KI, Siedlarz KM, et al. Sex-specific dissociations in autonomic and HPA responses to stress and cues in alcohol-dependent patients with cocaine abuse. Alcohol Alcohol. 2009;44:575–85.

    PubMed  Google Scholar 

  49. 49.

    Fox HC, Hong KH, Paliwal P, et al. Altered levels of sex and stress steroid hormones assessed daily over a 28-day cycle in early abstinent cocaine dependent females. Psychopharmacology. 2007;195:527–36.

    PubMed  Article  Google Scholar 

  50. 50.

    McDougle CJ, Black JE, Malison RT, et al. Noradrenergic dysregulation during discontinuation of cocaine use in addicts. Arch Gen Psychiatr. 1994;51:713–9.

    PubMed  CAS  Google Scholar 

  51. 51.

    Krystal JH, Webb E, Cooney NL, et al. Serotonergic and noradrenergic dysregulation in alcoholism: M-chrophenylpiperazine and yohimbine effects in recently detoxified alcoholics and healthy comparison subjects. Am J Psychiatr. 1996;153:83–92.

    PubMed  CAS  Google Scholar 

  52. 52.

    Bar KJ, Boettger MK, Neubauer R, et al. Heart rate variability and sympathetic skin response in male patients suffering from acute alcohol withdrawal syndrome. Alcohol Clin Exp Res. 2006;30:1592–8.

    PubMed  Article  Google Scholar 

  53. 53.

    Ingjaldsson JT, Thayer JF, Laberg JC. Craving for alcohol and pre-attentive processing of alcohol stimuli. Int J Psychophysiol. 2003;49:29–39.

    PubMed  Article  Google Scholar 

  54. 54.

    Junghanns K, Backhaus J, Tietz U. Impaired serum cortisol stress response is a predictor of early relapse. Alcohol Alcohol. 2003;38:189–93.

    PubMed  CAS  Google Scholar 

  55. 55.

    Brady KT, Back SE, Waldrop AE, et al. Cold pressor task reactivity: predictors of alcohol use among alcohol-dependent individuals with and without comorbid posttraumatic stress disorder. Alcohol Clin Exp Res. 2006;30:938–46.

    PubMed  Article  Google Scholar 

  56. 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).

  57. 57.

    Schoenbaum G, Stalnaker TA, Shaham Y. A role for BDNF in cocaine reward and relapse. Nat Neurosci. 2007;10:935–6.

    PubMed  Article  CAS  Google Scholar 

  58. 58.

    Nestler EJ. Is there a common molecular pathway for addiction. Nat Neurosci. 2005;8:1445–9.

    PubMed  Article  CAS  Google Scholar 

  59. 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.

  60. 60.

    Pfefferbaum A, Sullivan EV, Mathalon DH, et al. Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics. Alcohol Clin Exp Res. 1995;19:1177–91.

    PubMed  Article  CAS  Google Scholar 

  61. 61.

    Sullivan EV, Rosenbloom MJ, Pfefferbaum A. Pattern of motor and cognitive deficits in detoxified alcoholic men. Alcohol Clin Exp Res. 2000;24:611–21.

    PubMed  Article  CAS  Google Scholar 

  62. 62.

    Fein G, Di Sclafani V, Meyerhoff DJ. Prefrontal cortical volume reduction associated with frontal cortex function deficit in 6-week abstinent crack-cocaine dependent men. Drug Alcohol Depend. 2002;68:87–93.

    PubMed  Article  Google Scholar 

  63. 63.

    Tanabe J, Tregellas JR, Dalwani M, et al. Medial orbitofrontal cortex gray matter is reduced in abstinent substance-dependent individuals. Biol Psychiatr. 2009;65:160–4.

    Article  Google Scholar 

  64. 64.

    Pfefferbaum A, Sullivan EV, Rosenbloom MJ, et al. A controlled study of cortical gray matter and ventricular changes in alcoholic men over a 5-year interval. Arch Gen Psychiatr. 1998;55:905–12.

    PubMed  Article  CAS  Google Scholar 

  65. 65.

    Gazdzinski S, Durazzo TC, Meyerhoff DJ. Temporal dynamics and determinants of whole brain tissue volume changes during recovery from alcohol dependence. Drug Alcohol Depend. 2005;78:263–73.

    PubMed  Article  CAS  Google Scholar 

  66. 66.

    Wrase J, Makris N, Braus DF, et al. Amygdala volume associated with alcohol abuse relapse and craving. Am J Psychiatr. 2008;165:1179–84.

    PubMed  Article  Google Scholar 

  67. 67.

    Rando K, Hong KI, Bhagwagar Z. Association of frontal and posterior cortical gray matter volume with time to alcohol relapse: a prospective study. Am J Psychiatr. 2011;168:183–92.

    PubMed  Article  Google Scholar 

  68. 68.

    Childress A, Mozely PD, McElgin W, et al. Limbic activation during cue-induced cocaine craving. Am J Psychiatr. 1999;156:11–8.

    PubMed  CAS  Google Scholar 

  69. 69.

    Grant S, London ED, Newlin DB, et al. Activation of memory circuits during cue-elicited cocaine craving. Proc Natl Acad Sci USA. 1996;93:12040–5.

    PubMed  Article  CAS  Google Scholar 

  70. 70.

    Kilts C, Schweitzer JB, Quinn CK, et al. Neural activity related to drug craving in cocaine addiction. Arch Gen Psychiatr. 2001;58:334–41.

    PubMed  Article  CAS  Google Scholar 

  71. 71.

    Kilts C, Gross RE, Ely TD, Drexler KP. The neural correlates of cue-induced craving in cocaine-dependent women. Am J Psychiatr. 2004;161:233–41.

    PubMed  Article  Google Scholar 

  72. 72.

    Li C-S, Kemp KA, Milivojevic V, Sinha R. Neuroimaging reveals sex differences in the neuropathology of cocaine abuse. J Gend Med. 2005;2:174–82.

    Article  Google Scholar 

  73. 73.

    Sinha R, Li CS. Imaging stress- and cue-induced drug and alcohol craving: association with relapse and clinical implications. Drug Alcohol Rev. 2007;26:25–31.

    PubMed  Article  Google Scholar 

  74. 74.

    Sinha R, Lacadie C, Skudlarski P, et al. Neural activity associated with stress-induced cocaine craving: an fMRI study. Psychopharmacology. 2005;183(2):171–80.

    PubMed  Article  CAS  Google Scholar 

  75. 75.

    Seo D, Jia Z, Lacadie CM, et al. Sex differences in neural responses to stress and alcohol context cues. Hum Brain Mapp. 2010.

  76. 76.

    Volkow ND, Wang GJ, Telang F, et al. Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction. J Neurosci. 2006;26:6583–8.

    PubMed  Article  CAS  Google Scholar 

  77. 77.

    Wong MM, Nigg JT, Zucker RA, et al. Behavioral control and resiliency in the onset of alcohol and illicit drug use: a prospective study from preschool to adolescence. Child Dev. 2006;77:1016–33.

    PubMed  Article  Google Scholar 

  78. 78.

    Grusser S, Wrase J, Klein S, et al. Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharmacology (Berl). 2004;175:296–302.

    Article  Google Scholar 

  79. 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.

    CAS  Google Scholar 

  80. 80.

    Heinz A, Siessmeier T, Wrase J, et al. Correlation between dopamine D(2) receptors in the ventral striatum and central processing of alcohol cues and craving. Am J Psychiatr. 2004;161:1783–9.

    PubMed  Article  Google Scholar 

  81. 81.

    Martinez D, Gil R, Slifstein M, et al. Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum. Biol Psychiatr. 2005;58:779–86.

    Article  CAS  Google Scholar 

  82. 82.

    Martinez D, Kim JH, Krystal J, Abi-Dargham A. Imaging the neurochemistry of alcohol and substance abuse. Neuroimaging Clin N Am. 2007;17:539–55.

    PubMed  Article  Google Scholar 

  83. 83.

    Ersche KD, Clark L, London M, et al. Profile of executive and memory function associated with amphetamine and opiate dependence. Neuropsychopharmacology. 2006;31:1036–47.

    PubMed  Article  CAS  Google Scholar 

  84. 84.

    Ersche KD, Fletcher PC, Lewis SJ, et al. Abnormal frontal activations related to decision-making in current and former amphetamine and opiate dependent individuals. Psychopharmacology (Berl). 2005;180:612–23.

    Article  CAS  Google Scholar 

  85. 85.

    Ersche KD, Roiser JP, Robbins TW, Sahakian BJ. Chronic cocaine but not chronic amphetamine use is associated with perseverative responding in humans. Psychopharmacology (Berl). 2008;197:421–31.

    Article  CAS  Google Scholar 

  86. 86.

    Hester R, Garavan H. Executive dysfunction in cocaine addiction: evidence for discordant frontal, cingulate, and cerebellar activity. J Neurosci. 2004;24:11017–22.

    PubMed  Article  CAS  Google Scholar 

  87. 87.

    Kaufman J, Ross TJ, Stein EA, Garavan H. Cingulate hypoactivity in cocaine users during a GO-NOGO task as revealed by event-related functional magnetic resonance imaging. J Neurosci. 2003;23:7839–43.

    PubMed  CAS  Google Scholar 

  88. 88.

    Li CS, Sinha R. Inhibitory control and emotional stress regulation: neuroimaging evidence for frontal-limbic dysfunction in psycho-stimulant addiction. Neurosci Biobehav Rev. 2008;32:581–97.

    PubMed  Article  Google Scholar 

  89. 89.

    Noel X, Bechara A, Dan B, et al. Response inhibition deficit is involved in poor decision making under risk in nonamnesic individuals with alcoholism. Neuropsychology. 2007;21:778–86.

    PubMed  Article  Google Scholar 

  90. 90.

    Paulus MP, Tapert SF, Schuckit MA. Neural activation patterns of methamphetamine-dependent subjects during decision making predict relapse. Arch Gen Psychiatr. 2005;62:761–8.

    PubMed  Article  Google Scholar 

  91. 91.

    Kosten TR, Scanley BE, Tucker KA, et al. Cue-induced brain activity changes and relapse in cocaine dependent patients. Neuropsychopharm. 2006;31:644–50.

    Article  CAS  Google Scholar 

  92. 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.

    PubMed  Article  Google Scholar 

  93. 93.

    Naqvi NH, Rudrauf D, Damasio H, Bechara A. Damage to the insula disrupts addiction to cigarette smoking. Science. 2007;315(5811):531–4.

    PubMed  Article  CAS  Google Scholar 

  94. 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.

Download references

Acknowledgment

Preparation of this review was supported by grants from the National Institutes of Health (P50-DA165556, R01-AA13892, R01-DA27230, UL1-DE019589, PL1-DA024859).

Disclosure

No potential conflict of interest relevant to this article was reported.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Rajita Sinha.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sinha, R. New Findings on Biological Factors Predicting Addiction Relapse Vulnerability. Curr Psychiatry Rep 13, 398 (2011). https://doi.org/10.1007/s11920-011-0224-0

Download citation

Keywords

  • Addiction relapse
  • Stress dysregulation
  • Drug craving
  • Cortisol
  • Cortisol/ACTH ratio
  • Serum BDNF
  • Anterior cingulate
  • Biomarkers
  • Human studies
  • Biological factors
  • Vulnerability