The role of impulsivity in the pathogenesis and treatment of addictive behaviors

1. The role of impulsivity in the pathogenesis and treatment of addictive behaviors Wim van den Brink, MD PhD Amsterdam Institute for Addiction Research Academic Medical Center University of Amsterdam AEP, 15th European Congress of Psychiatry, Madrid 19 March 2007

2. Content • Pathogenesis of addiction: role of impulsivity • Impulsivity in addicted patients • Impulsivity based interventions in addiction • Treatment of impulsive co-morbidity • Conclusions

3. Pathogenesis of AddictionRole of Impulsivity

4. Phases in the Addiction Process Van den Brink, 2005, 2006; Van Ree, 2002; de Vries and Schippenberg, 2002; Kreek et al, 2002; Kosten and George, 2002; Koob, 2003

5. Decreased DA Binding in Corpus Striatum in Alcohol and Drug Addicts after Prolonged AbstinenceReward Deficiency?

6. Reward Deficiency

7. Frontal Cortex Under-Activity after Sustained Abstinence

8. Relation Striatal and Orbitofrontal Activity

9. I-RISA ModelImpaired Response Inhibition and Salience Attribution Goldstein and Volkow, 2002

10. I-RISA Model of Addiction Volkow (2004) Control Control Salience STOP GO Drive Salience Drive Memory Memory Non-Addicted Brain Addicted Brain

11. From the functional model to the brain Volkow, 2006

12. Attentional Bias – Craving - Relapse

13. Attentional Bias – Craving - Relapse

15. Attentional Bias – Craving - Relapse

16. Attentional Bias - Cue-Reactivity - Craving –Relapse Repeated Reward Detection Threshold Disinhibition Attentional Bias Cue-Reactivity Craving Relapse Conflict Registration

17. Conflict Registration and Control(Kerns et al., Science, 2004; Stroop) A1: ACC activity during conflict trials; A2: ACC activity during error trials D: ACC activity previous trial and activity PFC current trial

18. Impulsivity in Addicted Patients

19. Subtypes of Impulsivity Motor Impulsivity • self report: BIS-11 • cognitive tests: Stop-Signal Test (SST), Go/No-Go Task Cognitive Impulsivity • self report: BIS-11 • cognitive tests: Delay Discounting Task (DDT), Card Playing Task (CPT), Iowa Gambling Task (IGT) Decision making • self report: BIS-11 • cognitive tests: Tower of London (ToL)

21. Studies consistently demonstrate impaired decision-making in patients with substance use disorders relative to controls Relationship between decision-making tasks and brain activation is complex due to differences between tasks. However, OFC and ACC seem to be critically involved in reward-related behaviors Relationships between activation of OFC, cue-reactivity and craving are inconsistent

22. Sample Abstinent cocaine addicts (coc: n=13) Normal controls (norm: n=13) Test Iowa Gambling Task + Control Task PET rrCBF Conclusies: AB: right OFC coc > norm [Attentional Bias cocaine addicts?] C: right DLPFC/left MPFC coc < norm [Impulsivity cocaine addicts?]

23. Sample: • ▲ controls n=15 • ○ abst. alcoholics n=12 • □ alcoholics n=19 • Test: • Delay Discounting Task • 6 hrs-25 yrs • max 100-1000 US $ • max 15-150 bottles alc • Conclusion • Alcoholicst more impulsive • than controls, especially • with lower bets and • with alcohol rewards k=0.006 k=0.007 k=0.049 k=0.142 k=0.040 k=0.013 k=0.041 k=0.095 k=0.036 k=0.138 k=1.715 Reward in $ Reward in bottles alcohol

25. k=0.0072 k=0.0541 k=0.0541 k=0.0636 Full recovery in ex-smokers? Impulsivity stronger with cigarette reward Only non-impulsive smokers can quit? than with monetary reward

26. k = mean discount rates Sample: Controls (n=54) LAO alcoholics (n=46) EAO alcoholics (n=42) Test: Delay Discounting Task Conclusion: Only EAO alcoholics are more impulsive than controls

27. Sample: ▲Controls (n=33) ○ Substance abusers without ASP (n=75) □ Substance abusers with ASP (n=58) Test: Delay Discounting Task Conclusion: ASP co-morbidity only explains part of the excess impulsivity in substance abusers

28. Decision-making deficits in alcohol-dependent patients with and without co-morbid personality disorder Dom G, Hulstijn W, Sabbe B, Van den Brink W (2006) Sample Controls (n=53) Alcoholics without PD (n=38) Alcoholics with cluster A-C PD (n=19) Alcoholics with cluster B PD (n=23) Test Iowa Gambling Task (IGT) Conclusion Impulsivity in alcoholics not only due to comorbid cluster B PDs 1-20 21-40 41-60 61-80 81-100

29. Iowa Gambling Task Performance controls better than SUD and SUD-PG better than SUD+PG No sign correlations between IGT and self report measures

31. Iowa Gambling Task Card Playing Task PGs react faster than all others after both loss and reward NCs and Tourettes slow down after loss PGs en alcoholics do NOT slow down

32. Neurocognitive deficits predict relapse in pathological gamblingGoudriaan AE, Oosterlaan J, de Beurs E, van den Brink W (in press) • Sample • * N=46 pathological gamblers • Predictors of relapse within 14 months • * severity PG, duration PG, depression (BDI), IQ (WAIS) • * impulsivit phenotypical: BIS-11, SSS • * impulsivity endophenotypical: CPT, Stop Signal Reaction Time • Results • * Duration PG explained 24% of the variance in relapse • * CPT en SSRT additionally explained 34%  total 58% explained variance • * BIS-11 en SSS had no added predictive value to duration PG

33. Impulsivity Based Interventions in Addiction

34. Pharmacological Interventions Antagonist Anti-Craving Drug Cognitive Enhancer Agonist Naltrexone Acamprosate Modafinil Methadone Opioid dependence Alcohol dependence Cocaine dependence Opioid dependence Repeated Reward Antagonists Agonists Detection Threshold Disinhibition Attentional Bias Cue-Reactivity Craving Relapse Conflict Registration Cognitive Enhancers Anti-Craving Drugs

35. Attentional Bias - Cue-Reactivity - Craving –Relapse Repeated Reward Detection Threshold Disinhibition Attentional Bias Cue-Reactivity Craving Relapse Conflict Registration BioFeedback

36. Overactivity ACC in OCDduring error/conflict registration Overactivity ACC in OCD patients Continuous Performance Task Ursu et al., 2003

37. Underactivity ACC in adult ADHD patients What about addicted patients? What about motivational interviewing?

38. Effect EEG Biofeedback kinderen ADHD(Beauregard , Levesque, 2006) (Review: Holtmann en Stadler, 2006) EXP subjects were trained to enhance the amplitude of the SMR (12-15 Hz) and beta 1 activity (15-18 Hz), and decrease the amplitude of theta activity (4-7 Hz). ACC Thalamus Nc Caudatus Li Sup Parietaal ACC Nc Caudatus VLPFC EEG Biofeedback  activation ACC en Nc Caudatus during sel. attention and motor inhibition task EEG-Biofeedback  activation VLPFC during motor inhibition task EEG Biofeedback results in better behavioral output.

39. EEG Feedback and Addiction • Am J Drug Alcohol Abuse. 2005;31(3):455-69. • Effects of an EEG biofeedback protocol on a mixed substance abusing population. • Scott WC, Kaiser D, Othmer S, Sideroff SI This study examined whether an EEG biofeedback protocol could improve outcome measures for a mixed substance abusing inpatient population. METHOD: One hundred twenty-one volunteers undergoing an inpatient substance abuse program were randomly assigned to the EEG biofeedback or control group. EEG biofeedback included training in Beta and SMR to address attentional variables, followed by an alpha-theta protocol. Subjects received a total of 40 to 50 biofeedback sessions. The control group received additional time in treatment equivalent to experimental procedure time. The Test of Variables of Attention (TOVA), and MMPI, were administered with both tester and subject blind as to group placement to obtain unbiased baseline data. Treatment retention and abstinence rates as well as psychometric and cognitive measures were compared. RESULTS: Experimental subjects remained in treatment significantly longer than the control group (p <0.005). Of the experimental subjects completing the protocol, 77% were abstinent at 12 months, compared to 44% for the controls. Experimental subjects demonstrated significant improvement on the TOVA (p<.005) after an average of 13 beta-SMR sessions. Following alpha-theta training, significant differences were noted on 5 of the 10 MMPI-2 scales at the p<.005 level. • CONCLUSIONS: This protocol enhanced treatment retention, variables of attention, and abstinence rates one year following treatment.

40. DeCharms et al., 2006 (PNAS)

41. Conclusions

42. Conclusies • Addiction is a combination of • (a) a sensitised motivational system (salience/incentive sensitisation), and • (b) a hypoactive conflict monitoring and inhibition system (disinhibition) • In terms of impulsivity and decision making PG is more similar to substance use disorders than to other impulse regulation disorders. This has important repercussions for our thinking about addiction. • Phenotypical assessments need to be complemented or replaced by endophenotypical measures, including neurocognitive tests. • In the treatment of addiction more attention should be paid to the improvement of conflict monitoring and the reduction of impulsivity. • In addition to cognitive behavioral and pharmacological interventions, neurofeedback and other neurophysiological treatments (e.g. TMS, DBS) should be studied more intensively.

43. w.vandenbrink@amc.uva.nl