1. SOME THEORIES ON ADDICTION November 12, 2007 Kari Poikolainen www.kolumbus.fi/kari.poikolainen Finnish Foundation for Alcohol Studies www.alkoholitutkimussaatio.fi

2. WHAT IS NEEDED? Concepts Theories Explanations Correct assumptions

3. CONCEPTS Concepts Definitions Operationalizations Every concept is already a theory – in a minor way at least

4. THEORIES should Agree with the known facts Give insight Predict Can be tested, falsified

5. EXPLAINING ADDICTION A good theory should explain Causes of the onset Causes of the course – “natural” history How to intervene with the course - treatment When not to intervene

6. UNDERLYING ASSUMPTIONS Addiction is A category, distinct of non-addiction An unitary entity, not several different ones True or false?

7. ADDICTION AS A CHRONIC BRAIN DISEASE Cause: Repeated drug use + genetic disposition + learned environmental associations with drug use Kalivas PW & Volkow ND. Am J Psychiatry 2005;162:1403

8. ADDICTION AS A CHRONIC BRAIN DISEASE Process: “Normal”: drug high dopamine release in NA Repeated use -> switch from dopamine to glutamate-based behaviour -> cellular adaptations in glutamatergic projection from the prefrontal cortex to NA -> prefrontal regulation of behaviour and decision-making reduced except -> stimuli predicting drug availability - > activate!! activate!! activate!! -> uncontrollable urge to obtain drugs What causes repeated use? What kind of repeated use causes addiction?

9. BRAIN DISEASE – IMPLICATIONS Permanent defect in the brain - > maintenance treatment Only drug-related stimuli salient -> disinterest for other activities

10. BRAIN DISEASE – CONFLICT WITH FACTS Chronic and relapsing... * a good deal of DSM-addiction cases recover, many without treatment – remission or permanent? Permanent defect... * memory improves by abstinence Salience...* maintenance pat's active in work and social life

11. HYPERBOLIC DISCOUNTING rational choice theory (Becker and Murphy) presumes exponential discounting of future utilities -> order of preferences does not change if true, addicts are rational experiments show that discounting in humans and lower animals is hyperbolic -> order can change leads to voluntary temporary preferences (TP) short ones may seem to be involuntary but are not

12. HYPERBOLIC DISCOUNTING

13. SOMATIC MARKER HYPOTHESIS: INDUCTION Bilateral lesion in VM section of prefrontal cortex before lesion - normal successful persons after lesion - good or normal IQ, memory and problem solving abilities - decide against their best interests - bankruptcy Bechara A. Sem Clin Neuropsychiatry 2001;6:205

14. Normal VM prefrontal cortex 1. couples exteroceptive complex stimuli with 2. emotional (somatic) states previously associated with those stimuli 3. these (2) mark behaviour options with values 4. high values help in selecting good responses

15. SOMATIC MARKER HYPOTHESIS: PATHOLOGY If there are no somatic markers 1. no clear winners among markers 2. no rapid on-line decisions, therefore either - slow reasoned decision-making, or - inaction, or - decision based on the immediate reward of an option -> addiction

16. GAMBLING TASK VM patients - do not learn to predict and avoid high risk options - do not develop anticipatory SCR responses - make bad choices despite realizing the consequences of the action - say the right thing but do the wrong thing Substance dependent individuals - some behave like normal individuals, some like VM patients

17. IMPLICATIONS Two types? 1.Abusers: no VM disorder - > can stop or revert to social use 2. True addicts: VM disorder - > cannot stop substance use Cf.: Alcoholism types 1. Adult-onset, mild, low hereditability <- self-medication <- anxiety 2. Adolescent-onset, severe, high hereditability <- antisocial <- impulsivity <- difficult temperament

18. Catechol-O-methyltransferase (COMT) gene polymorfism “Warriors” have Val158 - stress and pain resistant - worse executive cognitive performance in most conditions - impulsivity, antisocial behaviour -> Adolescent- onset alcoholism? “Worriers” have Met158 - pain sensitive - prone to anxiety -> Adult-onset alcoholism?

19. PREDICTORS OF ALCOHOLISM – FOLLOW-UP STUDIES

21. PREDICTORS OF ALCOHOLISM

22. PREDICTORS OF ADDICTION many weak predictors, no strong ones in unadjusted or partly adjusted studies adjustments weaken risk estimates interactions E x E, E x G, G x G not yet much studied some mental disorders predict is addiction a disease, symptom, complication or something else?