1. Impulsivity and Alcohol Use Disorders Robert F. Leeman, Ph.D. Department of Psychiatry Yale School of Medicine VA (New England) VISN1 Mental Illness Research Education and Clinical Center (MIRECC)

2. © Alcohol Medical Scholars Program 2 Serious Alcohol Problems   Relatively common   Within prior year (current): 11% – – Males: 15% – – Females: 7%   Costly: $185 billion/year in U.S.   Lethal: 3 rd leading modifiable cause

3. © Alcohol Medical Scholars Program 3   Multiple factors → alcohol problems   Some before heavy drinking begins   Detect early factors for prevention   Impulsivity an example of risk factor – –Earlier onset of alcohol use – –More severe alcohol problems Contributing Factors

4. © Alcohol Medical Scholars Program 4 Onset of Use & Problems   Drinking usually begins in teens   Heaviest drinking: 18-25 yrs – – ~65% use in past month – – ~45% > 4/5 drinks/evening → risky   ~18% young adults alcohol problems   ↑ Impulsivity → ↑ problems

5. © Alcohol Medical Scholars Program 5 Lecture Covers   Definitions   Key characteristics & neurobiology   Problems, other conditions, course   Implications: prevention & treatment

6. © Alcohol Medical Scholars Program 6 Case 1: Phineas Gage   Railroad worker   Conscientious, mild manner, hard-work   Accident → steel rod pierced head   Changes in personality – – Profane, ↓ restraint: give in to desires – – Frequent changing of plans   Role of key brain regions in impulsivity

7. © Alcohol Medical Scholars Program 7 Case 2: Law Student   Prior DUI arrests   Participating in research project   Party: “spiked Gatorade”   1st day license: drives after ~4 drinks   Impulsivity contribute to problems?

8. © Alcohol Medical Scholars Program 8 Lecture Topics   Definitions   Key characteristics & neurobiology   Problems, other conditions, course   Implications: prevention & treatment

9. © Alcohol Medical Scholars Program 9 Alcohol Use Disorder (AUD)   Recurring problems   Affecting multiple life areas   DSM-5: > 2 criteria, past 12 mo.   Diagnosis associated with: – –Long-term alcohol problems – –Earlier death

10. © Alcohol Medical Scholars Program 10 AUD Criteria – – Tolerance – – Withdrawal – – ↑ Amount/time use – – Desire/inability to ↓ use – –↓ Other due to use – – ↓ Role obligations – Hazardous use – Strong craving – Interpersonal problems – Use despite problems –↑ Time obtain/use/recover

11. © Alcohol Medical Scholars Program 11 Impulsivity: Usual Definition   Acting rashly/without thinking   Repeated bad decisions   Recurrent out of control behavior   Trouble frequently without planning

12. © Alcohol Medical Scholars Program 12 Impulsivity: Research Definition   Rapid, unplanned reactions   Diminished regard for outcomes   Not really 1 thing   More a class of characteristics   2 main types: response, choice

13. © Alcohol Medical Scholars Program 13 Response Impulsivity   Difficulty suppressing actions   Ramifications include: – –Alcohol/cues = a strong impulse – –Failure plan for future: Rx impact – –Hard to maintain behavior change – –Emotions can ↓ drinking control

14. © Alcohol Medical Scholars Program 14 Choice Impulsivity   Immediate, definite rewards   Ramifications include: – –Alcohol: immediate definite reward – –Abstinence: weak, uncertain – –Hard to see future improvement

15. © Alcohol Medical Scholars Program 15 Ways to Measure   Cognitive tasks (computer)   Clinical interviews   Self-report questionnaires

16. © Alcohol Medical Scholars Program 16 Cognitive Tasks   Stop-signal tasks – –Respond to visual cue – –No response if hear auditory cue   Continuous performance tasks – –Respond to most cues (e.g., letters) – –Not to 1 cue (e.g., letter “X”)

17. © Alcohol Medical Scholars Program 17 Clinical Interviews  For conditions related to impulsivity  Childhood interviews: ADHD –Parent/teacher ratings: attention –E.g. child task: wait to eat cookie  Adolescent/adult structured interviews –SCID –Conditions like bipolar disorder

18. © Alcohol Medical Scholars Program 18 Questionnaires  Response: impulsive behavior scale – Lack planning and perseverance – Rash response to +/- emotions  Choice: monetary choice questionnaire – Choices: hypothetical $ payments – Now vs. later

19. © Alcohol Medical Scholars Program 19 Back to Cases  Case 1: Phineas Gage –Response: ↓ restraint –Choice: inability to adhere to plans  Case 2: law student –Response: didn’t stop drinking –Choice: drink(immediate), DUI(later)

20. © Alcohol Medical Scholars Program 20 Lecture Topics   Definitions   Key characteristics & neurobiology   Problems, other conditions, course   Implications: prevention & treatment

21. © Alcohol Medical Scholars Program 21 Observable Early in Life   Observable by age 8: – –Fidgety – –Trouble attention, directions – –Talking/acting out of turn – –Unpredictable/explosive behavior   Predictive value: early alcohol onset

22. © Alcohol Medical Scholars Program 22 Genetic Predisposition  Impulsivity: ~ 50% explained genes  Alcohol : ~ 50% explained genes  Alcohol & impulsivity genes overlap

23. © Alcohol Medical Scholars Program 23 Key Brain RegionsFrontal lobes Ventral striatum striatum Dorsal

24. © Alcohol Medical Scholars Program 24 Brain: Frontal Lobes  Ventromedial prefrontal cortex(vmPFC) –Response inhibition –Decision-making  Orbitofrontal cortex(OFC) –Linked to limbic system (reward) –Impulse control

25. Back to Phineas Gage © Alcohol Medical Scholars Program 25 Frontal lobes - severe injury - vmPFC, OFC Impulsive after

26. © Alcohol Medical Scholars Program 26 Brain: Striatum  Ventral –Nucleus accumbens –Reward anticipation  Dorsal –Caudate and putamen –Habit formation Caudate

27. © Alcohol Medical Scholars Program 27 Lecture Topics  Definitions  Key characteristics & neurobiology  Problems, other conditions, course  Implications: prevention & treatment

28. © Alcohol Medical Scholars Program 28 Relationship to AUD   ~25% higher impulsivity scores   Impulsive child (detectable early)   ~ 80% ↑ heavy drinking risk

29. © Alcohol Medical Scholars Program 29 Alcohol → Impulsivity   Alcohol ↑ impulsivity over time – –Frontal lobe volume loss in adults – –↓ White matter integrity, adolescents   Alcohol ↑ impulsivity acutely – –Intoxicating dose → 70% ↑ errors – –↑ preference for definite rewards

30. © Alcohol Medical Scholars Program 30 Back to Case Case 2: law student – –Impulsive child: fidgety, ↓ attn span – –Early alcohol onset: pre-high school – –AUD by early adulthood – –Alcohol acutely ↓ ability resist driving

31. © Alcohol Medical Scholars Program 31 Other Psychiatric Disorders  Attention Deficit Hyperactivity (ADHD) – ~ 60% ↑ Impulsivity score than without – ~ 2 x ↑ AUD risk than without  Bipolar disorder: ↑ arousal & depression – ~ 70% ↑ Impulsivity score than without – ~ 4 x ↑ AUD risk than without

32. © Alcohol Medical Scholars Program 32 Lecture Topics  Definitions  Key characteristics & neurobiology  Problems, other conditions, course  Implications: prevention & treatment

33. © Alcohol Medical Scholars Program 33 Prevention   Treatment challenging/$/time consuming   Prevention/early intervention preferable   Personality-based intervention 1. 1. ID students with high impulsivity 2. 2. Goals, ↑ motivation change coping 3. 3. ID negative coping & relation to alcohol 4. 4. Evidence ↓ probability heavy drinking

34. © Alcohol Medical Scholars Program 34 Psychosocial Treatments  Response impulsivity –Teach/practice coping urges, pass –Train improve focus, ↓ distractions  Choice impulsivity –↑ interest non-alcohol rewards –↓ interest in immediate rewards –↑ interest in long-term rewards

35. © Alcohol Medical Scholars Program 35 Pharmacologic Treatment  Relation to AUD and impulsivity –↓ Alcohol use, ↓ impulsivity –Some pharm. direct evidence  Examples with evidence: –Opioid antagonists  Naltrexone  Nalmefene –Varenicline

36. © Alcohol Medical Scholars Program 36 Opioid Antagonists   Naltrexone FDA approved alcohol   Bind to/block receptor activation   Efficacy: ~ 25% ↓ drinking days   Decreases rewarding effects   ↓ choice impulsivity, ICD efficacy

37. © Alcohol Medical Scholars Program 37 Varenicline  FDA approved: nicotine  Partial agonist – –Binds strongly to nicotine receptors – –Triggers partial response – –Block full alcohol/nicotine response  Efficacy: ~20% ↓ heavy drinking  Decreases rewarding effects  Improves relevant cognition

38. © Alcohol Medical Scholars Program 38 Conclusions   Two main types – –Response impulsivity – –Choice impulsivity   Strong genetics, early manifestation   Measurable behavioral, brain activity   ↑ impulsivity, ↑ risk AUD development

39. © Alcohol Medical Scholars Program 39 Conclusions  Important for prevention & treatment –Can identify impulsivity before AUD –Opportunity for early intervention –Measure ↓ impulsivity—intervention –Psychosocial/pharm ↓ impulsivity