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Impulsivity and Alcohol Use Disorders

© Alcohol Medical Scholars Program

Robert F. Leeman, Ph.D.

Department of Psychiatry, Yale School of MedicineVA New England (VISN 1) Mental Illness Research, Education and Clinical Center (MIRECC)

I. Introduction

A. Problems related alcohol to use are major public health concern (SLIDE 2)

1. Serious & repetitive alcohol problems relatively common1:

a. Serious alcohol problems within prior year (current) = 11%

b. Current serious alcohol problems by sex:

1’. Males: 15%

2’. Females: 7%

2. Alcohol use → problems and costs

a. Alcohol use can be costly even without serious problems

b. Heavier drinking & problems related to alcohol use

1’. Cost ~185 billion/yr in USA2

2’. 3rd leading modifiable cause of death USA3

B. Many factors contribute to heavy drinking/alcohol problems (SLIDE 3)

1. Some can be seen early in life and before heavy drinking begins

2. Impulsivity: e.g. of key factor observable early (other e.g.: trauma, family history)

a. Impulsivity related to earlier onset of alcohol use4

b. Impulsivity also related to more severe problems with alcohol5

C. Drinking & problems begin in teens; heaviest drinking 18 to 25 when: (SLIDE 4)

1. ~ 65% used alcohol in past month6

2. ~ 45% drank > 4 or 5 drinks in an evening (called a heavy drinking day)7 in past month

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3. ~ 18% of young adults have recurring alcohol problems past year1

4. Problems most common if person has high impulsivity5,8

D. Lecture reviews impulsivity and relation to alcohol use: (SLIDE 5)

1. Definitions

2. Key characteristics and neurobiology of impulsivity

3. Relation of impulsivity to alcohol problems, other conditions and clinical course

4. Implications for prevention and treatment

E. Will use 2 illustrative cases

1. Common characteristics:

a. Demonstrate wide-ranging impact of impulsivity

b. Illustrate implications for alcohol use and other risky behaviors

2. Famous/historic case: Phineas Gage (SLIDE 6)

a. Railroad worker

b. Considered conscientious, mild-mannered, hard-working

c. Accident → steel rod pierced head

d. Changed personality: profane, ↓ restraint-giving in to desires, changing plans

e. Locations of damage → key neurobiology for impulsivity

3. Clinical case: 23 year-old male law student (SLIDE 7)

a. Has prior DUI arrests

b. Is participating in research project

c. Goes to party, “accidentally” drank “spiked Gatorade”

d. First day with license returned: drives self to research site after ~4 drinks

e. Did his impulsivity contributed to his alcohol problems?

II. Definitions

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A. Alcohol use disorders (AUDs) (SLIDE 9)

1. AUDs are recurring patterns of alcohol-related problems in multiple life areas9

2. Diagnosis associated with

a. Long term alcohol problems

b. Earlier death

3. Diagnostic & Statistical Manual, Ver 5 (DSM-59) need 2+ in same 12 months of: (SL 10)

a. Missing work or school due to alcohol use

b. Drinking in hazardous situations (before driving is most common example)

c. Drinking despite social or personal problems

d. Craving (strong desire or urge) for alcohol

e. Developing tolerance to alcohol

1’. Need 50% more alcohol to get same effects

2’. If drink similar amounts, will get weaker effects

f. Withdrawal: feelings of discomfort & distress when ↓ or quit drinking

1’. Include shakes, sweats, mild anxiety

2’. Begins in hours after cutting down

g. Repeatedly drinking more or for longer periods than intended

h. Repeated attempts to quit or cut down without success

i. Spending lot of time seeking alcohol, drinking, recovering from drinking

j. Interference with important activities: work, friends, family, hobbies

k. Use despite health or psychological problems

B. How impulsivity defined to most people (SLIDE 11)

1. Doing things rashly/without thinking

2. Repeated bad decisions

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3. Recurrent out of control behavior

4. Getting into trouble frequently without planning

C. Definition from researchers (SLIDE 12)

1. Rapid, unplanned reactions without regard for self/others10

2. Or, some define as a “diminished regard” for others11

D. Impulsivity is really not 1 thing, more a class of characteristics

1. 2 main types: response and choice impulsivity12

2. Response impulsivity (SLIDE 13)

a. Difficulty suppressing actions12

b. Ramifications include:

1’. Alcohol & alcohol cues → a strong impulse13

2’. Failure to plan for future ↓ impact of Rx

3’. Difficulty maintaining behavior change

4’. Emotions can ↓ ability to moderate or stop drinking14

3. Choice impulsivity (SLIDE 14)

a. Want immediate and definite rewards15, 16

b. Ramifications include:

1’. Alcohol seen as immediate, definite reward

2’. Abstinence seen as weak, uncertain reward

3’. Can’t see how get much better in future

E. Impulsivity can be measured in multiple ways (SLIDE 15)

1. Cognitive tasks (often computer-based) (SLIDE 16)

a. Stop-signal tasks17:

1.’ Told to respond to a visual cue

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2.’ But also told not to respond if hear an auditory cue

3.’ ↑ Impulsivity → difficulty stopping response to first cue

b. Continuous performance tasks18:

1.’ Told to monitor screen & respond to most cues (e.g. letters)

2.’ Told NOT to respond to 1 particular cue (e.g. letter “X”)

3.’ ↑ Impulsivity → problems NOT responding when indicated

2. Clinical interviews for impulsive-related conditions include: (SLIDE 17)

a. Childhood interviews for attention deficit/hyperactivity

1.’ Parent rates child’s attention span, fidgeting, etc.19

2.’ Teachers rate same symptoms/behaviors20

3. ‘Child task: No cookie eating until adult claps21; can child hold out?

b. Adolescent & adult structured clinical diagnostic interviews 22

1.’ Example: Structured Clinical Interview for DSM-IV-TR

2.’ Covers conditions such as bipolar disorder

3. Questionnaires (SLIDE 18)

a. Response impulsivity: Urgency, Premeditation, Perseverance & Sensation

Seeking (UPPS) Impulsive Behavior Scale23

1.’ 59 items

2.‘ Subscales cover

a’. Lack of planning and perseverance

b’. Rash responses to positive and negative emotions

3.’ Sample items: trouble controlling impulses; give up too easily

4.’ Higher scores = ↑ response impulsivity

b. Choice impulsivity: Monetary Choice Questionnaire24

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1.’ 27 items

2.’ Series of choices: hypothetical $ payments now versus later

3.’ Sample item: $20 today vs $55 in 7 days

4.’ Higher scores = ↑ choice impulsivity: preference immediate rewards

F. Back to cases (SLIDE 19)

1. Case 1 (worker with head injury)

a. Response impulsivity indicated by ↓ restraint, frequently giving in to desires

b. Choice impulsivity indicated by repeated failure to adhere to future plans

2. Case 2 (law student): shows connection between impulsivity and alcohol

a. Response impulsivity: chugged Gatorade, didn’t stop due to smell/taste of alcohol

b. Choice impulsivity: drinking (immediate reward), avoiding DUI (later reward)

III. Key characteristics and relevant neurobiology

A. Impulsivity seen early in life (SLIDE 21)

1. By age 8 or earlier the following are observable27:

a. Fidgety

b. Trouble paying attention, following directions

c. Talking/acting out of turn

d. Unpredictable/explosive behavior

2. Predictive value: childhood impulsivity → early teen years onset alcohol use4

B. Genetic predisposition (SLIDE 22)

1. Percent explained by genes: ~50%25

2. Genes for impulsivity overlap with genes for alcohol problems26

C. Relevant brain function (SLIDE 23)

1. Frontal lobes (SLIDE 24)

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a. Ventromedial prefrontal cortex(vmPFC):response inhibition, decisions28, 29

b. Orbitofrontal cortex (OFC): limbic system (reward) link, impulse control30, 31

c. Gage case →importance of frontal lobes dysfunction to impulsivity28 (SL 25)

1’. His frontal lobes severely injured, including vmPFC and OFC

2’. Impulsivity only observable after injury

2. Striatum32 (SLIDE 26)

a. Ventral (especially nucleus accumbens) - reward anticipation

b. Dorsal (caudate and putamen) - habit formation: acting without thinking

IV. Relation to AUDs, other conditions and clinical course

A. Relationship to AUD (SLIDE 28)

1. Related to all alcohol and drug problem behaviors: will focus on alcohol

a. Those with AUD more likely to be impulsive than those without AUD

b. With AUD ~ 25% higher impulsivity scores than without AUD5

c. Very impulsive child ~ 80% greater chance heavy drinking33

d. Heavy drinker ~ 3 x more likely AUD than light drinkers

2. ↑ Alcohol → ↑ Impulsivity (SLIDE 29)

a. Alcohol use can exacerbate impulsive behavior over time

1.’ Ongoing drinking → adult frontal lobe volume loss34

2.’ Lower frontal lobe volume, ↑ likelihood of impulsivity

3.’ Adolescent drinkers: ↓ white matter integrity ↑ impulsivity35

b. Acutely, alcohol ↑ likelihood behaviors people typically restrict

1.’ ↑ Response impulsivity: 70% more errors with intoxicating dose36

2.’ ↑ Choice impulsivity: ↑ preference for definite rewards15

d. Back to case of law student (SLIDE 30)

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1.’ Impulsive as child: more fidgety, short attention span

2.’ Early onset of alcohol use: before high school

3.’ Effects on brain, ↓ white matter integrity ↑ impulsivity

4.’ Alcohol use & brain effects exacerbate drinking pattern

5.’ AUD by early adulthood

6.’ Alcohol acutely ↓ ability to inhibit: DUI, driving to research site

B. Relationship to many other psychiatric conditions, 2 examples: (SLIDE 31)

1. Attention Deficit Hyperactivity Disorder (ADHD)

a. Characterized by difficulty maintaining attention, over activity

b. Impulsivity scores ~ 60% higher than without diagnosis5

c. Adults with ADHD ~ 2 x greater risk of AUD than those without ADHD37

2. Bipolar Disorder

a. Characterized by strong shifts in mood, energy, ability to function38

b. Impulsivity ~70% higher than without diagnosis5

c. With bipolar, ~4x greater risk of AUD than those without bipolar1

V. Role in Prevention and Treatment

A. Prevention (SLIDE 33)

1. Treatment inherently challenging/costly/time consuming

2. Thus prevention/early intervention preferable

3. Adolescent personality-based intervention, main steps:39

a. Identify students with high impulsivity

b. Teach about relation impulsivity, coping strategies, and alcohol problems

c. Use goal-setting, ↑ motivation to change negative coping strategies

d. Identify own negative coping strategies, devise concrete ways to change them

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e. Evidence high risk adolescents ↓ probability heavy drinking with intervention

a. Common treatments

1. How aspects of psychosocial treatments may target impulsivity40: (SLIDE 34)

a. Response impulsivity (possible efficacy for CBT & mindfulness training)

1’. Teach/practice cope urges,→ let moments pass without acting

2’.Train to improve ability to focus, decrease distractions

3’. Some indirect supporting evidence: CBT41,42 & mindfulness43-45

b. Choice impulsivity (possible efficacy for CBT & contingency management)

1’. ↑ interest in and provide rewards other than alcohol

2’. ↓ Focus on immediate rewards, ↑ on long-term rewards

3’. Indirect supporting evidence: contingency management46

2. How pharmacologic treatment targets impulsivity40: (SLIDE 35)

a. Relation to AUD and impulsivity

1’. In theory, reduction in alcohol use → less impulsivity

2’. Some medications have direct evidence for alcohol and impulsivity

3’. Two examples : opioid antagonists and varenicline

b. Naltrexone and nalmefene (SLIDE 36)

1’. Naltrexone FDA approved for alcohol dependence

2’. Antagonists: bind to and block activation of opiate receptors47

3’. Thereby blocks alcohol-related reward activity at receptor47

4’. Decreases rewarding effects of alcohol48 may also ↓ impulsivity46

5’. Clinical efficacy: ~25% fewer heavy drinking days than placebo49,50

6’. Decrease choice impulsivity under influence of alcohol51

7’. Efficacy impulse control disorders (ICD)52-55: inherently impulsive56

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c. Varenicline (SLIDE 37)

1’. FDA approved for nicotine dependence

2’. Partial agonist57:

a’. Binds strongly to nicotinic receptors

b’. Triggers a partial response

c’. Blocks a full response from alcohol/nicotine

3’. Decreases rewarding effects58

4’. Improves cognition related to impulsivity: e.g., concentration59

5’. Efficacy: alcohol 20% fewer heavy drinking days than placebo60

VI. Conclusions

A. Two main types: (SLIDE 38)

1. Response impulsivity

2. Choice impulsivity

B. Strong genetic predisposition and begins manifest childhood

C. Measurable behavioral and brain alterations

D. ↑ Impulsivity strongly ↑ risk development AUD (and other SUDs)

E. Important for prevention & treatment (SLIDE 39)

1. Can clearly identify impulsivity prior develop AUD

2. Provides opportunity early intervention

3. Can measure decrease impulsivity from intervention anticipate efficacy of prevention

4. Both psychosocial and pharmacologic tx decrease impulsivity to decrease relapse

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