Transcript

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)

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Serious Alcohol Problems Relatively common

Within prior year (current): 11%– Males: 15%– Females: 7%

Costly: $185 billion/year in U.S.

Lethal: 3rd leading modifiable cause

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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

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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

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Lecture Covers Definitions

Key characteristics & neurobiology

Problems, other conditions, course

Implications: prevention & treatment

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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

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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?

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Lecture Topics

Definitions

Key characteristics & neurobiology

Problems, other conditions, course

Implications: prevention & treatment

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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

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AUD CriteriaAUD 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

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Impulsivity: Usual Definition

Acting rashly/without thinking

Repeated bad decisions

Recurrent out of control behavior

Trouble frequently without planning

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Impulsivity: Research Definition

Rapid, unplanned reactions

Diminished regard for outcomes

Not really 1 thing

More a class of characteristics

2 main types: response, choice

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Response ImpulsivityDifficulty suppressing

actions

Ramifications include:

–Alcohol/cues = a strong impulse–Failure plan for future: Rx impact–Hard to maintain behavior change–Emotions can ↓ drinking control

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Choice Impulsivity

Immediate, definite rewards

Ramifications include:

–Alcohol: immediate definite reward–Abstinence: weak, uncertain–Hard to see future improvement

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Ways to Measure

Cognitive tasks (computer)

Clinical interviews

Self-report questionnaires

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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”)

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Clinical Interviews For conditions related to impulsivityFor conditions related to impulsivity

Childhood interviews: ADHDChildhood interviews: ADHD

– Parent/teacher ratings: attentionParent/teacher ratings: attention

– E.g. child task: wait to eat cookieE.g. child task: wait to eat cookie

Adolescent/adult structured interviewsAdolescent/adult structured interviews

– SCIDSCID

– Conditions like bipolar disorderConditions like bipolar disorder

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Questionnaires Response: Response: impulsive behavior scaleimpulsive behavior scale

– Lack planning and perseveranceLack planning and perseverance

– Rash response to +/- emotionsRash response to +/- emotions

Choice: Choice: monetary choice questionnairemonetary choice questionnaire

– Choices: hypothetical $ paymentsChoices: hypothetical $ payments

– Now vs. laterNow vs. later

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Back to Cases Case 1: Phineas GageCase 1: Phineas Gage

–Response: Response: ↓ restraint↓ restraint

–Choice: inability to adhere to plansChoice: inability to adhere to plans

Case 2: law studentCase 2: law student

–Response: didn’t stop drinkingResponse: didn’t stop drinking

–Choice: drink(immediate), DUI(later)Choice: drink(immediate), DUI(later)

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Lecture Topics Definitions

Key characteristics & neurobiology

Problems, other conditions, course

Implications: prevention & treatment

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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

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Genetic Predisposition

Impulsivity: ~ 50% explained genesImpulsivity: ~ 50% explained genes

Alcohol : ~ 50% explained genesAlcohol : ~ 50% explained genes

Alcohol & impulsivity genes overlapAlcohol & impulsivity genes overlap

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Key Brain Regions

FrontalFrontal

lobeslobesVentral striatum Ventral striatum

striatumstriatumDorsalDorsal

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Brain: Frontal Lobes Ventromedial prefrontal cortex(vmPFC)Ventromedial prefrontal cortex(vmPFC)

– Response inhibitionResponse inhibition

– Decision-makingDecision-making

Orbitofrontal cortex(OFC)Orbitofrontal cortex(OFC)

– Linked to limbic system (reward)Linked to limbic system (reward)

– Impulse controlImpulse control

Back to Phineas Gage

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• Frontal lobes- severe injury- vmPFC, OFC

• Impulsive after

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Brain: Striatum VentralVentral

–Nucleus accumbensNucleus accumbens

–Reward anticipationReward anticipation

DorsalDorsal

–Caudate and putamenCaudate and putamen

–Habit formationHabit formation

Caudate

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Lecture Topics DefinitionsDefinitions

Key characteristics & neurobiologyKey characteristics & neurobiology

Problems, other conditions, courseProblems, other conditions, course

Implications: prevention & treatmentImplications: prevention & treatment

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Relationship to AUD

~25% higher impulsivity scores

Impulsive child (detectable early)

~ 80% ↑ heavy drinking risk

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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

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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

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Other Psychiatric Disorders Attention Deficit Hyperactivity (ADHD)Attention Deficit Hyperactivity (ADHD)

– ~ 60% ~ 60% ↑↑ Impulsivity score than without Impulsivity score than without

– ~ 2 x ~ 2 x ↑ ↑ AUD risk than withoutAUD risk than without

Bipolar disorder: Bipolar disorder: ↑↑arousal & depressionarousal & depression

– ~ 70% ~ 70% ↑↑ Impulsivity score than without Impulsivity score than without

– ~ 4 x ~ 4 x ↑ ↑ AUD risk than without AUD risk than without

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Lecture Topics DefinitionsDefinitions

Key characteristics & neurobiologyKey characteristics & neurobiology

Problems, other conditions, courseProblems, other conditions, course

Implications: prevention & treatmentImplications: prevention & treatment

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Prevention Treatment challenging/$/time consuming

Prevention/early intervention preferable

Personality-based intervention1. ID students with high impulsivity2. Goals, ↑ motivation change coping3. ID negative coping & relation to alcohol4. Evidence ↓ probability heavy drinking

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Psychosocial Treatments Response impulsivityResponse impulsivity

–Teach/practice coping urges, passTeach/practice coping urges, pass–Train improve focus, Train improve focus, ↓ distractions↓ distractions

Choice Choice impulsivityimpulsivity–↑ ↑ interest non-alcohol rewardsinterest non-alcohol rewards–↓ ↓ interest in immediate rewardsinterest in immediate rewards–↑ ↑ interest in long-term rewardsinterest in long-term rewards

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Pharmacologic Treatment Relation to AUD and impulsivityRelation to AUD and impulsivity

– ↓ ↓ Alcohol use, ↓ impulsivityAlcohol use, ↓ impulsivity– Some pharm. direct evidenceSome pharm. direct evidence

Examples with evidence:Examples with evidence:– Opioid antagonistsOpioid antagonists

NaltrexoneNaltrexone NalmefeneNalmefene

– VareniclineVarenicline

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Opioid Antagonists

Naltrexone FDA approved alcohol

Bind to/block receptor activation

Efficacy: ~ 25% ↓ drinking days

Decreases rewarding effects

↓ choice impulsivity, ICD efficacy

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Varenicline FDA approved: nicotineFDA approved: nicotine Partial agonistPartial agonist

–Binds strongly to nicotine receptors–Triggers partial response–Block full alcohol/nicotine response

Efficacy: ~20% ↓ heavy drinkingEfficacy: ~20% ↓ heavy drinking Decreases rewarding effectsDecreases rewarding effects Improves relevant cognitionImproves relevant cognition

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Conclusions

Two main types

– Response impulsivity

– Choice impulsivity

Strong genetics, early manifestation

Measurable behavioral, brain activity

↑ impulsivity, ↑ risk AUD development

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Conclusions

Important for prevention & treatmentImportant for prevention & treatment

– Can identify impulsivity before AUDCan identify impulsivity before AUD

– Opportunity for early interventionOpportunity for early intervention

– Measure Measure ↓ impulsivity—intervention↓ impulsivity—intervention

– Psychosocial/pharm ↓ impulsivityPsychosocial/pharm ↓ impulsivity


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