impulsivity and alcohol use disorders robert f. leeman, ph.d. department of psychiatry yale school...

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)

© Alcohol Medical Scholars Program© Alcohol Medical Scholars Program 22

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


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


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


Lecture Covers Definitions

Key characteristics & neurobiology

Problems, other conditions, course

Implications: prevention & treatment


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


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?


Lecture Topics

Definitions





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


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


Impulsivity: Usual Definition

Acting rashly/without thinking

Repeated bad decisions

Recurrent out of control behavior

Trouble frequently without planning


Impulsivity: Research Definition

Rapid, unplanned reactions

Diminished regard for outcomes

Not really 1 thing

More a class of characteristics

2 main types: response, choice


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


Choice Impulsivity

Immediate, definite rewards

Ramifications include:

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


Ways to Measure

Cognitive tasks (computer)

Clinical interviews

Self-report questionnaires


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”)


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


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


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)


Lecture Topics Definitions





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


Genetic Predisposition

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

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

Alcohol & impulsivity genes overlapAlcohol & impulsivity genes overlap


Key Brain Regions

FrontalFrontal

lobeslobesVentral striatum Ventral striatum

striatumstriatumDorsalDorsal


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


• Frontal lobes- severe injury- vmPFC, OFC

• Impulsive after


Brain: Striatum VentralVentral

–Nucleus accumbensNucleus accumbens

–Reward anticipationReward anticipation

DorsalDorsal

–Caudate and putamenCaudate and putamen

–Habit formationHabit formation

Caudate


Lecture Topics DefinitionsDefinitions

Key characteristics & neurobiologyKey characteristics & neurobiology

Problems, other conditions, courseProblems, other conditions, course

Implications: prevention & treatmentImplications: prevention & treatment


Relationship to AUD

~25% higher impulsivity scores

Impulsive child (detectable early)

~ 80% ↑ heavy drinking risk


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


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


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


Lecture Topics DefinitionsDefinitions

Key characteristics & neurobiologyKey characteristics & neurobiology

Problems, other conditions, courseProblems, other conditions, course

Implications: prevention & treatmentImplications: prevention & treatment


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


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


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


Opioid Antagonists

Naltrexone FDA approved alcohol

Bind to/block receptor activation

Efficacy: ~ 25% ↓ drinking days

Decreases rewarding effects

↓ choice impulsivity, ICD efficacy


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


Conclusions

Two main types

– Response impulsivity

– Choice impulsivity

Strong genetics, early manifestation

Measurable behavioral, brain activity

↑ impulsivity, ↑ risk AUD development


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

impulsivity and alcohol use disorders robert f. leeman, ph.d. department of psychiatry yale school...

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