Neurobiological Basis of Impulse Control Disorders

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Neurobiological Basis of Impulse Control
Disorders

• Timothy W. Fong
• Addiction Medicine Clinic
• Seminars in Addiction
• May19, 2005

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Overview

• What is impulsivity?
• Review of Impulse Control Disorders
• Neurobiology of Impulse Control Disorders
• (what I know, what you know, what we need to
  know)

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What is Impulsivity

• A predisposition toward rapid, unplanned
  reactions to internal or external stimuli without
  regard to the negative consequences of these
  reactions to themselves or others
• Moeller Am J Psychiatry 2001

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Other features of impulsivity

• Equated with impatience
• Motor, Cognitive and Non-planning component
• Sudden wish/urge/drive that prompts
  action/feeling
• Usually thought of as irrational but can be
  beneficial
• Diffuse versus targeted

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Defining Impulsivity

• Biological
• rapidity of response, lack of planning, mismatch
  between screening and generating behaviors (no
  brakes), prefer stimulation and arousal,
• Psychological
• decreased sensitivity to negative consequences,
  preference for immediate rewards,
  sensation-seeking, risk-taking, lack of planning,
• Social
• learns to act quickly

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Where do we see Impulsivity in DSM-IV?

• Personality Disorders
• ADHD
• Substance Abuse
• Mania
• Neurological Syndromes
• Impulse Control Disorders
• Dementia

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What are Impulse Control Disorders?

• Are they addictive disorders?
• OR
• Are they like obsessive-compulsive disorders?
  (OCSD)
• OR
• Are they part of an affective syndrome?

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DSM-IV Recognized Impulse Control Disorders

• Pathological Gambling
• Kleptomania
• Pyromania
• Trichotillomania
• Intermittent Explosive Disorder
• Impulse Control Disorders NOS

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Common features of Impulse Control Disorders

• Failure to resist impulses, urges to perform an
  act no brakes in the brain
• Rise in tension or arousal before committing the
  act and relief/pleasure after
• Most start in adolescence and are chronic
• Almost never is just one problem --
• comorbid psychiatric condtiions (depression,
  anxiety, OCD) and other impulsive conditions

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Overview of Impulse Control Disorders

• Similarities to Addictions
• Loss of control
• Preoccupation, urges, pathological wanting
• Negative impact on major areas of life
• Major impacts on mood. Judgment and insight
• Tolerance/ Withdrawal

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Overview of Impulse Control Disorders

• Differences from Addictions
• No toxicology test to diagnosis it easier to
  hide
• Behaviors are not due to drug effects (thus,
  makes it more open to shame/guilt)
• Greater uncertainty of outcome (i.e. anything can
  happen)
• Ego Dystonic or Ego Syntonic
• Mix of impulsive and compulsive

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Spectrums of Impulsivity
Impulsivity Compulsivity
Harm Minimization, underestimation Harm Avoidance, overestimation
Pleasure Seeking Pleasure Avoiding
Sensitive to reward, insensitive to punishment Insensitive to reward, sensitive to punishment
Acts too quickly Acts too slowly

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Assessing Impulsivity

• State and Trait Measures
• Self-Report
• (Barratt, NEO, Eysenck)
• Behavioral Measures
• (Go/No-Go, Stop Signal, Delayed Discounting)
• Physiological Measures
• (Prepulse Inhibition, Neurochemical Responses)

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Neurobiology of Impulse Control Disorders

• Neuroanatomical
• Neurochemical
• Genetic Differences
• Treatment Responses

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Neurobiology of Impulsivity(Neuroanatomy)

• Lesions in Nucleus Accumbens
• Induces hyperactivity,
• impulsivity in delay discounting task
• Rats choose smaller, immediate rewards over
  larger, delayed rewards
• (hypersensitive to delay or hyposensitive to
  reward?)

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Neurobiology of Impulsivity(Neuroanatomy)

• Lesions in the Amygdala
• Impaired decision making
• Increased impulsive choice

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Neurobiology of Impulsivity

• Lesions in the Anterior Cingulate
• Preclinical
• Increased motor activity, overresponding
• Assessment of response effort

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Neurobiology of ICD(Neuroanatomy)

• Prefrontal Cortex (OFC, DLPFC, VMPFC)
• Assessment of reward value, central evaluator,
  brakes
• somatic-marker hypothesis
• Similar performances as those with drug abuse,
  ADHD,
• impaired on Gambling Task, Delay Discounting
  Tasks, Go-No-Go Tasks,

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Neurobiology of ICD(Neuroanatomy)

• Potenzas Imaging Studies (PG vs Normals)
• Decreased activity in
• Left ventromedial PFC (Decision-making)
• Orbitofrontal cortex (processing of rewards,
  dealing with uncertainty, inhibiting responses)
• Anterior Cingulate (Decision-making)
• Ventral striatum (NA, Limbic system)

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Neurobiology of ImpulsivityNeurochemicals

• Serotonin
• Dopamine
• Norepinephrine

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Serotonin in ICD

• Serotonin (Raphe Nuclei, Hypothalamus)
• decreased levels of CSF 5-HIAA
• suicide, personality disorders, gamblers,
• impulsive aggression
• neuroendocrine challenges suggest blunted
  prolactin response (fenfluramine, M-CPP)
• treatment response with SSRIs

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Dopamine and Impulsivity

• Known to code for reward, promotion of
  motivational drives,
• Amphetamine decreases impulsivity in ADHD
• How?
• 5-HTDA balance in NaC
• Alter reinformcement patterns (delayed rewards
  become more meaningful)
• Chronic Meth, appears to increase impulsivity

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Dopamine in Pathological Gambling

• Dopamine
• urge to gamble activates same circuits as
  drug-craving
• higher metabolites found in the urine
• too low in mesocortical areas and too high in
  mesolimbic areas
• impaired acoustic startle

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Neurotransmitters in Pathological Gambling

• Dopamine (Reward)
• Altered levels found in pathological gamblers
• Altered function may lead to different responses
  to rewards
• higher highs
• Parkinsons Link

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Neurobiology of Impulse Control DisordersOther
Neurotransmitters

• Noradrenergic
• deficit states requiring hyperaousal
• GABA lack of proper inhibitory process,
• Opiate Systems Improper control of rewarding
  processes and regulatory mechanisms

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Neurobiology of Impulse Control
DisordersGenetics

• Genetic Vulnerability
• Twin and Family studies
• Same genes for both substance use disorders and
  pathological gambling (Dopamine Receptors)
• Serotonin (Impulsive Aggression, BPD)
• Tryptophan Hydroxylase
• Serotonin Transporter
• Serotonin Receptor

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Clinical Features of Impulsivity in Pathological
Gamblers

• Biological
• Rapidity of Response (Slots, Betting Patterns, no
  time to screen and think)
• Chasing behaviors
• failure to inhibit behaviors, no brakes in the
  brain

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Clinical Features of Impulsivity in Pathological
Gamblers

• Psychological
• Sensation-seeking, risk taking (naturally)
• Excessive sensitivity to rewards (Jackpots)
• Excessive insensitivity to punishment (Continued
  playing despite losses)
• Present-day orientation (dont think about the
  future)

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Clinical Features of Impulsivity in Pathological
Gamblers

• Social
• Environmental setting prime for impulsive
  behaviors (no clocks, fast-paced, quick
  decisions, supposed to be impulsive)
• Society values risk-taking, spontaneity and
  impulsiveness (the Hare)

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Neurotransmitters in Pathological Gambling

• Endogenous Opiates (Urges / Cravings)
• Medications that block gambling urges
• (Naltrexone and Nalmefene)
• Epinephrine (Arousal) or Cortisol (Stress)
• PG may have disruptions in attention,
  sensation-seeking juice
• Altered responses to stress

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Neurotransmitters in Pathological Gambling

• Meyer (2000)
• N 10 male pathological gamblers
• Blackjack versus control game, 2 hours, in the
  casino
• Measured HR, Salivary Cortisol at 0, 30 min and
  60 min
• Findings Increased HR and increased cortisol of
  BJ gt Control

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Neurotransmitters in Pathological Gambling

• Meyer (2004)
• N 14 male PG, 15 male non-PG
• Blackjack vs. Card Game
• Increased HR, NE, Dopamine. (PGgtNon-PG)
• Increased cortisol both groups (NS)
• at baseline and over time

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Impulsivity and Pathological Gamblers Research
Questions

• Does impulsivity worsen gambling?
• Does gambling worsen impulsivity?
• Does impulsivity lead to gambling?
• What are the factors that make gamblers more
  impulsive (sleep, drugs?)
• Can impulsivity be a target for interventions

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Kleptomania Pathological Stealing

• Characterized by
• Failure to resist impulses to steal objects that
  are NOT needed for personal use or for their
  monetary value.
• Increasing tension BEFORE stealing and then
  pleasure/relief at the time or AFTER stealing

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Kleptomania

• Mean age of onset is 20 years old.
• Prevalence estimated at 0.6 of the population
  and only 8 of shoplifters
• Women 4x more than men
• Very different from premeditated stealing or
  robbery (where money or personal use is the
  goal). Usually not fun.

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Pharmacotherapy of Kleptomania

• Case Series
• Prozac , Paxil
• Li Prozac
• VPA Luvox
• Topamax (Dannon 2003), n3,
• disinhibition of GABA in nucleus accumbens?

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Pharmacotherapy of Kleptomania

• Open Labeled
• Grant (2002)
• n 10, Naltrexone 145 mg/day, 11 wk
• improved over all measures compared to baseline
• outcome scales, urges, GAF, SDS

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Pyromania

• Characterized by
• Deliberate and purposeful fire setting
• Tension or arousal BEFORE setting fire and then
  pleasure/relief when setting fires or watching
  the aftermath
• Fascination with fire

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Pyromania

• Based on arsonists, true pyromania is rare.
• Ritchie (1999) 3/283 cases of arsonists were
  pyromaniacs.
• Motives were anger, delusions, revenge, money
• Usually men more than women
• Associated with decreased 5-HIAA and MHPG
  (although high PD comorbidity)
• Involvement with fire early on in life

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TrichotillomaniaCraving to pull out hair

• Characterized by
• Recurrent pulling out of hair resulting in
  noticeable hair loss
• Tension BEFORE pulling out the hair and
  pleasure/relief when or AFTER pulling.

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Trichotillomania

• Women more than men
• Prevalence somewhere between 0.6-3 of population
• Children more frequent than adults and oftentimes
  starts in teenage years
• OCD --------------------- Tourettes

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Pharmacotherapy of Trichotillomania

• Open Label (small n, longest length 22wks)
• SSRIs (6) Symptom Remission
• Lithium (1) Symptom Remission
• Typical Antipsychotics Symptom Remission
• Atypicals (5) OLP, RISP, QTP Symptom Remission
  
• Augmentation (3) Risp SSRI Symptom Remission

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Pharmacotherapy of Trichotillomania

• Double- Blind Placebo
• 1 negative study with FXT (Streichewein 1995)
• n23, crossover to PBO, 31 wks
• no differences in urges, daily counts of hair
  pulled, or days of hair pulling

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Pharmacotherapy of Trichotillomania

• Ninan (2000)
• CBT Clomipramine VS. CBT PBO
• N 23, 9 weeks, dose 150-200 mg
• outcomes scales,
• Results
• CBT gt Clomipramine gt PBO

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Intermittent Explosive Disorder

• Best Exemplified by Homer Simpson,
• Characterized by
• Failure to resist aggressive impulses that result
  in destroying stuff or assaultive acts
• Degree of aggressiveness is out of proportion to
  the triggering event
• All other Axis I/ II ruled out
• Recurrent
• Tends to be more ego dystonic,

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Intermittent Explosive Disorder

• McElroy (1999)
• Interviewed 27 IED
• Accompanied by affective sx -- increased energy,
  racing thoughts and subsequent depression and
  reduction in energy
• 12/20 got better (50 less episodes)
• 50 response rate to SSRI
• 75 response rate to MS

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Compulsive Shopping/Buying

• Pathological Shopping
• Characterized by excessive, and uncontrolled
  preoccupations regarding shopping and spending.
• Tension before, relief after
• Causes marked distress
• 2-8 of population, almost 80 female
• Average debt is 23,000

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Pharmacotherapy of Compulsive Shopping

• Open Label
• Black (1997)
• 9/10 improved on Luvox
• Koran (2002)
• n 24, Celexa (20-60),
• 17/21 responded on CGI and YBOCS- SV

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Pharmacotherapy of Compulsive Shopping

• Double Blind
• Black (2000) -- Iowa
• N 24, 9 wk, PBO washout, Luvox (300 mg), no
  therapy
• Outcomes Scales -- CGI, SDS, YBOCS- SV
• Result
• Luvox PBO, both improved significantly (54 vs.
  64)

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Pharmacotherapy of Compulsive Shopping

• Philip (2000) -- Emory
• N37, 1 wk PBO washout, 12 weeks of Luvox (300mg)
  vs. PBO.
• No statistical differences but both groups
  improved (9/20 vs 8/17)

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Compulsive Sexual Behaviors

• Characterized by excessive or uncontrolled sexual
  behaviors
• Paraphilias vs. Conventional
• Key is subjective distress and continued behavior
  despite negative consequences
• Rise in tension before, pleasure after

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Compulsive Sexual Behaviors

• Prevalence 5?
• No good genetic studies

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CSB Pharmacotherapy

• Case Reports
• Lithium (3)
• TCAs 1)
• SSRIs (gt15)
• Buspar (2)
• Serzone (1)
• Atypicals (1)
• Naltrexone (1)

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CSB Pharmacotherapy

• Other Agents
• Antiandrogens Progesterone (lower testosterone)
• GNRH Agonists (IM)

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Pathological Internet Use

• Similar patterns to other Impulse control
  disorders
• Chat rooms, games, surfing
• Shapira (2000)
• n 20, ego-syntonic, 80 had comorbid dx
  mainly BP, responded to mood stabilizers over
  antidepressants