Neurobiological Basis of Impulse Control Disorders

1. Neurobiological Basis of Impulse Control Disorders Timothy W. Fong Addiction Medicine Clinic Seminars in Addiction May19, 2005

2. 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)

3. 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

4. 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

5. 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

6. Where do we see Impulsivity in DSM-IV? • Personality Disorders • ADHD • Substance Abuse • Mania • Neurological Syndromes • Impulse Control Disorders • Dementia

7. 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?

8. DSM-IV Recognized Impulse Control Disorders • Pathological Gambling • Kleptomania • Pyromania • Trichotillomania • Intermittent Explosive Disorder • Impulse Control Disorders NOS

9. 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

10. 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

11. 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

12. Spectrums of Impulsivity

13. 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)

14. Neurobiology of Impulse Control Disorders • Neuroanatomical • Neurochemical • Genetic Differences • Treatment Responses

16. 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?)

18. Neurobiology of Impulsivity(Neuroanatomy) • Lesions in the Amygdala • Impaired decision making • Increased impulsive choice

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

21. 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,

24. Neurobiology of ICD(Neuroanatomy) • Potenza’s 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)

25. Neurobiology of ImpulsivityNeurochemicals Serotonin Dopamine Norepinephrine

26. 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

27. Dopamine and Impulsivity Known to code for reward, promotion of motivational drives, Amphetamine decreases impulsivity in ADHD How? 5-HT:DA balance in NaC Alter reinformcement patterns (delayed rewards become more meaningful) Chronic Meth, appears to increase impulsivity

28. 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

29. Neurotransmitters in Pathological Gambling Dopamine (Reward) Altered levels found in pathological gamblers Altered function may lead to different responses to rewards “higher highs” Parkinson’s Link

30. 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

31. 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

32. 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

33. 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: (don’t think about the future)

34. 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)

35. 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

36. 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 > Control

37. Neurotransmitters in Pathological Gambling Meyer (2004) N= 14 male PG, 15 male non-PG Blackjack vs. Card Game Increased HR, NE, Dopamine. (PG>Non-PG) Increased cortisol both groups (NS) at baseline and over time

38. 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

39. 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

40. 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”.

41. Pharmacotherapy of Kleptomania • Case Series: • Prozac , Paxil • Li + Prozac • VPA + Luvox • Topamax (Dannon 2003), n=3, • disinhibition of GABA in nucleus accumbens?

42. 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

43. 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

44. 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

45. Trichotillomania“Craving 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.

46. 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 --------------------- Tourette’s

47. 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

48. Pharmacotherapy of Trichotillomania • Double- Blind Placebo: • 1 negative study with FXT (Streichewein 1995) • n=23, crossover to PBO, 31 wks • no differences in urges, daily counts of hair pulled, or days of hair pulling

49. Pharmacotherapy of Trichotillomania • Ninan (2000) • CBT + Clomipramine VS. CBT +PBO • N= 23, 9 weeks, dose = 150-200 mg • outcomes: scales, • Results • CBT > Clomipramine > PBO

50. 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,