Gambling Disorder A Lens Through Which to Understand the Rest of the Process Addictions

Transcription

1 Gambling Disorder A Lens Through Which to Understand the Rest of the Process Addictions Kirk Moberg, MD, PhD, FASAM Executive Medical Director, UnityPoint Illinois Institute for Addiction Recovery Clinical Professor of Internal Medicine and Psychiatry & Behavioral Medicine University of Illinois College of Medicine Wisconsin Council on Problem Gambling Annual Conference Elkhart Lake, WI March 23, 2017

2 Appearances to the mind are of four kinds. Things either are what they appear to be; or they neither are, nor appear to be; or they are, and do not appear to be; or they are not, and yet appear to be. Epictetus, 60 ACE Translation: Elizabeth Carter (1768); T.W. Higginson (1897) Quoted in Berridge and Robinson. What is the role of Dopamine in Reward: Hedonic Impact, Reward Learning, or Incentive Salience? Brain Res Rev. 1998; 28:

3 The Process Addictions Gambling Sex Internet gaming/internet Eating disorders Spending/Shopping Hoarding Tanning, Sugar, Chocolate

4 What do we know? We know less about process addictions than substance use disorders. We know more about gambling disorder than the other process addictions. Dopamine, a chemical that plays a role in chemical addictions, also plays a role in gambling disorder. There is evidence for involvement of other neurotransmitters as well. The mesolimbic and mesocortical systems are involved in both chemical and gambling disorders. Parkinson s disease patients provide an interesting model to study some process addictions.

5 Functionally Dopamine D2 Receptors are Decreased by Addiction Cocaine Meth Alcohol Heroin Control Addicted

6 Individual Differences in Response to Drugs: DA Receptors influence drug liking High DA receptor high Low DA receptor low As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999.

7 Some definitions Reward (reinforcement) Vulnerability (risk factors) Neuroplasticity (learning)

8 THE REWARD SYSTEM: THE CORE MESOCORTICAL AND MESOLIMBIC

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11 Kalivas and O Brien. Drug Addiction as a Pathology of Staged Neuroplasticity. Neuropsychopharmacology. 2008;33:

12 Definitions Transient neuroplasticity = changes necessary to developing new behavior Stable neuroplasticity = information retrieved to guide execution of learned behavior Regulated relapse choice Compulsive relapse automatic

13 Compulsive use; Unconscious behaviors Social use Conscious decision making

14 PFC = Prefrontal cortex NA = Nucleus accumbens VP = Ventral pallidum* BLA = Basolateral amygdala VTA = Ventral tegmental area *final common pathway for reward 1. More dopamine released as a result of addictive drugs. 2. Tolerance develops to biological stimuli *Smith et al. Ventral Pallidum Roles in Reward and Motivation. Behav Brain Res. 2009;196(2):

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18 DSM-5 Diagnostic Criteria Requires four or more criteria from criteria A Criteria A. Needs to gamble with increasing amounts of money in order to achieve desired excitement (TOLERANCE) Is restless or irritable when attempting to cut down or stop (WITHDRAWAL) Has made repeated unsuccessful efforts to control, cut back or stop Is often preoccupied with gambling Often gambles when feeling distressed After losing money, often returns another day to get even Lies to conceal the extent of involvement with gambling Has jeopardized or lost a significant relationship, job, or educational or career opportunity because of gambling Relies on others to provide money to relieve desperate financial situations caused by gambling Criteria B. Gambling is not better explained by mania

19 Severity Mild 4-5 Moderate 6-7 Severe 8-9

20 Clinical Similarities Early age of onset Chronic relapsing patterns Tolerance and withdrawal Inability to abstain or cut down Persistent use despite negative consequences Tension or arousal before (anxiety vs. excitement) Relief during ( high ) Many resolve on their own Probability discounting (going for larger, less probable reward) Altered delay discounting (going for immediate, smaller rewards) Telescoping Grant et al., 2010; Kor et al., 2013

21 Many resolve on their own Fyodor Dostoyevsky The Gambler

22 False beliefs = Cognitive distortions Gambler s fallacy Chasing one s losses Near miss Superstitions

23 Co-morbidities 28% working compulsively 26% spending compulsively 38% disordered eating 60.4% nicotine dependence 49.6% mood disorder 41.3% anxiety disorder 60.8% personality disorder

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25 MRI Scans of Healthy Children and Teens Over Time GM loss = maturation Copyright 2004 by the National Academy of Sciences Gogtay, Giedd, et al. Proc. Natl. Acad. Sci., 2004

26 Neuroanatomical hypothesis Cilia 2010 and 2011 Is gambling disorder a neural disconnectivity disorder? 3 populations Parkinson s disease + gambling (group 1) Parkinson s disease w/o gambling (group 2) Normal controls (group 3) Single Photon Emission Computed Tomography (SPECT) Normal connection between anterior cingulate cortex and striatum Anterior cingulate cortex error detection (visualized by increasing activity) losing Striatum shifts behavior in the context in increasing errors stopping Shifting strategy abnormal in group 1 Conclusion: behaviors don t change despite errors

27 Cingulate = error detection Striatum = appropriate response

28 Implicated neurotransmitters Norepinephrine arousal and excitement Serotonin impulse control Dopamine rewarding and reinforcing aspects Opioids pleasures and urges Cortisol stress responsiveness Glutamate cognitive functioning and flexibility Potenza, 2013

29 Is gambling disorder a dopamine deficiency disorder? Low dopamine levels may be baseline Low dopamine levels may be the result and the results are equivocal in gambling Joutsa et al., 2012; Probst & Eimeren, 2013

30 Where does dopamine fit in? Reward deficiency hypothesis Vulnerable individuals have low D2 receptor density and have a need for strong reinforcers. Blum et al., Sensitization theory (salience attribution results in dopamine release) Vulnerable individuals are sensitized to triggers and cues after repeated use. Robinson & Berridge, Impaired response inhibition and salience attribution Low D2 receptor density creates and is maintained by salience attribution. Goldstein & Volkow, Reuter et al., 2005; Grant et al., 2006; Grant et al., 2010; van Holst et al., 2010, Karim & Chaudhri, 2012; Probst & Elmeren, 2012; Grant et al., 2013; Potenza et al., 2013; Potenza, 2013

31 Berridge and Robinson, 1998 Salience

32 Where does dopamine fit in? Reward deficiency hypothesis Vulnerable individuals have low D2 receptor density and have a need for strong reinforcers. Blum et al., Sensitization theory (salience attribution) Vulnerable individuals are sensitized to triggers and cues after repeated use. Robinson & Berridge, Impaired response inhibition and salience attribution Low D2 receptor density creates vulnerability and is maintained by salience attribution. Goldstein & Volkow, Reuter et al., 2005; Grant et al., 2006; Grant et al., 2010; van Holst et al., 2010, Karim & Chaudhri, 2012; Probst & Elmeren, 2012; Grant et al., 2013; Potenza et al., 2013; Potenza, 2013

33 Additional observations Mesolimbic dopamine release is linked to symptom severity in pathological gambling Joutsa et al., 2012

34 Design Two groups of 12 men (one group with pathological gambling and one without) Each group was PET scanned to determine dopamine release during three tasks Each group was evaluated for mood (subjective high ) during three tasks Three tasks were Control Low reward (no marked net win nor loss) High reward (mean payback 371%)

35 a. Screen view of slot machine used in high reward and low reward task b. Screen view of sensorimotor control task c. Mean net win curves for high reward task (upper curves) and low reward task (lower curves); blue = control; red = pathological gamblers Joutsa et al., 2012

36 a. Dopamine release in right striatal region during high reward tasks associative area and ventral striatum (nucleus accumbens). b. Dopamine release in right striatal region during low reward tasks associative area Joutsa et al., 2012

37 a. Change in binding potential in striatum increases in high reward as it does in low reward. b. High in high reward is positively correlated with dopamine release. c. SOGS (South Oaks Gambling Screen) score positively correlated with dopamine release D BP=change in binding potential of [11-C] raclopride Blue = control Red = pathological gambling

38 Where does dopamine fit in? Gambling releases dopamine for those with no net wins or net wins. High is only experienced by those with net wins. Dopamine release during high reward correlates with low reward for both pathological gamblers and controls. Dopamine release correlates with addiction severity.* Joutsa et al., 2012

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40 And another Striatal dopamine release codes uncertainty in pathological gambling Linnet et al., 2012

41 The test Iowa Gambling Task Feedback 2 good decks = initially small gain followed by low penalty leading to net gains 2 bad decks = initially high gain followed by high penalty leading to net losses Probability calculated that participants chose an advantageous deck P(IGT)

42 Sample curves so which is it? Linnet et al., 2012 Iowa Gambling Task Binding Potential Neo-striatum [11C]raclopride

43 Results Pathological gambling (18) Control (16) Linnet et al., 2012

44 Does this explain chasing losses?

45 Does this explain chasing losses? OR CHASING WINS, FOR THAT MATTER.

46 Another dopamine observation Ecopipam (D1/D5 antagonist) has been linked to reducing gambling behaviors. Aripriprazole is a partial D2/D3 agonist and has been linked to impulsive behaviors (Gaboriau et al., 2014). Potenza, 2013

47 Aripiprazole (Abilify ) Abilify Warning Issued by FDA D2 WASHINGTON The Food and Drug Administration on Tuesday warned of rare cases in which patients taking the antipsychotic medication Abilify have experienced uncontrollable urges to gamble, binge eat, shop and engage in sex. The drug is also sold under the generic name aripiprazole and the brand names Abilify Maintena and Aristada. The FDA noted that such cases, while rare, can in theory affect anyone taking the medication WSJ, May 3, 2016

48 The lens of Parkinson s Disease: a known dopamine deficiency syndrome

49 Adding another dopamine circuit VTA to NA: reward pathway SN to dorsal striatum: coordination of motor function and motivation

50 Symptomatic complications Dopamine deficiency syndrome (intrinsic) Loss of dopamine due to underlying disease process Movement Cognitive Impulsiveness Dopamine dependency syndrome (intrinsic and extrinsic) Dysphoria during abstinence Dopamine dysregulation syndrome (intrinsic and extrinsic) Dependency plus punding Impulse control disorders (extrinsic) Refer to specific process addictions (gambling, sex, Internet, shopping, binge eating, skin picking among others)

51 Punding

52 Anti-Parkinsonian Medications Dopamine replacement therapy all D receptors levodopa Monoamine oxidase inhibitors inhibit metabolism Selegiline Dopamine agonists D2/D3 Bromocriptine Parlodel Amantadine* Symmetrel Ropinirole Requip Pramipexole Mirapex * Indirect: increases release and inhibits re-uptake of dopamine

53 Anti-Parkinsonian Medications Gambling Hypersexuality Spending Binge Eating Skin picking Pathological internet use Punding Fenu et al., 2009

54 Anti-Parkinsonian Medications Dopamine replacement therapy all D receptors levodopa Monoamine oxidase inhibitors inhibit metabolism Selegiline Dopamine agonists D2/D3 Bromocriptine Parlodel Amantadine* Symmetrel Ropinirole Requip Pramipexole Mirapex * Indirect: increases release and inhibits re-uptake of dopamine

55 In total there are 5 dopamine receptors D3 receptors High in limbic area Low in motor area and cortical areas ergo, cortical impulse control remains impaired Thank You Fenu et al., 2009

56 THERE ARE NO FDA APPROVED MEDICATIONS TO TREAT GAMBLING DISORDER OR ANY OTHER PROCESS ADDICTION

57 Medication Assisted Treatment Opioid antagonists (family history of alcoholism) Nalmefene Grant et al., 2006; Grant et al., 2010 Naltrexone Kim et al., 2001; Grant et al., 2008; Grant et al., 2008 Selective serotonin reuptake inhibitors (mixed to negative) Paroxetine Kim et al., 2002 Fluvoxamine Hollander et al., 2000; Blanco et al., 2002 Sertraline Saiz-Ruiz et al., 2005 Escitalopram Grant & Potenza, 2006; Black et al., 2007 N-Acetyl Cysteine Grant et al., 2007 Carbamazepine Black et al., 2008 Lithium Pallanti et al., 2002Hollander et al., 2005 (patients with bipolar disorder) Amantadine Pettorruso et al, 2012 (CR); Thomas et al., 2010 (PD patients) Topirimate Dannon et al., 2005 (may limit impulsivity) Modafanil Zack & Poulos, 2009 Memantine Grant et al., 2010 Acamprosate Black et al, 2011 Tolcapone Grant et al., 2013 Bupropion Dannon et al., 2005 Yip and Potenza, 2014

58 Medication Assisted Treatment for Process Addictions Hypersexuality Opioid antagonists naltrexone (Bostwick & Bucci, 2008) Kleptomania Opioid antagonists naltrexone (Grant & Kim, 2002) Shopping/spending SSRIs citalopram (Koran et al., 2002) Hoarding SSRIs paroxetine (Saxena et al., 2006) Binge eating SSRIs sertraline (McElroy et al., 2000); citalopram (McElroy et al., 2003) Internet gaming SSRIs escitalopram (Dell Osso et al., 2008) Trichotillomania Opioid antagonists naltrexone (Carrion, 1995)

59 Amantadine is a complex medication or a drug looking for an indication Anti-viral (influenza) Dopaminergic (Parkinson s, cocaine withdrawal) NMDA receptor antagonist (Alzheimer s, gambling) Hubsher et al., 2012

60 Burning Question: Can You Get Addicted to Sunbathing? WSJ, July 19, 2016

61 Tanning Tanning an addiction Met DSM IV-TR criteria Warthan et al Arch. Derm. UV light hypothesis UV light vs placebo Wagner and Kaur 2005 Brain imaging Adinoff et al (SPECT imaging increased activity striatum) Body dysmorphic disorder Withdrawal phenomenon Naltrexone (2006) varying doses 50 mg Starting with 5mg and increasing Kaur et al., 2006

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