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Defining the Boundaries of Addiction: A Biological Perspective

Defining the Boundaries of Addiction: A Biological Perspective. Marc N. Potenza, M.D., Ph.D. Associate Professor of Psychiatry Director, Problem Gambling Clinic Director, Women and Addictions Core, Women’s Health Research at Yale Director of Neuroimaging, VA VISN1

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Defining the Boundaries of Addiction: A Biological Perspective

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  1. Defining the Boundaries of Addiction: A Biological Perspective Marc N. Potenza, M.D., Ph.D. Associate Professor of Psychiatry Director, Problem Gambling Clinic Director, Women and Addictions Core, Women’s Health Research at Yale Director of Neuroimaging, VA VISN1 MIRECC, West Haven VA Hospital Yale University School of Medicine 3rd Mind & World Conference, May 4, 2007

  2. Overview • Explore the Boundaries of Addiction - Are Pathological Gambling (PG) and Other Impulse Control Disorders (ICDs) “Behavioral Addictions”? • Examine the Relationship Between PG, Substance Use Disorders (SUDs) and Other Mental Health Disorders • Describe the Clinical Implications (Prevention, Treatment) of Conceptualizing PG and Other ICDs as Behavioral Addictions 3rd Mind & World Conference, May 4, 2007

  3. What is Addiction? • Addict (verb) - “to devote or give (oneself) habitually or compulsively”; from Latin addicere - bound to or enslaved • Historical Shifts in Usage of Term • Core Components of Addiction (Shaffer, 1999) • - Continued Behavior Despite Adverse Consequences • - Diminished or Lost Control / Compulsive Engagement • - Craving or Urge State Component 3rd Mind & World Conference, May 4, 2007

  4. What is Gambling? • Gambling Is Placing Something of Value at Risk in Hopes of Achieving Something of Greater Value (Potenza et al, JAMA, 2001) • Perception Influenced by the Relative Amounts of Risk and Reward • - Mutual Funds Vs. Day Trading 3rd Mind & World Conference, May 4, 2007

  5. A Gambling Spectrum • Non-gambling <-> Recreational Gambling <-> Problem Gambling <-> Pathological Gambling • Recreational Gamblers Constitute a Majority • Health Associations of Specific Levels of Gambling Incompletely Understood • - Problem and Pathological Gambling Appear Most Disruptive and Costly on a Per Capita Basis 3rd Mind & World Conference, May 4, 2007

  6. Problem and Pathological Gambling Are Associated with High Rates of: - Divorce - Poor General Health - Mental Health Problems - Job Loss and Lost Wages - Bankruptcy - Arrest and Incarceration Problem & Pathological Gambling Associated w/ Estimated Annual Societal Cost of $5 Billion Gambling Impact & Behavior Study 3rd Mind & World Conference, May 4, 2007

  7. When Is Gambling a Problem? • Pathological Gambling (PG) (Level 3) • - Most Disordered Form of Gambling • - DSM-IV-TR Disorder • - Analogous to “Substance Dependence” • Problem Gambling (Level 2) • - Widely Used But Not a DSM-IV-TR Disorder • - Analogous to “Substance Abuse” 3rd Mind & World Conference, May 4, 2007

  8. Impulse Control Disorders As “Behavioral Addictions” • “ICDs Not Elsewhere Classified” • - Pathological Gambling, Kleptomania, Pyromania, Intermittent Explosive Disorder, Trichotillomania, ICD NOS • ICDs Under Consideration • - Compulsive Buying, Compulsive Sexual Behavior, Compulsive Computer Use • ICDs Common in Hospitalized Psychiatric Pts • - Among 204 Adult In-pts, 31% Had a Current ICD, with <2% Diagnosed Upon Admission (Grant et al, Am J Psych, 2005) • Among 102 Patients Adolescent In-pts, 40% Had a Current ICD, with <1% Dx’ed Upon Admission (Grant et al, J Clin Psych, in press) 3rd Mind & World Conference, May 4, 2007

  9. Past-Year Lifetime Compulsive Buying 9.3% 9.3% Kleptomania 7.8% 9.3% Pathological Gambling 6.9% 6.9% Intermittent Explosive D/O 6.4% 6.9% Compulsive Sexual Behaviors 4.4% 4.9% Pyromania 3.4% 5.9% Trichotillomania 3.4% 4.4% Frequencies of ICDs in Adult Psychiatric Inpatients Grant et al, Am J Psychiatry, 2005 3rd Mind & World Conference, May 4, 2007

  10. No Differences in Admission Diagnoses for Mood, Psychotic or Substance Use Disorders Between Adult Pts with an ICD Vs. Those Without Adults With an ICD More Likely (Trend) To Have Multiple non-ICD Diagnoses (62.7% vs. 49.6%; p<0.08) Among Adolescents, ICD Presence was Associated with Internalizing Disorders (78.0% vs. 55.7%; p<0.02) and Prior Hospitalization (75.6% vs. 41.0%; p<0.001) Adolescents As Compared with Adults Showed Different Patterns of ICDs, with Intermittent Explosive Disorder Being Most Common (12.7% of Sample) Psychiatric Diagnoses and ICDs Grant et al, AJP, 2005; JCP, in press 3rd Mind & World Conference, May 4, 2007

  11. PG and Co-Occurring Disorders Rec Gam Vs Prob Gam Disorder Non Gam Vs Non Gam Major Depression 1.7 (1.1, 2.6)* 3.3 (1.6, 6.8)* Dysthymia 1.8 (1.0, 3.0)* 2.1 (0.8, 5.7) Schizophrenia 0.6 (0.2, 1.8) 3.5 (1.3, 9.7)* Phobias 1.2 (0.9, 1.7) 2.3 (1.2, 4.3)* Somatization 1.7 (1.1, 2.8)* 3.0 (1.6, 5.8)* Antisocial PD 2.3 (1.6, 3.4)* 6.1 (3.2, 11.6)* Alcohol Use 3.9 (2.4, 6.3)* 7.2 (2.3, 23.0)* Alcohol Abuse/Dep 1.9 (1.3, 2.7)* 3.3 (1.9, 5.6)* Nicotine Use 1.9 (1.6, 2.4)* 2.6 (1.6, 4.4)* Nicotine Dep 1.3 (1.0, 1.7)* 2.1 (1.1, 3.8)* NS = Mania, Suicidality, OCD, Panic, GAD, Drug Use, Drug Abuse/Dep *=p<0.05 3rd Mind & World Conference, May 4, 2007 Source: Cunningham-Williams et al, 1998

  12. High Rates of Co-Occurrence - Population and Clinical Samples Similar Clinical Courses - High Rates in Adolescence, Lower Rates in Older Adults - “Telescoping” Pattern in Women Similar Clinical Characteristics - Tolerance, Withdrawal, Repeated Attempts to Cut Back or Quit - Appetitive Urge or Craving States Similar Biologies - Genetic Contributions, Neural Circuits Similar Treatments - Self-Help, CBT, MI, Naltrexone and Nalmefene Relationship Between PG and SUDs 3rd Mind & World Conference, May 4, 2007

  13. Clinical Relevance of PG & SUDs • Individuals with Co-Occurring PG and SUDs Experience More Severe Symptoms Than Those With SUDs Alone (Kaplan & Davis, 1997) • - Increased Rates of Admission for Detoxification (> Two-Fold Rate) • - Increased Rates of Admission for Psychiatric Stabilization (> 50% Increased Rate) • - More Suicidality (Federman et al, 1998) 3rd Mind & World Conference, May 4, 2007

  14. Impulsivity as an Endophenotype • Defining Impulsivity (Moeller et al, 2001) • - “A Predisposition Toward Rapid, Unplanned Reactions to Internal or External Stimuli [With Diminished] Regard to the Negative Consequences of These Reactions to the Impulsive Individual or to Others” • Impulsivity Across Psychiatric Groups • - ICDs, SUDs, Bipolar D/O, ADHD, ASPD, BPD, Suicidality, SIB • Behavioral Measures of Impulsivity • - Risk/Reward Assessment & Decision-Making Paradigms (Monetary Reward/Punishment, Discounting, Gambling Tasks) • - Response Disinhibition/Attentional Paradigms (Go/No-Go, Stroop) 3rd Mind & World Conference, May 4, 2007

  15. Mesocorticolimbic Dopamine System (“Overactive Motor”) - Ventral Tegmental Area, Nucleus Accumbens Frontal Serotonin Systems (“Bad Brakes”) - Frontal/Prefrontal Cortical Function Role for Neurotransmitter Systems Modulating DA, 5HT Function - GABA, Glutamate, Opioids, ... Neural Systems and Addiction 3rd Mind & World Conference, May 4, 2007

  16. Neurotransmitter Role in Impulse Control Norepinephrine (NE) Arousal, Excitement Serotonin (5HT) Behavior Initiation/Cessation Dopamine (DA) Reward, Reinforcement Opioids Pleasure, Urges Roles for Neurotransmitters 3rd Mind & World Conference, May 4, 2007 Potenza and Hollander, 2002

  17. 5-HT & Impulse Control • Low CSF 5-HIAA Associated w/ Impaired Impulse Control (Potenza and Hollander, 2002) • Altered Biochemical and Behavioral Responses to m-CPP (5HT1R and 5HT2R Partial Agonist) (DeCaria et al, 1998) • Blunted 5HT Response in vmPFC in Impulsive Aggression (Siever et al, 1999; New et al, 2002) 3rd Mind & World Conference, May 4, 2007

  18. Serotonergic Drugs (e.g., SSRIs) Have Shown Mixed Results in the Tx of PG (Grant et al, 2003) SSRI Tx May Be Particularly Effective for Particular Groups of Individuals with PG Individuals with PG and Co-Occurring Affective Disorders (Grant and Potenza, 2006a) Impulsivity and Addiction 3rd Mind & World Conference, May 4, 2007

  19. Individuals with PG or SUDs Perform Disadvantageously or Impulsively on Gambling Tasks, and Performance Correlates with Real-Life Measures (Petry et al, 2001; Bechara, 2003) Individuals with PG or SUDs Discount Rewards Rapidly Over Time (Bickel et al, 1999; Petry et al, 2001) Behavioral Measures of Reward Discounting Are Associated with SUD Tx Outcome (Krishnan-Sarin et al, 2007) Decision-Making, Reward Processing and Addiction 3rd Mind & World Conference, May 4, 2007

  20. Adults w/ AD vs Those w/o AD Show Less Activation of NAc in Anticipation of Working for Monetary Reward (Hommer et al, 2004) Similar Findings in Adolescents and Adults FH+ Vs. FH- for AD (Hommer et al, 2004) Extends Across Addictions - Less Activation of NAc in PG vs. Control During Monetary Wins vs. Losses (Reuter et al, 2005) Reward Processing in Addiction 3rd Mind & World Conference, May 4, 2007

  21. PG and Other ICDs Reported in Association with Parkinson’s Disease (Dodd et al, 2005) Association Linked to Dopamine Agonist Treatment (Weintraub & Potenza, 2006) Prior ICD and FH of EtOHism Associated with ICD Presence in PD (Weintraub et al, 2006; Voon et al, 2006) Need to Identify Neurobiological Factors Underlying Vulnerability to ICDs in PD Dopamine and ICDs in PD 3rd Mind & World Conference, May 4, 2007

  22. Genetics of PG, AD and AAB • Shared Genetic Contributions to PG and AD • - 12%-20% of Genetic Variation in the Risk for PG Accounted for by the Risk for AD (Slutske et al, 2000) • Shared Genetic Contributions to PG and AAB • - 16%-22% of Genetic Variation in the Risk for PG Accounted for by the Risk for Anti-Social Behaviors (Slutske et al, 2001) • Shared Risks Suggest Shared Genetic Contributions to Risk for Impulsiveness 3rd Mind & World Conference, May 4, 2007

  23. Pharmacological Treatment of AD • FDA-Approved Drugs for AD (None for PG) • - Disulfiram, Naltrexone, Acamprosate • Naltrexone and Other Opioid Antagonists Indirectly Modulate Dopamine Neurotransmission in VTA-NAc Pathway • Might Naltrexone or Other Mu-Opioid Receptor Antagonists Be Effective in Treating PG? 3rd Mind & World Conference, May 4, 2007

  24. High-Dose Naltrexone (Avg Dose: 188 mg/day) Effective in Targeting PG Sxs (Kim et al, 2001) High Rates of Drop-Out & LFT Abnormalities Greater Drug-Related Improvement in Subjects with High Initial Gambling Urge Measures - Similar to Naltrexone & Cravings in AD Encouraging Findings with Opioid Antagonist Nalmefene (Grant et al, 2006) Opioid Antagonists 3rd Mind & World Conference, May 4, 2007

  25. Association Between PG and MD in VET Sample Variable OR (95% CI) p-value Alcohol Abuse/Dependence 2.7 (1.5, 4.7) 0.001 Drug Abuse/Dependence 1.9 (1.0, 3.3) 0.04 Antisocial Personality D/O 2.5 (1.1, 5.5) 0.02 Generalized Anxiety D/O 3.0 (1.3, 6.5) 0.007 Major Depression 2.0 (1.1, 3.4) 0.02 NS = Age, Income, HS Education, College Education, Nicotine Dependence, PTSD, Panic D/O Unadjusted OR for MD = 4.1 (2.6-6.5) OR for MD Adjusting for Sociodemographics = 4.1 (2.6-6.5)

  26. Bivariate Biometric Model for PG & MD Potenza et al, 2005, Arch Gen Psychiatry

  27. PG and Other ICDs Are Common, Particularly Among Psychiatric Pts There Exist Multiple Shared Features Between ICDs and SUDs Characterizing Biological Mechanisms of ICDs Has Implications for Categorizing Disorders and Tx Development Identification of PG and Other ICDs Critical For Optimizing Clinical Care Overall Conclusions 3rd Mind & World Conference, May 4, 2007

  28. The International Society for Research on Impulsivity and Impulse Control Disorders (ISRI) www.impulsivity. org (or contact marc.potenza@yale.edu)

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