Defining the Boundaries of Addiction A Biological Perspective

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Slide 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
Slide 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
Slide 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
Slide 4 : Addiction As a Disorder of Motivation “The Study of Obesity, Pathological Gambling, and Other Motivated States Associated With Or Leading to Compulsive Behavior Will Provide An Opportunity to Learn About the Possible Predispositions and Variations in the “Reward Circuit” That Lead to Uncontrollable, Compulsive Behavior, Independent of Direct Pharmacological Activation of Brain Reward Circuits” (NIDA, Neuron, 2002) 3rd Mind & World Conference, May 4, 2007
Slide 5 : 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
Slide 6 : 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
Slide 7 : Gambling Impact & Behavior Study 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 3rd Mind & World Conference, May 4, 2007
Slide 8 : 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
Slide 9 : 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
Slide 10 : Frequencies of ICDs in Adult Psychiatric Inpatients 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% Grant et al, Am J Psychiatry, 2005 3rd Mind & World Conference, May 4, 2007
Slide 11 : Psychiatric Diagnoses and ICDs 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) Grant et al, AJP, 2005; JCP, in press 3rd Mind & World Conference, May 4, 2007
Slide 12 : 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
Slide 13 : Relationship Between PG and SUDs 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 3rd Mind & World Conference, May 4, 2007
Slide 14 : 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
Slide 15 : Motivation in Addiction Motivated Behaviors Become Increasingly Limited Over Time to Addiction-Related Actions Neural System Abnormalities Underlying Motivated Behaviors in Addiction Represent Important Targets for Treatment Motivational Neurocircuitry Differences Are Likely Present At Specific Stages of Addiction - Impulsive Decision-Making (Early (& Late)) vs. Compulsive Engagement (Late) 3rd Mind & World Conference, May 4, 2007
Slide 16 : 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
Slide 17 : Neural Systems and Addiction 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, ... 3rd Mind & World Conference, May 4, 2007
Slide 18 : Roles for Neurotransmitters Neurotransmitter Role in Impulse Control Norepinephrine (NE) Arousal, Excitement Serotonin (5HT) Behavior Initiation/Cessation Dopamine (DA) Reward, Reinforcement Opioids Pleasure, Urges Potenza and Hollander, 2002 3rd Mind & World Conference, May 4, 2007
Slide 19 : 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
Slide 20 : Impulsivity and Addiction 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) 3rd Mind & World Conference, May 4, 2007
Slide 21 : Decision-Making, Reward Processing and Addiction 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) 3rd Mind & World Conference, May 4, 2007
Slide 22 : Reward Processing in Addiction 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) 3rd Mind & World Conference, May 4, 2007
Slide 23 : Dopamine and ICDs in PD 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 3rd Mind & World Conference, May 4, 2007
Slide 24 : 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
Slide 25 : 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
Slide 26 : Opioid Antagonists 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) 3rd Mind & World Conference, May 4, 2007
Slide 27 : 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)
Slide 28 : Bivariate Biometric Model for PG & MD Potenza et al, 2005, Arch Gen Psychiatry
Slide 29 : Overall Conclusions 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 3rd Mind & World Conference, May 4, 2007
Slide 30 : www.impulsivity. org (or contact marc.potenza@yale.edu) The International Society for Research on Impulsivity and Impulse Control Disorders (ISRI)

 


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