Behavioral Addictions in Addiction Medicine From Mechanisms to
Behavioral Addictions in Addiction Medicine: From Mechanisms to Practical Considerations Marc N. Potenza, M. D. , Ph. D. Professor of Psychiatry, Child Study, and Neurobiology Director, Yale Gambling Center of Research Excellence (CORE) Director, Women and Addictions Core, Women’s Health Research at Yale Senior Scientist, The National Center on Addiction and Substance Abuse Yale University School of Medicine
Disclosures • Consultant to Ironwood, Lundbeck, Shire, INSYS, River. Mend Health, Opiant / Lakelight Therapeutics, and Jazz Pharmaceuticals • Research Grants from National Center for Responsible Gaming • Research Gift from Mohegan Sun • Consultant to Gambling and Legal Entities on Issues Related to Impulse Control Disorders SSA, York, UK, Nov 11, 2016
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 SSA, York, UK, Nov 11, 2016
Changing Perspectives on Addiction 2001 SSA, York, UK, Nov 11, 2016 2010 Holden, Science, 2001, 2010; Frascella et al, Ann NY Acad Sci, 2010
DSM-5 Experience and Changes • Two DSM Research Workgroups - Gambling-Related Articles Generated (Petry, 2006; Potenza et al, 2009) • PG Re-Classified with SUDs - May Facilitate Integrated Treatment - Discussion Re: Which Behaviors Might be Considered Addictive - Other Domains (Sex, Food, Internet Use/Gaming) Considered • PG Termed “Gambling Disorder” - Concerns About Stigma of “Pathological” Term • Thresholding Differences Between GD and SUDs - May Lead to Inaccurate Perceptions of Relative Health Impacts SSA, York, UK, Nov 11, 2016 Potenza, Curr Op Neurobio, 2013
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, N-AC SSA, York, UK, Nov 11, 2016
Risk/Reward Decision-Making, Reward Processing & Addiction • Individuals with PG or SUDs Perform Disadvantageously on Decision. Making Tasks and Discount Rewards More Rapidly (Petry et al, 2001; Bechara, 2003) • Decision-Making and Delay Discounting Associated with Clinically Relevant Measures Like Treatment Outcome (Krishnan-Sarin et al, 2007) SSA, York, UK, Nov 11, 2016
vm. PFC, PG and SUDs Simulated Gambling Reuter et al, 2005, Nat Neurosci Stroop PG - Control (Potenza et al, 2003, Am J Psychiatry) Gambling Reward OC Tape PG-Control (Balodis et al, (Potenza et al, 2012, 2003, Arch Gen Biol Psych) Psychiatry) Controls > SUD/PG in vm. PFC on IGT SSA, York, UK, Nov 11, 2016 Tanabe et al, 2007, Hum Brain Mapp
Reward Processing in Addiction • Adults w/ Alcohol Dependence (AD) vs Those w/o AD Show Less Activation of Ventral Striatum (VS) in Anticipation of Working for Monetary Reward (Hommer et al, 2004; Wrase et al, 2007) • Similar Findings in Adolescents and Adults FH+ Vs. FH - for AD, Nicotine Dependence, PG, and Binge-Eating Disorder (Hommer et al, 2004; Andrews et al, 2011; Peters et al, 2011; Choi et al, 2012; Balodis et al, 2012, 2013) • In AD and PG, Diminished VS Activation Correlates with Impulsivity (Beck et al, 2009; Balodis et al, 2012) SSA, York, UK, Nov 11, 2016
Less Ventral Striatal Activation in PG Addiction Tapes (PG-CPG)+(CD-CCD) (Potenza, 2008) SSA, York, UK, Nov 11, 2016 Reward Anticipation PG-Control (Balodis et al, 2012) Simulated Gambling (Reuter et al, 2005)
Pharmacological Treatment of AD • Shared Genetic Contributions to PG and Et. OH Dependence (Slutske et al, 2000) • FDA-Approved Drugs for AD (None for PG/ICDs) - Disulfiram, Naltrexone, Acamprosate • Naltrexone and Other Opioid Antagonists Indirectly Modulate Dopamine Neurotransmission in VTA-NAc Pathway • Four RCTs Have Found Naltrexone or Nalmefene to Be Superior to Placebo in the Tx of PG (Grant et al, 2006, 2008, 2010) SSA, York, UK, Nov 11, 2016
Predicting Outcome • Among Subjects Receiving Active Drug (n=214) in Two Placebo-Controlled Trials of Naltrexone and Nalmefene, The Factor Most Strongly Associated with Outcome was a Family History of Alcoholism (OR=1. 74; p=0. 006) • Among Subjects Receiving Higher Doses of Active Drug, Gambling Urges Were Associated with Treatment Outcome (OR=5. 86; p<0. 05) • Among Those Receiving Placebo (n=70), Response Was Most Strongly Associated with Younger Age (OR=0. 70; p=0. 01) SSA, York, UK, Nov 11, 2016 Source: Grant et al, 2008
SSA, York, UK, Nov 11, 2016 Bullock and Potenza, 2012
Differences in Secondary Crossing Fibers in Addictions Regions Implicated Include Corticostriatal and Parieto-Occipital Tracts Previously Implicated in Reward Processing and Addiction SSA, York, UK, Nov 11, 2016 Yip et al, in press, Biol Psychiatry CNNI
Secondary Crossing Fiber Findings Not Attributable to AUDs SSA, York, UK, Nov 11, 2016 Yip et al, in press, Biol Psychiatry CNNI
Gray Matter Volume in PG and CD SSA, York, UK, Nov 11, 2016 Yip et al, submitted
Internet Use in DSM-5 and ICD-11 • IGD Included in Section 3 (Future Research) • Inclusionary Criteria Similar to Those For Gambling Disorder • Non-gaming Forms of Internet Use (and Arguably Non-Internet-based Forms of Gaming) Currently Not Directly Addressed in DSM-5 • Current Focus of WHO SSA, York, UK, Nov 11, 2016 Petry and O’Brien, 2013
Diagnosing IGD • Diagnosis Involves Meeting 5 of 9 Inclusionary Criteria • Inclusionary Criteria Target Tolerance, Withdrawal, Interference in Life, Unsuccessful Control, Preoccupation, Loss of Interests, Lying, Gaming to Escape, Continued Excessive Gaming Despite Problems • Like with GD and SUDs, Severity Range from Mild to Severe • Unlike SUDs, A More Stringent Threshold for Diagnosis Exists SSA, York, UK, Nov 11, 2016
Technology and Youth: PIU • Problematic Internet Use Found to Be Present in 4% of CT High School Students (3. 5% of Boys; 4. 5% of Girls) • PIU Defined as Having: 1) Irresistible Urge; 2) Growing Tension Relieve by IU; and 3) Trying to Cut Back on Internet Use • Boys Spent More Time on Internet; Girls More Likely to Think They Have a Problem • Similarities with Gambling (Desai et al 2005) • More Common in Asian (7. 9%) and Hispanic (6. 1%) Youth • PIU Associated with Substance Use (p=. 001), Depression (p<. 0001) and Aggression (p<. 0001) • More Research Needed on Types of Internet Use SSA, York, UK, Nov 11, 2016 Liu et al, 2011
Video Gaming and PVG • Among CT HS Students, Boys (76%) More Likely Than Girls (29%) to Report Playing Video Games (51% Overall) • Among Boys, VG Play Associated with Lower Odds of Smoking; Among Girls, VG Play Associated with Depression, Fights and Carrying a Weapon • Among Gamers, 4. 9% Had PVG (5. 8% of Boys, 3% of Girls) • Across Sexes, Correlates of PVG Included Regular Tobacco Use, Drug Use, Depression and Getting into Serious Fights • VG Playing Appears Largely Normative Amongst Boys, and PVG is Associated with Negative Health Measures, Particularly Externalizing Behaviors • Future Studies Should Assess Gaming Types (FPS, MMOG) SSA, York, UK, Nov 11, 2016 Desai et al, 2010
Neurobiologies of PIU and PVG • Similarities and Differences Between PIU, PVG, PG and SUDs (Yau et al, 2012) - Similarities in Co-occurrences, Core Features and Associations with Mental-Health Conditions - Differences in Some Neurobiological Features (e. g. , in White. Matter Integrity) • Adolescents with ARPIU (Versus Adolescents Without) Show Blunted FRN and P 300 Responses During Reward Feedback (Yau et al, 2015) SSA, York, UK, Nov 11, 2016
Resting State Functional Connectivity in Executive-Control Networks Decreased in IGD and Linked to Stroop Performance SSA, York, UK, Nov 11, 2016 Dong, Lin and Potenza, 2015 Yau et al, 2013
Theoretical Models of IGD Based on Knowledge of SUDs and PG/GD Levels of Problem-Gambling Severity Non. Gambling Low-Risk Gambling At-Risk Gambling Possible Effects Neurotransmitters DA, NE, Opioids, 5 HT, Glutamate, Cortisol, et al. Brain Structure/ Function vm. PFC, VS, white matter, circuitry, et al. Problem Gambling Pathological Gambling Possible Interactions Genetic Factors Allelic Variants Relating to Brain Structure & Function Environment Exposure to Possible Risk (Trauma, Stress) and Protective Factors Individual Differences Relating to Sex, Race/ Ethnicity, Temperament, Co-Occurring Disorders, et al. Possible Factors Influencing Problem. Gambling Severity and Related Transitions Yale Department of Psychiatry Grand Rounds - March 21, 2003 SSA, Nov, 2016 Dong and Potenza, 2014
An I-PACE Model for Types of IUDs SSA, York, UK, Nov 11, 2016 Brand et al, 2016, Neurosci Biobehav Rev
Conclusions & Future Directions • Which Disorders Constitute Addictions Has Been Debated and Recent Data Suggest Similarities Between SUDs, GD, and IGD • The Existence of Neurobiological Similarities Suggests that Common Pharmacological and Behavioral Treatments May be Effective Across Conditions • Additional Research Is Needed to to Develop Improved Prevention, Treatment and Policy Efforts Relating to Promoting Public Health Regarding Substance-Use, Gambling, Internet-Use, and Other Addictive Behaviors and Conditions SSA, York, UK, Nov 11, 2016
Acknowledgments Women & Addictions Carolyn Mazure Rani Desai Paul Maciejewski Div Substance Abuse Bruce Rounsaville Kathleen Carroll Suchitra Krishnan-Sarin Stephanie O’Malley Elaine Lavelle Dana Cavallo Ran Wu Imaging Todd Constable Gambling Center Godfrey Pearlson Genetics Of Excellence Rajita Sinha Joel Gelernter Iris Balodis Bruce Wexler Seth Eisen Corey Pilver Robert Fulbright Hong Xian Sarah Yip Cheryl Lacadie Justin Wareham Patrick Worhunsky Jeff Scherrer Justine Giddens Scott Bullock Translational Jiansong Xu Jane Taylor RCTs Priya Kundu Judson Brewer R. A. Chambers Jon Grant Monica Solorzano Hedy Kober CT Partnerships SW Kim Ardeshir Rahman Elise De. Vito Marvin Steinberg & CCPG Michael Stevens Carlos Blanco Yvonne Yau Loreen Rugle & PGS Eric Hollander And Many Others! Alex Neumeister NIH (NIDA, NIAAA, ORWH) VA (MIRECC, REAP) WHR DMHAS NCRG Moh Sun
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