presentation - Society for the Study of Addiction

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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, RiverMend 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
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Changing Perspectives on Addiction
2001
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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, 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
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Risk/Reward Decision-Making,
Reward Processing & Addiction
• Individuals with PG or SUDs Perform
Disadvantageously on DecisionMaking 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)
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vmPFC, 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
PG-Control (Balodis et al,
(Potenza et al,
2012,
2003, Arch Gen Biol Psych)
Psychiatry)
Controls > SUD/PG in vmPFC on IGT
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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 BingeEating 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)
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Less Ventral Striatal Activation in PG
Addiction Tapes
(PG-CPG)+(CD-CCD)
(Potenza, 2008)
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Reward Anticipation
PG-Control
(Balodis et al,
2012)
Simulated Gambling
(Reuter et al, 2005)
Pharmacological Treatment of AD
• Shared Genetic Contributions to PG and EtOH
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)
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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)
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Source: Grant et al, 2008
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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
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Yip et al, in press, Biol Psychiatry CNNI
Secondary Crossing Fiber Findings
Not Attributable to AUDs
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Yip et al, in press, Biol Psychiatry CNNI
Gray Matter Volume in PG and CD
A. Main effects of diagnos*c group
x=46
z=-3
p=.006
p=.07
DSM-IV Diagnos*c Group
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z=-16
Modulated GM Volumes
Modulated GM Volumes
x=-5
B. Associa*ons with impulsivity
BarraE Impulsiveness Scale (BIS-11)
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
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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
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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
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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)
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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 WhiteMatter Integrity)
• Adolescents with ARPIU (Versus Adolescents Without)
Show Blunted FRN and P300 Responses During Reward
Feedback (Yau et al, 2015)
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Resting State
Functional
Connectivity in
Executive-Control
Networks Decreased
in IGD and Linked to
Stroop Performance
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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
NonGambling
Low-Risk
Gambling
At-Risk
Gambling
Possible
Effects
Neurotransmitters
DA, NE,
Opioids,
5HT,
Glutamate,
Cortisol,
et al.
Brain
Structure/
Function
vmPFC,
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 ProblemGambling
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
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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
Translational
Justine Giddens Scott Bullock
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 DeVito
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