Week 3 Discussion

Week3IntrotoBehavioralAddictions.pdf

Home >Psychology homework help >Week 3 Discussion

Introduction to Behavioral Addictions

Jon E. Grant, M.D., J.D., M.P.H. University of Minnesota School of Medicine, Minneapolis, Minnesota, USA

Marc N. Potenza, M.D., Ph.D. Yale University School of Medicine, New Haven, Connecticut, USA

Aviv Weinstein, Ph.D. Hadassah University Hospital, Jerusalem, Israel

David A. Gorelick, M.D., Ph.D. Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, Maryland, USA

Background: Several behaviors, besides psychoactive substance ingestion, produce short-term reward that may engender persis- tent behavior, despite knowledge of adverse consequences, i.e., diminished control over the behavior. These disorders have his- torically been conceptualized in several ways. One view posits these disorders as lying along an impulsive-compulsive spectrum, with some classified as impulse control disorders. An alternate, but not mutually exclusive, conceptualization considers the disorders as non-substance or “behavioral” addictions. Objectives: Inform the discussion on the relationship between psychoactive substance and behavioral addictions. Methods: We review data illustrating similarities and differences between impulse control disorders or behavioral addictions and substance addictions. This topic is par- ticularly relevant to the optimal classification of these disorders in the forthcoming fifth edition of the American Psychiatric Associa- tion Diagnostic and Statistical Manual of Mental Disorders (DSM- V). Results: Growing evidence suggests that behavioral addictions resemble substance addictions in many domains, including natu- ral history, phenomenology, tolerance, comorbidity, overlapping genetic contribution, neurobiological mechanisms, and response to treatment, supporting the DSM-V Task Force proposed new cate- gory of Addiction and Related Disorders encompassing both sub- stance use disorders and non-substance addictions. Current data suggest that this combined category may be appropriate for patho- logical gambling and a few other better studied behavioral addic- tions, e.g., Internet addiction. There is currently insufficient data to justify any classification of other proposed behavioral addictions. Conclusions and Scientific Significance: Proper categorization of behavioral addictions or impulse control disorders has substan- tial implications for the development of improved prevention and treatment strategies.

Address correspondence to Dr. David A. Gorelick, 251 Bayview Boulevard, Baltimore, MD 21224, USA. E-mail: dgorelic@intra.nida.nih.gov

Keywords behavioral addiction, classification, diagnosis, impulse control disorder, substance use disorder

INTRODUCTION Several behaviors, besides psychoactive substance ingestion,

produce short-term reward that may engender persistent behav- ior despite knowledge of adverse consequences, i.e., diminished control over the behavior. Diminished control is a core defining concept of psychoactive substance dependence or addiction. This similarity has given rise to the concept of non-substance or “behavioral” addictions, i.e., syndromes analogous to substance addiction, but with a behavioral focus other than ingestion of a psychoactive substance. The concept of behavioral addictions has some scientific and clinical heuristic value, but remains controversial. Issues around behavioral addictions are currently being debated in the context of development of Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) (1, 2)

Several behavioral addictions have been hypothesized as hav- ing similarities to substance addictions. The current Diagnos- tic and Statistical Manual, Fourth Edition (DSM-IV-TR) has designated formal diagnostic criteria for several of these dis- orders (e.g., pathological gambling, kleptomania), classifying them as impulse control disorders, a separate category from substance use disorders. Other behaviors (or impulse control disorders) have been considered for inclusion in the forthcom- ing DSM–compulsive buying, pathologic skin picking, sexual addiction (non-paraphilic hypersexuality), excessive tanning, computer/video game playing, and internet addiction. Which behaviors to include as behavioral addictions is still open for debate (3). Not all impulse control disorders, or disorders characterized by impulsivity, should be considered behavioral

233

234 J. E. GRANT ET AL.

addictions. Although many of the impulse control disorders (e.g., pathological gambling, kleptomania) appear to share core features with substance addictions, others, such as intermittent explosive disorder, may not. In the hope of contributing to this debate, this article reviews the evidence for similarities between behavioral addictions and substance use disorders, their distinc- tion from obsessive compulsive disorder, and identifies areas of uncertainty warranting future research. It also serves as an in- troduction to the succeeding articles in this issue, which review some putative addictive behaviors in more detail.

COMMON FEATURES OF BEHAVIORAL ADDICTIONS: RELATIONSHIP TO SUBSTANCE USE DISORDERS

The essential feature of behavioral addictions is the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the person or to others (4). Each behavioral addiction is characterized by a recurrent pattern of behavior that has this essential feature within a specific domain. The repetitive engagement in these behaviors ultimately interferes with functioning in other domains. In this respect, the behavioral addictions resemble substance use disorders. Individuals with substance addictions report difficulties in resisting the urge to drink or use drugs.

Behavioral and substance addictions have many similarities in natural history, phenomenology, and adverse consequences. Both have onset in adolescence and young adulthood and higher rates in these age groups than among older adults (5). Both have natural histories that may exhibit chronic, relapsing patterns, but with many people recovering on their own without formal treatment (so-called “spontaneous” quitting) (6).

Behavioral addictions are often preceded by feelings of “ten- sion or arousal before committing the act” and “pleasure, grat- ification, or relief at the time of committing the act” (4). The ego-syntonic nature of these behaviors is experientially similar to the experience of substance use behaviors. This contrasts with the ego-dystonic nature of obsessive-compulsive disorder. How- ever, both behavioral and substance addictions may become less ego-syntonic and more ego-dystonic over time, as the behavior (including substance taking) itself becomes less pleasurable and more of a habit or compulsion (2, 7), or becomes motivated less by positive reinforcement and more by negative reinforcement (e.g., relief of dysphoria or withdrawal).

Behavioral and substance addictions have phenomenologi- cal similarities. Many people with behavioral addictions report an urge or craving state prior to initiating the behavior, as do individuals with substance use disorders prior to substance use. Additionally, these behaviors often decrease anxiety and result in a positive mood state or “high,” similar to substance intoxica- tion. Emotional dysregulation may contribute to cravings in both behavioral and substance use disorders (8). Many people with pathological gambling, kleptomania, compulsive sexual behav- ior, and compulsive buying report a decrease in these positive mood effects with repeated behaviors or a need to increase the

intensity of behavior to achieve the same mood effect, analogous to tolerance (9–11). Many people with these behavioral addic- tions also report a dysphoric state while abstaining from the behaviors, analogous to withdrawal. However, unlike substance withdrawal, there are no reports of physiologically prominent or medically serious withdrawal states from behavioral addictions.

Pathological gambling, the most thoroughly studied of the behavioral addictions, provides further insight into the relation- ship of behavioral addictions and substance use disorders (see also Wareham and Potenza, this issue). Pathological gambling usually begins in childhood or adolescence, with males tend- ing to start at an earlier age (5, 12), mirroring the pattern of substance use disorders. Higher rates of pathological gambling are observed in men, with a telescoping phenomenon observed in females (i.e., women have a later initial engagement in the addictive behavior, but foreshortened time period from initial engagement to addiction) (13). The telescoping phenomenon has been extensively documented in a variety of substance use disorders (14).

As in substance use disorders, financial and marital prob- lems are common in behavioral addictions. Individuals with behavioral addictions, like those with substance addictions, will frequently commit illegal acts, such as theft, embezzlement, and writing bad checks, to either fund their addictive behavior or cope with the consequences of the behavior (15).

Personality Individuals with behavioral addictions and those with sub-

stance use disorders both score high on self-report measures of impulsivity and sensation-seeking and generally low on mea- sures of harm avoidance (16–20). However, individuals with some behavioral addictions, such as internet addiction or patho- logical gambling, may also report high levels of harm avoidance (21) (see also Weinstein and Lejoyeux, this issue). Other re- search has suggested that aspects of psychoticism, interpersonal conflict, and self-directedness may all play a role in internet addiction (see Weinstein and Lejoyeux, this issue). In contrast, individuals with obsessive compulsive disorder generally score high on measures of harm avoidance and low on impulsivity (17, 21). Individuals with behavioral addictions also score high on measures of compulsivity, but these may be limited to im- paired control over mental activities and worries about losing control over motor behaviors (22). Impaired inhibition of mo- tor responses (impulsivity) has been found in individuals with obsessive compulsive disorder and pathologic skin picking (a behavioral addiction with arguably closer phenomenological links to obsessive compulsive disorder), whereas cognitive in- flexibility (thought to contribute to compulsivity) was limited to obsessive compulsivity disorder (23, 24).

Comorbidity Although most nationally representative studies have

not included assessment of behavioral addictions, existing

BEHAVIORAL ADDICTIONS 235

TABLE 1. Lifetime estimates of substance use disorders in behavioral

addictions.

Behavioral addictions Lifetime estimates of

substance use disorder

Pathological gambling 35%–63% Kleptomania 23%–50% Pathologic skin picking 38% Compulsive sexual behavior 64% Internet addiction 38% Compulsive buying 21%–46%

Source: (102).

epidemiological data support a relationship between patholog- ical gambling and substance use disorders, with high rates of co-occurrence in each direction (25, 26). The St. Louis Epi- demiologic Catchment Area (ECA) study found high rates of co-occurrence for substance use disorders (including nicotine dependence) and pathological gambling, with the highest odds ratios generally observed between gambling, alcohol use dis- orders, and antisocial personality disorder (25). A Canadian epidemiological survey estimated that the relative risk for an alcohol use disorder increased 3.8-fold when disordered gam- bling was present (27). Among individuals with substance de- pendence, the risk of moderate to high severity gambling was 2.9 times higher (28). Odds ratios ranging from 3.3 to 23.1 have been reported between pathological gambling and alcohol use disorders in U.S. population–based studies (25, 29). Internet ad- diction was associated with harmful alcohol use (odds ratio of 1.84) in a study of 2,453 college students, after controlling for gender, age and depression (30).

Clinical samples of other behavioral addictions suggest that co-occurrence with substance use disorders is common (Table 1). These findings suggest that behavioral addictions may share a common pathophysiology with substance use disorders.

However, data about substance use comorbidity must be in- terpreted cautiously because any causal associations may man- ifest on a behavioral level (for example, alcohol use disinhibits a range of inappropriate behaviors, including those identified as addictive) or on a syndromal level (for example, a behav- ioral addiction starts after alcoholism treatment, possibly as a substitute for drinking). Problem gamblers with frequent alco- hol use have greater gambling severity and more psychosocial problems resulting from gambling than those without alcohol use histories (31), and adolescents who are moderate to high fre- quency drinkers are more likely to gamble frequently than those who are not (32), suggesting a behavioral interaction between alcohol and gambling. In contrast, a similar finding regarding nicotine use suggests a syndromal interaction, as does the fact that adults with pathological gambling who are current or prior smokers had significantly stronger urges to gamble (33). Prob- lem gamblers who use tobacco daily are more likely to have alcohol and drug use problems (34).

Other psychiatric disorders, such as major depressive disor- der, bipolar disorder, obsessive compulsive disorder, and atten- tion deficit hyperactivity disorder, are also commonly reported in association with behavioral addictions (35, 36) (see also We- instein and Lejoyeux, this issue). However, many of these co- morbidity studies were based on clinical samples. The extent to which these findings generalize to community samples remains to be determined.

Neurocognition Behavioral addictions and substance use disorders may have

common cognitive features. Both pathological gamblers and individuals with substance use disorders typically discount re- wards rapidly (37) and perform disadvantageously on decision- making tasks (38) such as the Iowa Gambling Task, a paradigm that assesses risk-reward decision making (39). In contrast, a study of individuals with internet addiction demonstrated no such deficits in decision-making on the Iowa Gambling Task (40). A study using a comprehensive neurocognitive battery in 49 pathological gamblers, 48 abstinent alcohol-dependent sub- jects, and 49 controls found that gamblers and alcoholics both showed diminished performance on tests of inhibition, cognitive flexibility, and planning tasks, but had no differences on tests of executive functioning (41).

Common Neurobiological Processes A growing body of literature implicates multiple neurotrans-

mitter systems (e.g., serotonergic, dopaminergic, noradrenergic, opioidergic) in the pathophysiology of behavioral addictions and substance use disorders (42). In particular, serotonin (5-HT), which is involved with inhibition of behavior, and dopamine, involved with learning, motivation, and the salience of stimuli, including rewards, may contribute significantly to both sets of disorders (42, 43).

Evidence for serotonergic involvement in behavioral addic- tions and substance use disorders comes in part from studies of platelet monoamine oxidase B (MAO-B) activity, which corre- lates with cerebrospinal fluid (CSF) levels of 5-hydroxyindole acetic acid (5-HIAA, a metabolite of 5-HT) and is considered a peripheral marker of 5-HT function. Low CSF 5-HIAA levels correlate with high levels of impulsivity and sensation-seeking and have been found in pathological gambling and substance use disorders (44). Pharmacologic challenge studies that measure hormonal response after administration of serotonergic drugs also provide evidence for serotonergic dysfunction in both be- havioral addictions and substance use disorders (45).

The repetitive use of substances or engagement in a behav- ioral addiction following an urge may reflect a unitary process. Preclinical and clinical studies suggest that an underlying bi- ological mechanism for urge-driven disorders may involve the processing of incoming reward input by the ventral tegmen- tal area/nucleus accumbens/orbital frontal cortex circuit (46, 47). The ventral tegmental area contains neurons that release

236 J. E. GRANT ET AL.

dopamine to the nucleus accumbens and orbital frontal cortex. Alterations in dopaminergic pathways have been proposed as underlying the seeking of rewards (gambling, drugs) that trig- ger the release of dopamine and produce feelings of pleasure (48).

Limited evidence from neuroimaging studies supports a shared neurocircuitry of behavioral addictions and substance use disorders (7). Diminished activity of the ventral medial pre- frontal cortex (vmPFC) has been associated with impulsive de- cision making in risk-reward assessments and with decreased response to gambling cues in pathological gamblers (49). Sim- ilarly, abnormal vmPFC functioning has been found in people with substance use disorders (50). Game cue-associated brain activation in Internet gaming addicts occurs in the same brain re- gions (orbitofrontal, dorsolateral prefrontal, anterior cingulate, nucleus accumbens) as with drug cue-associated brain activa- tion in drug addicts (51) (see also Weinstein and Lejoyeux, this issue).

Brain imaging research suggests that the dopaminergic mesolimbic pathway from the ventral tegmental area to the nucleus accumbens may be involved in both substance use dis- orders and pathological gambling. Subjects with pathological gambling demonstrated less ventral striatal neuronal activity with fMRI while performing simulated gambling than did con- trol subjects (52), similar to observations in alcohol-dependent subjects when processing monetary rewards (53). Diminished ventral striatal activation has also been implicated in the cravings associated with substance and behavioral addictions (42). Par- ticipation in a gambling task appears to elicit greater dopamine release in the ventral striatum in individuals with Parkinson’s disease (PD) and pathological gambling than in individuals with PD alone (54), a response similar to that elicited by drug or drug- associated cues in drug addicts (55).

Dopamine involvement in behavioral addictions is also sug- gested by studies of medicated PD patients (56, 57). Two stud- ies of patients with PD found that more than 6% experienced a new onset behavioral addiction or impulse control disor- der (e.g., pathological gambling, sexual addiction), with sub- stantially higher rates among those taking dopamine agonist medication (58, 59). A higher levo-dopa dose equivalence was associated with greater likelihood of having a behavioral addic- tion (59). Contrary to what might be expected from dopamine involvement, antagonists at dopamine D2/D3 receptors enhance gambling-related motivations and behaviors in non-PD individ- uals with pathological gambling (60) and have no efficacy in the treatment of pathological gambling (61, 62). Further research is warranted to clarify the precise role of dopamine in pathological gambling and other behavioral addictions.

Family History and Genetics Relatively few family history/genetics studies of behav-

ioral addiction have been designed with appropriate control groups (7). Small family studies of probands with pathological

gambling (63), kleptomania (64), or compulsive buying (65) each found that first-degree relatives of the probands had sig- nificantly higher lifetime rates of alcohol and other substance use disorders, and of depression and other psychiatric disor- ders, than did control subjects. These controlled family studies support the view that behavioral addictions may have a genetic relationship to substance use disorders.

The genetic versus environmental contributions to specific behaviors and disorders can be estimated by comparing their concordance in identical (monozygotic) and fraternal (dizy- gotic) twin pairs. In a study of male twins using the Vietnam Era Twin Registry, 12% to 20% of the genetic variation in risk for pathological gambling and 3% to 8% of the nonshared en- vironmental variation in risk for pathological gambling was accounted for by risk for alcohol use disorders (66). Two-thirds (64%) of the co-occurrence between pathological gambling and alcohol use disorders was attributable to genes that influence both disorders, suggesting overlap in the genetically transmit- ted underpinnings of both conditions. These findings are similar to those suggesting common genetic contributions to a range of substance use disorders (67).

There are very few molecular genetic studies of behav- ioral addictions. The D2A1 allele of the D2 dopamine re- ceptor gene (DRD2) increases in frequency from individuals with non-problematic gambling to pathological gambling and co-occurring pathological gambling and substance use disor- ders (68). Several DRD2 gene single nucleotide polymorphisms (SNPs) have been associated with personality measures of im- pulsivity and experimental measures of behavioral inhibition in healthy volunteers (69), but these have not been evaluated in people with behavioral addictions. Excessive internet users had higher frequencies of the long-arm allele (SS) of the serotonin transporter gene (5HTTLPR) than healthy controls, and this was associated with greater harm avoidance (70) (see also Weinstein and Lejoyeux, this issue).

Responsiveness to Treatment Behavioral addictions and substance use disorders often

respond positively to the same treatments, both psychoso- cial and pharmacological. The 12-step self-help approaches, motivational enhancement, and cognitive behavioral therapies commonly used to treat substance use disorders have been suc- cessfully used to treat pathological gambling, compulsive sexual behavior, kleptomania, pathologic skin picking, and compulsive buying (71–74). Psychosocial interventions for both behavioral addictions and substance use disorders often rely on a relapse prevention model that encourages abstinence by identifying pat- terns of abuse, avoiding or coping with high risk situations, and making lifestyle changes that reinforce healthier behaviors. In contrast, successful psychosocial treatments for obsessive- compulsive disorder emphasize exposure and response preven- tion strategies (2).

BEHAVIORAL ADDICTIONS 237

There are no medications currently approved for the treat- ment of behavioral addictions, but some medications that have shown promise in treating substance use disorders have also shown promise in treating behavioral addictions (75). Naltrex- one, a mu-opioid receptor antagonist approved by the U.S. Food and Drug Administration for the treatment of alcoholism and opioid dependence, has shown efficacy in controlled clinical trials for the treatment of pathological gambling and kleptoma- nia (76–79), and promise in uncontrolled studies of compulsive buying (80), compulsive sexual behavior (81), internet addiction (82), and pathologic skin picking (83). These findings suggest that mu-opioid receptors play a similar role in behavioral ad- dictions as they do in substance use disorders, possibly through modulation of the dopaminergic mesolimbic pathway. In con- trast, the short-acting mu-opioid receptor antagonist naloxone exacerbates symptoms in obsessive-compulsive disorder (84).

Medications that alter glutamatergic activity have also been used to treat both behavioral addictions and substance depen- dence. Topiramate, an anticonvulsant which blocks the AMPA subtype of glutamate receptor (among other actions), has shown promise in open-label studies of pathological gambling, com- pulsive buying, and compulsive skin picking (85), as well as efficacy in reducing alcohol (86), cigarette (87), and cocaine (88) use. N-acetyl cysteine, an amino acid that restores extra- cellular glutamate concentration in the nucleus accumbens, re- duced gambling urges and behavior in one study of pathological gamblers (89), and reduces cocaine craving (90) and cocaine use (91) in cocaine addicts. These studies suggest that glutamatergic modulation of dopaminergic tone in the nucleus accumbens may be a mechanism common to behavioral addiction and substance use disorders (92).

Diagnostic Issues Only one behavioral addiction, pathological gambling, is

a recognized diagnosis in DSM-IV and ICD-10. Its diagnos- tic criteria are conceptually similar to those for substance abuse/dependence, i.e., preoccupation with the behavior, dimin- ished ability to control the behavior, tolerance, withdrawal, and adverse psychosocial consequences. The DSM-V Task Force has suggested moving pathological gambling from its current classification as an impulse control disorder to a new classi- fication tentatively termed “Addiction and Related Disorders,” which would include both substance use disorders and “non- substance addictions” (www.dsm5.org, accessed Feb. 10, 2010). The only substantive proposed change in diagnostic criteria is dropping of the criterion regarding commission of illegal acts to finance gambling, which was found to have low prevalence and little effect on the diagnosis.

Several other behavioral addictions have proposed diagnostic criteria, including compulsive buying (93), Internet addiction (94), video/computer game addiction (95), sexual addiction (96), and excessive tanning (see Kouroush et al., this issue). These are usually based on the existing DSM-IV criteria for

substance abuse or dependence, e.g., excessive time spent in the behavior, repeated unsuccessful attempts to cut down or stop the behavior, diminished control over the behavior, tolerance, with- drawal, and adverse psychosocial consequences. The DSM-V Substance-Related Disorders work group is considering sev- eral of these non-substance addictions for inclusion in DSM-V, specifically mentioning Internet addiction (www.dsm5.org; ac- cessed Feb. 10, 2010). However, for many of the disorders, there are little or no validating data for these diagnostic criteria; they are currently most useful as survey instruments to estimate the prevalence of the problem.

One diagnostic question raised in the literature is where do behavioral addictions (and substance addictions) fall on an impulsivity-compulsivity dimension (97), i.e., are they more like impulse control disorders or obsessive compulsive disor- ders? Some have argued that this unitary dimension approach is overly simplistic, and that impulsivity and compulsivity rep- resent orthogonal dimensions, rather than opposite poles of a single dimension (98). Consistent with the latter argument are findings such as substantial variation in degree of impulsivity among people with a behavioral addiction, variation that may be associated with response to pharmacological treatment (48, 99).

In DSM-IV, substance addictions (substance use disorders) are an independent category, while pathological gambling is considered an impulse control disorder, similar to, for exam- ple, pyromania and kleptomania. ICD-10 classifies pathological gambling as a “habit and impulse” disorder, but recognizes that “the behavior is not compulsive in the technical sense,” even though it is sometimes called “compulsive gambling.”

A related issue is the association, or clustering, if any, among different behavioral addictions. A cluster analysis of demo- graphic and clinical variables in 210 patients with primary ob- sessive compulsive disorder identified two separate clusters of patients with behavioral addictions (100): patients with patho- logical gambling or sexual addiction (“hypersexuality”) had ear- lier age of onset and were more likely male, as compared to patients with compulsive shopping. Further research is needed to confirm and extend this finding. One research approach that might substantially contribute to the field would be a compre- hensive evaluation of a large, heterogeneous, well characterized group of individuals with various behavioral and substance ad- dictions in terms of discrete components of impulsivity and compulsivity in both psychological (cognitive) and behavioral (motor) domains, e.g., sensitivity to reward delay (temporal dis- counting of reward), risk-reward decision-making, conceptual rigidity, premature anticipatory responding, perseverative re- sponding, response inhibition, and reversal learning.

SUMMARY AND CONCLUSIONS Growing evidence indicates that behavioral addictions re-

semble substance addictions in many domains, including nat- ural history (chronic, relapsing course with higher incidence

238 J. E. GRANT ET AL.

and prevalence in adolescents and young adults), phenomenol- ogy (subjective craving, intoxication [“high”], and withdrawal), tolerance, comorbidity, overlapping genetic contribution, neu- robiological mechanisms (with roles for brain glutamatergic, opioidergic, serotonergic, and dopamine mesolimbic systems), and response to treatment. However, existing data are most ex- tensive for pathological gambling (see Wareham and Potenza, this issue), with only limited data for compulsive buying (see Lejoyeaux and Weinstein, this issue), internet addiction (see Weinstein and Lejoyeaux, this issue), and video/computer game addiction (see Weinstein, this issue), and almost no data for other behavioral addictions such as sexual addiction (see Garcia and Thibaut, this issue), love addiction (see Reynaud, this is- sue), pathologic skin picking (see Odlaug and Grant, this issue), or excessive tanning (see Kouroush et al., this issue).

There is sufficient evidence to warrant considering patholog- ical gambling as a non-substance or behavioral addiction; the DSM-V Task Force has proposed moving its classification in DSM-V from an impulse control disorder to an addiction and related disorders (a new category encompassing both substance- related and non-substance addictions). In the current state of knowledge, especially in the absence of validated diagnostic criteria and prospective, longitudinal studies, it is still prema- ture to consider other behavioral addictions as full-fledged in- dependent disorders, much less classify them all as similar to substance addictions, rather than as impulse control disorders. Substantial future research, including both human and animal studies (101), is needed to bring our knowledge of behavioral addictions to the level of that for substance addictions, espe- cially in the domains of genetics, neurobiology (including brain imaging), and treatment.

ACKNOWLEDGMENTS Supported by the Intramural Research Program, National In-

stitutes of Health, National Institute on Drug Abuse (DAG); NIH (NIDA) grants R01 DA019139 (MNP) and RC1 DA028279 (JEG); and the Minnesota and Yale Centers of Excellence in Gambling Research, which are supported by the National Cen- ter for Responsible Gaming and its Institute for Research on Gambling Disorders. Dr. Weinstein is supported by the Is- rael National Institute for Psychobiology. The contents of the manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the National Cen- ter for Responsible Gaming or the Institute for Research on Gambling Disorders or any of the other funding agencies.

Declaration of Interest All authors reported no conflict of interest regarding the con-

tent of this article. Dr. Grant has received research grants from NIMH, NIDA, National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, and Forest Pharmaceuticals. Dr. Grant receives yearly compensa- tion from Springer Publishing for acting as Editor-in-Chief of

the Journal of Gambling Studies, has performed grant reviews for NIH and the Ontario Gambling Association, has received royalties from Oxford University Press, American Psychiatric Publishing, Inc., Norton Press, and McGraw Hill, has received honoraria from Indiana University Medical School, University of South Florida, the Mayo Medical School, the California So- ciety of Addiction Medicine, the State of Arizona, the State of Massachusetts, the State of Oregon, the Province of Nova Scotia, and the Province of Alberta. Dr. Grant has received compensation as a consultant for law offices on issues related to impulse control disorders. Dr. Potenza has received financial support or compensation for the following: consultant for and an advisor to Boehringer Ingelheim; financial interests in So- maxon; research support from the National Institutes of Health, Department of Veterans Affairs, Mohegan Sun Casino, National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, and Forest Laboratories; has participated in surveys, mailings or telephone consultations re- lated to drug addiction, impulse control disorders, or other health topics; has consulted for law offices on issues related to addic- tions or impulse control disorders; has provided clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program; and has gen- erated books or book chapters for publishers of mental health texts. Dr. Weinstein has received research grants from the Israeli Anti-Drug Authority, the Israel National Institute for Psychobi- ology, the Chief Scientist of the Israeli Ministry of Health, and the Rashi Trust (Paris, France) and fees for lectures on drug addiction from the Israeli Ministry of Education. Dr. Gorelick reports no outside funding or conflicts of interest.

REFERENCES 1. Potenza MN. Should addictive disorders include non-substance-related

conditions? Addiction 2006; 101:142–151. 2. Potenza MN, Koran LM, Pallanti S. The relationship between impulse-

control disorders and obsessive-compulsive disorder: A current under- standing and future research directions. Psychiatry Res 2009; 170:22– 31.

3. Holden C. Behavioral addictions debut in proposed DSM-V. Science 2010; 327:935.

4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., text revision (DSM-IV-TR). Washington, DC: American Psychiatric Publishing, Inc., 2000.

5. Chambers RA, Potenza MN. Neurodevelopment, impulsivity, and adoles- cent gambling. J Gambl Stud 2003; 19:53–84.

6. Slutske WS. Natural recovery and treatment-seeking in pathological gam- bling: Results of two U.S. national surveys. Am J Psychiatry 2006; 163:297–302.

7. Brewer JA, Potenza MN. The neurobiology and genetics of impulse control disorders: relationships to drug addictions. Biochem Pharmacol 2008; 75:63–75.

8. de Castro V, Fong T, Rosenthal RJ, Tavares H. A comparison of craving and emotional states between pathological gamblers and alcoholics. Addict Behav 2007; 32:1555–1564.

9. Blanco C, Moreyra P, Nunes EV, Sáiz-Ruiz J, Ibáñez A. Pathological gambling: addiction or compulsion? Semin Clin Neuropsychiatry 2001; 6:167–176.

BEHAVIORAL ADDICTIONS 239

10. Grant JE, Brewer JA, Potenza MN. The neurobiology of substance and behavioral addictions. CNS Spectr 2006; 11:924–930.

11. Grant JE, Potenza MN. Gender-related differences in individuals seeking treatment for kleptomania. CNS Spectr 2008; 13:235–245.

12. Grant JE, Kim SW. Demographic and clinical features of 131 adult patho- logical gamblers. J Clin Psychiatry 2001; 62:957–962.

13. Potenza MN, Steinberg MA, McLaughlin SD, Wu R, Rounsaville BJ, O’Malley SS. Gender-related differences in the characteristics of problem gamblers using a gambling helpline. Am J Psychiatry 2001; 158:1500–1505.

14. Brady KT, Randall CL. Gender differences in substance use disorders. Psychiatr Clin North Am 1999; 22:241–252.

15. Ledgerwood DM, Weinstock J, Morasco BJ, Petry NM. Clinical features and treatment prognosis of pathological gamblers with and without re- cent gambling-related illegal behavior. J Am Acad Psychiatry Law 2007; 35:294–301.

16. Lejoyeux M, Tassain V, Solomon J, Adès J. Study of compulsive buying in depressed patients. J Clin Psychiatry 1997; 58:169–173.

17. Kim SW, Grant JE. Personality dimensions in pathological gam- bling disorder and obsessive-compulsive disorder. Psychiatry Res 2001; 104:205–212.

18. Grant JE, Kim SW. Temperament and early environmental influences in kleptomania. Compr Psychiatry 2002; 43:223–228.

19. Raymond NC, Coleman E, Miner MH. Psychiatric comorbidity and com- pulsive/impulsive traits in compulsive sexual behavior. Compr Psychiatry 2003; 44:370–380.

20. Kelly TH, Robbins G, Martin CA, Fillmore MT, Lane SD, Harrington NG, Rush CR. Individual differences in drug abuse vulnerability: d- Amphetamine and sensation-seeking status. Psychopharmacology (Berl) 2006; 189:17–25.

21. Tavares H, Gentil V. Pathological gambling and obsessive-compulsive disorder: Towards a spectrum of disorders of volition. Rev Bras Psiquiatr 2007; 29:107–117.

22. Blanco C, Potenza MN, Kim SW, Ibáñez A, Zaninelli R, Saiz-Ruiz J, Grant JE. A pilot study of impulsivity and compulsivity in pathological gambling. Psychiatry Res 2009; 167:161–168.

23. Chamberlain SR, Fineberg NA, Blackwell AD, Robbins TW, Sahakian BJ. Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. Am J Psychiatry 2006; 163:1282–1284.

24. Odlaug BL, Grant JE, Chamberlain SR. Motor inhibition and cognitive flexibility in pathological skin picking. Prog Neuropharm Biol Psych 2010; 34:208–211..

25. Cunningham-Williams RM, Cottler LB, Compton WM 3rd, Spitz- nagel EL. Taking chances: problem gamblers and mental health disorders—Results from the St. Louis Epidemiologic Catchment Area Study. Am J Public Health 1998; 88:1093–1096.

26. Petry NM, Stinson FS, Grant BF. Comorbidity of DSM-IV pathological gambling and other psychiatric disorders: results from the National Epi- demiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2005; 66:564–574.

27. Bland RC, Newman SC, Orn H, Stebelsky G. Epidemiology of patholog- ical gambling in Edmonton. Can J Psychiatry 1993; 38:108–112.

28. el-Guebaly N, Patten SB, Currie S, Williams JV, Beck CA, Maxwell CJ, Wang JL. Epidemiological associations between gambling behavior, substance use & mood and anxiety disorders. J Gambl Stud 2006; 22:275– 287.

29. Welte JW, Barnes GM, Tidwell MC, Hoffman JH. The prevalence of problem gambling among U.S. adolescents and young adults: Results from a national survey. J Gambl Stud 2008; 24:119–133.

30. Yen JY, Ko CH, Yen CF, Chen CS, Chen CC. The association between harmful alcohol use and Internet addiction among college students: Com- parison of personality. Psychiatry Clin Neurosci 2009; 63:218–224.

31. Stinchfield R, Kushner MG, Winters KC. Alcohol use and prior substance abuse treatment in relation to gambling problem severity and gambling treatment outcome. J Gambl Stud 2005; 21:273–297.

32. Duhig AM, Maciejewski PK, Desai RA, Krishnan-Sarin S, Potenza MN. Characteristics of adolescent past-year gamblers and non-gamblers in re- lation to alcohol drinking. Addict Behav 2007; 32:80–89.

33. Grant JE, Potenza MN. Tobacco use and pathological gambling. Ann Clin Psychiatry 2005; 17:237–241.

34. Potenza MN, Steinberg MA, McLaughlin SD, Wu R, Rounsaville BJ, Krishnan-Sarin S, George TP, O’Malley SS. Characteristics of tobacco- smoking problem gamblers calling a gambling helpline. Am J Addict 2004; 13:471–493.

35. Presta S, Marazziti D, Dell’Osso L, Pfanner C, Pallanti S, Cassano GB. Kleptomania: clinical features and comorbidity in an Italian sample. Compr Psychiatry 2002; 43:7–12.

36. Di Nicola M, Tedeschi D, Mazza M, Martinotti G, Harnic D, Catalano V, Bruschi A, Pozzi G, Bria P, Janiri L. Behavioural addictions in bipolar disorder patients: Role of impulsivity and personality dimensions. J Affect Disord 2010; [ePub ahead of print doi:10.1016/j.jad.2009.12.016].

37. Petry NM, Casarella T. Excessive discounting of delayed rewards in sub- stance abusers with gambling problems. Drug Alcohol Depend 1999; 56:25–32.

38. Bechara A. Risky business: emotion, decision-making, and addiction. J Gambl Stud 2003; 19:23–51.

39. Cavedini P, Riboldi G, Keller R, D’Annucci A, Bellodi L. Frontal lobe dysfunction in pathological gambling patients. Biol Psychiatry 2002; 51:334–341.

40. Ko CH, Hsiao S, Liu GC, Yen JU, Yang MJ, Yen CF. The characteristics of decision making, potential to take risks, and personality of college students with Internet addiction. Psychiatry Res 2010; 175:121–125.

41. Goudriaan AE, Oosterlaan J, de Beurs E, Van Den Brink W. Neurocog- nitive functions in pathological gambling: a comparison with alcohol dependence, Tourette syndrome and normal controls. Addiction 2006; 101:534–547.

42. Potenza MN. Review. The neurobiology of pathological gambling and drug addiction: An overview and new findings. Philos Trans R Soc Lond B Biol Sci 2008; 363:3181–3189.

43. Fineberg NA, Potenza MN, Chamberlain SR, Berlin HA, Menzies L, Bechara A, Sahakian BJ, Robbins TW, Bullmore ET, Hollander E. Probing compulsive and impulsive behaviors, from animal models to endopheno- types: A narrative review. Neuropsychopharmacology 2010; 35:591–604.

44. Blanco C, Orensanz-Muñoz L, Blanco-Jerez C, Saiz-Ruiz J. Pathologi- cal gambling and platelet MAO activity: a psychobiological study. Am J Psychiatry 1996; 153:119–121.

45. Hollander E, Kwon J, Weiller F, Cohen L, Stein DJ, DeCaria C, Liebowitz M, Simeon D. Serotonergic function in social phobia: comparison to nor- mal control and obsessive-compulsive disorder subjects. Psychiatry Res 1998; 79:213–217.

46. Dagher A, Robbins TW. Personality, addiction, dopamine: Insights from Parkinson’s disease. Neuron 2009; 61:502–510.

47. O’Sullivan SS, Evans AH, Lees AJ. Dopamine dysregulation syndrome: an overview of its epidemiology, mechanisms and management. CNS Drugs 2009; 23:157–170.

48. Zack M, Poulos CX. Parallel roles for dopamine in pathological gambling and psychostimulant addiction. Curr Drug Abuse Rev 2009; 2:11–25.

49. Potenza MN, Leung HC, Blumberg HP, Peterson BS, Fulbright RK, La- cadie CM, Skudlarski P, Gore JC. An FMRI Stroop task study of ventrome- dial prefrontal cortical function in pathological gamblers. Am J Psychiatry 2003; 160:1990–1994.

50. London ED, Ernst M, Grant S, Bonson K, Weinstein A. Orbitofrontal cortex and human drug abuse: functional imaging. Cereb Cortex 2000; 10:334–342.

51. Ko CH, Liu GC, Hsiao S, Yen JY, Yang MJ, Lin WC, Yen CF, Chen CS. Brain activities associated with gaming urge of online gaming addiction. J Psychiatr Res 2009; 43:739–747.

52. Reuter J, Raedler T, Rose M, Hand I, Gläscher J, Büchel C. Pathological gambling is linked to reduced activation of the mesolimbic reward system. Nat Neurosci 2005; 8:147–148.

240 J. E. GRANT ET AL.

53. Wrase J, Schlagenhauf F, Kienast T, Wüstenberg T, Bermpohl F, Kahnt T, Beck A, Ströhle A, Juckel G, Knutson B, Heinz A. Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics. Neuroimage 2007; 35:787–794.

54. Steeves TD, Miyasaki J, Zurowski M, Lang AE, Pellecchia G, Van Eimeren T, Rusjan P, Houle S, Strafella AP. Increased striatal dopamine release in Parkinsonian patients with pathological gambling: A [11C] raclopride PET study. Brain 2009;132:1376–1385.

55. Bradberry CW. Cocaine sensitization and dopamine mediation of cue effects in rodents, monkeys, and humans: Areas of agreement, disagree- ment, and implications for addiction. Psychopharmacology (Berl) 2007; 191:705–717.

56. Weintraub D, Potenza MN. Impulse control disorders in Parkinson’s dis- ease. Curr Neurol Neurosci Rep 2006; 6:302–306.

57. Voon V, Fernagut P-O, Wickens J, Baunez C, Rodriguez M, Pavon N, Juncos JL, Obeso JA, Bezard E. Chronic dopaminergic stimulaton in Parkinson’s disease: From dyskinesias to impulse control disorders. Lancet Neurol 2009; 8:1140–1149.

58. Voon V, Hassan K, Zurowski M, de Souza M, Thomsen T, Fox S, Lang AE, Miyasaki J. Prevalence of repetitive and reward-seeking behaviors in Parkinson disease. Neurology 2006; 67:1254–1257.

59. Weintraub D, Siderowf AD, Potenza MN, Goveas J, Morales KH, Duda JE, Moberg PJ, Stern MB. Association of dopamine agonist use with impulse control disorders in Parkinson disease. Arch Neurol 2006; 63: 969–973.

60. Zack M, Poulos CX. A D2 antagonist enhances the rewarding and priming effects of a gambling episode in pathological gamblers. Neuropsychophar- macology 2007; 32:1678–1686.

61. Fong T, Kalechstein A, Bernhard B, Rosenthal R, Rugle L. A double- blind, placebo-controlled trial of olanzapine for the treatment of video poker pathological gamblers. Pharmacol Biochem Behav 2008; 89: 298–303.

62. McElroy SL, Nelson EB, Welge JA, Kaehler L, Keck PE Jr. Olanzapine in the treatment of pathological gambling: A negative randomized placebo- controlled trial. J Clin Psychiatry 2008; 69:433–440.

63. Black DW, Monahan PO, Temkit M, Shaw M. A family study of patho- logical gambling. Psychiatry Res 2006; 141:295–303.

64. Grant JE. Family history and psychiatric comorbidity in persons with kleptomania. Compr Psychiatry 2003; 44:437–441.

65. Black DW, Repertinger S, Gaffney GR, Gabel J. Family history and psy- chiatric comorbidity in persons with compulsive buying: Preliminary find- ings. Am J Psychiatry 1998; 155:960–963.

66. Slutske WS, Eisen S, True WR, Lyons MJ, Goldberg J, Tsuang M. Com- mon genetic vulnerability for pathological gambling and alcohol depen- dence in men. Arch Gen Psychiatry 2000; 57:666–673.

67. Tsuang MT, Lyons MJ, Meyer JM, Doyle T, Eisen SA, Goldberg J, True W, Lin N, Toomey R, Eaves L. Co-occurrence of abuse of different drugs in men: The role of drug-specific and shared vulnerabilities. Arch Gen Psychiatry 1998; 55:967–972.

68. Comings DE. Why different rules are required for polygenic inheritance: Lessons from studies of the DRD2 gene. Alcohol 1998; 16:61–70.

69. Hamidovic A, Dlugos A, Skol A, Palmer AA, de Wit H. Evaluation of genetic variability in the dopamine receptor D2 in relation to behavioral inhibition and impulsivity/sensation seeking: An exploratory study with d-amphetamine in healthy participants. Exp Clin Psychopharmacol 2009; 17:374–383.

70. Lee Y, Han D, Yang K, Daniels M, Na C, Kee B, Renshaw P. Depression- like characteristics of 5HTTLPR polymorphism and temperament in ex- cessive internet users. Journal of Affective Disorders 2009; 109:165–169.

71. Petry NM, Ammerman Y, Bohl J, Doersch A, Gay H, Kadden R, Molina C, Steinberg K. Cognitive-behavioral therapy for pathological gamblers. J Consult Clin Psychol 2006; 74:555–567.

72. Teng EJ, Woods DW, Twohig MP. Habit reversal as a treatment for chronic skin picking: a pilot investigation. Behav Modif 2006; 30:411–422.

73. Mitchell JE, Burgard M, Faber R, Crosby RD, de Zwaan M. Cognitive behavioral therapy for compulsive buying disorder. Behav Res Ther 2006; 44:1859–1865.

74. Toneatto T, Dragonetti R. Effectiveness of community-based treatment for problem gambling: A quasi-experimental evaluation of cognitive- behavioral vs. twelve-step therapy. Am J Addict 2008; 17:298–303.

75. Dannon PN, Lowengrub K, Musin E, Gonopolsky Y, Kotler M. 12-month follow-up study of drug treatment in pathological gamblers: A primary outcome study. J Clin Psychopharmacol 2007; 27:620–624.

76. Kim SW, Grant JE, Adson DE, Shin YC. Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling. Biol Psychiatry 2001; 49:914–921.

77. Grant JE, Potenza MN, Hollander E, Cunningham-Williams R, Nurminen T, Smits G, Kallio A. Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling. Am J Psychiatry 2006; 163:303–312.

78. Grant JE, Kim SW, Hartman BK. A double-blind, placebo-controlled study of the opiate antagonist naltrexone in the treatment of pathological gambling urges. J Clin Psychiatry 2008; 69:783–789.

79. Grant JE, Kim SW, Odlaug BL. A double-blind, placebo-controlled trial of the opioid antagonist, naltrexone, in the treatment of kleptomania. Biol Psychiatry 2009; 65:600–606.

80. Grant JE. Three cases of compulsive buying treated with naltrexone. Int J Psychiatr Clin Practice 2003; 7:223–225.

81. Raymond NC, Grant JE, Kim SW, Coleman E. Treatment of compulsive sexual behaviour with naltrexone and serotonin reuptake inhibitors: Two case studies. Int Clin Psychopharmacol 2002; 17:201–205.

82. Bostwick JM, Bucci JA. Internet sex addiction treated with naltrexone. Mayo Clin Proc 2008; 83:226–230.

83. Arnold LM, Auchenbach MB, McElroy SL. Psychogenic excoriation. Clinical features, proposed diagnostic criteria, epidemiology and ap- proaches to treatment. CNS Drugs 2001; 15:351–359.

84. Insel TR, Pickar D. Naloxone administration in obsessive-compulsive disorder: report of two cases. Am J Psychiatry 1983; 140:1219–1220.

85. Roncero C, Rodriguez-Urrutia A, Grau-Lopez L, Casas M. Antiepilectic drugs in the control of the impulses disorders. Actas Esp Psiquiatr 2009; 37:205–212.

86. Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, Beyers K, McKay A, Ait-Daoud N, Anton RF, Ciraulo DA, Kranzler HR, Mann K, O’Malley SS, Swift RM. Topiramate for treating alcohol dependence: a randomized controlled trial. JAMA 2007; 298:1641–1651.

87. Johnson BA, Swift RM, Addolorato G, Ciraulo DA, Myrick H. Safety and efficacy of GABAergic medications for treating alcoholism. Alcohol Clin Exp Res 2005; 29:248–254.

88. Kampman KM, Pettinati H, Lynch KG, Dackis C, Sparkman T, Weigley C, O’Brien, CP. A pilot trial of topiramate for the treatment of cocaine dependence. Drug Alcohol Depend 2004; 75:233–240.

89. Grant JE, Kim SW, Odlaug BL. N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: A pilot study. Biol Psy- chiatry 2007; 62:652–657.

90. LaRowe SD, Myrick H, Hedden S, Mardikian P, Saladin M, McRae A, Brady K, Kalivas PW, Malcolm R. Is cocaine desire reduced by N- acetylcysteine? Am J Psychiatry 2007; 164:1115–1117.

91. Mardikian PN, LaRowe SD, Hedden S, Kalivas PW, Malcolm RJ. An open-label trial of N-acetylcysteine for the treatment of cocaine depen- dence: A pilot study. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31:389–394.

92. Kalivas PW, Hu XT. Exciting inhibition in psychostimulant addiction. Trends Neurosci 2006; 29:610–616.

93. Black DW. Compulsive buying: A review. J Clin Psychiatry 1996; 57:50–54.

94. Ko CH, Yen JY, Chen SH, Yang MJ, Lin HC, Yen CF. Proposed diagnostic criteria and the screening and diagnosing tool of Internet addiction in college students. Compr Psychiatry 2009; 50:378–384.

BEHAVIORAL ADDICTIONS 241

95. Porter G, Starcevic V, Berle D, Fenech P. Recognizing problem video game use. Aust N Z J Psychiatry 2010; 44:120–128.

96. Goodman A. Sexual addiction: Designation and treatment. J Sex Marital Ther 1992; 18:303–314.

97. Hollander E, Wong CM. Body dysmorphic disorder, pathological gam- bling, and sexual compulsions. J Clin Psychiatry 1995; 56:7–12.

98. Lochner C, Stein DJ. Does work on obsessive-compulsive spectrum disorders contribute to understanding the heterogeneity of obsessive- compulsive disorder? Prog Neuropsychopharmacol Biol Psychiatry 2006; 30:353–361.

99. Grant JE. Novel pharmacological targets for reward inhibition in patho- logical gambling. Presented at the Symposium on Translational Studies of

Pathological Gambling at American College of Neuropsychopharmacol- ogy, 48th Annual Meeting, Hollywood, FL, 2009.

100. Lochner C, Hemmings SM, Kinnear CJ, Niehaus DJ, Nel DG, Corfield VA, Moolman-Smook JC, Seedat S, Stein DJ. Cluster analysis of obsessive- compulsive spectrum disorders in patients with obsessive-compulsive dis- order: clinical and genetic correlates. Compr Psychiatry 2005; 46:14–19.

101. Potenza MN. The importance of animal models of decision making, gam- bling, and related behaviors: implications for translational research in addiction. Neuropsychopharmacology 2009; 34:2623–2624.

102. Grant JE. Impulse Control Disorders: A Clinician’s Guide to Understand- ing and Treating Behavioral Addictions. New York, NY: Norton Press, 2008.

content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's

express written permission. However, users may print, download, or email articles for individual use.