Jon E. Grant

Introduction to Behavioral Addictions

Background: Several behaviors, besides psychoactive substance ingestion, produce short-term reward that may engender persistent behavior, despite knowledge of adverse consequences, i.e., diminished control over the behavior. These disorders have historically 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 particularly relevant to the optimal classification of these disorders in the forthcoming fifth edition of the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Results: Growing evidence suggests that behavioral addictions resemble substance addictions in many domains, including natural history, phenomenology, tolerance, comorbidity, overlapping genetic contribution, neurobiological mechanisms, and response to treatment, supporting the DSM-V Task Force proposed new category of Addiction and Related Disorders encompassing both substance use disorders and non-substance addictions. Current data suggest that this combined category may be appropriate for pathological gambling and a few other better studied behavioral addictions, 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 substantial implications for the development of improved prevention and treatment strategies.

Risk factors for problematic gambling: a critical literature review

This article is a critical review of risk factors for pathological gambling categorized by demographics, physiological and biological factors, cognitive distortions, comorbidity and concurrent symptoms, and personality symptoms and characteristics. There is also a varia section (availability, parents playing, sensory characteristics, schedules of reinforcement, age of onset, and playing duration). The review found very few well established risk factors for pathological gambling (i.e. more than two studies to support the conclusions). Well established risk factors included demographic variables (age, gender), cognitive distortions (erroneous perceptions, illusion of control), sensory characteristics, schedules of reinforcement, comorbid disorders (OCD, drug abuse), and delinquency/illegal acts. An understanding of risk factors for pathological gambling should enhance prevention and treatment approaches.

The neurobiology of substance and behavioral addictions.

Behavioral addictions, such as pathological gambling, kleptomania, pyromania, compulsive buying, and compulsive sexual behavior, represent significant public health concerns and are associated with high rates of psychiatric comorbidity and mortality. Although research into the biology of these behaviors is still in the early stages, recent advances in the understanding of motivation, reward, and addiction have provided insight into the possible pathophysiology of these disorders. Biochemical, functional neuroimaging, genetic studies, and treatment research have suggested a strong neurobiological link between behavioral addictions and substance use disorders. Given the substantial co-occurrence of these groups of disorders, improved understanding of their relationship has important implications not only for further understanding the neurobiology of both categories of disorders but also for improving prevention and treatment strategies.

Atomoxetine Modulates Right Inferior Frontal Activation During Inhibitory Control: A Pharmacological Functional Magnetic Resonance Imaging Study

BACKGROUND Atomoxetine, a selective noradrenaline reuptake inhibitor (SNRI) licensed for the treatment of attention-deficit/hyperactivity disorder (ADHD), has been shown to improve response inhibition in animals, healthy volunteers, and adult patients. However, the mechanisms by which atomoxetine improves inhibitory control have yet to be determined. METHODS The effects of atomoxetine (40 mg) were measured with a stop-signal functional magnetic resonance imaging (fMRI) paradigm in 19 healthy volunteers, in a within-subject, double-blind, placebo-controlled design. RESULTS Atomoxetine improved inhibitory control and increased activation in the right inferior frontal gyrus when volunteers attempted to inhibit their responses (irrespective of success). Plasma levels of drug correlated significantly with right inferior frontal gyrus activation only during successful inhibition. CONCLUSIONS These results show that atomoxetine exerts its beneficial effects on inhibitory control via modulation of right inferior frontal function, with implications for understanding and treating inhibitory dysfunction of ADHD and other disorders.

N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study.

BACKGROUND Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. N-acetyl cysteine (NAC), an amino acid, seems to restore extracellular glutamate concentration in the nucleus accumbens and therefore offers promise in reducing addictive behavior. METHODS Twenty-seven subjects (12 women) with DSM-IV PG were treated in an 8-week open-label trial of NAC with responders (defined as a > or = 30% reduction in Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling [PG-YBOCS] total score at end point) randomized to 6 weeks of double-blind NAC or placebo. RESULTS The PG-YBOCS scores decreased from a mean of 20.3 +/- 4.1 at baseline to 11.8 +/- 9.8 at the end of the open-label phase (p < .001). Sixteen of 27 subjects (59.3%) met responder criteria. The mean effective dose of NAC was 1476.9 +/- 311.3 mg/day. Of 16 responders, 13 entered the double-blind phase. Of those assigned to NAC, 83.3% still met responder criteria at the end of the double-blind phase, compared with only 28.6% of those assigned to placebo. CONCLUSIONS The efficacy of NAC lends support to the hypothesis that pharmacological manipulation of the glutamate system might target core symptoms of reward-seeking addictive behaviors such as gambling. Larger, longer, placebo-controlled double-blind studies are warranted.

Disorders of compulsivity: a common bias towards learning habits

Why do we repeat choices that we know are bad for us? Decision making is characterized by the parallel engagement of two distinct systems, goal-directed and habitual, thought to arise from two computational learning mechanisms, model-based and model-free. The habitual system is a candidate source of pathological fixedness. Using a decision task that measures the contribution to learning of either mechanism, we show a bias towards model-free (habit) acquisition in disorders involving both natural (binge eating) and artificial (methamphetamine) rewards, and obsessive-compulsive disorder. This favoring of model-free learning may underlie the repetitive behaviors that ultimately dominate in these disorders. Further, we show that the habit formation bias is associated with lower gray matter volumes in caudate and medial orbitofrontal cortex. Our findings suggest that the dysfunction in a common neurocomputational mechanism may underlie diverse disorders involving compulsion.

Clinical spectrum of impulse control disorders in Parkinson's disease

Impulse control disorders (ICDs), including compulsive gambling, buying, sexual behavior, and eating, are a serious and increasingly recognized psychiatric complication in Parkinsons disease (PD). Other impulsive‐compulsive behaviors (ICBs) have been described in PD, including punding (stereotyped, repetitive, purposeless behaviors) and dopamine dysregulation syndrome (DDS; compulsive PD medication overuse). ICDs have been most closely related to the use of dopamine agonists (DAs), perhaps more so at higher doses; in contrast, DDS is primarily associated with shorter‐acting, higher‐potency dopaminergic medications, such as apomorphine and levodopa. Possible risk factors for ICDs include male sex, younger age and younger age at PD onset, a pre‐PD history of ICDs, and a personal or family history of substance abuse, bipolar disorder, or gambling problems. Given the paucity of treatment options and potentially serious consequences, it is critical for PD patients to be monitored closely for development of ICDs as part of routine clinical care.

Preliminary validity and reliability testing of a structured clinical interview for pathological gambling

The psychometric properties of a clinician-administered, DSM-IV-based, structured clinical interview for pathological gambling (SCI-PG) were examined. Seventy-two consecutive subjects requesting treatment for gambling problems were administered the SCI-PG. Reliability and validity were determined. Classification accuracy was examined using longitudinal course of illness. The SCI-PG demonstrated excellent inter-rater and test-retest reliability. Concurrent validity was observed with the South Oaks Gambling Screen (SOGS). Discriminant validity was observed with measures of anxiety and depression. The SCI-PG demonstrated both high sensitivity and specificity based on longitudinal assessment. The SCI-PG demonstrated excellent reliability and validity in diagnosing PG in subjects presenting with gambling problems. These findings require replication in other groups to examine their generalizability.

Reliability and Validity of the Pathological Gambling Adaptation of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS)

The Yale Brown Obsessive Compulsive Scale adapted for Pathological Gambling (PG-YBOCS) was developed to measure the severity and change in severity of pathological gambling symptoms. The PG-YBOCS is a 10-item clinician-administered questionnaire that measures the severity of PG over a recent time interval (usually within the past one/two week(s)). In order to assess and validate the scale, it was administered to 337 subjects: 188 pathological gamblers and 149 healthy controls. Internal consistency and correlations between individual items and total score were assessed for various permutations of the sample. Other scales were administered to assess convergent, discriminant and content validity. Sensitivity to change was evaluated in treatment studies with fluovoxamine, lithium, and valproate. Each item was frequently endorsed across a range of severity. Good inter-rater reliability and internal consistency were obtained. The PG-YBOCS showed high validity and reliability for total score, item-total correlations, and for each subscale (Thoughts/Urges and Behavior). PG-YBOCS scores correlated with global severity and South Oaks Gambling Screen (SOGS) scores. The scale was also sensitive to change in pathological gambling severity. PG-YBOCS thus appears to be a reliable and valid measure of pathological gambling severity, and can be regarded as an important tool for clinicians and researchers treating pathological gamblers.

Paroxetine treatment of pathological gambling: a multi-centre randomized controlled trial.

&NA; Previous studies have suggested the efficacy of serotonergic agents in the treatment of pathological gambling. The aim of the present study was to determine whether treatment with paroxetine in a large sample of subjects with pathological gambling would effectively diminish the severity of gambling symptoms. A 16‐week, double‐blind, placebo‐controlled trial was conducted at five outpatient academic research centres in two countries (USA and Spain). Seventy‐six outpatients (mean age 45.4±10.6 years; 30 women, 46 men) with pathological gambling were randomized to acute treatment with paroxetine in flexible daily dosages of 10–60 mg/day (n=36) or placebo (n=40). The primary outcome measure was the Clinical Global Impressions scale. Both the paroxetine‐ and the placebo‐treated groups demonstrated comparable improvement at 16 weeks (59% response rate in the paroxetine group, 49% rate in the placebo group; chi squared=0.737; d.f.=1; P=0.390). Paroxetine consistently resulted in a greater percentage of responders at each study visit compared to placebo but failed to demonstrate statistical superiority to placebo on scores on the Clinical Global Impressions scale, the Yale–Brown Obsessive–Compulsive Scale Modified for Pathological Gambling, or the Gambling Symptom Assessment Scale. High rates of symptom improvement were observed in pathological gamblers receiving either paroxetine or placebo after 16 weeks. Paroxetine consistently demonstrated an advantage over placebo on the Clinical Global Impressions scale; however, a larger sample size may have registered significant differences.