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1.  Changes of Functional MRI Findings in a Patient Whose Pathological Gambling Improved with Fluvoxamine 
Yonsei Medical Journal  2009;50(3):441-444.
Legalized gambling is a growing industry, and is probably a factor in the presently increasing prevalence of pathological gambling. We present a case of a 36-year-old pathological gambler who was treated with fluvoxamine, a selective serotonin reuptake inhibitor, and who was assessed by functional MRI before and after drug administration. During activation periods, the pathological gambler was shown cards as stimuli, and fMRI results in several brain regions showed differential effects before and after medication and a maintenance period. This case demonstrates that the treatment response to fluvoxamine in a pathological gambler was observed not only by subjective self-report, but also by objective fMRI results. Therefore, fMRI may be a useful tool in the diagnosis and prediction of treatment response in patients afflicted with pathological gambling.
doi:10.3349/ymj.2009.50.3.441
PMCID: PMC2703770  PMID: 19568609
Fluvoxamine; functional MRI; pathological gambling
2.  Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study 
Brain : a journal of neurology  2009;132(Pt 5):1376-1385.
Pathological gambling is an impulse control disorder reported in association with dopamine agonists used to treat Parkinson’s disease. Although impulse control disorders are conceptualized as lying within the spectrum of addictions, little neurobiological evidence exists to support this belief. Functional imaging studies have consistently demonstrated abnormalities of dopaminergic function in patients with drug addictions, but to date no study has specifically evaluated dopaminergic function in Parkinson’s disease patients with impulse control disorders. We describe results of a [11C] raclopride positron emission tomography (PET) study comparing dopaminergic function during gambling in Parkinson’s disease patients, with and without pathological gambling, following dopamine agonists. Patients with pathological gambling demonstrated greater decreases in binding potential in the ventral striatum during gambling (13.9%) than control patients (8.1%), likely reflecting greater dopaminergic release. Ventral striatal bindings at baseline during control task were also lower in patients with pathological gambling. Although prior imaging studies suggest that abnormality in dopaminergic binding and dopamine release may be markers of vulnerability to addiction, this study presents the first evidence of these phenomena in pathological gambling. The emergence of pathological gambling in a number of Parkinson’s disease patients may provide a model into the pathophysiology of this disorder.
doi:10.1093/brain/awp054
PMCID: PMC3479148  PMID: 19346328 CAMSID: cams2369
Parkinson’s disease; dopamine; impulse control disorders; pathological gambling; PET; functional imaging
3.  Pathological gambling after bilateral subthalamic nucleus stimulation in Parkinson disease 
We describe a patient with advanced Parkinson's disease who developed pathological gambling within a month after successful bilateral subthalamic nucleus (STN) stimulation. There was no history of gambling. On neuropsychological testing, slight cognitive decline was evident 1 year after surgery. Stimulation of the most dorsal contact with and without medication induced worse performances on decision making tests compared with the more ventral contact. Pathological gambling disappeared after discontinuation of pergolide and changing the stimulation parameters. Pathological gambling does not seem to be associated with decision making but appears to be related to a combination of bilateral STN stimulation and treatment with dopamine agonists.
doi:10.1136/jnnp.2006.102061
PMCID: PMC2117849  PMID: 17210626
4.  Chronic exposure to a gambling-like schedule of reward predictive stimuli can promote sensitization to amphetamine in rats 
Addiction is considered to be a brain disease caused by chronic exposure to drugs. Sensitization of brain dopamine (DA) systems partly mediates this effect. Pathological gambling (PG) is considered to be a behavioral addiction. Therefore, PG may be caused by chronic exposure to gambling. Identifying a gambling-induced sensitization of DA systems would support this possibility. Gambling rewards evoke DA release. One episode of slot machine play shifts the DA response from reward delivery to onset of cues (spinning reels) for reward, in line with temporal difference learning principles. Thus, conditioned stimuli (CS) play a key role in DA responses to gambling. In primates, DA response to a CS is strongest when reward probability is 50%. Under this schedule the CS elicits an expectancy of reward but provides no information about whether it will occur on a given trial. During gambling, a 50% schedule should elicit maximal DA release. This closely matches reward frequency (46%) on a commercial slot machine. DA release can contribute to sensitization, especially for amphetamine. Chronic exposure to a CS that predicts reward 50% of the time could mimic this effect. We tested this hypothesis in three studies with rats. Animals received 15 × 45-min exposures to a CS that predicted reward with a probability of 0, 25, 50, 75, or 100%. The CS was a light; the reward was a 10% sucrose solution. After training, rats received a sensitizing regimen of five separate doses (1 mg/kg) of d-amphetamine. Lastly they received a 0.5 or 1 mg/kg amphetamine challenge prior to a 90-min locomotor activity test. In all three studies the 50% group displayed greater activity than the other groups in response to both challenge doses. Effect sizes were modest but consistent, as reflected by a significant group × rank association (ϕ = 0.986, p = 0.025). Chronic exposure to a gambling-like schedule of reward predictive stimuli can promote sensitization to amphetamine much like exposure to amphetamine itself.
doi:10.3389/fnbeh.2014.00036
PMCID: PMC3920462  PMID: 24574987
pathological gambling; sensitization; amphetamine; dopamine; uncertainty
5.  The four As associated with pathological Parkinson disease gamblers: anxiety, anger, age, and agonists 
Several studies have related pathological gambling in PD to dopamine agonist therapy. A mail-in survey was sent to PD patients seen at the University of Florida Movement Disorders Center to determine gambling frequency and behavior, and any lifestyle or environmental factors associated with compulsive gambling in PD. 462 surveys were sent and 127 completed surveys were returned, of which ten were from patients who met criteria for compulsive gambling. All ten were taking dopamine agonists coincident with the compulsive gambling. Compulsive gamblers were younger, and psychological distress measures revealed that compulsive gamblers exhibited higher levels of anxiety, anger, and confusion. Thus in this cohort, we have uncovered the several characteristics of the most likely PD compulsive gambler, namely: (young) age, “angry”, “anxious”, and using a (dopamine) agonist.
PMCID: PMC2654528  PMID: 19300546
Parkinson; gambling; compulsive behavior; dopamine agonist; anxiety
6.  Dopamine Agonists Diminish Value Sensitivity of the Orbitofrontal Cortex: A Trigger for Pathological Gambling in Parkinson’s Disease? 
The neurobehavioral underpinnings of pathological gambling are not well understood. Insight might be gained by understanding pharmacological effects on the reward system in patients with Parkinson’s disease (PD). Treatment with dopamine agonists (DAs) has been associated with pathological gambling in PD patients. However, how DAs are involved in the development of this form of addiction is unknown. We tested the hypothesis that tonic stimulation of dopamine receptors specifically desensitizes the dopaminergic reward system by preventing decreases in dopaminergic transmission that occurs with negative feedback. Using functional magnetic resonance imaging, we studied PD patients during three sessions of a probabilistic reward task in random order: off medication, after levodopa (LD) treatment, and after an equivalent dose of DA (pramipexole). For each trial, a reward prediction error value was computed using outcome, stake, and probability. Pramipexole specifically changed activity of the orbitofrontal cortex (OFC) in two ways that were both associated with increased risk taking in an out-of-magnet task. Outcome-induced activations were generally higher with pramipexole compared with LD or off medication. In addition, only pramipexole greatly diminished trial-by-trial correlation with reward prediction error values. Further analysis yielded that this resulted mainly from impaired deactivation in trials with negative errors in reward prediction. We propose that DAs prevent pauses in dopamine transmission and thereby impair the negative reinforcing effect of losing. Our findings raise the question of whether pathological gambling may in part stem from an impaired capacity of the OFC to guide behavior when facing negative consequences.
doi:10.1038/sj.npp.npp2009124
PMCID: PMC2972251  PMID: 19741594 CAMSID: cams1534
fMRI; impulse control disorder; dopamine agonist; reward; addiction; reinforcement
7.  Opioidergic and dopaminergic manipulation of gambling tendencies: a preliminary study in male recreational gamblers 
Gambling is characterized by cognitive distortions in the processing of chance and skill that are exacerbated in pathological gambling. Opioid and dopamine dysregulation is implicated in pathological gambling, but it is unclear whether these neurotransmitters modulate gambling distortions. The objective of the current study was to assess the effects of the opioid receptor antagonist naltrexone and the dopamine D2 receptor antagonist haloperidol on gambling behavior. Male recreational gamblers (n = 62) were assigned to receive single oral doses of naltrexone 50 mg, haloperidol 2 mg or placebo, in a parallel-groups design. At 2.5 h post-dosing, participants completed a slot machine task to elicit monetary wins, “near-misses,” and a manipulation of personal choice, and a roulette game to elicit two biases in sequential processing, the gambler's fallacy and the hot hand belief. Psychophysiological responses (electrodermal activity and heart rate) were taken during the slot machine task, and plasma prolactin increase was assessed. The tasks successfully induced the gambling effects of interest. Some of these effects differed across treatment groups, although the direction of effect was not in line with our predictions. Differences were driven by the naltrexone group, which displayed a greater physiological response to wins, and marginally higher confidence ratings on winning streaks. Prolactin levels increased in the naltrexone group, but did not differ between haloperidol and placebo, implying that naltrexone but not haloperidol may have been functionally active at these doses. Our results support opioid modulation of cognition during gambling-like tasks, but did not support the more specific hypothesis that naltrexone may act to ameliorate cognitive distortions.
doi:10.3389/fnbeh.2013.00138
PMCID: PMC3791382  PMID: 24109443
naltrexone; haloperidol; pathological gambling; addiction; reward; motivation; decision-making; psychophysiology
8.  Dopaminergic and Clinical Correlates of Pathological Gambling in Parkinson’s Disease: A Case Report 
Dopaminergic medication for motor symptoms in Parkinson’s disease (PD) recently has been linked with impulse control disorders, including pathological gambling (PG), which affects up to 8% of patients. PG often is considered a behavioral addiction associated with disinhibition, risky decision-making, and altered striatal dopaminergic neurotransmission. Using [11C]raclopride with positron emission tomography, we assessed dopaminergic neurotransmission during Iowa Gambling Task performance. Here we present data from a single patient with PD and concomitant PG. We noted a marked decrease in [11C]raclopride binding in the left ventral striatum upon gambling, indicating a gambling-induced dopamine release. The results imply that PG in PD is associated with a high dose of dopaminergic medication, pronounced motor symptomatology, young age at disease onset, high propensity for sensation seeking, and risky decision-making. Overall, the findings are consistent with the hypothesis of medication-related PG in PD and underscore the importance of taking clinical variables, such as age and personality, into account when patients with PD are medicated, to reduce the risk of PG.
doi:10.3389/fnbeh.2013.00095
PMCID: PMC3725950  PMID: 23908610
Parkinson’s disease; pathological gambling; impulse control disorders; decision-making; dopamine
9.  Gambling Pathology is Associated with Dampened Cortisol Response Among Men and Women 
Physiology & behavior  2009;99(2):230.
Pathological gambling has many similarities to pharmacological addiction. Notably, both pathological gambling and drug addiction are characterized by aberrations in hypothalamic-pituitary-adrenal (HPA) axis responding. As well, there are indications that gender differences may play a role in these processes. Whether gender and/or HPA response are associated with pathological gambling was of interest. Recreational and pathological gamblers (15 men and 6 women per group) had the HPA factor, cortisol, assessed in saliva collected before and after watching a video of their preferred mode of gambling (slot machines, horse race betting, scratch-off tickets, blackjack, video poker, craps, sports betting, online casino games, or lottery tickets), and a video of neutral stimuli (a rollercoaster ride). Basal levels of salivary cortisol did not significantly differ among recreational and pathological gamblers. However, recreational gamblers demonstrated significantly increased salivary cortisol levels after the gambling and rollercoaster videos, whereas pathological gamblers demonstrated no salivary cortisol increase in response to either video stimulus. There was also a non-significant trend for women to have a greater cortisol response to video stimuli compared to men. These data suggest that pathological gambling is associated with hypoactive HPA response to gambling stimuli, similar to chronic drug exposure, and gender may contribute to this effect.
doi:10.1016/j.physbeh.2009.04.002
PMCID: PMC2813972  PMID: 19361537
Addiction; Gender Differences; Hypothalamic-Pituitary-Adrenal Axis; Pathological Gambling; Problem Gambling; Recreational Gambling
10.  Problem gamblers share deficits in impulsive decision-making with alcohol-dependent individuals 
Addiction (Abingdon, England)  2009;104(6):1006-1015.
Aims
Problem gambling has been proposed to represent a ‘behavioural addiction’ that may provide key insights into vulnerability mechanisms underlying addiction in brains that are not affected by the damaging effects of drugs. Our aim was to investigate the neurocognitive profile of problem gambling in comparison with alcohol dependence. We reasoned that shared deficits across the two conditions may reflect underlying vulnerability mechanisms, whereas impairments specific to alcohol dependence may reflect cumulative effects of alcohol consumption.
Design
Cross-sectional study.
Setting
Out-patient addiction treatment centres and university behavioural testing facilities.
Participants
A naturalistic sample of 21 male problem and pathological gamblers, 21 male alcohol-dependent out-patients and 21 healthy male control participants.
Measurements
Neurocognitive battery assessing decision-making, impulsivity and working memory.
Findings
The problem gamblers and alcohol-dependent groups displayed impairments in risky decision-making and cognitive impulsivity relative to controls. Working memory deficits and slowed deliberation times were specific to the alcohol-dependent group.
Conclusions
Gambling and alcohol-dependent groups shared deficits in tasks linked to ventral prefrontal cortical dysfunction. Tasks loading on dorsolateral prefrontal cortex were selectively impaired in the alcohol-dependent group, presumably as a consequence of long-term alcohol use.
doi:10.1111/j.1360-0443.2009.02533.x
PMCID: PMC2773538  PMID: 19466924
Addiction; alcohol; decision-making; impulsivity; pathological gambling; prefrontal cortex; risk-taking; vulnerability
11.  Brain activity and desire for internet video game play 
Comprehensive psychiatry  2011;52(1):88-95.
Objective
Recent studies have suggested that the brain circuitry mediating cue induced desire for video games is similar to that elicited by cues related to drugs and alcohol. We hypothesized that desire for internet video games during cue presentation would activate similar brain regions to those which have been linked with craving for drugs or pathological gambling.
Methods
This study involved the acquisition of diagnostic MRI and fMRI data from 19 healthy male adults (ages 18–23 years) following training and a standardized 10-day period of game play with a specified novel internet video game, “War Rock” (K-network®). Using segments of videotape consisting of five contiguous 90-second segments of alternating resting, matched control and video game-related scenes, desire to play the game was assessed using a seven point visual analogue scale before and after presentation of the videotape.
Results
In responding to internet video game stimuli, compared to neutral control stimuli, significantly greater activity was identified in left inferior frontal gyrus, left parahippocampal gyrus, right and left parietal lobe, right and left thalamus, and right cerebellum (FDR <0.05, p<0.009243). Self-reported desire was positively correlated with the beta values of left inferior frontal gyrus, left parahippocampal gyrus, and right and left thalamus. Compared to the general players, members who played more internet video game (MIGP) cohort showed significantly greater activity in right medial frontal lobe, right and left frontal pre-central gyrus, right parietal post-central gyrus, right parahippocampal gyrus, and left parietal precuneus gyrus. Controlling for total game time, reported desire for the internet video game in the MIGP cohort was positively correlated with activation in right medial frontal lobe and right parahippocampal gyrus.
Discussion
The present findings suggest that cue-induced activation to internet video game stimuli may be similar to that observed during cue presentation in persons with substance dependence or pathological gambling. In particular, cues appear to commonly elicit activity in the dorsolateral prefrontal, orbitofrontal cortex, parahippocampal gyrus, and thalamus.
doi:10.1016/j.comppsych.2010.04.004
PMCID: PMC3039876  PMID: 21220070
internet video game play; functional MRI; frontal cortex; parahippocampal gyrus; thalamus
12.  Pathological Gamblers Discount Probabilistic Rewards Less Steeply than Matched Controls 
Nineteen treatment-seeking men meeting DSM-IV diagnostic criteria for pathological gambling and 19 demographic-matched controls participated. Participants provided demographic information, information about their recent drug-use and gambling activities, and biological samples (to confirm drug abstinence). They also completed the Eysenck Personality Questionnaire, the South Oaks Gambling Screen (SOGS), and two questionnaires designed to separately quantify probability and delay discounting. Pathological gamblers discounted probabilistic rewards significantly less steeply than matched controls. A significant correlation revealed that more shallow probability discounting was associated with higher SOGS scores. Across groups, there was no significant difference in delay discounting, although this difference approached significance when education and ethnicity were included as covariates. These findings, collected for the first time with pathological gamblers, are consistent with previous reports that problem-gambling college students discount probabilistic rewards less steeply than controls. The nature of the relation between probability discounting and severity of problem gambling is deserving of further study.
doi:10.1037/a0016806
PMCID: PMC2855821  PMID: 19803627
probability discounting; pathological gambling; delay discounting; SOGS
13.  Common and unique responses to dopamine agonist therapy and deep brain stimulation in Parkinson’s disease: an H215O PET study 
Brain stimulation  2011;5(4):605-615.
Background
Dopamine agonist therapy and deep brain stimulation (DBS) of the subthalamic nucleus (STN) are antiparkinsonian treatments that act on a different part of the basal ganglia-thalamocortical motor circuitry, yet produce similar symptomatic improvements.
Objective/Hypothesis
The purpose of this study was to identify common and unique brain network features of these standard treatments.
Methods
We analyzed images produced by H215O positron emission tomography (PET) of patients with Parkinson’s disease (PD) at rest. Nine patients were scanned before and after injection of apomorphine, and eleven patients were scanned while bilateral stimulators were off and while they were on.
Results
Both treatments produced common deactivations of the neocortical sensorimotor areas, including the supplementary motor area, precentral gyrus, and postcentral gyrus, and in subcortical structures, including the putamen and cerebellum. We observed concomitant activations of the superior parietal lobule and the midbrain in the region of the substantia nigra/STN. We also detected unique, treatment-specific changes with possible motor-related consequences in the basal ganglia, thalamus, neocortical sensorimotor cortex, and posterolateral cerebellum. Unique changes in non-motor regions may reflect treatment-specific effects on verbal fluency and limbic functions.
Conclusions
Many of the common effects of these treatments are consistent with the standard pathophysiological model of PD. However, the common effects in the cerebellum are not readily explained by the model. Consistent deactivation of the cerebellum is interesting in light of recent reports of synaptic pathways directly connecting the cerebellum and basal ganglia, and may warrant further consideration for incorporation into the model.
doi:10.1016/j.brs.2011.09.002
PMCID: PMC3276692  PMID: 22019080
Parkinson’s disease; deep brain stimulation; apomorphine; positron emission tomography
14.  Frequency of New-Onset Pathologic Compulsive Gambling or Hypersexuality After Drug Treatment of Idiopathic Parkinson Disease 
Mayo Clinic Proceedings  2009;84(4):310-316.
OBJECTIVE: To determine the frequency of new-onset compulsive gambling or hypersexuality among regional patients with Parkinson disease (PD), ascertaining the relationship of these behaviors to PD drug use.
PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients from 7 rural southeastern Minnesota counties who had at least 1 neurology appointment for PD between July 1, 2004, and June 30, 2006. The main outcome measure was compulsive gambling or hypersexuality developing after parkinsonism onset, including the temporal relationship to PD drug use.
RESULTS: Of 267 patients with PD who met the study inclusion criteria, new-onset gambling or hypersexuality was documented in 7 (2.6%). All were among the 66 patients (10.6%) taking a dopamine agonist. Moreover, all 7 (18.4%) were among 38 patients taking therapeutic doses (defined as ≥2 mg of pramipexole or 6 mg of ropinirole daily). Behaviors were clearly pathologic and disabling in 5: 7.6% of all patients taking an agonist and 13.2% of those taking therapeutic doses. Of the 5 patients, 2 had extensive treatment for what was considered a primary psychiatric problem before the agonist connection was recognized.
CONCLUSION: Among the study patients with PD, new-onset compulsive gambling or hypersexuality was documented in 7 (18.4%) of 38 patients taking therapeutic doses of dopamine agonists but was not found among untreated patients, those taking subtherapeutic agonist doses, or those taking carbidopa/levodopa alone. Behaviors abated with discontinuation of agonist therapy or dose reduction. Because this is a retrospective study, cases may have been missed, and hence this study may reflect an underestimation of the true frequency. Physicians who care for patients taking these drugs should recognize the drug's potential to induce pathologic syndromes that sometimes masquerade as primary psychiatric disease.
In patients with Parkinson disease, new-onset compulsive gambling or hypersexuality was documented in 7 of 38 patients taking therapeutic doses of dopamine agonists but was not found among untreated patients, those taking subtherapeutic agonist doses, or those taking carbidopa/levodopa alone.
PMCID: PMC2665974  PMID: 19339647
15.  A Case of Frontotemporal Dementia with Amyotrophic Lateral Sclerosis Presenting with Pathological Gambling 
Background
Pathological gambling (PG), which is characterized by consistent, repetitive gambling and unsuccessful quitting attempts, is classified as an impulse control disorder. PG has also been reported in patients with Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis.
Case Report
A 53-year-old male visited the outpatient clinic due to excessive gambling and personality changes. Based on electrophysiological findings and neuropsychiatric assessment, he was diagnosed as frontotemporal dementia-amyotrophic lateral sclerosis.
Conclusions
This case report underlines that PG can also be seen in patients with neurological disorders involving the orbitofrontal cortex.
doi:10.3988/jcn.2013.9.2.133
PMCID: PMC3633192  PMID: 23626653
frontotemporal dementia; pathological gambling; amyotrophic lateral sclerosis
16.  Characteristics of Treatment Seeking Finnish Pathological Gamblers: Baseline Data from a Treatment Study 
This article describes the socio-demographic characteristics and gambling behavior of 39 pathological gamblers who participated in our treatment study in 2009. The inclusion criteria of the study were: score of five or more on both the South Oaks Gambling Screen (SOGS) and a pathological gambling screen based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The first 39 patients meeting the inclusion criterion were recruited into the study. The average age of the subjects was 39 years, and 80 % were males. The lag-time between active gambling (at least three times per week) and the onset of a pathological gambling problem was short: within 2 years of active gambling, 62 % of the subjects reported having become pathological gamblers. Our results also indicated certain gender-specific differences in the age at initiation and in the severity of the gambling problem.
doi:10.1007/s11469-012-9411-4
PMCID: PMC3663198  PMID: 23710159
SOGS; DSM-IV; Pathological gambling; Gambling
17.  Discounting of probabilistic rewards is associated with gambling abstinence in treatment-seeking pathological gamblers 
Journal of abnormal psychology  2011;121(1):151-159.
Individuals with addictive disorders, including substance abusers and pathological gamblers, discount or devalue rewards delayed in time more than controls. Theoretically, preference for probabilistic rewards is directly related to gambling, but limited empirical research has examined probabilistic discounting in individuals with pathological gambling. This study evaluated probability and delay discounting in treatment-seeking pathological gamblers and their association with gambling treatment outcomes during and following treatment. At time of treatment entry, 226 pathological gamblers completed probability and delay discounting tasks. They were then randomized to one of three treatment conditions, and gambling behavior was measured throughout treatment and at a one-year follow-up assessment. After controlling for possibly confounding variables and treatment condition, more shallow probability discounting was associated with greater reductions in amounts wagered during treatment and likelihood of gambling abstinence at the end of treatment and throughout the follow-up period. No associations were noted between delay discounting and gambling treatment outcomes. These data suggest that probability discounting may be an important construct in understanding pathological gambling and its treatment.
doi:10.1037/a0024782
PMCID: PMC3773696  PMID: 21842965
probability discounting; pathological gambling; treatment
18.  BEHAVIORAL TREATMENT FOR PATHOLOGICAL GAMBLING IN PERSONS WITH ACQUIRED BRAIN INJURY 
The present investigation examined a behavior-analytic clinical treatment package designed to reduce the pathological gambling of 3 individuals with acquired brain injury. A prior history of pathological gambling of each patient was assessed via caregiver report, psychological testing, and direct observation of gambling behavior. Using an 8-week one-on-one client–patient format, a treatment program was developed in which the patient learned about the antecedents, consequences, and motivating operations that controlled the emission of gambling behavior. Data were collected on both self-report of gambling urges and behavior following therapy and during in situ gambling opportunities. The therapy program reduced urges to gamble and actual gambling for all patients. The potential of behavior-analytic therapy for reducing the pathological gambling of patients with and without brain injury is discussed.
doi:10.1901/jaba.2012.45-485
PMCID: PMC3469300  PMID: 23060663
gambling therapy; impulsivity; brain injury; cognitive behavior therapy
19.  A Cross Sectional Study of Problem and Pathological Gambling in Patients with Schizophrenia/Schizoaffective Disorder 
The Journal of clinical psychiatry  2009;70(9):1250-1257.
Background
Community data suggest frequent co-occurrence between schizophrenia/schizoaffective disorder and problem gambling. However, gambling behaviors in large samples of patients with schizophrenia/schizoaffective disorder have not been systematically examined to date.
Methods
A sample of outpatient subjects (n=337) diagnosed with schizophrenia/schizoaffective disorder or schizoaffective disorder and treated in either a VA hospital or a local state mental health center was interviewed in order to examine the prevalence estimates and clinical correlates of problem and pathological gambling. Multinomial logistic regression models investigated clinically relevant measures in recreational or problem/pathological gamblers, as compared to non-gamblers.
Results
Sixty-five participants (19%) met criteria for past-year problem/pathological gambling, with 10% meeting criteria for pathological gambling. Significant correlates of problem and pathological gambling from multivariable models included greater alcohol use severity (p=0.007), higher depression scores (p=0.04), and more outpatient mental health care utilization (p=0.03). Participants with problem/pathological gambling were more likely than recreational gamblers to gamble for excitement, gamble more frequently and heavily, and report either sports or card gambling as favorite.
Conclusions
A substantial proportion of individuals in treatment for psychotic disorders report past-year gambling problems. Patients with co-occurring alcohol use problems and depression may be at particularly high risk. These findings suggest the need for improved prevention and treatment efforts related to problem/pathological gambling in individuals with psychotic disorders.
doi:10.4088/JCP.08m04359
PMCID: PMC3695825  PMID: 19538900
20.  Effects of Acute Pramipexole on Preference for Gambling-like Schedules of Reinforcement in Rats 
Psychopharmacology  2010;213(1):11-18.
Rationale
Pramipexole and other direct dopamine agonist medications have been implicated in the development of impulsive behavior such as pathological gambling among those taking the drug to control symptoms of Parkinson’s disease or restless leg syndrome. Few laboratory studies examining pramipexole’s effects on gambling-like behavior have been conducted.
Objectives
The present study used a rodent model approximating some aspects of human gambling to examine within-subject effects of acute pramipexole (0.03, 0.1, 0.18, & 0.3 mg/kg) on rat’s choices to earn food reinforcement by completing variable-ratio (i.e., gambling-like) or fixed-ratio response requirements.
Results
In a condition in which the variable-ratio alternative was rarely selected, all but the lowest dose of pramipexole significantly increased choice of the variable-ratio alternative (an average of 15% above saline).. The same doses did not affect choice significantly in a control condition designed to evaluate the involvement of nonspecific drug effects. Pramipexole increased latencies to initiate trials (+ 9.12 s) and to begin response runs on forced-choice trials (variable-ratio: + 0.21 s; fixed-ratio: + 0.88 s), but did not affect measures of response perseveration (conditional probabilities of “staying”).
Conclusions
The findings are consistent with clinical reports linking pramipexole to the expression of increased gambling in humans. Results are discussed in the context of neurobehavioral evidence suggesting that dopamine agonists increase sensitivity to reward delay and disrupt appropriate feedback from negative outcomes.
doi:10.1007/s00213-010-2006-5
PMCID: PMC3747984  PMID: 20814781
pramipexole; dopamine agonist; gambling; impulsive behavior; Parkinson’s disease; rat
21.  Parallel Appearance of Compulsive Behaviors and Artistic Creativity in Parkinson's Disease 
Case Reports in Neurology  2012;4(1):77-83.
A 55-year-old male with idiopathic Parkinson's disease developed three behavioral changes under combination therapy with selegiline, cabergoline and levodopa. Co-existent behaviors included severe pathological gambling, punding and novel skills in writing poetry (published poetry books). Brain [18F]fluorodopa PET imaging showed decreased tracer uptake in the striatum contralateral to the predominant motor symptoms, consistent with the clinical diagnosis of Parkinson's disease. Uptake in the ventral striatum was markedly high. Brain MRI before and after behavioral changes showed no pathological findings. The patient was diagnosed as having Parkinson's disease together with DSM-IV criteria-fulfilling pathological gambling and punding-like stereotyped behavior. There are no established criteria for the classification of emerged artistic creativity, although there are descriptions of the phenomenon in the literature. Inspired by the case, we conducted a preliminary survey – including 290 patients with Parkinson's disease – exploring the possible relationship between creativity and impulsive-compulsive behaviors. The case, supported by the results of the survey, adds to the cumulative evidence of the association between dopaminergic medication and enhanced creativity, and suggests a possible linkage between increased artistic creativity and impulsive-compulsive behaviors in Parkinson's disease. Furthermore, it could be speculated that the high mesolimbic dopamine function might relate to the behavioral changes observed in this patient, and is suggestive of the overlapping neurobiological mechanisms of compulsive behaviors and artistic creativity.
doi:10.1159/000338759
PMCID: PMC3369413  PMID: 22679432
Parkinson's disease; Impulse control disorder; Gambling; Punding; Mesolimbic; Dopamine; Ventral striatum; Creativity
22.  Apomorphine reduces subthalamic neuronal entropy in parkinsonian patients 
Experimental neurology  2010;225(2):455-458.
Dopamine depletion in Parkinson's disease (PD) alters the neuronal activity in basal ganglia circuits. Characterizing these changes in network activity is an important step in understanding the disease and how therapies mitigate symptoms. Non-linear analysis methods can complement the traditional description of neuronal firing characteristics. Here we examine the entropy of subthalamic neurons in PD patients undergoing stereotactic surgery for deep brain stimulation (DBS). The activity of 8 neurons was recorded prior to, during, and following systemic administration of the dopamine agonist apomorphine at clinically effective doses. Apomorphine induced a decrease in entropy measured in the inter-spike intervals of subthalamic neurons in 6 of the 8 neurons. This is the first report that anti-parkinsonian drugs affect non-linear features of neuronal firing in the basal ganglia of parkinsonian patients.
doi:10.1016/j.expneurol.2010.07.016
PMCID: PMC2939318  PMID: 20659454
nonlinear; firing pattern; interspike interval
23.  Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach 
Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders.
doi:10.3389/fnhum.2013.00625
PMCID: PMC3784685  PMID: 24098282
fMRI; graph theory; network; connectivity; pathological gambling; reward; behavioral addiction; small world
24.  Longitudinal patterns of gambling activities and associated risk factors in college students 
Addiction (Abingdon, England)  2009;104(7):1219.
Aims
To investigate which clusters of gambling activities exist within a longitudinal study of college health, how membership in gambling clusters change over time and whether particular clusters of gambling are associated with unhealthy risk behaviour.
Design
Four-year longitudinal study (2002–2006).
Setting
Large, public university.
Participants
Undergraduate college students.
Measurements
Ten common gambling activities were measured during 4 consecutive college years (years 1–4). Clusters of gambling activities were examined using latent class analyses. Relations between gambling clusters and gender, Greek membership, alcohol use, drug use, personality indicators of behavioural undercontrol and psychological distress were examined.
Findings
Four latent gambling classes were identified: (1) a low-gambling class, (2) a card gambling class, (3) a casino/slots gambling class and (4) an extensive gambling class. Over the first college years a high probability of transitioning from the low-gambling class and the card gambling class into the casino/slots gambling class was present. Membership in the card, casino/slots and extensive gambling classes were associated with higher scores on alcohol/drug use, novelty seeking and self-identified gambling problems compared to the low-gambling class. The extensive gambling class scored higher than the other gambling classes on risk factors.
Conclusions
Extensive gamblers and card gamblers are at higher risk for problem gambling and other risky health behaviours. Prospective examinations of class membership suggested that being in the extensive and the low gambling classes was highly stable across the 4 years of college.
doi:10.1111/j.1360-0443.2009.02573.x
PMCID: PMC2818490  PMID: 19438422
College student population; gambling; gambling activities; longitudinal; risk factors
25.  Egocentric Social Network Analysis of Pathological Gambling 
Addiction (Abingdon, England)  2012;108(3):584-591.
Aims
To apply social network analysis (SNA) to investigate whether frequency and severity of gambling problems were associated with different network characteristics among friends, family, and co-workers. is an innovative way to look at relationships among individuals; the current study was the first to our knowledge to apply SNA to gambling behaviors.
Design
Egocentric social network analysis was used to formally characterize the relationships between social network characteristics and gambling pathology.
Setting
Laboratory-based questionnaire and interview administration.
Participants
Forty frequent gamblers (22 non-pathological gamblers, 18 pathological gamblers) were recruited from the community.
Findings
The SNA revealed significant social network compositional differences between the two groups: pathological gamblers (PGs) had more gamblers, smokers, and drinkers in their social networks than did nonpathological gamblers (NPGs). PGs had more individuals in their network with whom they personally gambled, smoked, and drank with than those with who were NPG. Network ties were closer to individuals in their networks who gambled, smoked, and drank more frequently. Associations between gambling severity and structural network characteristics were not significant.
Conclusions
Pathological gambling is associated with compositional but not structural differences in social networks. Pathological gamblers differ from non-pathological gamblers in the number of gamblers, smokers, and drinkers in their social networks. Homophily within the networks also indicates that gamblers tend to be closer with other gamblers. This homophily may serve to reinforce addictive behaviors, and may suggest avenues for future study or intervention.
doi:10.1111/add.12014
PMCID: PMC3578111  PMID: 23072641
Pathological gambling; social network analysis; egocentric; alcohol; tobacco

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