Pathological Gambling Subjects Research Articles

Distinct Response Inhibition Patterns in Obsessive Compulsive Disorder Patients and Pathological Gamblers.

Background: Obsessive-compulsive disorder (OCD) and pathological gambling (PG) are common disorders. The cognitive models of OCD and PG focus on abnormalities in response inhibition. Although, these functions have been studied in different PG and OCD samples, no study has compared the response inhibition in both.Methods: Medication-naïve OCD (n = 61) and PG subjects (n = 109) and healthy controls (n = 131) performed CPT and Go/NoGo tasks.Results: Compared to healthy controls (HC), PG and OCD groups underperformed on speed and exhibited larger time variability on the CPT and Go/NoGo task. Only in OCD patients, a positive correlation between omission errors and response time (RT) was observed in the CPT. At the Go/NoGo task, a negative correlation between false alarms and RT (a fast-errors trade-off) was significant only in the PG group. The HC group had greater sensitivity values (d') than the OCD and PG groups in the Go/NoGo task. The PG group displayed lower d' values and more conservative response criterion in the CPT. In addition, only the OCD group expressed a high switching cost compared to both the PG and HC groups in terms of the RT and d' values.Conclusions: Both the PG and OCD groups demonstrated impaired response inhibition compared to the HC group. On several measures, the OCD and PG groups showed comparable impairments, and in others these were distinct. Thus, it appears that distinct neurocognitive patterns are involved in performance of the CPT and the Go/NoGo tasks among OCD and PG subjects whose cognitive status is currently under intensive investigation.

Heterogeneity of Loss Aversion in Pathological Gambling.

Pathological gambling (PG) is characterized by continual repeated gambling behavior despite negative consequences. PG is considered to be a disorder of altered decision-making under risk, and behavioral economics tools were utilized by studies on decision-making under risk. At the same time, PG was suggested to be a heterogeneous disorder in terms of personality traits as well as risk attitude. We aimed to examine the heterogeneity of PG in terms of loss aversion, which means that a loss is subjectively felt to be larger than the same amount of gain. Thirty-one male PG subjects and 26 male healthy control (HC) subjects underwent a behavioral economics task for estimation of loss aversion and personality traits assessment. Although loss aversion in PG subjects was not significantly different from that in HC subjects, distributions of loss aversion differed between PG and HC subjects. HC subjects were uniformly classified into three levels (low, middle, high) of loss aversion, whereas PG subjects were mostly classified into the two extremes, and few PG subjects were classified into the middle range. PG subjects with low and high loss aversion showed a significant difference in anxiety, excitement-seeking and craving intensity. Our study suggested that PG was a heterogeneous disorder in terms of loss aversion. This result might be useful for understanding cognitive and neurobiological mechanisms and the establishment of treatment strategies for PG.

The Relationship Between Stress and Motivation in Pathological Gambling: a Focused Review and Analysis

This article reviews key findings on stress, motivation, and pathological gambling (PG). Environmental and dispositional sources of stress that promote PG are described, along with effects of acute stressors on risk-based decision-making. Gambling itself has stress-like physiological effects, activating norepinephrine (NE), cortisol (CORT), and, in PG subjects, dopamine (DA). Chronic exposure to gambling could evoke neuroadaptations in these systems, and motivation to gamble in PG subjects may partly reflect an effort to restore homeostasis. Alpha-2 NE receptors tonically inhibit, and alpha-1 NE receptors augment, striatal DA release and hypothalamic-pituitary axis-mediated CORT response. Gambling-induced dysregulation of this circuitry, coupled with environmental and dispositional stressors, may lead to allostasis, sensitization, and disturbances in cognitive function that promote further gambling. Interventions that mitigate stress may therefore deter onset and restore control over compulsive motivation to gamble in individuals with PG.

Sociodemographic, neuropsychiatric and cognitive characteristics of pathological gambling and impulse control disorders NOS in Parkinson׳s disease

Despite of previous evidence supporting the association between impulse control disorder (ICD) and several demographic, clinical and therapeutic features in Parkinson׳s disease (PD), the relationships between pathological gambling (PG) or other variants of ICD (ICD-NOS) and specific neuropsychiatric or cognitive domains are not entirely defined.In this study, 155 PD patients without dementia or cognitive impairment underwent: i. the ICD diagnoses, using the Questionnaire for Impulsive–Compulsive Disorders, ii. the mood and anxiety disorders diagnoses, according to the DSM-IV-TR criteria, and iii. a comprehensive battery for measuring severity of psychopathology and neuropsychology domains. Patients were divided in those with pathological gambling (PG), ICDs not otherwise specified (ICD-NOS), or the lack of ICD (No-ICD).There was a progression in age and age at onset from the younger PG subjects throughout ICD-NOS to No-ICD. PG and ICD-NOS subjects had longer disease duration and were taking significantly higher dosages of antiparkinsonian drugs than No-ICD ones. PG subjects had significantly higher severity of depressive and anxious symptoms with respect to the other 2 groups. Both PG and ICD-NOS subjects suffer from increased severity of psychotic symptoms than No-ICD ones. The 3 groups did not differ in any cognitive measure.Our results support the concept that the different sociodemographic and neuropsychiatric profiles of PD patients are associated with different ICDs. Moreover, we clearly demonstrate the lack of relationship between ICD and cognitive performances in undemented PD patients.

OR08-1 * INSULAR ACTIVATION DURING REWARD ANTICIPATION REFLECTS DURATION OF ILLNESS IN ABSTINENT PATHOLOGICAL GAMBLERS

Pathological gambling (PG) is a chronic mental disorder characterized by difficulty inhibiting gambling behavior despite negative consequences. Accumulating evidence suggests that PG has many similarities with substance use disorders. Although brain abnormalities in patients of substance use disorders are facilitated by repetitive drug use and recover partly with drug abstinence, the relationship between brain activity and duration of illness or abstinence of gambling behavior in PG patients remains unclear. Here, using functional magnetic resonance imaging, we compared the brain activity of 23 PG patients recruited from a treatment facility with 27 demographically-matched healthy control subjects during reward anticipation, and examined the correlation between brain activity and duration of illness or abstinence in PG subjects. During reward anticipation, PG patients showed decreased activity compared to healthy controls in a broad range of the reward system regions, including insula and cingulate cortex. In PG patients, activation in left insula was negatively correlated with duration of illness, and showed a modest positive correlation with duration of abstinence. Our findings suggest that insular activation during reward anticipation may serve as a marker of progression and recovery of PG.

Higher volume of ventral striatum and right prefrontal cortex in pathological gambling

Functional neuroimaging studies have implicated an involvement of the prefrontal cortex and mesolimbic reward system (i.e., ventral striatum) in pathological gambling (PG). However, there is a lack of studies focusing on structural changes in frontostriatal brain regions in adult subjects with PG. In order to study differences in local grey matter volume, 20 male subjects with PG and 21 matched controls underwent structural magnetic resonance imaging. Structural brain data were analysed via voxel-based morphometry with a focus on prefrontal areas and ventral striatum. By comparing grey matter volumes in brain regions highly relevant for brain functional changes in PG, the present study found a higher volume in right ventral striatum and right prefrontal cortex by means of voxel-wise morphometry in PG subjects as compared to controls. Our findings demonstrate local grey matter changes in brain areas that have previously been associated with functional changes in PG. Hypertrophy in the prefrontal cortex might be an adaptation at least partly induced by the higher grey matter volume in the ventral striatum and may help to increase cognitive control over gambling impulses. Future research should explore the relationship between functional and structural alterations as well as the course of changes in PG.

Commentary on Boileau et al. (2013): Distinguishing D2/D3 dopaminergic contributions to addictions

Boileau and colleagues address a clinically and scientifically important topic: the role of dopamine D2-like (particularly D2/D3) receptors in pathological gambling (PG) [1]. As the authors note, PG is recommended for reclassification in DSM-5, with a proposed move from the category of ‘Impulse Control Disorders Not Elsewhere Classified’ to one entitled ‘Addiction and Related Disorders’ [2]. This move is supported by epidemiological, phenomenological, clinical, behavioral and biological similarities between substance-use disorders and PG [3,4]. Despite these similarities, it is only recently that investigators have used positron emission tomography (PET) to investigate the neurobiology of PG. Given the importance of dopaminergic projections from the ventral tegmental area to ventral striatum in substance addictions, it was reasonable to hypothesize a similar involvement in PG [5]. The absence of between-group differences in D2/D3 [11C]-raclopride binding is consistent with findings from two other studies of community PG subjects [6,7], although one study suggested a between-group difference (lower binding in PG) among individuals performing less advantageously on the Iowa Gambling Task. Additionally, among Parkinson’s disease patients, those with PG versus those without demonstrated lower [11C]-raclopride binding in the ventral striatum at baseline and greater [11C]-raclopride displacement during a gambling task [8]. Thus, the extent to which D2/D3 receptor availability relates to gambling-related decision-making warrants further consideration. The associations between D3-related [11C]-(+)-PHNO binding and impulsivity and problem-gambling severity in the present study are important. These findings resonate with others, indicating in limbic regions and ventral striatum an inverse correlation in PG between mood-related impulsivity and [11C]-raclopride binding [7] and a positive correlation between problem-gambling severity and [11C]-P943 binding [9]. [11C]-P943 assesses the availability of serotonin 1B receptors, implicated in striatal dopamine regulation and showing increased availability in alcohol-dependent subjects [10]. The impulsivity related findings suggest that this important construct (one that has been linked to addiction risk and addictive disorders) may relate to D3 function in PG, whereas the latter findings suggest that PG severity may link both to aspects of dopamine and serotonin function in the striatum, although conjoint PET imaging of PG subjects using dopaminergic and serotonergic radioligands has yet to be performed to examine their interrelationships. Additionally, as impulsivity has multiple aspects (e.g. relating to response and choice [4]), future studies should examine howfacets of impulsivity relate to neurochemical functioning and addictive processes. The dual radiotracer approach performed here, which used a D3-preferring radioligand ([11C]-(+)-PHNO) [11] and the D2/D3 receptor radioligand ([11C]-raclopride), is a novel aspect of the study and potentially represents an emerging line of research in the molecular imaging field. Given knowledge about regional receptor binding of these radioligands [12,13], the ratios of D3 to D2 receptors and high- to low-affinity D2/D3 receptors were evaluated, as were overall D2 and D3 levels. Although overall binding potentials of either radioligand did not differ between participants with and without PG, this approach demonstrated a positive correlation between D3 receptor density and problem-gambling severity and impulsivity in the PG group. The specificity of the positive finding was facilitated by the dual-receptor approach and prior data demonstrating that 100% of PHNO binding in the substantia nigra relates to D3 receptor binding [13]. Together, the observed range of relationships between clinical features and D2 versus D3 receptor availabilities may help to explain why medications having affinities for D2 and D3 receptors show limited efficacy in the treatment of substance and non-substance addictions [14]. With increasing availability of reliable radioligands for neuroimaging, the dual radioligand approach with PET provides insight into relationships between molecules and behavior. In one study examining both the pre-synaptic serotonin (5-HT) transporter and post-synaptic 5-HT(2A) receptor [15], impulsive aggression was associated with higher brainstem pre-synaptic 5-HT transporter levels and lower post-synaptic 5-HT(2A) levels, implying overactive serotonin release. In another study [16], current ecstasy [3,4-methylenedioxy-N-methylamphetamine (MDMA)] users demonstrated lower 5-HT transporter binding and higher 5-HT(2A) receptor binding in cortical regions, implying that MDMA use leads to damage in 5-HT neuron terminals innervating the cortex. In a third study [17], no differences were found in serotonin transporter or receptor levels between those with and without Asperger’s disorder. In addition to allowing for detailed associations between neurotransmitter systems and behavior, dual radiotracer approaches may provide insight into receptor profiles of antipsychotic [18] and antidepressant [19] medications, yielding more detailed accounts of receptor occupancies in vivo. Thus, the use of more than one radiotracer in a single study to gain detailed information about neurotransmitter systems of known importance is a novel area of research for which the Boileau et al. study is a strong addition to the field of PG. Additionally, using single and dual radioligand PET information in conjunction with other imaging modalities (such as magnetic resonance imaging approaches that investigate volumetric, white matter and functional characteristics), genetic assessments and other clinical information, such as treatment outcome, will help to advance prevention and treatment approaches for PG and substance addictions.

Altered Serum Levels of Brain-Derived Neurotrophic Factor in Patients with Pathological Gambling

Background: Brain-derived neurotrophic factor (BDNF) plays important roles in neurotransmitter release and synaptic plasticity and has been hypothesized to be involved in the development and maintenance of addictive disorders. The objective of this study was to investigate alterations of BDNF expression in a non-substance-related addiction, i.e. pathological gambling (PG). Methods: Serum levels of BDNF were assessed in male patients with PG (n = 14) and healthy control subjects (n = 13) carefully matched for sex, age, body mass index, smoking status and urbanicity. Symptoms and severity of PG were measured by the adapted form of the Yale-Brown Obsessive-Compulsive Scale. Results: BDNF serum levels were significantly increased in patients with PG in comparison to healthy control subjects (p = 0.016). There were no significant correlations between BDNF serum levels and severity of PG or clinical and demographic variables. Conclusions: Our results show alterations of BDNF serum levels in patients suffering from a behavioural addiction and suggest that non-substance-related addictions like PG might be associated with neuroendocrinological changes similar to the changes observed in substance-related addictions.

Do pathological gambling and obsessive-compulsive disorder overlap? a neurocognitive perspective

Pathological gambling (PG) is a severe and persistent pattern of problem gambling that has been aligned with obsessive-compulsive disorder (OCD). However, no study has compared the neurocognitive profiles of individuals with PG and OCD. We compared neurocognitive functioning, including executive function, verbal learning and memory, and visual-spatial organization and memory among 16 pathological gamblers, 31 drug-naïve OCD subjects, and 52 healthy controls. The only neurocognitive marker common to both groups was increased fragmentation errors on the Rey-Osterrieth Complex Figure Test (ROCF). The PG subjects showed increased nonperseverative error on the Wisconsin Card Sorting Test and organization difficulties in the ROCF, whereas the OCD subjects revealed longer response times on the Stroop test and retention difficulties on the immediate recall scale of the ROCF. A more careful approach is required in considering whether PG is a part of the OCD spectrum, as little evidence of neurocognitive overlap between PG and OCD has been reported.

Yohimbine-Induced Amygdala Activation in Pathological Gamblers: A Pilot Study

Rationale and ObjectivesThere is evidence that drug addiction is associated with increased physiological and psychological responses to stress. In this pilot functional magnetic resonance imaging (fMRI) study we assessed whether a prototype behavioral addiction, pathological gambling (PG), is likewise associated with an enhanced response to stress.MethodsWe induced stress by injecting yohimbine (0.2–0.3 mg/kg, IV), an alpha-2 adrenoceptor antagonist that elicits stress-like physiological and psychological effects in humans and in laboratory animals, to four subjects with PG and to five non-gamblers mentally healthy control subjects. Their fMRI brain responses were assessed along with subjective stress and gambling urges ratings.ResultsVoxelwise analyses of data sets from individual subjects, utilizing generalized linear model approach, revealed significant left amygdala activation in response to yohimbine across all PG subjects. This amygdala effect was not observed in the five control individuals. Yohimbine elicited subjective stress ratings in both groups with greater (albeit not statically significantly) average response in the PG subjects. On the other hand, yohimbine did not induce urges to gamble.ConclusionsThe present data support the hypothesis of brain sensitization to pharmacologically-induced stress in PG.

Neural Correlates of Pathological Gamblers Preference for Immediate Rewards During the Iowa Gambling Task: An fMRI Study

The Iowa Gambling Task (IGT) involves exploratory learning via rewards and penalties, where most advantageous task performance requires subjects to forego potential large immediate rewards for small longer-term rewards to avoid larger punishments. Pathological gambling (PG) subjects perform worse on the IGT compared to controls, relating to their persistence at high risk decisions involving the continued choice of potential large immediate rewards despite experiencing larger punishments. We wished to determine if neural processing of risk and reward within striatal and frontal cortex is associated with this behaviour observed in PG. Functional magnetic resonance imaging (fMRI) was used to assess brain activity in response to a computerized version of the IGT. Thirteen male PG subjects with no active comorbidities were compared to 13 demographically matched control subjects. In agreement with previous behavioural studies, PG subjects performed worse on the IGT and made more high-risk choices compared to controls, particularly after experiencing wins and losses. During high-risk gambling decisions, fMRI demonstrated that PG subjects exhibited relatively increased frontal lobe and basal ganglia activation, particularly involving the orbitofrontal cortex (OFC), caudate and amygdala. Increased activation of regions encompassing the extended reward pathway in PG subjects during high risk choices suggests that the persistence of PG may be due to the increased salience of immediate and greater potential monetary rewards relative to lower monetary rewards or potential future losses. Whether this over activation of the reward pathway is associated with the development of PG warrants further investigation.

Serotonin 1B receptor imaging in pathological gambling

Objectives. Although serotonergic mechanisms have been implicated in pathological gambling (PG), no ligand-based imaging studies have assessed serotonin receptors in individuals with PG. Given its role in substance addictions and its abundance in brain regions implicated in PG, we evaluated serotonin 1B receptors (5-HT1BRs) in PG. Methods. Ten medication-free subjects with PG (mean ± SD age = 36.3 ± 9.4 years, nine men) and ten control comparison (CC) subjects (mean ± SD age = 35.8 ± 9.9 years, nine men) underwent [11C]P943 positron emission scanning on a high resolution research tomograph. Results. 5-HT1BR BPND values were similar in PG and CC subjects (P > 0.1). Among PG subjects, scores on the South Oaks Gambling Screen (SOGS) correlated positively with 5-HT1BR BPND values in the ventral striatum (r = 0.66; P = 0.04), putamen (r = 0.67; P = 0.03) and anterior cingulate cortex (r = 0.73; P = 0.02). Conclusions. These findings provide the first evidence that PG severity in humans is linked to increased levels of 5-HT1BRs in regions previously implicated in functional neuroimaging studies of PG. These findings indicate a potential role for serotonergic function in the ventral striatum and anterior cingulate cortex contributing to problem gambling severity and warrant further studies to investigate whether numbers of available 5-HT1BRs might represent a vulnerability factor for PG or develop in relationship to problem gambling.

A Preliminary Study of the Neural Correlates of the Intensities of Self-Reported Gambling Urges and Emotions in Men with Pathological Gambling

Although self-reported gambling urge intensities have clinical utility in the treatment of pathological gambling (PG), prior studies have not investigated their neural correlates. Functional magnetic resonance imaging (fMRI) was conducted while 10 men with PG and 11 control comparison (CON) men viewed videotaped scenarios of gambling, happy or sad content. Participants rated the intensity of their emotions and motivations and reported the qualities of their responses. Relative to the CON group, the PG group reported similar responses to sad and happy scenarios, but stronger emotional responses and gambling urges when viewing the gambling scenarios. Correlations between self-reported responses and brain activations were typically strongest during the period of reported onset of emotional/motivational response and more robust in PG than in CON subjects for all conditions. During this epoch, corresponding with conscious awareness of an emotional/motivational response, subjective ratings of gambling urges in the PG group were negatively correlated with medial prefrontal cortex activation and positively correlated with middle temporal gyrus and temporal pole activations. Sadness ratings in the PG group correlated positively with activation of the medial orbitofrontal cortex, middle temporal gyrus, and retrosplenial cortex, while self-reported happiness during the happy videos demonstrated largely inverse correlations with activations in the temporal poles. Brain areas identified in the PG subjects have been implicated in explicit, self-referential processing and episodic memory. The findings demonstrate different patterns of correlations between subjective measures of emotions and motivations in PG and CON subjects when viewing material of corresponding content, suggesting in PG alterations in the neural correlates underlying experiential aspects of affective processing.

Reduced genual corpus callosal white matter integrity in pathological gambling and its relationship to alcohol abuse or dependence

Objective. Magnetic resonance imaging (MRI) studies have demonstrated functional prefrontal cortical (PFC) abnormalities in pathological gambling (PG) and other psychiatric disorders characterized by impaired impulse control; e.g., cocaine dependence and bipolar disorder. These abnormalities are accompanied by impairments in white matter microstructures in the anterior (genual) corpus callosum (CC) in cocaine dependence and bipolar disorder. Prior studies have not examined white matter integrity in PG. We predicted impairments in genual CC white matter in PG. Methods. Nineteen participants with PG and 19 matched control participants underwent diffusion tensor imaging (DTI) to compare white matter integrity in the CC, as assessed using fractional anisotropy (FA). Results. In PG subjects as compared to control subjects, reduced FA values in the left and right genu of the CC were observed. Multiple regression analyses confirmed that PG status – in addition to age and past alcohol abuse/dependence (AA/AD) – was a significant predictor of genual FA values. Among PG participants, left and right genu FA values were negatively correlated with scores on the Behavioral Activation System Fun-Seeking (BAS-FS) subscale. Limitations. Limitations include a reliance on self-report measures of impulsivity and related constructs and a relatively small sample of PG subjects with past AA/AD. Conclusion. Findings of decreased FA values in the genu of the CC in PG subjects suggest that, like with other disorders of behavioral dyscontrol, white matter microstructural abnormalities contribute to the pathophysiology of PG. These differences appear particularly relevant to individuals with remitted AA/AD, highlighting the importance of considering co-occurring substance use disorders when investigating PG.

Pathological gambling: Relation of skin conductance response to dopaminergic neurotransmission and sensation-seeking

Absent Skin Conductance Response (SCR) in pathological gambling (PG) may relate to dopaminergic mechanisms. We recruited equal numbers of PG subjects and healthy control (HC) subjects, and then tested the claim that SCR is less conditioned by dopaminergic activity in PG subjects. During active gambling, SCR differed in PG and HC subjects (P < 0.05), but positron emission tomography revealed the same dopamine receptor availability. However, highly sensation-seeking (HS) PG subjects had lower dopamine receptor availability (P < 0.0001) in the baseline, compared to normal sensation-seeking (NS) PG subjects. We find that HS versus NS controls had the same observation of significant increase of binding potential ( BP ND ) in high compared to normal sensation seekers. In both groups, PG and HC, highly sensation-seeking subjects had significant increase of receptor availability in striatum, compared to normally sensation-seeking subjects, separately (P < 0.05 and P = 0.02, respectively) and together (P < 0.0005). We conclude that SCR is less conditioned by dopaminergic activity in highly sensation-seeking subjects, regardless of PG status.

Haloperidol modifies instrumental aspects of slot machine gambling in pathological gamblers and healthy controls

Instrumental conditioning has been implicated in persistence at slot machine gambling, but its specific role remains unclear. Dopamine (DA) mediates aspects of instrumental responding, and D2 antagonists reliably alter this process. This study investigated the effects of the preferential D2 antagonist, haloperidol (3 mg) on reward-related betting behavior in 20 subjects with pathological gambling (PG) and 18 healthy controls. Hierarchical regression assessed the prospective relationship between Payoff and Bet Size on consecutive trials, along with potential moderating effects of Cumulative Winnings and Phase of game (early/late) under drug and placebo. Payoff predicted Bet Size on the next trial regardless of other factors, consistent with an instrumental view of slot machine gambling. Under placebo, this correlation varied as a function of Winnings and Phase in PG subjects but was strong and invariant in Controls. Under haloperidol, the Payoff-Bet Size correlation in PG subjects resembled the invariant pattern of Controls under placebo. In contrast, the Payoff-Bet Size correlation rose then fell sharply over trials under haloperidol in controls. The correlation of Payoff with Bet Size is remarkable given that there is no actual contingency between winning and betting, and suggests that reward expectancies largely drive slot machine gambling. By blocking inhibitory D2 receptors, haloperidol may have reversed 'tolerance' to monetary reward mediated by increased tonic DA in PG subjects. Disturbance of the Payoff-Bet Size correlation in controls may reflect indiscriminate reward signaling under haloperidol in subjects with normal DA function. Indirect enhancement of DA transmission may reduce undue reward-related responding in PG subjects.

Parallel Roles for Dopamine in Pathological Gambling and Psychostimulant Addiction

A variety of evidence suggests important commonalities in the neurochemical basis of reinforcement in pathological gambling (PG) and psychostimulant addiction. This article focuses on the parallel and specific roles that dopamine (DA) activation plays in these two disorders, beyond its generic role in reinforcement. A psychostimulant-mimetic model for PG is proposed based on evidence from the following domains: Acute subjective-behavioral effects of gambling and psychostimulants; Effects of anticipated rewards and uncertainty of reward delivery (key elements of gambling) on DA release; Relationship between DA release and positive arousal; Cross-priming of motivation for gambling by amphetamine; Effects of DA D2 antagonists on gambling and amphetamine reward; Effects of mixed D1-D2 antagonists on clinical symptoms of PG; Effects of DA D2 agonists on experimental measures of risk-taking, gambling, and induction of PG in patients with Parkinson's disease; Electrophysiological and cognitive disturbances associated with chronic exposure to gambling and psychostimulants, and the possible role of sensitization in these effects. Limitations of the model regarding the exclusive role of DA are discussed with particular reference to genetic risk, co-morbidity, and sub-types of PG. Suggestions for future research include isolating the roles of DA receptor subtypes in PG, and parallel within-subject assessment of DA manipulations on gambling and psychostimulant reinforcement in PG subjects and controls.

Effects of the atypical stimulant modafinil on a brief gambling episode in pathological gamblers with high vs. low impulsivity

Pathological gambling (PG) is a serious psychiatric disorder afflicting 1-3% of the general population. Experimental evidence indicates shared neurochemical substrates for PG and psychostimulant addiction. Impulsivity characterizes one key subtype of PG. Therefore, medications that ameliorate psychostimulant addiction and impulsive syndromes might also benefit impulsive PG subjects. The atypical stimulant, modafinil reduces cocaine abuse and impulsivity in patients with ADHD. The present study sought to determine if modafinil (200 mg) would reduce the reinforcing effects of slot machine gambling in PG subjects, and if this effect was stronger in high (H-I) vs. low (L-I) impulsivity subjects (N = 20). A placebo-controlled, double-blind, counterbalanced, repeated measures design was employed. Apart from bet size, which declined uniformly in both groups under drug, modafinil had bi-directional effects in the two groups. In H-I subjects, the drug decreased desire to gamble, salience of Gambling words, disinhibition and risky decision-making. In L-I subjects, modafinil increased scores on these indices. Modafinil also differentially affected blood pressure response to the game in the two groups. These findings for modafinil appear to fit well with a growing literature demonstrating bi-directional effects of D2 agonists as a function of trait impulsivity. Impulsivity could critically moderate medication response in PG.

Predicting response to opiate antagonists and placebo in the treatment of pathological gambling

Although opiate antagonists have shown promise in the treatment of pathological gambling (PG), individual responses vary. No studies have systematically examined predictors of medication treatment outcome in PG. Understanding clinical variables related to treatment outcome should help generate treatment algorithms for PG. We sought to identify clinical variables associated with treatment outcome in PG subjects receiving opiate antagonists. Two hundred eighty-four subjects [137 (48.2%) women] with DSM-IV PG were treated in one of two double-blind placebo-controlled trials (16 weeks of nalmefene or 18 weeks of naltrexone). Gambling severity was assessed with the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) with positive response defined as > or =35% reduction in PG-YBOCS score for at least 1 month by study endpoint. Depression, anxiety, and psychosocial functioning were included in stepwise logistic regression analyses designed to identify clinical factors independently associated with treatment response. The clinical variable most strongly associated with a positive response to an opiate antagonist was a positive family history of alcoholism (p = 0.006). Among individuals receiving higher doses of opiate antagonists (i.e., nalmefene 50 or 100 mg/day or naltrexone 100 or 150 mg/day), intensity of gambling urges (PG-YBOCS urge subscale) was associated with a positive response on a trend level (p = 0.036). Among individuals receiving placebo, younger age was associated, on a trend level, with positive treatment outcome (p = 0.012). A family history of alcoholism appears to predict response to an opiate antagonist in PG. Future research is needed to identify specific factors (e.g., genetic) mediating favorable responses.

Late-onset pathological gambling: Clinical correlates and gender differences

Age at illness onset has significant clinical implications for psychiatric disorders. Prior research has not systematically examined age at illness onset and its relationship to the clinical characteristics of pathological gambling (PG). Among a sample of 322 consecutive subjects with current DSM-IV PG, those with late-onset (at or after age 55 years) PG were compared to those with earlier onsets (at or prior to age 25, 26–54 years old) on measures of PG severity, co-occurring disorders, social and legal problems, and family history. Forty-two (13.4%) subjects reported onset of PG at or after age 55 years, 63 (19.6%) reported onset prior to age 25 years, and the majority ( n = 217; 67.4%) reported onset between the ages of 26 and 54 years. The late-onset group were less likely to declare bankruptcy ( p = .029) or have credit card debt attributable to gambling ( p = .006). Late-onset PG subjects were significantly more likely to have an anxiety disorder ( p < .001) and significantly less likely to have a father ( p = .025) or a mother ( p = .048) with a gambling problem. Exploratory analyses identified an age-by-gender interaction with respect to treatment-seeking, with more pronounced age-related shortening in the duration between problem onset and treatment seeking observed in men. Age at onset of PG is associated with multiple important clinical features. Long durations of PG prior to treatment-seeking indicate the need for improved prevention efforts among individuals with early PG onset. Late-onset PG is relatively common and has distinct clinical characteristics suggesting that this population might benefit from unique prevention and treatment strategies.