Altered Brain Activity during Reward Anticipation in Pathological Gambling and Obsessive-Compulsive Disorder

Background

Pathological gambling (PG) and obsessive-compulsive disorder (OCD) are conceptualized as a behavioral addiction, with a dependency on repetitive gambling behavior and rewarding effects following compulsive behavior, respectively. However, no neuroimaging studies to date have examined reward circuitry during the anticipation phase of reward in PG compared with in OCD while considering repetitive gambling and compulsion as addictive behaviors.

Methods/Principal Findings

To elucidate the neural activities specific to the anticipation phase of reward, we performed event-related functional magnetic resonance imaging (fMRI) in young adults with PG and compared them with those in patients with OCD and healthy controls. Fifteen male patients with PG, 13 patients with OCD, and 15 healthy controls, group-matched for age, gender, and IQ, participated in a monetary incentive delay task during fMRI scanning. Neural activation in the ventromedial caudate nucleus during anticipation of both gain and loss decreased in patients with PG compared with that in patients with OCD and healthy controls. Additionally, reduced activation in the anterior insula during anticipation of loss was observed in patients with PG compared with that in patients with OCD which was intermediate between that in OCD and healthy controls (healthy controls < PG < OCD), and a significant positive correlation between activity in the anterior insula and South Oaks Gambling Screen score was found in patients with PG.

Conclusions

Decreased neural activity in the ventromedial caudate nucleus during anticipation may be a specific neurobiological feature for the pathophysiology of PG, distinguishing it from OCD and healthy controls. Correlation of anterior insular activity during loss anticipation with PG symptoms suggests that patients with PG fit the features of OCD associated with harm avoidance as PG symptoms deteriorate. Our findings have identified functional disparities and similarities between patients with PG and OCD related to the neural responses associated with reward anticipation.     

Increased Functional Connectivity between Prefrontal Cortex and Reward System in Pathological Gambling

Pathological gambling (PG) shares clinical characteristics with substance-use disorders and is thus discussed as a behavioral addiction. Recent neuroimaging studies on PG report functional changes in prefrontal structures and the mesolimbic reward system. While an imbalance between these structures has been related to addictive behavior, whether their dysfunction in PG is reflected in the interaction between them remains unclear. We addressed this question using functional connectivity resting-state fMRI in male subjects with PG and controls. Seed-based functional connectivity was computed using two regions-of-interest, based on the results of a previous voxel-based morphometry study, located in the prefrontal cortex and the mesolimbic reward system (right middle frontal gyrus and right ventral striatum). PG patients demonstrated increased connectivity from the right middle frontal gyrus to the right striatum as compared to controls, which was also positively correlated with nonplanning aspect of impulsiveness, smoking and craving scores in the PG group. Moreover, PG patients demonstrated decreased connectivity from the right middle frontal gyrus to other prefrontal areas as compared to controls. The right ventral striatum demonstrated increased connectivity to the right superior and middle frontal gyrus and left cerebellum in PG patients as compared to controls. The increased connectivity to the cerebellum was positively correlated with smoking in the PG group. Our results provide further evidence for alterations in functional connectivity in PG with increased connectivity between prefrontal regions and the reward system, similar to connectivity changes reported in substance use disorder.     

Neurological Soft Signs in Individuals with Pathological Gambling

Increased neurological soft signs (NSSs) have been found in a number of neuropsychiatric syndromes, including chemical addiction. The present study examined NSSs related to perceptual-motor and visuospatial processing in a behavioral addiction viz., pathological gambling (PG). As compared to mentally healthy individuals, pathological gamblers displayed significantly poorer ability to copy two- and three-dimensional figures, to recognize objects against a background noise, and to orient in space on a road-map test. Results indicated that PG is associated with subtle cerebral cortical abnormalities. Further prospective clinical research is needed to address the NSSs'' origin and chronology (e.g., predate or follow the development of PG) as well as their response to therapeutic interventions and/or their ability to predict such a response.     

Yohimbine-induced amygdala activation in pathological gamblers: a pilot study

Rationale and Objectives

There 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.

Methods

We 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.

Results

Voxelwise 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.

Conclusions

The present data support the hypothesis of brain sensitization to pharmacologically-induced stress in PG.     

Expansion of gambling in Canada: implications for health and social policy

Canada experienced a dramatic increase in legalized gambling in the 1990s, primarily because of governments'' need to increase revenue without additional taxation. This article examines gambling from a public health perspective. The major public health issues include gambling addiction, family dysfunction and gambling by youth. Debates have emerged about the health, social and economic costs and benefits of gambling. Stakeholder and social policy groups have expressed concern about the impact of expanded gambling on the quality of life of individuals, families and communities. Epidemiological studies show that the prevalence of gambling in the general adult population is low but increasing. Of particular concern is the high though steady prevalence of gambling among youth. New technologies have been linked to gambling-related problems such as addiction to gambling by video lottery terminals. Gambling by means of the Internet represents another emerging issue. The article concludes with recommendations for health and social policy related to gambling. These recommendations incorporate a broad public health approach to create a strong research program and to balance risks and benefits.     

Precursor or sequela: pathological disorders in people with Internet addiction disorder

Background

This study aimed to evaluate the roles of pathological disorders in Internet addiction disorder and identify the pathological problems in IAD, as well as explore the mental status of Internet addicts prior to addiction, including the pathological traits that may trigger Internet addiction disorder.

Methods and Findings

59 students were measured by Symptom CheckList-90 before and after they became addicted to the Internet. A comparison of collected data from Symptom Checklist-90 before Internet addiction and the data collected after Internet addiction illustrated the roles of pathological disorders among people with Internet addiction disorder. The obsessive-compulsive dimension was found abnormal before they became addicted to the Internet. After their addiction, significantly higher scores were observed for dimensions on depression, anxiety, hostility, interpersonal sensitivity, and psychoticism, suggesting that these were outcomes of Internet addiction disorder. Dimensions on somatisation, paranoid ideation, and phobic anxiety did not change during the study period, signifying that these dimensions are not related to Internet addiction disorder.

Conclusions

We can not find a solid pathological predictor for Internet addiction disorder. Internet addiction disorder may bring some pathological problems to the addicts in some ways.     

Focus: Addiction: Case Report: Internet Gaming Disorder Associated With Pornography Use

Internet gaming disorder (IGD) is not currently a recognized diagnosis in the Diagnostic and Statistical Manual for Mental Disorders-5 (DSM-5). However, IGD has been noted to warrant further research for possible future inclusion in the DSM. In many ways, IGD strongly resembles substance and gambling addictions. Such characteristics include tolerance, withdrawal, and social and occupational neglect resulting from increased time invested in video game use and acquisition. The use of similar or closely related media is also seen, which mirrors the natural course of substance and gambling addictions. We present a case of a 22-year-old man who exhibited IGD and problems associated with pornography use. This case report exemplifies the sequelae of IGD. Our paper also reviews the possible mechanisms of behavioral addiction, as well as the status of IGD as a potential subcategory of behavioral addiction. Additional research is needed to determine if IGD co-occurs with problematic use of pornography.     

Abnormal Spontaneous Neural Activity in Obsessive-Compulsive Disorder: A Resting-State Functional Magnetic Resonance Imaging Study

Neuroimaging studies of obsessive-compulsive disorder have found abnormalities in orbitofronto-striato-thalamic circuitry, including the orbitofrontal cortex, anterior cingulate cortex, caudate, and thalamus, but few studies have explored abnormal intrinsic or spontaneous brain activity in the resting state. We investigated both intra- and inter-regional synchronized activity in twenty patients with obsessive-compulsive disorder and 20 healthy controls using resting-state functional magnetic resonance imaging. Regional homogeneity (ReHo) and functional connectivity methods were used to analyze the intra- and inter-regional synchronized activity, respectively. Compared with healthy controls, patients with obsessive-compulsive disorder showed significantly increased ReHo in the orbitofrontal cortex, cerebellum, and insula, and decreased ReHo in the ventral anterior cingulate cortex, caudate, and inferior occipital cortex. Based on ReHo results, we determined functional connectivity differences between the orbitofrontal cortex and other brain regions in both patients with obsessive-compulsive disorder and controls. We found abnormal functional connectivity between the orbitofrontal cortex and ventral anterior cingulate cortex in patients with obsessive-compulsive disorder compared with healthy controls. Moreover, ReHo in the orbitofrontal cortex was correlated with the duration of obsessive-compulsive disorder. These findings suggest that increased intra- and inter-regional synchronized activity in the orbitofrontal cortex may have a key role in the pathology of obsessive-compulsive disorder. In addition to orbitofronto-striato-thalamic circuitry, brain regions such as the insula and cerebellum may also be involved in the pathophysiology of obsessive-compulsive disorder.     

Psychophysiology of sports addictions (exercise addiction)

Addictive behavior is an attempt to escape real life by means of artificial changing one’s own psychical state by taking drugs or performing certain activities. Depending on the means of the escape, pharmacological or chemical and nonchemical or behavioral addictions may be distinguished. During recent years, researchers focused their attention on nonchemical addictions, in which a behavioral pattern becomes an object of dependence instead of a psychoactive substance. In Russia, the first classification of nonchemical addictions was suggested by Korolenko. He pointed out direct nonchemical addictions, such as gambling, addiction of relationships between individuals, sexual and love addiction, avoidance addiction, ergomania, overspending addiction, and urgent addiction and intermediate addictions, including eating addiction, i.e., either overeating or starvation, which involve biochemical mechanisms. In addition to the above-mentioned types of addictions, a substantial number of other nonchemical addictions have been described. Some of them are various dependences on computers or the Internet, addiction to exercises or sports, and others.     

Diagnostic Criteria for Problematic Internet Use among U.S. University Students: A Mixed-Methods Evaluation

Empirical studies have identified increasing rates of problematic Internet use worldwide and a host of related negative consequences. However, researchers disagree as to whether problematic Internet use is a subtype of behavioral addiction. Thus, there are not yet widely accepted and validated diagnostic criteria for problematic Internet use. To address this gap, we used mixed-methods to examine the extent to which signs and symptoms of problematic Internet use mirror DSM-5 diagnostic criteria for substance use disorder, gambling disorder, and Internet gaming disorder. A total of 27 university students, who self-identified as intensive Internet users and who reported Internet-use-associated health and/or psychosocial problems were recruited. Students completed two measures that assess problematic Internet use (Young’s Diagnostic Questionnaire and the Compulsive Internet Use Scale) and participated in focus groups exploring their experiences with problematic Internet use. Results of standardized measures and focus group discussions indicated substantial overlap between students’ experiences of problematic Internet use and the signs and symptoms reflected in the DSM-5 criteria for substance use disorder, gambling disorder, and Internet gaming disorder. These signs and symptoms included: a) use Internet longer than intended, b) preoccupation with the Internet, c) withdrawal symptoms when unable to access the Internet, d) unsuccessful attempts to stop or reduce Internet use, e) craving, f) loss of interest in hobbies or activities other than the Internet, g) excessive Internet use despite the knowledge of related problems, g) use of the Internet to escape or relieve a negative mood, and h) lying about Internet use. Tolerance, withdrawal symptoms, and recurrent Internet use in hazardous situations were uniquely manifested in the context of problematic Internet use. Implications for research and practice are discussed.     

Evidence for a Shared Etiological Mechanism of Psychotic Symptoms and Obsessive-Compulsive Symptoms in Patients with Psychotic Disorders and Their Siblings

The prevalence of obsessive-compulsive disorder in subjects with psychotic disorder is much higher than in the general population. The higher than chance co-occurrence has also been demonstrated at the level of subclinical expression of both phenotypes. Both extended phenotypes have been shown to cluster in families. However, little is known about the origins of their elevated co-occurrence. In the present study, evidence for a shared etiological mechanism was investigated in 3 samples with decreasing levels of familial psychosis liability: 987 patients, 973 of their unaffected siblings and 566 healthy controls. The association between the obsessive-compulsive phenotype and the psychosis phenotype c.q. psychosis liability was investigated. First, the association was assessed between (subclinical) obsessive-compulsive symptoms and psychosis liability. Second, in a cross-sib cross-trait analysis, it was examined whether (subclinical) obsessive-compulsive symptoms in the patient were associated with (subclinical) psychotic symptoms in the related unaffected sibling. Evidence was found for both associations, which is compatible with a partially shared etiological pathway underlying obsessive-compulsive and psychotic disorder. This is the first study that used a cross-sib cross-trait design in patients and unaffected siblings, thus circumventing confounding by disease-related factors present in clinical samples.     

Addiction,Heroin‐Assisted Treatment and the Idea of Abstinence: A reply to Henden

In our previous article on the question whether heroin addicts are able to give informed consent voluntarily to research on heroin‐assisted treatment, we criticized the ongoing bioethical discussion of a flawed conceptualization of heroin addicts' options. As a participant in this discussion, Edmund Henden defends the conceptualization as sufficient for determining whether heroin addicts are able to give informed consent to the research on heroin‐assisted treatment voluntarily. This discussion on research on heroin‐assisted treatment seems to go astray in several respects. In his reply to our article Henden maintains some of the biases, such as the necessity of abstinence in recovery, that seem to prevail in addiction research on a more general level as well. These biases run the danger of having implausible ethical implications on stakeholders in addiction research and treatment. In our reply to him, we will further clarify and discuss the importance of describing the relevant issues in plausible terms that do justice to the realities of the cases of informed consent in research on heroin‐assisted treatment and also raise a wider issue of the ethics of wording as well as of the narrow scope, or ‘tunnel vision’, in addiction research as currently conducted.     

Neurobiology of obsessive-compulsive disorder: insights into neural circuitry dysfunction through mouse genetics

The precise causal factors for obsessive-compulsive disorder (OCD) are not known, although, decades of research have honed in on the cortico-striatal-thalamo-cortical (CSTC) circuitry in the brain as a critical pathway involved in obsessions and the intimately linked compulsive-repetitive behaviors. Recent progress in human and mouse genetics have led to the identification of novel candidate susceptibility genes, which in turn have facilitated a more focused approach to unraveling the nature of circuitry dysfunction in OCD. The ability to perform invasive techniques in genetic animal models of OCD will be crucial for rapid advances in this field, and as such we review the most recent developments and highlight the importance of searching out common circuitry defects underlying compulsive-repetitive behaviors.     

Time Devours Things: How Impulsivity and Time Affect Temporal Decisions in Pathological Gamblers

Impulsivity is associated with several psychiatric disorders in which the loss of control of a specific behavior determines the syndrome itself. One particularly interesting population characterized by reported high impulsivity and problematic decision-making are those diagnosed with pathological gambling. However the association between impulsivity and decision making in pathological gambling has been only partially confirmed until now. We tested 23 normal controls and 23 diagnosed pathological gamblers in an intertemporal choice task, as well as other personality trait measurements. Results showed that gamblers scored higher on impulsivity questionnaires, and selected a higher percentage of impatient choices (higher percentage of smaller, sooner rewards), when compared to normal controls. Moreover, gamblers were faster in terms of reaction times at selecting the smaller, sooner options and discounted rewards more rapidly over time. Importantly, regression analyses clarified that self-reported measures of impulsivity played a significant role in biasing decisions towards small but more rapidly available rewards. In the present study we found evidence for impulsivity in personality traits and decisions in pathological gamblers relative to controls. We conclude by speculating on the need to incorporate impulsivity and decision biases in the conceptualization of pathological gambling for a better understanding and treatment of this pathology.     

The Impact of Selective Dopamine D2, D3 and D4 Ligands on the Rat Gambling Task

Gambling is an addictive disorder with serious societal and personal costs. To-date, there are no approved pharmacological treatments for gambling disorder. Evidence suggests a role for dopamine in gambling disorder and thus may provide a therapeutic target. The present study therefore aimed to investigate the effects of selective antagonists and agonists of D2, D3 and D4 receptors in a rodent analogue of the Iowa gambling task used clinically. In this rat gambling task (rGT), animals are trained to associate different response holes with different magnitudes and probabilities of food pellet rewards and punishing time-out periods. As in the Iowa gambling task, the optimal strategy is to avoid the tempting high-risk high-reward options, and instead favor those linked to smaller per-trial rewards but also lower punishments, thereby maximizing the amount of reward earned over time. Administration of those selective ligands did not affect decision making under the rGT. Only the D4 drug had modest effects on latency measures suggesting that D4 may contribute in some ways to decision making under this task.     

Review. Neurobiological mechanisms for opponent motivational processes in addiction

The conceptualization of drug addiction as a compulsive disorder with excessive drug intake and loss of control over intake requires motivational mechanisms. Opponent process as a motivational theory for the negative reinforcement of drug dependence has long required a neurobiological explanation. Key neurochemical elements involved in reward and stress within basal forebrain structures involving the ventral striatum and extended amygdala are hypothesized to be dysregulated in addiction to convey the opponent motivational processes that drive dependence. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission such as dopamine and opioid peptides in the ventral striatum, but also recruitment of brain stress systems such as corticotropin-releasing factor (CRF), noradrenaline and dynorphin in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, anxiety-like responses and extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence and to contribute to stress-induced relapse. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for the long hypothesized opponent motivational processes responsible for the negative reinforcement driving addiction.     

Lack of Association between Oxytocin Receptor (OXTR) Gene Polymorphisms and Alexithymia: Evidence from Patients with Obsessive-Compulsive Disorder

Oxytocin receptor gene single nucleotide polymorphisms have been associated with structural and functional alterations in brain regions, which involve social-emotional processing. Therefore, oxytocin receptor gene polymorphisms may contribute to individual differences in alexithymia, which is considered to be a dysfunction of emotional processing. The aim of this study was to evaluate the association between oxytocin receptor gene single nucleotide polymorphisms or haplotypes and alexithymia in patients with obsessive-compulsive disorder. We recruited 355 patients with obsessive-compulsive disorder (234 men, 121 women). Alexithymia was measured by using the Toronto Alexithymia Scale. We performed single-marker and haplotype association analyses with eight single nucleotide polymorphisms (rs237885, rs237887, rs2268490, rs4686301, rs2254298, rs13316193, rs53576, and rs2268498) in the oxytocin receptor gene. There were no significant associations between any of the eight single nucleotide polymorphism of the oxytocin receptor gene and alexithymia. In addition, a six-locus haplotype block (rs237885-rs237887-rs2268490-rs4686301-rs2254298-rs13316193) was not significantly associated with alexithymia. These findings suggest that genetic variations in the oxytocin receptor gene may not explain a significant part of alexithymia in patients with obsessive-compulsive disorder.     

Machines, Medication, Modulation: Circuits Of Dependency And Self-Care In Las Vegas

The intensive entertainment infrastructure of Las Vegas is overlaid with a robust therapeutic network for those who become addicted to its technologies. Although the objectives of gambling machines and addiction therapeutics are seemingly at odds—the first work to encourage play, the second to stop it—both gear their interventions around a model of the self as a continuum of behavioral potentials that can be externally modulated. For compulsive gamblers implicated in this circuit of modulation, pharmaceutical drugs that have been prescribed to dampen cravings for machine play sometimes function as intensifiers of its effects. Caught in an intractable play between technologies of harm and technologies of care, recovering gambling addicts are challenged to assemble a technical array through which they can maintain balance; health itself, for these individuals, becomes a state of managed dependency. This essay explores the shifting terms and changing stakes of subjectivity and health in the contemporary United States by way of ethnographic research on compulsive gamblers who live and work in Las Vegas. The analysis draws on interviews with gamblers as well as on observations in local self-help groups, directed group therapy sessions, and chat rooms of Internet recovery Web sites.     

Tourette's disorder and associated complex behaviors: a case report

A case of a man with Tourette's disorder associated with obsessive-compulsive disorder, multiple sexual paraphilias, and aggressive behavior is described. Treatment with haloperidol led to improvement in the characteristic tics of Tourette's disorder as well as to improvement in these three complex-associated behaviors. After haloperidol was discontinued, an exacerbation of tics and the associated behaviors occurred.     

Disgust implicated in obsessive-compulsive disorder.

Psychiatric classificatory systems consider obsessions and compulsions as forms of anxiety disorder. However, the neurology of diseases associated with obsessive-compulsive symptoms suggests the involvement of fronto-striatal regions likely to be involved in the mediation of the emotion of disgust, suggesting that dysfunctions of disgust should be considered alongside anxiety in the pathogenesis of obsessive-compulsive behaviours. We therefore tested recognition of facial expressions of basic emotions (including disgust) by groups of participants with obsessive-compulsive disorder (OCD) and with Gilles de la Tourette''s syndrome (GTS) with an without co-present obsessive-compulsive behaviours (GTS with OCB; GTS without OCB). A group of people suffering from panic disorder and generalized anxiety were also included in the study. Both groups with obsessive-compulsive symptoms (OCD; GTS with OCB) showed impaired recognition of facial expressions of disgust. Such problems were not evident in participants with panic disorder and generalized anxiety, or for participants with GTS without obsessions or compulsions, indicating that the deficit is closely related to the presence of obsessive-compulsive symptoms. Participants with OCD were able to assign words to emotion categories without difficulty, showing that their problem with disgust is linked to a failure to recognize this emotion in others and not a comprehension or response criterion effect. Impaired recognition of disgust is consistent with the neurology of OCD and with the idea that abnormal experience of disgust may be involved in the genesis of obsessions and compulsions.