Sarah W. Yip

Health/functioning characteristics, gambling behaviors, and gambling-related motivations in adolescents stratified by gambling problem severity: findings from a high school survey.

In adults, different levels of gambling problem severity are differentially associated with measures of health and general functioning, gambling behaviors, and gambling-related motivations. Here we present data from a survey of 2,484 Connecticut high school students, and investigate the data stratifying by gambling problem severity based on DSM-IV criteria for pathological gambling. Problem/pathological gambling was associated with a range of negative functions; for example, poor academic performance, substance use, dysphoria/depression, and aggression. These findings suggest a need for improved interventions related to adolescent gambling and a need for additional research into the relationship (eg, mediating factors) between gambling and risk and protective behaviors.

Risk/reward decision-making in schizophrenia: A preliminary examination of the influence of tobacco smoking and relationship to Wisconsin Card Sorting Task performance

BACKGROUND Individuals with schizophrenia show deficits in cognitive functioning, as evidenced by deficits on neurocognitive tasks such as the Wisconsin Card Sorting Task (WCST). Studies of risk/reward decision-making in individuals with schizophrenia have yielded mixed results, and few studies have examined systematically the relationship between these domains and their relationship with clinical factors. METHOD Thirty-two smokers with schizophrenia, ten non-smokers with schizophrenia, nine non-psychiatric non-smokers and ten non-psychiatric smokers were administered computerized versions of the Iowa Gambling Task (IGT) and the WCST. Smokers were allowed to smoke adlibitum during designated breaks in order to prevent deprivation. RESULTS Subjects with schizophrenia performed significantly worse than non-psychiatric controls on both the IGT and the WCST, and performance on these tasks was significantly correlated across subject groups. Among women with schizophrenia, smokers performed significantly better than non-smokers on the IGT. CONCLUSIONS Individuals with schizophrenia perform worse than controls on the IGT, suggesting impairments in risk/reward decision-making. Correlations between IGT and WCST performance suggest a shared element underlying task performance, such as a deficit in set-shifting or perseverance. Further research is needed to establish the relationship between cigarette smoking and IGT performance in schizophrenia.

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

Abstract 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.

Activation of the ventral and dorsal striatum during cue reactivity in Internet gaming disorder.

Studies conducted in drug addiction suggest a transition in processing of drug‐related cues from the ventral to the dorsal component of the striatum. However, this process has not been studied in a behavioral addiction. Assessment of this process in a non‐drug addiction can provide insight into the pathophysiology of both substance and behavioral addictions. Thirty‐nine male Internet gaming disorder (IGD) subjects and 23 male matched healthy controls (HCs) participated in functional magnetic resonance imaging during performance of a cue‐reactivity task involving alternating presentation of Internet gaming‐related stimuli (game cues) and general Internet surfing‐related stimuli (control cues). Cue‐induced neural activations in the ventral and dorsal striatum (DS) were compared between IGD and HC participants. Associations between cue‐reactivity within these regions and cue‐induced craving and severity and duration of IGD were also explored. IGD participants exhibited higher cue‐induced activations within both the ventral and DS when compared with HCs. Within the IGD group, activity within the left ventral striatum (VS) was correlated negatively with cue‐induced craving; positive associations were found between activations within the DS (right putamen, pallidum and left caudate) and duration of IGD. Cue‐induced activity within the left putamen was negatively associated with right VS volumes among IGD participants. Consistent with studies in substance addictions, our results suggest that a transition from ventral to dorsal striatal processing may occur among individuals with IGD, a condition without the impact of substance intake.

Pretreatment measures of brain structure and reward-processing brain function in cannabis dependence: An exploratory study of relationships with abstinence during behavioral treatment1

BACKGROUND Cannabis is widely abused, and efficacies of therapeutics for cannabis dependence remain suboptimal. Magnetic resonance imaging (MRI) may aid in the identification of biological markers for successful treatment outcomes (i.e., abstinence). METHODS Twenty men with cannabis dependence and twenty non-substance-using healthy comparison (HC) men underwent MRI scanning. Cannabis-dependent individuals then participated in a 12-week randomized clinical trial of behavioral treatments (contingency management (CM), cognitive behavioral therapy (CBT) or both). Pretreatment functional and structural data were compared between the cannabis-dependent and HC participants. In addition, individuals with cannabis dependence were subdivided based on the successful achievement of 21 days of consecutive abstinence during treatment to assess whether abstinent versus non-abstinent cannabis-dependent participants displayed different pretreatment functional and structural characteristics when compared to HC participants. RESULTS In comparison to HC participants, cannabis-dependent participants demonstrated greater ventral striatal activation during the receipt of losing outcomes and smaller putamenal volumes. Cannabis-dependent participants who did not subsequently achieve 21 days of consecutive abstinence had increased activity within the striatum during the receipt of losing outcomes, relative to HC participants. Cannabis-dependent participants who did not achieve 21 days of abstinence had decreased bilateral putamen volumes prior to treatment, relative to HC participants. CONCLUSIONS Individual differences in pretreatment striatal function and structure may relate to individual differences in treatment responses for cannabis dependence. While mechanisms underlying these associations require further exploration, the striatum might mediate treatment responses via its role in associative reward-learning (e.g., through skills training in CBT or reinforcement of abstinence in CM).

Treatment of Gambling Disorders

Opinion statementPreclinical and clinical research implicate several neurotransmitter systems in the pathophysiology of gambling disorder (GD). In particular, neurobiological research suggests alterations in serotonergic, dopaminergic, glutamatergic and opioidergic functioning. The relative efficacy of medications targeting these systems remains a topic of ongoing research, and there is currently no Food and Drug Administration (FDA) approved medication with an indication for GD. Considering co-occurring disorders may be particularly important when devising a treatment plan for GD: extant data suggest that the opioid antagonist naltrexone may by the most effective form of current pharmacotherapy for GD, particularly for individuals with a co-occurring substance-use disorder (SUD) or with a family history of alcoholism. In contrast, lithium or other mood stabilizers may be most effective for GD for patients presenting with a co-occurring bipolar spectrum disorder (BSD). Further, serotonin reuptake inhibitors (SRIs) may be efficacious in reducing GD symptoms for individuals also presenting with a (non-BSD) mood or anxiety disorder. Finally, elevated rates of GD (and other impulse control disorders; ICDs) have been noted among individuals with Parkinson’s disease (PD), and clinicians should assess for vulnerability to GD when considering treatment options for PD. Reducing levodopa or dopamine agonist (DA) dosages may partially reduce GD symptoms among patients with co-occurring PD. For GD patients not willing to consider drug treatment, n-acetyl cysteine or behavioral therapies may be effective. Ongoing research into the effectiveness of combined behavioral and pharmacotherapies is being conducted; thus combined treatments should also be considered.

Hypoactivation of the Ventral and Dorsal Striatum During Reward and Loss Anticipation in Antipsychotic and Mood Stabilizer-Naive Bipolar Disorder

Increased activity within known reward-processing neurocircuitry (eg, ventral striatum, VS) has been reported among medicated individuals with bipolar disorder (BD) I and II. However, such findings are confounded by the potential ameliorative effects of mood-stabilizing and antipsychotic medications on neural activations. This study tests the hypothesis that a pathophysiological locus of alterations in reward processing is present within the striatum in antipsychotic and lithium-naive individuals with BD. Twenty antipsychotic and lithium-naive individuals with BD II or BD not-otherwise specified (NOS) and 20 matched healthy comparison individuals participated in functional magnetic resonance imaging during the performance of a monetary incentive delay task. Between-group comparisons were conducted using small-volume correction focusing on orthogonal a priori regions of interest centered in the VS and dorsal striatum (DS), respectively. During reward anticipation, unmedicated individuals with BD II/NOS had decreased activity within the DS (but not VS). During loss anticipation, on the other hand, decreased activation within both the VS and DS was observed. Across all participants, DS activity (during reward anticipation) was positively associated with putamen volume. This is the first report of decreased dorsal and ventral striatal activity among unmedicated individuals with BD II/NOS. These data contradict a simple ‘reward hypersensitivity’ model of BD, and add to a growing body of literature suggesting that blunted reward processing may be a vulnerability factor for both mood- and addiction-related disorders.

Reduced subjective response to acute ethanol administration among young men with a broad bipolar phenotype.

Elevated lifetime prevalence rates of alcohol use disorders (AUDs) are a feature of bipolar disorder (BD). Individuals at-risk for AUDs exhibit blunted subjective responses to alcohol (low levels of response), which may represent a biomarker for AUDs. Thus, individuals at-risk for BD may exhibit low responses to alcohol. Participants were 20 unmedicated adult males who reported high rates of hypomanic experiences (bipolar phenotype participants; BPPs), aged 18 to 21 years, and 20 healthy controls matched on age, gender, IQ, BMI, and weekly alcohol intake. Subjective and pharmacokinetic responses to acute alcohol (0.8 g/kg) vs placebo administration were collected in a randomized, double-blind, cross-over, placebo-controlled, within-subjects design. BPP participants reported significantly lower subjective intoxication effects (‘feel high’: F=14.2, p=0.001; ‘feel effects’: F=8.1, p=0.008) across time, but did not differ in their pharmacokinetic, stimulant, or sedative responses. Paradoxically, however, the BPP participants reported significantly higher expectations of the positive effects of alcohol than controls. Our results suggest that unmedicated young males with previous hypomanic experiences exhibit diminished subjective responses to alcohol. These blunted alcohol responses are not attributable to differences in weekly alcohol intake, pharmacokinetic effects (eg, absorption rates), or familial risk of AUDs. These observations suggest that the dampened intoxication may contribute to the increased rates of alcohol misuse in young people at-risk for BD, and suggest possible shared etiological factors in the development of AUDs and BD.

An Exploratory Study of Clinical Measures Associated with Subsyndromal Pathological Gambling in Patients with Binge Eating Disorder

Both binge eating disorder (BED) and pathological gambling (PG) are characterized by impairments in impulse control. Subsyndromal levels of PG have been associated with measures of adverse health. The nature and significance of PG features in individuals with BED is unknown. Ninety-four patients with BED (28 men and 66 women) were classified by gambling group based on inclusionary criteria for Diagnostic and Statistical Manual-IV (DSM-IV) PG and compared on a range of behavioral, psychological and eating disorder (ED) psychopathology variables. One individual (1.1% of the sample) met criteria for PG, although 18.7% of patients with BED displayed one or more DSM-IV criteria for PG, hereafter referred to as problem gambling features. Men were more likely than women to have problem gambling features. BED patients with problem gambling features were distinguished by lower self-esteem and greater substance problem use. After controlling for gender, findings of reduced self-esteem and increased substance problem use among patients with problem gambling features remained significant. In patients with BED, problem gambling features are associated with a number of heightened clinical problems.

Large-scale functional network overlap is a general property of brain functional organization: Reconciling inconsistent fMRI findings from general-linear-model-based analyses.

Functional magnetic resonance imaging (fMRI) studies regularly use univariate general-linear-model-based analyses (GLM). Their findings are often inconsistent across different studies, perhaps because of several fundamental brain properties including functional heterogeneity, balanced excitation and inhibition (E/I), and sparseness of neuronal activities. These properties stipulate heterogeneous neuronal activities in the same voxels and likely limit the sensitivity and specificity of GLM. This paper selectively reviews findings of histological and electrophysiological studies and fMRI spatial independent component analysis (sICA) and reports new findings by applying sICA to two existing datasets. The extant and new findings consistently demonstrate several novel features of brain functional organization not revealed by GLM. They include overlap of large-scale functional networks (FNs) and their concurrent opposite modulations, and no significant modulations in activity of most FNs across the whole brain during any task conditions. These novel features of brain functional organization are highly consistent with the brains properties of functional heterogeneity, balanced E/I, and sparseness of neuronal activity, and may help reconcile inconsistent GLM findings.