Brian L. Odlaug

Pharmacological treatments in pathological gambling

Pathological gambling (PG) is a relatively common and often disabling psychiatric condition characterized by intrusive urges to engage in deleterious gambling behaviour. Although common and financially devastating to individuals and families, there currently exist no formally approved pharmacotherapeutic interventions for this disorder. This review seeks to examine the history of medication treatments for PG. A systematic review of the 18 double‐blind, placebo‐controlled pharmacotherapy studies conducted for the treatment of pathological gambling was conducted. Study outcome and the mean dose of medication administered was documented in an effort to determine a preferred medication choice in this population. A variety of medication classes have been examined in the treatment of PG with varying results. Antidepressants, atypical antipsychotics and mood stabilizers have demonstrated mixed results in controlled clinical trials. Although limited information is available, opioid antagonists and glutamatergic agents have demonstrated efficacious outcomes, especially for individuals with PG suffering from intense urges to engage in the behaviour. Given that several studies have demonstrated their efficacy in treating the symptoms associated with PG, opioid antagonists should be considered the first line treatment for PG at this time. Most published studies, however, have employed relatively small sample sizes, are of limited duration and involve possibly non‐representative clinical groups (e.g. those without co‐occurring psychiatric disorders). Response measures have varied across studies. Heterogeneity of PG treatment samples may also complicate identification of effective treatments. Identification of factors related to treatment response will help inform future studies and advance treatment strategies for PG.

Problematic Internet use and associated risks in a college sample.

OBJECTIVEnThe Internet is commonly used among young adults; however, Internet use may become a problematic behavior. Past research has examined Internet behavior in young adults and its relationship to other behaviors and health issues, yet further research is needed to gain a more comprehensive understanding of this relationship.nnnMETHODnA sample (n=2108) of college students (56.9% female) was examined using a self-report Internet survey concerning demographic characteristics, Internet use, health behaviors, psychosocial functioning, and psychiatric comorbidities. The IAT was used to determine levels of problematic Internet use (limited use (none or almost no use), mild use (typical user), moderate use (occasional problems) and severe use (frequent, serious problems)) and the MINI for testing for psychiatric problems.nnnRESULTSnWe found that 237 students (12.9%) met criteria for limited Internet use, 1502 (81.8%) for mild Internet use and 98 (5.3%) for moderate to severe Internet use. Variables significantly associated with greater frequency of Internet use included lower Grade Point Average (p=.006), less frequent exercise (p=.018), higher PHQ-9 scores (p<.0001) (indicative of greater depression symptoms) and higher Perceived Stress Scores (p<.0001).nnnCONCLUSIONSnThese data indicate that moderate to severe Internet use is associated with a range of psychosocial problems in young adults. More research is needed to better understand the relationship between Internet use and physical and mental health, as well as academic variables.

The opiate antagonist, naltrexone, in the treatment of trichotillomania: Results of a double-blind, placebo-controlled study

Abstract Trichotillomania (TTM) is characterized by repetitive hair pulling resulting in hair loss. Data on the pharmacological treatment of TTM are limited. This study examined the opioid antagonist, naltrexone, in adults with TTM who had urges to pull their hair. Fifty-one individuals with TTM were randomized to naltrexone or placebo in an 8-week, double-blind trial. Subjects were assessed with measures of TTM severity and selected cognitive tasks. Naltrexone failed to demonstrate significantly greater reductions in hair pulling compared to placebo. Cognitive flexibility, however, significantly improved with naltrexone (P = 0.026). Subjects taking naltrexone with a family history of addiction showed a greater numerical reduction in the urges to pull, although it was not statistically significant. Future studies will have to examine whether pharmacological modulation of the opiate system may provide promise in controlling pulling behavior in a subgroup of individuals with TTM.

A randomized, placebo-controlled trial of N-acetylcysteine plus imaginal desensitization for nicotine-dependent pathological gamblers

OBJECTIVEnPathological gambling is associated with elevated proportions of nicotine dependence, and tobacco smoking in pathological gamblers has been associated with increased problem-gambling severity. This study examined the addition of N-acetylcysteine to imaginal desensitization in adults with co-occurring nicotine dependence and pathological gambling.nnnMETHODnTwenty-eight individuals with co-occurring DSM-IV nicotine dependence and pathological gambling who were receiving behavioral therapy were recruited from December 2009 to February 2012 and randomized to augmentation with N-acetylcysteine or placebo in an 12-week, double-blind trial. Subjects were assessed with measures of nicotine and gambling severity and followed for 3 months after treatment. The primary outcomes were the Fagerström Test for Nicotine Dependence and the pathological gambling adaptation of the Yale-Brown Obsessive-Compulsive Scale.nnnRESULTSnDuring the first 6 weeks, there was a significant benefit of N-acetylcysteine treatment versus placebo on Fagerström Test for Nicotine Dependence total scores (t = -2.224; P = .031). After the initial 6 weeks, all subjects significantly (P < .001) benefited from imaginal desensitization. During the 3-month follow-up, there was a significant additional benefit for N-acetylcysteine versus placebo on measures of problem-gambling severity (t = 2.069; P = .043).nnnCONCLUSIONSnN-acetylcysteine treatment during therapy facilitates long-term application of behavioral therapy techniques once patients are in the community after therapy has been completed.nnnTRIAL REGISTRATIONnClinicalTrials.gov identifier: NCT00967005.

Neural and psychological underpinnings of gambling disorder: A review

Gambling disorder affects 0.4 to 1.6% of adults worldwide, and is highly comorbid with other mental health disorders. This article provides a concise primer on the neural and psychological underpinnings of gambling disorder based on a selective review of the literature. Gambling disorder is associated with dysfunction across multiple cognitive domains which can be considered in terms of impulsivity and compulsivity. Neuroimaging data suggest structural and functional abnormalities of networks involved in reward processing and top-down control. Gambling disorder shows 50-60% heritability and it is likely that various neurochemical systems are implicated in the pathophysiology (including dopaminergic, glutamatergic, serotonergic, noradrenergic, and opioidergic). Elevated rates of certain personality traits (e.g. negative urgency, disinhibition), and personality disorders, are found. More research is required to evaluate whether cognitive dysfunction and personality aspects influence the longitudinal course and treatment outcome for gambling disorder. It is hoped that improved understanding of the biological and psychological components of gambling disorder, and their interactions, may lead to improved treatment approaches and raise the profile of this neglected condition.

Impaired response inhibition and excess cortical thickness as candidate endophenotypes for trichotillomania

Trichotillomania is characterized by repetitive pulling out of ones own hair. Impaired response inhibition has been identified in patients with trichotillomania, along with gray matter density changes in distributed neural regions including frontal cortex. The objective of this study was to evaluate impaired response inhibition and abnormal cortical morphology as candidate endophenotypes for the disorder. Subjects with trichotillomania (N = 12), unaffected first-degree relatives of these patients (N = 10), and healthy controls (N = 14), completed the Stop Signal Task (SST), a measure of response inhibition, and structural magnetic resonance imaging scans. Group differences in SST performance and cortical thickness were explored using permutation testing. Groups differed significantly in response inhibition, with patients demonstrating impaired performance versus controls, and relatives occupying an intermediate position. Permutation cluster analysis revealed significant excesses of cortical thickness in patients and their relatives compared to controls, in right inferior/middle frontal gyri (Brodmann Area, BA 47 & 11), right lingual gyrus (BA 18), left superior temporal cortex (BA 21), and left precuneus (BA 7). No significant differences emerged between groups for striatum or cerebellar volumes. Impaired response inhibition and an excess of cortical thickness in neural regions germane to inhibitory control, and action monitoring, represent vulnerability markers for trichotillomania. Future work should explore genetic and environmental associations with these biological markers.

Gender-related clinical and neurocognitive differences in individuals seeking treatment for pathological gambling

OBJECTIVESnUnderstanding variations in disease presentation in men and women is clinically important as differences may reflect biological and sociocultural factors and have implications for selecting appropriate prevention and treatment strategies. The aim of this study was to investigate clinical and cognitive differences in treatment-seeking people with pathological gambling as a function of gender.nnnMATERIALS AND METHODSn501 adult subjects (nxa0=xa0274 [54.7%] females) with DSM-IV pathological gambling presenting for various clinical research trials over a 9-year period were assessed in terms of sociodemographics and clinical characteristics. A subset (nxa0=xa077) had also undertaken neuropsychological assessment with the Stop-signal and set-shift tasks.nnnRESULTSnPG in females was associated with significantly worse disease severity, elevated mood and anxiety scores, and history of affective disorders, later age of study presentation, later age of disease onset, and elevated risk of having a first-degree relative with gambling or alcohol problems. These findings were of small effect size (0.20-0.35). Additionally, PG in females was associated with proportionately more non-strategic gambling with medium effect size (0.61). In contrast, PG in males was associated with a significantly greater lifetime history of an alcohol use disorder and any substance use disorder (small effect sizes 0.22-0.38); and slower motoric reaction times (medium effect size, 0.50). Response inhibition and cognitive flexibility were similar between the groups.nnnCONCLUSIONSnThese data suggest that important differences exist in the features of pathological gambling in women and men. Findings are of considerable relevance to clinicians and in terms of targeted treatments.

Telescoping phenomenon in pathological gambling: association with gender and comorbidities.

Abstract The course of pathological gambling (PG) in women has been described as having a later age of initiation but a shorter time to problematic gambling (“telescoped”). This study examined evidence for telescoping and its relationship with comorbidities. Seventy-one treatment-seeking individuals with PG underwent a diagnostic interview to examine gambling behaviors, age at initiation of gambling, and time from initiation to meeting criteria for PG. The women had a higher mean age at gambling initiation compared with that of the men (mean [SD] age, 31.3 [13.0] years, compared with 22.4 [7.9] years; p = 0.0003) and a significantly shorter time from initiation of gambling to meeting the criteria for PG (8.33 [8.7] years compared with 11.97 [9.1] years; p = 0.0476) after controlling for demographic and clinical variables. This study presents evidence for a gender-specific course of PG unrelated to psychiatric comorbidities and suggests a need for greater clinical focus on the gender differences of gambling behavior.

A proof of concept study of tolcapone for pathological gambling: Relationships with COMT genotype and brain activation

Pathological gambling (PG) is a disabling disorder experienced by 1-3% of adults, and empirically validated treatments are lacking. Perturbations of prefrontal-dependent cognitive functions are implicated in the pathophysiology of PG. The enzyme catechol-O-methyl-transferase (COMT) is responsible for degradation of dopamine in the cortices and thereby is known to regulate such cognitive functions and their neural substrates. The objective of this study was to determine whether tolcapone, a COMT inhibitor, improves symptoms of PG and to explore whether such effects are dependent on COMT val-158-met polymorphism status and relate to concomitant changes in fronto-parietal activation. Twenty-four individuals with PG were enrolled in an 8-week trial of oral tolcapone (100mg/day titrated to 100mg thrice/day) and 12 undertook pre- and post-treatment fMRI to examine brain activation during an executive planning task in a pre-defined fronto-parietal network. At baseline, patients with PG showed fronto-parietal under-activation versus controls during executive planning. Treatment was associated with statistically significant reductions on PG-Yale Brown Obsessive Compulsive Scale (PG-YBOCS), the extent of which correlated significantly with augmentation of planning-related fronto-parietal activation. Symptom improvement was also significantly more pronounced in subjects with the val/val COMT polymorphism. Tolcapone improved PG symptoms, and the extent of symptomatic improvement was significantly related to augmentation of fronto-parietal activation (fMRI probe) and COMT status. Objective genetic and fMRI markers hold promise in the search for targeting treatment and elucidating brain mechanisms associated with optimal clinical outcomes.

Skin picking disorder in university students: health correlates and gender differences

OBJECTIVEnThis study sought to examine the prevalence of skin picking disorder (SPD) in a university sample and assess associated physical and mental health correlates.nnnMETHODSnA 54-item anonymous, voluntary survey was distributed via random email generation to a sample of 6000 university students. Current psychological and physical status was assessed, along with academic performance. Positive screens for SPD were determined based upon individuals meeting full proposed DSM-V criteria.nnnRESULTSnA total of 1916 participants (31.9%; mean age 22.7 ± 5.1; 58.1% female) responded and were included in the analysis. The overall prevalence of SPD was 4.2% (females=5.8%; males=2.0%). SPD was associated with significantly higher lifetime rates of affective, anxiety, eating, substance use and impulse control disorders. Men with SPD had significantly higher BMI ratings and perceived themselves as significantly less attractive to others while women had significantly higher depressive symptoms.nnnCONCLUSIONnSPD is common in both genders and is associated with significant mental and physical health detriments, including higher levels of stress, more psychiatric comorbidity and poorer perceived health. Academic institutions, clinicians and public health officials should be aware of the multimodal presentation of SPD and screen for it in primary care and dermatologic settings.