Eric W. Leppink

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.

Obesity and dissociable forms of impulsivity in young adults

OBJECTIVE Obesity is one of the leading causes of preventable morbidity and mortality, and young people are increasingly affected. The aim of this study was to examine relationships between obesity and dissociable forms of impulsivity in young adults. METHODS A group of young adults (511) was recruited from city areas in the United States using media advertisements. These young adults were administered careful and extensive clinical and neurocognitive assessment in order to quantify different aspects of impulsivity (behavioral/phenomenological-, cognitive-, and personality-related measures). Associations between obesity and impulsivity were explored using multivariate analysis of variance and discriminant function analysis. RESULTS 10.8% of the sample was obese, and 21.5% was overweight. Compared to controls, subjects with obesity showed significantly elevated rates of maladaptive gambling behaviors, monetary amounts lost to gambling, nicotine consumption, impulsive action (prolonged stop-signal reaction times in the Stop-Signal Test), and impulsive decision-making (reduced modulation of behavior as a function of risk in the Cambridge Gamble Test). Even accounting for potential confounding variables, obesity was significantly predicted by female gender, older age, more maladaptive gambling behaviors, and worse inhibitory control (stop-signal reaction times). CONCLUSION Obesity is associated with several dissociable forms of impulsivity in young people, especially gambling and impulse dyscontrol. Family doctors should screen for gambling problems in obese young adults. Successful treatment of nicotine dependence in young obese people is likely to require intensive weight management support. Neuropsychological deficits relating to impulsivity occur in obese people in early adulthood, and may represent vulnerability markers rather than being due to chronic untoward metabolic effects on brain function.

N-Acetylcysteine in the Treatment of Excoriation Disorder: A Randomized Clinical Trial

IMPORTANCE Excoriation (skin-picking) disorder (SPD) is a disabling, underrecognized condition in which individuals repeatedly pick at their skin, leading to noticeable tissue damage. To date, there has been no clearly effective pharmacologic or psychological treatment for SPD. OBJECTIVE To determine whether N-acetylcysteine, an amino acid that appears to restore extracellular glutamate concentration in the nucleus accumbens, will be more effective than placebo in reducing compulsive picking behavior. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind trial was conducted at ambulatory care centers at the University of Minnesota (September 12, 2011, to June 15, 2012) and the University of Chicago (December 17, 2012, to June 26, 2015) and included 66 adults with SPD. Data analysis was performed from July 16 to September 9, 2015. INTERVENTIONS N-acetylcysteine (dosing range, 1200-3000 mg/d) or placebo was administered for 12 weeks. MAIN OUTCOMES AND MEASURES Participants were assessed using measures of skin-picking severity, including the modified Yale-Brown Obsessive Compulsive Scale (NE-YBOCS); total scores range from 0 to 40, with higher scores reflective of greater symptom severity. Another measure of skin-picking severity was the Clinical Global Impression-Severity Scale; total scores range from 1 (normal) to 7 (among the most extremely ill patients), and improvement ratings range from 7 (very much worse) to 1 (very much improved). Selected cognitive tasks included the Intra-dimensional/Extra-dimensional Shift Task to examine cognitive flexibility, with the key outcome measures being the number of errors, and Stop-Signal Reaction Time task, which evaluates motor inhibition. Outcomes were examined using a linear mixed-effects model. RESULTS Of the 66 participants (31 randomized to placebo and 35 to N-acetylcysteine) included in the analysis, 59 (89%) were women; mean (SD) age was 34.8 (11.0) years. Compared with placebo, N-acetylcysteine treatment was associated with significant improvements in the NE-YBOCS. At baseline, NE-YBOCS scores were 18.9 and 17.9 for the treatment and placebo groups, respectively, and at 12 weeks, the scores were 11.5 and 14.1 for the treatment and placebo groups, respectively (P = .048). For the Clinical Global Impression-Severity scale, baseline scores were 3.5 and 4.0 and 12-week scores were 3.0 and 4.2, respectively (P = .003). These effects were significant both in terms of treatment by time interactions and post hoc tests at 1 or more individual time points. At the studys end point, of the 53 participants who completed the study, 15 of the 32 participants (47%) receiving N-acetylcysteine were much or very much improved compared with 4 of the 21 participants (19%) receiving placebo (P = .03). There were no significant differences between the active and placebo arms in terms of psychosocial functioning. CONCLUSIONS AND RELEVANCE N-acetylcysteine treatment resulted in significant reductions in skin-picking symptoms and was well tolerated. The glutamate system may prove a beneficial target in treating SPD and other compulsive behaviors. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01063348.

Impulsivity and gambling: A complex clinical association across three measures

BACKGROUND AND OBJECTIVES Gambling disorder (GD) is often characterized as an impulsive condition, but results to date have varied substantially by the measure used to assess impulsivity and the modality of the assessment. The purpose of this analysis was to assess the clinical associations between three measures of impulsivity (Eysenck impulsiveness questionnaire [EIQ], Barratt impulsiveness scale [BIS], and stop-signal task [SST]) and GD symptom severity. METHODS One hundred and fifty-four participants with a current GD diagnosis were assessed on at least one of the three measures of impulsivity and additional clinical measures of gambling severity. Groups within each domain of the measures were divided using a mean split to compare high and low impulsivity (HI and LI) across clinical and demographic variables. RESULTS Of the included domains, the motor impulsivity domain of the BIS showed multiple clinical differences between the HI and LI groups. The attentional impulsivity domain of the BIS showed limited clinical associations. Surprisingly, HI and LI groups from the SST and EIQ domains did not show any differences in symptom severity. DISCUSSION AND CONCLUSIONS These findings emphasize the complex nature of impulsivity, particularly as it relates to GD. With disparate results between different measures, it will be important to clarify the specific features assessed by each measure, and their optimal use clinically. SCIENTIFIC SIGNIFICANCE This analysis suggests that the motor impulsivity feature of the BIS shows the strongest clinical utility for predicting gambling severity. It also emphasizes the importance of sub-typing impulsivity, rather than considering it a single neurocognitive feature.

Obesity and gambling: neurocognitive and clinical associations

Research on health correlates in gamblers has found an association between gambling and obesity. The neurocognitive underpinnings of impulsivity may be useful targets for understanding and ultimately treating individuals with both gambling and obesity problems.

Neurocognitive Deficits Associated with Antisocial Personality Disorder in Non-treatment Seeking Young Adults

Antisocial personality disorder (ASPD) is a relatively common problem, but the neuropsychological profile of affected individuals has seldom been studied outside of criminal justice recruitment settings. Non-treatment-seeking young adults (18-29 years) were recruited from the general community by media advertisements. Participants with ASPD (n = 17), free from substance use disorders, were compared with matched controls (n = 229) using objective computerized neuropsychological tasks tapping a range of cognitive domains. Compared with controls, individuals with ASPD showed significantly elevated pathological gambling symptoms, previous illegal acts, unemployment, greater nicotine consumption, and relative impairments in response inhibition (Stop-Signal Task) and decision-making (less risk adjustment, Cambridge Gamble Task). General response speed, set-shifting, working memory, and executive planning were intact. ASPD was also associated with higher impulsivity and venturesomeness on the Eysenck Questionnaire. These findings implicate impaired inhibitory control and decision-making in the pathophysiology of ASPD, even in milder manifestations of the disorder. Future work should explore the neural correlates of these impairments and use longitudinal designs to examine the temporal relationship between these deficits, antisocial behavior, and functional impairment.

Cognitive flexibility correlates with gambling severity in young adults

Although gambling disorder (GD) is often characterized as a problem of impulsivity, compulsivity has recently been proposed as a potentially important feature of addictive disorders. The present analysis assessed the neurocognitive and clinical relationship between compulsivity on gambling behavior. A sample of 552 non-treatment seeking gamblers age 18-29 was recruited from the community for a study on gambling in young adults. Gambling severity levels included both casual and disordered gamblers. All participants completed the Intra/Extra-Dimensional Set Shift (IED) task, from which the total adjusted errors were correlated with gambling severity measures, and linear regression modeling was used to assess three error measures from the task. The present analysis found significant positive correlations between problems with cognitive flexibility and gambling severity (reflected by the number of DSM-5 criteria, gambling frequency, amount of money lost in the past year, and gambling urge/behavior severity). IED errors also showed a positive correlation with self-reported compulsive behavior scores. A significant correlation was also found between IED errors and non-planning impulsivity from the BIS. Linear regression models based on total IED errors, extra-dimensional (ED) shift errors, or pre-ED shift errors indicated that these factors accounted for a significant portion of the variance noted in several variables. These findings suggest that cognitive flexibility may be an important consideration in the assessment of gamblers. Results from correlational and linear regression analyses support this possibility, but the exact contributions of both impulsivity and cognitive flexibility remain entangled. Future studies will ideally be able to assess the longitudinal relationships between gambling, compulsivity, and impulsivity, helping to clarify the relative contributions of both impulsive and compulsive features.

COMT genotype, gambling activity, and cognition

Neuropsychological studies of adults with problem gambling indicate impairments across multiple cognitive domains. Catechol-O-methyltransferase (COMT) plays a unique role in the regulation of dopamine in the prefrontal cortex, and has been implicated in the cognitive dysfunction evident in problem gambling. This study examined adults with varying levels of gambling behavior to determine whether COMT genotype was associated with differences in gambling symptoms and cognitive functioning. 260 non-treatment-seeking adults aged 18-29 years with varying degrees of gambling behavior provided saliva samples for genotyping COMT val158met (rs4680). All subjects underwent clinical evaluations and neurocognitive assessment of decision-making, working memory, and impulsivity. The Val/Val COMT genotype was associated with the largest percentage of subjects with gambling disorder (31.8%), a rate significantly different from the Val/Met (13.2%) group (p = 0.001). The Val/Val COMT group was also associated with significantly more gambling disorder diagnostic criteria being met, greater frequency of gambling behavior, and significantly worse cognitive performance on the Cambridge Gamble Task (risk adjustment and delay aversion) and the Spatial Working Memory task (total errors). This study adds to the growing literature on the role of COMT in impulsive behaviors by showing that the Val/Val genotype was associated with specific clinical and cognitive elements among young adults who gamble, in the absence of differences on demographic measures and other cognitive domains. Future work should consider using genotyping to explore whether certain polymorphisms predict subsequent development of impulsive behaviors including gambling disorder, and treatment outcomes.

Impact of ADHD symptoms on clinical and cognitive aspects of problem gambling.

BACKGROUND Problem gambling is common across cultures, and has been conceptualized in terms of impulsivity. While elevated rates of attention deficit hyperactivity disorder (ADHD) have been observed in problem gamblers, the relationship between these two conditions, and other dissociable forms of impulsivity, has received little research attention. METHODS N=126 non-treatment seeking young adults with problem gambling were recruited from the community, and were grouped according to the presence or absence of probable current ADHD. Clinical and cognitive measures pertaining to impulsivity were collected via detailed psychiatric assessment, questionnaires, and computerized neuropsychological tests. These variables were compared between groups. RESULTS Probable current ADHD was identified in 21.4% of the sample, and was associated with earlier age at onset of gambling behaviors, higher Barratt impulsivity scores (all three subscales), greater caffeine intake, worse response inhibition (Stop-Signal Test), and impaired decision-making (greater proportion of points gambled, Cambridge Gamble Test). Problem gamblers with and without ADHD did not differ on demographic characteristics or the rate of other psychiatric disorders, depression scores, nicotine and alcohol consumption, and body mass index. No significant group differences were found for general response speed, working memory, or executive planning. CONCLUSIONS ADHD is common in young adults with dysfunctional gambling behaviors and is associated with elevated questionnaire and cognitive based measures of impulsivity, along with heightened caffeine use. Future work should study the causal nature between these factors and the treatment implications of these findings.

The Young and the Stressed: Stress, Impulse Control, and Health in College Students.

Abstract High levels of stress are common among young adults, particularly those enrolled in college. These degrees of stress have shown numerous deleterious effects across both academic and health variables. Findings regarding the role of stress in the presentation of impulse control disorders, particular among college students, are limited. This study examined potential associations between perceived stress, academic achievement, physical/mental health, and impulse control disorders in young adults. A total of 1805 students completed an online survey and were included in the analysis. Responders were grouped by their overall score on the Perceived Stress Scale into mild, moderate, or severe. Severe perceived stress was associated with worse academic achievement and worse physical health, as well as higher rates of psychiatric and impulsive disorders. These findings may suggest associations between stress and numerous aspects of mental/physical health in young adults, which could be an important consideration for individuals working with college students.