Sarah A. Redden

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.

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.

Latent class analysis of gambling subtypes and impulsive/compulsive associations: Time to rethink diagnostic boundaries for gambling disorder?

Background Gambling disorder has been associated with cognitive dysfunction and impaired quality of life. The current definition of non-pathological, problem, and pathological types of gambling is based on total symptom scores, which may overlook nuanced underlying presentations of gambling symptoms. The aims of the current study were (i) to identify subtypes of gambling in young adults, using latent class analysis, based on individual responses from the Structured Clinical Interview for Gambling Disorder (SCI-GD); and (ii) to explore relationships between these gambling subtypes, and clinical/cognitive measures. Methods Total 582 non-treatment seeking young adults were recruited from two US cities, on the basis of gambling five or more times per year. Participants undertook clinical and neurocognitive assessment, including stop-signal, decision-making, and set-shifting tasks. Data from individual items of the Structured Clinical Interview for Gambling Disorder (SCI-GD) were entered into latent class analysis. Optimal number of classes representing gambling subtypes was identified using Bayesian Information Criterion and differences between them were explored using multivariate analysis of variance. Results Three subtypes of gambling were identified, termed recreational gamblers (60.2% of the sample; reference group), problem gamblers (29.2%), and pathological gamblers (10.5%). Common quality of life impairment, elevated Barratt Impulsivity scores, occurrence of mainstream mental disorders, having a first degree relative with an addiction, and impaired decision-making were evident in both problem and pathological gambling groups. The diagnostic item ‘chasing losses’ most discriminated recreational from problem gamblers, while endorsement of ‘social, financial, or occupational losses due to gambling’ most discriminated pathological gambling from both other groups. Significantly higher rates of impulse control disorders occurred in the pathological group, versus the problem group, who in turn showed significantly higher rates than the reference group. The pathological group also had higher set-shifting errors and nicotine consumption. Conclusions Even problem gamblers who had a relatively low total SCI-PG scores (mean endorsement of two items) exhibited impaired quality of life, objective cognitive impairment on decision-making, and occurrence of other mental disorders that did not differ significantly from those seen in the pathological gamblers. Furthermore, problem/pathological gambling was associated with other impulse control disorders, but not increased alcohol use. Groups differed on quality of life when classified using the data-driven approach, but not when classified using DSM cut-offs. Thus, the current DSM-5 approach will fail to discriminate a significant fraction of patients with biologically plausible, functionally impairing illness, and may not be ideal in terms of diagnostic classification. Cognitive distortions related to ‘chasing losses’ represent a particularly important candidate treatment target for early intervention.

ADHD symptoms in non-treatment seeking young adults: relationship with other forms of impulsivity.

OBJECTIVE Attention-deficit hyperactivity disorder (ADHD) has been associated with various manifestations of impulsivity in adults, including elevated rates of other impulsive disorders, substance use, questionnaire-based impulsivity scores, and inhibitory dysregulation on neurocognitive tests. The relationship between ADHD and all these other forms of impulsivity has yet to be explored within the context of a single comprehensive study. METHODS A total of 423 young adults, who gambled ≥5 times in the preceding year, were recruited using media advertisements and undertook detailed assessment including structured psychiatric interview, questionnaires, and neurocognitive tests. Participants with ADHD symptoms were identified using the Adult ADHD Self-Report Scale Screener (ASRS-V1.1) and were compared to controls using multivariate analysis of variance (MANOVA). RESULTS ADHD symptoms were found in 20.3% of the sample, but only 7.3% of these subjects had ever received a formal diagnosis. ADHD symptoms were associated with significantly lower quality of life, lower self-esteem, higher emotional dysregulation, higher impulsivity questionnaire scores, more problematic Internet use, greater occurrence of psychiatric disorders, and impaired stop-signal reaction times. Of these variables, stop-signal reaction times and Barratt attentional impulsiveness were the strongest predictors of group classification. CONCLUSIONS ADHD symptoms are common and under-diagnosed in young adults who gamble, and are most strongly linked with certain other types of impulsivity (questionnaire- and cognitive-based measures) and with emotional dysregulation, suggesting that these are each important considerations in understanding the pathophysiology of the disorder, but also potential treatment targets. It is necessary to question whether treatment for adult ADHD could be enhanced by considering self-esteem, emotional reactivity, and impaired inhibitory control as specific treatment targets, in addition to the core diagnostic symptoms of the disorder.

Psychosocial dysfunction associated with skin picking disorder and trichotillomania.

Skin picking disorder (SPD) and trichotillomania (TTM) are common and oftentimes disabling disorders. 125 Participants with SPD and 152 with TTM undertook clinical and neurocognitive evaluation, and were grouped according to mild, moderate, or severe levels of psychosocial dysfunction. Relationships between functional impairment and other variables were explored using linear regression and categorical analyses. Greater functional impairment was associated with worse disease severity in both groups, and by later symptom onset and lower quality of life in TTM subjects. These results indicate that levels of self-reported psychosocial dysfunction have a strong association with specific clinical aspects of SPD and TTM.

A structural MRI study of excoriation (skin-picking) disorder and its relationship to clinical severity

Excoriation (skin-picking) disorder (SPD) shares symptomology with other obsessive-compulsive and related disorders. Few studies, however, have examined the neurological profile of patients with SPD. This study examined differences in cortical thickness and basal ganglia structural volumes between 20 individuals with SPD and 16 healthy controls using magnetic resonance imaging (MRI). There were no significant differences in demographic variables (age, gender, education and race) between groups. All subjects completed a structural MRI scan and completed a battery of clinical assessments focusing on SPD symptom severity, depression and anxiety symptoms, and quality of life. No statistically significant differences in basal ganglia (caudate, putamen, and nucleus accumbens) structural volumes were found between groups. In individuals with SPD, increasing impulsiveness correlated positively with increased cortical thickness in the left insula, and skin picking severity correlated negatively with cortical thickness in the left supramarginal gyrus and a region encompassing the right inferior parietal, right temporal and right supramarginal gyrus. This study suggests similarities and differences exist in symptomology between SPD and the other obsessive-compulsive and related disorders. Additional neuroimaging research is needed to better delineate the underlying neurobiology of SPD.

Gambling disorder: Association between duration of illness, clinical, and neurocognitive variables

Background and aims Gambling disorder (GD) may have its onset in a wide range of ages, from adolescents to old adults. In addition, individuals with GD tend to seek treatment at different moments in their lives. As a result of these characteristics (variable age at onset and variable age at treatment seeking), we find subjects with diverse duration of illness (DOI) in clinical practice. DOI is an important but relatively understudied factor in GD. Our objective was to investigate clinical and neurocognitive characteristics associated with different DOI. Methods This study evaluated 448 adults diagnosed with GD. All assessments were completed prior to treatments being commenced. Results Our main results were: (a) there is a negative correlation between DOI and lag between first gambling and onset of GD; (b) lifetime history of alcohol use disorder (AUD) is associated with a longer duration of GD; (c) the presence of a first-degree relative with history of AUD is associated with a more extended course of GD; and (d) there is a negative correlation between DOI and quality of life. Discussion This study suggests that some important variables are associated with different DOI. Increasing treatment-seeking behavior, providing customized psychological interventions, and effectively managing AUD may decrease the high levels of chronicity in GD. Furthermore, research on GD such as phenomenological studies and clinical trials may consider the duration of GD in their methodology. DOI might be an important variable when analyzing treatment outcome and avoiding confounders.

Trichotillomania and its clinical relationship to depression and anxiety

Abstract Objective: Trichotillomania (TTM) is associated with high rates of co-occurring depression and anxiety disorders. What the co-occurrence of TTM, depression or anxiety disorders means clinically and cognitively, however, has garnered little research attention. Methods: About 530 adults with TTM were examined on a variety of clinical measures including symptom severity, psychosocial measures of functioning, psychiatric comorbidity and neurocognitive testing assessing motor inhibition and cognitive flexibility. Clinical features and cognitive functioning were compared between TTM patients with current comorbid major depressive disorder (MDD), a current anxiety disorder, both MDD and an anxiety disorder, or neither. Results: Of 530 participants, 58 (10.3%) had MDD only, 97 (18.3%) had an anxiety disorder only, 58 (10.3%) had both MDD and an anxiety disorder, and 317 (59.8%) had neither. For almost all clinical measures, those with MDD only reported worse symptoms than those with an anxiety disorder only, and the combination of MDD and an anxiety disorder reported the worst level of symptom severity. Conclusions: These results suggest that adults with TTM and co-occurring MDD and anxiety disorders exhibit unique clinical differences. The clinical differences may also have treatment implications.