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To identify Gambling Disorder (GD) subtypes, in a population of men seeking treatment for GD, according to specific executive function domains (i.e., cognitive flexibility, inhibition and working memory as well as decision making) which are usually impaired in addictive behaviors. A total of 145 males ranging from 18 to 65 years diagnosed with GD were included in this study. All participants completed: (a) a set of questionnaires to assess psychopathological symptoms, personality and impulsivity traits, and (b) a battery of neuropsychological measures to test different executive functioning domains. Two clusters were identified based on the individual performance on the neuropsychological assessment. Cluster 1 [n = 106; labeled as Low Impaired Executive Function (LIEF)] was composed by patients with poor results in the neuropsychological assessment; cluster 2 patients [n = 46; labeled as High Impaired Executive Function (HIEF)] presented significantly higher deficits on the assessed domains and performed worse than the ones of LIEF cluster. Regarding the characterization of these two clusters, patients in cluster 2 were significantly older, unemployed and registered higher mean age of GD onset than patients in cluster 1. Additionally, patients in cluster 2 also obtained higher psychopathological symptoms, impulsivity (in both positive and negative urgency as well as sensation seeking) and some specific personality traits (higher harm avoidance as well as lower self-directedness and cooperativeness) than patients in cluster 1. The results of this study describe two different GD subtypes based on different cognitive domains (i.e., executive function performance). These two GD subtypes display different impulsivity and personality traits as well as clinical symptoms. The results provide new insight into the etiology and characterization of GD and have the potential to help improving current treatments.

Background and aims The main aim of this study was to analyze and describe the clinical characteristics and shared personality traits in different impulsivity-compulsivity spectrum disorders: substance use disorders (SUD), gambling disorder (GD), and bulimia nervosa (BN). The specific aims were to compare personality differences among individuals with pure SUD, BN with and without SUD, and GD with and without SUD. In addition, we assessed the differential predictive capacity of clinical and personality variables in relation to diagnostic subtype. Methods The sample comprised 998 subjects diagnosed according to DSM-IV-TR criteria: 101 patients were diagnosed with SUD, 482 with GD, 359 with BN, 11 with GD + SUD, and 45 patients with BN + SUD. Various assessment instruments were administered, as well as other clinical measures, to evaluate their predictive capacity. Results Marked differences in personality traits were observed between groups. Novelty seeking, harm avoidance, self-directedness, cooperation, and self-transcendence best differentiated the groups. Notably, novelty seeking was significantly higher in the two dual pathology subgroups. Patients with dual pathology showed the most dysfunctional personality profiles. Discussion and conclusion Our results indicate the existence of shared dysfunctional personality traits among the groups studied, especially in novelty seeking and self-directedness.

Objectives: Impulsivity is a construct that is strongly associated with Gambling Disorder (GD). The main objectives in the present study are: 1) to explore the role of sex and age on impulsivity levels in GD patients; 2) to identify the relationship of the different impulsivity facets with comorbid psychopathology and other personality traits in GD patients; and (3) to assess whether impulsivity is a predictor for the severity of GD., Method: The final sample consisted of 406 consecutive participants. All of them were seeking treatment for GD (88.4% male and 11.6% female) and completed the South Oaks Gambling Screen (SOGS), the UPPS-P Impulsive Behavior Scale, the Symptom Checklist (SCL-90-R), the Temperament and Character Inventory-R (TCI-R) as well as other clinical and psychopathological measures., Results: Results show a negative linear trend between age and lower sensation seeking levels as well as lack of premeditation (the higher the age the lower the UPPS-P scores), and a positive linear trend between age and positive urgency (UR) (the higher the age the higher the UPPS-P score). However, no sex differences were found for the assessed impulsivity dimensions. Lack of perseverance was positively associated with obsessive-compulsive symptoms and harm avoidance trait, and negatively related to persistence and self-directedness traits. Positive UR and negative UR were positively correlated with general psychopathology and the total number of DSM-IV criteria, and negatively associated to the following personality traits: self-directedness and cooperativeness. Finally, only the sensation seeking and negative UR of the UPPS-P showed predictive capacity on the severity of the disorder (the higher the impulsivity scores the higher the illness severity)., Conclusions: These findings highlight the association between impulsivity traits (measured by the UPPS-P) and GD in a large and consecutively recruited clinical sample with GD, taking into account the variables sex and age., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Addictions are associated with decision making impairments. The present study explores decision making in Substance use disorder (SUD), Gambling disorder (GD) and Obesity (OB) when assessed by Iowa Gambling Task (IGT) and compares them with healthy controls (HC)., Methods: For the aims of this study, 591 participants (194 HC, 178 GD, 113 OB, 106 SUD) were assessed according to DSM criteria, completed a sociodemographic interview and conducted the IGT., Results: SUD, GD and OB present impaired decision making when compared to the HC in the overall task and task learning, however no differences are found for the overall performance in the IGT among the clinical groups. Results also reveal some specific learning across the task patterns within the clinical groups: OB maintains negative scores until the third set where learning starts but with a less extend to HC, SUD presents an early learning followed by a progressive although slow improvement and GD presents more random choices with no learning., Conclusions: Decision making impairments are present in the studied clinical samples and they display individual differences in the task learning. Results can help understanding the underlying mechanisms of OB and addiction behaviors as well as improve current clinical treatments., Competing Interests: I have read the journal's policy and one of the authors of this manuscript have the following competing interests: Susana Jimenez Murcia is an academic editor of this journal.

Objective: The aim of this study was to examine the implication of personality, impulsivity, and emotion regulation difficulties in patients with a bulimic-spectrum disorder (BSD) and suicide attempts (SA), BSD patients with non-suicidal self-injury (NSSI), and BSD patients without these behaviors., Method: One hundred and twenty-two female adult BSD patients were assessed using self-report questionnaires. Patients were clustered post-hoc into three groups depending on whether they presented BSD without NSSI or SA (BSD), BSD with lifetime NSSI (BSD + NSSI) or BSD with lifetime SA (BSD + SA)., Results: The BSD + NSSI and BSD + SA groups presented more emotion regulation difficulties, more eating and general psychopathology, and increased reward dependence in comparison with the BSD group. In addition, BSD + SA patients specifically showed problems with impulse control, while also presenting higher impulsivity than both the BSD and BSD + NSSI groups. No differences in impulsivity between the BSD and BSD + NSSI groups were found., Conclusions: The results show that BSD + NSSI and BSD + SA share a common profile characterized by difficulties in emotion regulation and low reward dependence, but differ in impulsivity and cooperativeness. This suggests that self-injury, in patients without a history of suicide attempts (i.e., BSD + NSSI), may have a regulatory role rather than being due to impulsivity.

Whether the executive profile is different between obesity (OB) and morbid obesity (MO) remains unclear. Recent evidence suggests that physical activity (PA) can act as a cognitive enhancer. Irisin is a recently discovered hormone associated with some of the positive effects of PA. The objective of the study was to investigate the executive profile in OB and MO, and to explore the role of PA and irisin. 114 participants were included (21 OB, 44 MO and 49 healthy controls-HC) in the study and assessed with the Wisconsin Card Sorting Test, Stroop Color and Word Test, and Iowa Gambling Task. All participants were female, aged between 18 and 60 years. Results showed a similar dysfunctional profile on decision making in OB and MO compared with HC. Thus, no specific neuropsychological profiles between OB and MO can be clearly observed in our sample. However, a negative correlation was found between irisin and executive functioning. These results demonstrate a specific executive profile in OB and a relevant and negative modulation of irisin on executive functioning. Although irisin might be a promising target for the treatment of obesity, its effects on cognition might be considered when thinking about its therapeutic use.

Background: The 600 kb BP4-BP5 copy number variants (CNVs) at the 16p11.2 locus have been associated with a range of neurodevelopmental conditions including autism spectrum disorders and schizophrenia. The number of genomic copies in this region is inversely correlated with body mass index (BMI): the deletion is associated with a highly penetrant form of obesity (present in 50% of carriers by the age of 7 years and in 70% of adults), and the duplication with being underweight. Mechanisms underlying this energy imbalance remain unknown., Objective: This study aims to investigate eating behavior, cognitive traits and their relationships with BMI in carriers of 16p11.2 CNVs., Methods: We assessed individuals carrying a 16p11.2 deletion or duplication and their intrafamilial controls using food-related behavior questionnaires and cognitive measures. We also compared these carriers with cohorts of individuals presenting with obesity, binge eating disorder or bulimia., Results: Response to satiety is gene dosage-dependent in pediatric CNV carriers. Altered satiety response is present in young deletion carriers before the onset of obesity. It remains altered in adolescent carriers and correlates with obesity. Adult deletion carriers exhibit eating behavior similar to that seen in a cohort of obesity without eating disorders such as bulimia or binge eating. None of the cognitive measures are associated with eating behavior or BMI., Conclusions: These findings suggest that abnormal satiety response is a strong contributor to the energy imbalance in 16p11.2 CNV carriers, and, akin to other genetic forms of obesity, altered satiety responsiveness in children precedes the increase in BMI observed later in adolescence.

The aim of the study is to assess a mediational pathway, which includes patients' sex, personality traits, age of onset of gambling disorder (GD) and gambling-related variables. The South Oaks Gambling Screen, the Symptom Checklist (SCL-90-R) and the Temperament and Character Inventory-R were administered to a large sample of 1632 outpatients attending a specialized outpatient GD unit. Sociodemographic variables were also recorded. A Structural Equation Model was adjusted to assess the pathway. Age of onset mediated between personality profile (novelty seeking and self-transcendence) and GD severity and depression symptoms (measured by SCL-90-R). Sex had a direct effect on GD onset and depression symptoms: men initiated the GD earlier and reported fewer depression symptoms. Age of onset is a mediating variable between sex, personality traits, GD severity and depression symptoms. These empirical results provide new evidence about the underlying etiological process of dysfunctional behaviors related to gambling, and may help to guide the development of more effective treatment and prevention programs aimed at high-risk groups such as young men with high levels of novelty seeking and self-transcendence.

The endocannabinoid (eCB) system can promote food intake by increasing odor detection in mice. The eCB system is over-active in human obesity. Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system. The study sample was made up of 161 females with five groups of body mass index sub-categories ranging from under-weight to morbidly obese. We assessed olfactory capacity with the "Sniffin´Sticks" test, which measures olfactory threshold-discrimination-identification (TDI) capacity. We measured plasma concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine or anandamide (AEA), and several eCB-related compounds, 2-acylglycerols and N-acylethanolamines. 2-AG and other 2-acylglycerols fasting plasma circulating plasma concentrations were higher in obese and morbidly obese subjects. AEA and other N-acylethanolamine circulating concentrations were lower in under-weight subjects. Olfactory TDI scores were lower in obese and morbidly obese subjects. Lower TDI scores were independently associated with higher 2-AG fasting plasma circulating concentrations, higher %body fat, and higher body mass index, after controlling for age, smoking, menstruation, and use of contraceptives. Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity. In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects.

(1) The objective of this study is to analyze differences in smell-taste capacity between females in extreme weight/eating conditions (EWC) and (2) to explore the interaction between smell/taste capacity, gastric hormones, eating behavior and body mass index (BMI). The sample comprised 239 females in EWC [64 Anorexia nervosa (AN) and 80 age-matched healthy-weight controls, and 59 obese and 36 age-matched healthy-weight controls]. Smell and taste assessments were performed through "Sniffin' Sticks" and "Taste Strips," respectively. The assessment measures included the eating disorders inventory-2, the symptom check list 90-revised, and The Dutch Eating Behavior Questionnaire, as well as peptides from the gastrointestinal tract [Ghrelin, peptide YY, cholecystokinin]. Smell capacity was differentially associated across EWC groups. Smell was clearly impaired in obese participants and increased in AN (hyposmia in Obesity was 54.3 and 6.4 % in AN), but taste capacity did not vary across EWC. Ghrelin levels were significantly decreased in obese subjects and were related to smell impairment. EWC individuals showed a distinct smell profile and circulating ghrelin levels compared to controls. Smell capacity and ghrelin may act as moderators of emotional eating and BMI.

The aims of this study are: to explore empirical clusters in a sample of individuals with a gambling disorder (GD) according to the presence of illegal behaviors, to describe the subgroups at a clinical level and to examine whether a temporal change has taken place across the last 9 years. The sample consisted of 378 patients with a GD who consecutively received outpatient treatment, and who reported the presence of the DSM-IV criteria "presence of illegal behavior". Two-step clustering procedure revealed the existence of four empirical groups, which differed in both sociodemographic and clinical profiles. The patients, who have committed illegal acts due to their gambling behavior, are a heterogeneous group in which it is possible to identify different subtypes, based on sociodemographic, psychopathological, clinical and personality characteristics.

Down syndrome (DS) is an intellectual disability (ID) disorder in which language and specifically, verbal fluency are strongly impaired domains; nearly all adults show neuropathology of Alzheimer's disease (AD), including amyloid deposition by their fifth decade of life. In the general population, verbal fluency deficits are considered a strong AD predictor being the semantic verbal fluency task (SVFT) a useful tool for enhancing early diagnostic. However, there is a lack of information about the association between the semantic verbal fluency pattern (SVFP) and the biological amyloidosis markers in DS. In the current study, we used the SVFT in young adults with DS to characterize their SVFP, assessing total generated words, clustering, and switching. We then explored its association with early indicators of dementia, adaptive behavior and amyloidosis biomarkers, using the Dementia Questionnaire for Persons with Intellectual Disability (DMR), the Adaptive Behavior Assessment System-Second Edition (ABAS-II), and plasma levels of Aβ peptides (Aβ40 and Aβ42), as a potent biomarker of AD. In DS, worse performance in SVFT and poorer communication skills were associated with higher plasma Aβ42 concentrations, a higher DMR score and impaired communication skills (ABAS-II). The total word production and switching ability in SVFT were good indicators of plasma Aβ42 concentration. In conclusion, we propose the SVFT as a good screening test for early detection of dementia and amyloidosis in young adults with DS.

The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior. The objective is to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders (ED) and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1352 articles, titles were first excluded by title (n = 64) and then by abstract and fulltext resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings support that olfaction is altered in AN and in obesity and indicates toward there being little to no difference in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior.

Background: Several studies have highlighted the implications of impulsivity and novelty seeking for both the maintenance and the process of recovery from bulimia nervosa (BN). Cognitive behavioral therapy (CBT) is the treatment of choice for BN, but for some cases, this treatment alone might not be sufficient for reducing the high levels of impulsivity. The paper presents a case report of a patient with BN, examining the effectiveness of using a videogame (VG; Playmancer) as an additional intervention designed to address impulsivity., Design: Psychometric and neuropsychological measures were collected at baseline. After this assessment, Playmancer was applied prior to CBT, following an "A-B-A-C-A" single case experimental design. Impulsivity levels were assessed with the Conner's Continuous Performance Test II (CPT-II). After the Playmancer treatment, the patient started CBT, and the levels of impulsivity were recorded again. Finally, psychometric and neuropsychological measures were collected after treatment. Weekly frequency of binges and vomiting were also recorded during the entire procedure., Results: After the VG intervention, psychometric measures such as anxiety levels, impulsivity and novelty seeking decreased. Regarding the neuropsychological measures, impulsivity levels (measured with the CPT-II) progressively decreased throughout the intervention, and an improvement in decision making capacities was observed. Furthermore, the frequency of binges also decreased during and after the VG intervention., Discussion: This case report suggests that using the Playmancer VG to reduce impulsivity prior to CBT may enhance the final results of the treatment for BN.

To update the knowledge about attentional processing of food stimuli, a systematic review of electrophysiological studies was conducted using PubMed, PsychInfo and Web of Knowledge (2000-2014). Twenty-one studies were included into a qualitative synthesis. Presentation of food and control pictures was used to analyze event-related potentials related to sensory processing and motivated attention. Results show consistent attentional bias towards food pictures compared with neutral pictures for patient and control groups. Group comparisons between individuals with abnormal-eating and healthy-eating participants were more inconsistent. Results suggest that temporal differences in the millisecond range are essential for the understanding of visual food processing. In obesity, early attention engagement to food is followed by relatice disengagement. Loss of control eating, as well as external and emotional eating, are associated with a sustained maintenance of attention towards high-caloric food. There is a lack of studies in anorexia nervosa, bulimia nervosa and binge eating disorder., (Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.)

The prefrontal (PFC) and orbitofrontal cortex (OFC) appear to be associated with both executive functions and olfaction. However, there is little data relating olfactory processing and executive functions in humans. The present study aimed at exploring the role of olfaction on executive functioning, making a distinction between primary and more cognitive aspects of olfaction. Three executive tasks of similar difficulty were used. One was used to assess hot executive functions (Iowa Gambling Task-IGT), and two as a measure of cold executive functioning (Stroop Colour and Word Test-SCWT and Wisconsin Card Sorting Test-WCST). Sixty two healthy participants were included: 31 with normosmia and 31 with hyposmia. Olfactory abilities were assessed using the ''Sniffin' Sticks'' test and the olfactory threshold, odour discrimination and odour identification measures were obtained. All participants were female, aged between 18 and 60. Results showed that participants with hyposmia displayed worse performance in decision making (IGT; Cohen's-d = 0.91) and cognitive flexibility (WCST; Cohen's-d between 0.54 and 0.68) compared to those with normosmia. Multiple regression adjusted by the covariates participants' age and education level showed a positive association between odour identification and the cognitive inhibition response (SCWT-interference; Beta = 0.29; p = .034). The odour discrimination capacity was not a predictor of the cognitive executive performance. Our results suggest that both hot and cold executive functions seem to be associated with higher-order olfactory functioning in humans. These results robustly support the hypothesis that olfaction and executive measures have a common neural substrate in PFC and OFC, and suggest that olfaction might be a reliable cognitive marker in psychiatric and neurologic disorders.

In the present study, we investigated the association between Non-Suicidal Self-Injury (NSSI) and the UPPS-P impulsivity facets in eating disorder patients and healthy controls. The prevalence of NSSI in eating disorder (ED) patients ranged from 17% in restrictive anorexia nervosa (AN-R) patients to 43% in patients with bulimia nervosa (BN). In healthy controls (HC), the prevalence of NSSI was 19%. Eating disorder patients from the binge eating/purging type showed significantly more NSSI compared to restrictive ED and HC participants. Binge-eating/purging ED patients also scored significantly higher on Negative/Positive Urgency, Lack of Premeditation and Lack of Perseverance compared to HC and restrictive ED patients. Comparable findings were found between ED patients and HC with and without NSSI; ED patients and HC with NSSI scored significantly higher in four of the five UPPS-P dimensions compared to participants without NSSI; Sensation Seeking was the exception. Finally, the presence of NSSI in HC/ED patients was particularly predicted by low levels of Perseverance. Therefore, the treatment of ED patients with NSSI certainly needs to focus on the training of effortful control.

Background: Studies examining gambling preferences have identified the importance of the type of gambling practiced on distinct individual profiles. The objectives were to compare clinical, psychopathological and personality variables between two different groups of individuals with a gambling disorder (strategic and non-strategic gamblers) and to evaluate the statistical prediction capacity of these preferences with respect to the severity of the disorder., Method: A total sample of 2010 treatment-seeking patients with a gambling disorder participated in this stand-alone study. All were recruited from a single Pathological Gambling Unit in Spain (1709 strategic and 301 non-strategic gamblers). The design of the study was cross-sectional and data were collected at the start of treatment. Data was analysed using logistic regression for binary outcomes and analysis of variance (ANOVA) for quantitative responses., Results: There were significant differences in several socio-demographic and clinical variables, as well as in personality traits (novelty seeking and cooperativeness). Multiple regression analysis showed harm avoidance and self-directedness were the main predictors of gambling severity and psychopathology, while age at assessment and age of onset of gambling behaviour were predictive of gambling severity. Strategic gambling (as opposed to non-strategic) was significantly associated with clinical outcomes, but the effect size of the relationships was small., Conclusions: It is possible to identify distinct phenotypes depending on the preference of gambling. While these phenotypes differ in relation to the severity of the gambling disorder, psychopathology and personality traits, they can be useful from a clinical and therapeutic perspective in enabling risk factors to be identified and prevention programs targeting specific individual profiles to be developed.

The present study investigates the association between non-suicidal self-injury (NSSI) and impulsivity in anorexia nervosa (AN) patients by means of self-report and behavioural tasks. In total, 60 female AN patients were included in the study, filled out the Barratt Impulsiveness Scale-11 (BIS-11) and performed three performance-based tasks to assess different facets of impulsivity. Overall, 30% of the AN patients engaged in at least one form of NSSI during their lifetime. AN patients with and without NSSI did not significantly differ on the BIS-11 impulsiveness scale. On the performance-based measures, few differences emerged between AN patients with and without NSSI. Patients with NSSI showed more perseverations and perseveration errors (p < .05). The associations between self-report and performance-based measures were rather low, except for the association between the BIS-11 and Wisconsin Card Sorting Task perseveration responses and errors (correlations |r| range between .32 and .42). The implications for theory and treatment of AN patients with and without NSSI will be discussed., (Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.)

Objectives: (1) To assess the current presence of ADHD symptoms among patients seeking treatment for gambling disorder; (2) to explore clinical and sociodemographic differences between patients who score high and low on the measure of ADHD symptoms; (3) to analyze whether the presence of ADHD symptoms is associated with more severe psychopathology and with specific personality traits; (4) to analyze the mediating role of ADHD symptoms in the relationship between novelty seeking and gambling severity., Method: A total of 354 consecutive patients were administered an extensive battery assessing gambling behavior, psychopathology, and personality traits., Results: Male and female gamblers did not differ significantly in their mean scores on the ADHD measure. However, younger participants aged 18-35 scored higher. Higher ADHD scores were also associated with greater severity of gambling disorder and more general psychopathology. Regarding personality traits, high persistence and self-directedness were negatively related to ADHD scores, while in women alone a positive correlation was found between ADHD scores and scores on harm avoidance and self-transcendence., Conclusion: The presence of ADHD symptoms in both male and female gambling disorder patients may act as an indicator of the severity of gambling, general psychopathology, and dysfunctional personality traits.

Aims: The aim of this study was to evaluate posttreatment changes of individuals with a diagnosis of gambling disorder (GD) treated with group cognitive behavioral therapy (CBT), to assess the potential moderator effect of sex on CBT outcome, and to explore the best predictors of posttreatment changes, relapse, and dropout rates., Methods: A cohort design was applied with a prospective follow-up. The sample comprised 440 patients and the CBT intervention consisted of 16 weekly outpatient group sessions and a 3-month follow-up period., Results: Patients showed significant improvements in both the level of psychopathology and the severity of the gambling behavior. High self-transcendence and the involvement of the spouse or partner in the therapy predicted a higher risk of relapse. Younger age and low education predicted a higher risk of dropout., Conclusion: Many patients with GD can be treated with strategies to improve self-control and emotional regulation, but other techniques should be incorporated to address the individual characteristics of each patient. This is particularly important in group therapy, in which the same treatment is applied to several patients simultaneously. The involvement of a family member needs to be carefully considered since it may have a negative effect on the response to treatment if not adequately managed.

Like drug addiction, pathological gambling (PG) has been associated with impairments in executive functions and alterations in dopaminergic functioning; however, the role of dopamine (DA) in the executive profile of PG remains unclear. The aim of this study was to identify whether the DRD2/ANKK1 Taq1A-rs1800497 and the DAT1-40 bp VNTR polymorphisms are associated with cognitive flexibility (measured by Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT)) and inhibition response (measured by Stroop Color and Word Test (SCWT)), in a clinical sample of 69 PG patients. Our results showed an association between DA functioning and cognitive flexibility performance. The Taq1A A1+ (A1A2/A1A1) genotype was associated with poorer TMT performance (p<0.05), while DAT1 9-repeat homozygotes displayed better WCST performance (p<0.05) than either 10-repeat homozygotes or heterozygotes. We did not find any association between the DRD2 or DAT1 polymorphisms and the inhibition response. These results suggested that pathological gamblers with genetic predispositions toward lower availability of DA and D2 receptor density are at a higher risk of cognitive flexibility difficulties. Future studies should aim to shed more light on the genetic mechanisms underlying the executive profile in PG., (© The Author(s) 2014.)

Although the concept of 'food addiction' (FA) has raised growing interest because of evidence for similarities between substance dependence and excessive food intake, there is a lack of studies that explore this construct among the wide spectrum of eating disorders (EDs). Besides providing validation scores of a Spanish version of the Yale FA Scale (YFAS-S), this study examined the prevalence of 'FA' among ED subtypes compared with healthy-eating controls (HCs) and the association between 'FA' scores, eating symptomatology and general psychopathology. A sample of 125 adult women with ED, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders 5 criteria, and 82 healthy-eating women participated in the study. All participants were assessed with the YFAS-S, the ED Inventory-2 and the Symptom Checklist-Revised. Results showed that the internal structure of the one-dimensional solution for the YFAS-S was very good (α = 0.95). The YFAS-S has a good discriminative capacity to differentiate between ED and controls (specificity = 97.6% and sensitivity (Se) = 72.8%; area under receiver operating characteristic curve = 0.90) and a good Se to screen for specific ED subtypes. YFAS-S scores were associated with higher levels of negative affect and depression, higher general psychopathology, more severe eating pathology and greater body mass index. When comparing the prevalence of 'FA' between ED subtypes, the lowest prevalence of 'FA', measured with the YFAS-S, was for the anorexia nervosa (AN) restrictive subtype with 50%, and the highest was for the AN binge-purging subtype (85.7%), followed by bulimia nervosa (81.5%) and binge eating disorder (76.9%). In conclusion, higher YFAS-S scores are associated with bingeing ED-subtype patients and with more eating severity and psychopathology. Although the 'FA' construct is able to differentiate between ED and HC, it needs to be further explored., (Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.)

Background: PlayMancer is a video game designed to increase emotional regulation and reduce general impulsive behaviors, by training to decrease arousal and improve decision-making and planning. We have previously demonstrated the usefulness of PlayMancer in reducing impulsivity and improving emotional regulation in bulimia nervosa (BN) patients. However, whether these improvements are actually translated into brain changes remains unclear., Objective: The aim of this case study was to report on a 28-year-old Spanish woman with BN, and to examine changes in physiological variables and brain activity after a combined treatment of video game therapy (VGT) and cognitive behavioral therapy (CBT)., Methods: Ten VGT sessions were carried out on a weekly basis. Anxiety, physiological, and impulsivity measurements were recorded. The patient was scanned in a 1.5-T magnetic resonance scanner, prior to and after the 10-week VGT/CBT combined treatment, using two paradigms: (1) an emotional face-matching task, and (2) a multi-source interference task (MSIT)., Results: Upon completing the treatment, a decrease in average heart rate was observed. The functional magnetic resonance imaging (fMRI) results indicated a post-treatment reduction in reaction time along with high accuracy. The patient engaged areas typically active in healthy controls, although the cluster extension of the active areas decreased after the combined treatment., Conclusions: These results suggest a global improvement in emotional regulation and impulsivity control after the VGT therapy in BN, demonstrated by both physiological and neural changes. These promising results suggest that a combined treatment of CBT and VGT might lead to functional cerebral changes that ultimately translate into better cognitive and emotional performances.

Background: Endocannabinoids and temperament traits have been linked to both physical activity and body mass index (BMI) however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1) examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical activity (MVPA), temperament traits and plasma endocannabinoid concentrations; and 2) explore the association and interaction between MVPA, temperament, endocannabinoids and BMI., Methods: Physical activity was measured with the wrist-worn accelerometer Actiwatch AW7, in a sample of 189 female participants (43 morbid obese, 30 obese, and 116 healthy-weight controls). The Temperament and Character Inventory-Revised questionnaire was used to assess personality traits. BMI was calculated by bioelectrical impedance analysis via the TANITA digital scale. Blood analyses were conducted to measure levels of endocannabinoids and endocannabinoid-related compounds. Path-analysis was performed to examine the association between predictive variables and MVPA., Results: Obese groups showed lower MVPA and dysfunctional temperament traits compared to healthy-weight controls. Plasma concentrations of 2-arachidonoylglyceryl (2-AG) were greater in obese groups. Path-analysis identified a direct effect between greater MVPA and low BMI (b = -0.13, p = .039) and high MVPA levels were associated with elevated anandamide (AEA) levels (b = 0.16, p = .049) and N-oleylethanolamide (OEA) levels (b = 0.22, p = .004), as well as high Novelty seeking (b = 0.18, p<.001) and low Harm avoidance (b = -0.16, p<.001)., Conclusions: Obese individuals showed a distinct temperament profile and circulating endocannabinoids compared to controls. Temperament and endocannabinoids may act as moderators of the low MVPA in obesity.

Expression of emotional state is considered to be a core facet of an individual's emotional competence. Emotional processing in BN has not been often studied and has not been considered from a broad perspective. This study aimed at examining the implicit and explicit emotional expression in BN patients, in the acute state and after recovery. Sixty-three female participants were included: 22 BN, 22 recovered BN (R-BN), and 19 healthy controls (HC). The clinical cases were drawn from consecutive admissions and diagnosed according to DSM-IV-TR diagnostic criteria. Self reported (explicit) emotional expression was measured with State-Trait Anger Expression Inventory-2, State-Trait Anxiety Inventory, and Symptom Check List-90 items-Revised. Emotional facial expression (implicit) was recorded by means of an integrated camera (by detecting Facial Feature Tracking), during a 20 minutes therapeutic video game. In the acute illness explicit emotional expression [anxiety (p<0.001) and anger (p<0.05)] was increased. In the recovered group this was decreased to an intermediate level between the acute illness and healthy controls [anxiety (p<0.001) and anger (p<0.05)]. In the implicit measurement of emotional expression patients with acute BN expressed more joy (p<0.001) and less anger (p<0.001) than both healthy controls and those in the recovered group. These findings suggest that there are differences in the implicit and explicit emotional processing in BN, which is significantly reduced after recovery, suggesting an improvement in emotional regulation.

Neuroimaging studies have shown that chronic consumption of cannabis may result in alterations in brain morphology. Recent work focusing on the relationship between brain structure and the catechol-O-methyltransferase (COMT) gene polymorphism suggests that functional COMT variants may affect brain volume in healthy individuals and in schizophrenia patients. We measured the influence of COMT genotype on the volume of four key regions: the prefrontal cortex, neostriatum (caudate-putamen), anterior cingulate cortex and hippocampus-amygdala complex, in chronic early-onset cannabis users and healthy control subjects. We selected 29 chronic cannabis users who began using cannabis before 16 years of age and matched them to 28 healthy volunteers in terms of age, educational level and IQ. Participants were male, Caucasians aged between 18 and 30 years. All were assessed by a structured psychiatric interview (PRISM) to exclude any lifetime Axis-I disorder according to Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition. COMT genotyping was performed and structural magnetic resonance imaging data was analyzed by voxel-based morphometry. The results showed that the COMT polymorphism influenced the volume of the bilateral ventral caudate nucleus in both groups, but in an opposite direction: more copies of val allele led to lesser volume in chronic cannabis users and more volume in controls. The opposite pattern was found in left amygdala. There were no effects of COMT genotype on volumes of the whole brain or the other selected regions. Our findings support recent reports of neuroanatomical changes associated with cannabis use and, for the first time, reveal that these changes may be influenced by the COMT genotype., (© 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.)

Background: Recreational drugs are generally used to intentionally alter conscious experience. Long-lasting cannabis users frequently seek this effect as a means to relieve negative affect states. As with conventional anxiolytic drugs, however, changes in subjective feelings may be associated with memory impairment. We have tested whether the use of cannabis, as a psychoactive compound, is associated with alterations in spontaneous activity in brain networks relevant to self-awareness, and whether such potential changes are related to perceived anxiety and memory performance., Methods: Functional connectivity was assessed in the Default and Insula networks during resting state using fMRI in 28 heavy cannabis users and 29 control subjects. Imaging assessments were conducted during cannabis use in the unintoxicated state and repeated after one month of controlled abstinence., Results: Cannabis users showed increased functional connectivity in the core of the Default and Insula networks and selective enhancement of functional anticorrelation between both. Reduced functional connectivity was observed in areas overlapping with other brain networks. Observed alterations were associated with behavioral measurements in a direction suggesting anxiety score reduction and interference with memory performance. Alterations were also related to the amount of cannabis used and partially persisted after one month of abstinence., Conclusions: Chronic cannabis use was associated with significant effects on the tuning and coupling of brain networks relevant to self-awareness, which in turn are integrated into brain systems supporting the storage of personal experience and motivated behavior. The results suggest potential mechanisms for recreational drugs to interfere with higher-order network interactions generating conscious experience., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The purposes of this study were to examine the specific contribution of illegal acts to the diagnostic criteria of pathological gambling, to assess the possibility of differential item functioning across patients' sex and age, and to explore the existence of different clinical phenotypes based on the presence of illegal acts. The sample consisted of 2,155 patients seeking treatment for pathological gambling at the University Hospital of Bellvitge in Barcelona, Spain. The illegal acts item did not show different item functioning, and younger patients presented higher latent means than middle-aged and older patients, whereas no differences were found across sex. This item also showed the lowest discrimination coefficient; its exclusion would maintain satisfactory internal consistency for the remaining 9 symptoms and was poorly related to psychopathology and the severity of the gambling behavior. The relevance of the illegal acts as a diagnostic criterion appears to be limited, and its elimination from the Diagnostic and Statistical Manual for Mental Disorders, 5th edition, seems justified. However, illegal acts have implications for both the clinical and legal domains and contribute to increase the patients' impairment.

The aim of this study was to explore the association between pathological gambling (PG) and anger by assessing whether psychopathology and personality are related to PG and to evaluate gender differences. The sample comprised 71 PGs and 37 healthy controls. Anger, psychopathology and personality were assessed with the STAXI-2, SCL-90-R and TCI-R respectively. Gender did not affect anger expression after stratifying by diagnostic condition (p > .05). Among PG patients, anger, psychopathology and personality measures were correlated with good effect-size (r > .30). Scores in the Anger Temperament (B = 0.21, p = .038) and Anger External-Expression (B = 0.27, p = .029) scales were positively associated with PG severity scores. Anger expression in PG should be considered in future treatment programs.

FNDC5/irisin has been recently postulated as beneficial in the treatment of obesity and diabetes because it is induced in muscle by exercise, increasing energy expenditure. However, recent reports have shown that WAT also secretes irisin and that circulating irisin is elevated in obese subjects. The aim of this study was to evaluate irisin levels in conditions of extreme BMI and its correlation with basal metabolism and daily activity. The study involved 145 female patients, including 96 with extreme BMIs (30 anorexic (AN) and 66 obese (OB)) and 49 healthy normal weight (NW). The plasma irisin levels were significantly elevated in the OB patients compared with the AN and NW patients. Irisin also correlated positively with body weight, BMI, and fat mass. The OB patients exhibited the highest REE and higher daily physical activity compared with the AN patients but lower activity compared with the NW patients. The irisin levels were inversely correlated with daily physical activity and directly correlated with REE. Fat mass contributed to most of the variability of the irisin plasma levels independently of the other studied parameters. Conclusion. Irisin levels are influenced by energy expenditure independently of daily physical activity but fat mass is the main contributing factor.

Objective: We studied the prevalences of video game use (VGU) and addiction (VGA) in gambling disorder (GD) patients and compared them with subjects with non-video game use (non-VGU) in relation to their gambling behavior, psychopathology, and personality characteristics., Method: A sample of 193 GD patients (121 non-VGU, 43 VGU, and 29 VGA) consecutively admitted to our pathological gambling unit participated in the study. Assessment. Measures included the video game dependency test (VDT), symptom checklist-90-revised, and the temperament and character inventory-revised, as well as a number of other GD indices., Results: In GD, the observed prevalence of VG (use or addiction) was 37.3% (95% CI :30.7% ÷ 44.3),VGU 22.3% (95% CI :17.0% ÷ 28.7), and VGA 15% (95% CI :10.7% ÷ 20.7). Orthogonal polynomial contrast into logistic regression showed positive linear trends for VG level and GD severity and other measures of general psychopathology. After structural equation modeling, higher VG total scores were associated with younger age, general psychopathology, and specific personality traits, but not with GD severity. Patients' sex and age were involved in the mediational pathways between personality traits and VG impairment., Conclusions: GD patients with VG are younger and present more dysfunctional personality traits, and more general psychopathology. The presence of VG did not affect the severity of GD.

Although standard psychological treatments have been successful in treating several core features in eating disorders (ED), other characteristics such as emotional regulation or impulsivity appear to be more resistant to change. There is a growing body of evidence to support the efficacy of cognitive remediation for cognitive and emotional difficulties in ED. Playmancer/ Islands is a video game (VG) designed to specifically treat mental disorders, characterized by problems in impulse control. The objective of the game is to increase self-control over emotions, decision making and behaviours. The aim of this study is to describe the results from a consecutive series of nine bulimia nervosa patients who were treated with the VG in addition to cognitive behaviour therapy (CBT). The outcomes included clinical and psychopathological questionnaires, and physiological measures were obtained during the VG. Emotional regulation improved, heart rate variability increased, and respiratory rate and impulsivity measures reduced after the treatment. These findings suggest that VG training may enhance treatment for ED., (Copyright © 2013 John Wiley & Sons, Ltd and Eating Disorders Association.)

Objective: The aim of this study is to explore empirical clusters within the population of young Spanish individuals attending outpatient pathological gambling treatment., Method: The South Oaks Gambling Screen (SOGS), the Symptom Checklist (SCL-90-R), the Temperament and Character Inventory-R (TCI-R) and other clinical and psychopathological measures were administered to 154 patients (between 17 and 25 years old). The two-step cluster analysis explored the presence of empirical heterogeneous groups based on clinical and socio-demographic characteristics., Results: Three clusters of young pathological gambling patients emerged. Type I showed less psychopathology and more functional personality traits. Type II showed a profile characterized by major emotional distress, shame, immaturity, hostility and negative feelings. Type III showed the most severe psychopathological profile and most psychopathological disturbances and schizotypal traits., Conclusions: These results suggest that three distinct endophenotypes exist, and that environmental factors have a stronger influence in the first, while in the second and third, individual factors related to deficits of emotional regulation stand out., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: Pathological gambling (PG) and eating disorders (ED) rarely co-occur. We explored the prevalence of lifetime PG in ED, compared severity of ED symptoms, personality traits, and psychopathological profiles across individuals with ED and PG (ED+PG) and without PG (ED-PG). Finally, we assessed the incremental predictive value of gender on the presentation of a comorbid PG., Method: A total sample of 1681 consecutively admitted ED patients (1576 females and 105 males), participated in the current study (25 ED+PG and 1656 ED-PG). All participants were diagnosed according to DSM-IV criteria. Assessment measures included the Symptom Checklist and the Temperament and Character Inventory-Revised, as well as other clinical and psychopathological indices., Results: The observed lifetime prevalence of PG was 1.49%. ED subtype was associated with lifetime PG (p=.003), with PG being more frequent in binge eating disorder (5.7%). ED+PG was more prevalent in males than in females (16% vs. 1.26%, respectively). Additionally, ED+PG patients exhibited more impulsive behaviours, lower impulse regulation and higher novelty seeking. Best predictors of ED+PG were novelty seeking (OR 1.030, p=.035), sex (OR 3.295, p=.048) and BMI (OR 1.081, p=.005)., Conclusions: Some personality traits (novelty seeking), being male and higher BMI are strongly related to the presence of lifetime PG in specific ED subtypes (namely binge eating disorder)., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The adverse effects of cannabis use on executive functions are still controversial, fostering the need for novel biomarkers able to unveil individual differences in the cognitive impact of cannabis consumption. Two common genetic polymorphisms have been linked to the neuroadaptive impact of Δ9-tetrahydrocannabinol (THC) exposure and to executive functions in animals: the catechol-O-methyltransferase (COMT) gene val158met polymorphism and the SLC6A4 gene 5-HTTLPR polymorphism. We aimed to test if these polymorphisms moderate the harmful effects of cannabis use on executive function in young cannabis users. We recruited 144 participants: 86 cannabis users and 58 non-drug user controls. Both groups were genotyped and matched for genetic makeup, sex, age, education, and IQ. We used a computerized neuropsychological battery to assess different aspects of executive functions: sustained attention (CANTAB Rapid Visual Information Processing Test, RVIP), working memory (N-back), monitoring/shifting (CANTAB ID/ED set shifting), planning (CANTAB Stockings of Cambridge, SOC), and decision-making (Iowa Gambling Task, IGT). We used general linear model-based analyses to test performance differences between cannabis users and controls as a function of genotypes. We found that: (i) daily cannabis use is not associated with executive function deficits; and (ii) COMT val158met and 5-HTTLPR polymorphisms moderate the link between cannabis use and executive performance. Cannabis users carrying the COMT val/val genotype exhibited lower accuracy of sustained attention, associated with a more strict response bias, than val/val non-users. Cannabis users carrying the COMT val allele also committed more monitoring/shifting errors than cannabis users carrying the met/met genotype. Finally, cannabis users carrying the 5-HTTLPR s/s genotype had worse IGT performance than s/s non-users. COMT and SLC6A4 genes moderate the impact of cannabis use on executive functions.

Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = -.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = -.17) or AEA (r = -.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches.

Background: Attention-deficit/hyperactivity disorder (ADHD) has commonly been described in psychiatric disorders. Although several studies have found positive associations between abnormal eating patterns during childhood and ADHD, there is a lack of studies on ADHD and Eating Disorders (ED). The aims of this exploratory study were 1) to assess the ADHD symptoms level in ED and to ascertain whether there are differences among ED subtypes; 2) to analyze whether the presence of ADHD symptoms is associated with more severe eating disorder symptoms and greater general psychopathology; and 3) to assess whether the ADHD symptoms level is associated with specific temperament and character traits., Methods: 191 female ED patients were included. Assessment was carried out with the EDI-2, ASRS-v1.1, the SCL-90-R and the TCI-R., Results: The ADHD symptoms level was similar in bulimia, eating disorder not otherwise specified and binge eating subtypes, and lower in anorexic patients. Obsessiveness and Hostility were significantly positively associated with ADHD symptoms. A path model showed that ADHD was associated with high Novelty Seeking and low Self-Directedness, whereas ED severity was influenced by ADHD severity and low Self-Directedness., Conclusions: Bingeing/purging ED subtypes have a high ADHD symptoms level, also related with more severe eating, general and personality psychopathology.

Background: Extreme weight conditions (EWC) groups along a continuum may share some biological risk factors and intermediate neurocognitive phenotypes. A core cognitive trait in EWC appears to be executive dysfunction, with a focus on decision making, response inhibition and cognitive flexibility. Differences between individuals in these areas are likely to contribute to the differences in vulnerability to EWC. The aim of the study was to investigate whether there is a common pattern of executive dysfunction in EWC while comparing anorexia nervosa patients (AN), obese subjects (OB) and healthy eating/weight controls (HC)., Methods: Thirty five AN patients, fifty two OB and one hundred thirty seven HC were compared using the Wisconsin Card Sorting Test (WCST); Stroop Color and Word Test (SCWT); and Iowa Gambling Task (IGT). All participants were female, aged between 18 and 60 years., Results: There was a significant difference in IGT score (F(1.79); p<.001), with AN and OB groups showing the poorest performance compared to HC. On the WCST, AN and OB made significantly more errors than controls (F(25.73); p<.001), and had significantly fewer correct responses (F(2.71); p<.001). Post hoc analysis revealed that the two clinical groups were not significantly different from each other. Finally, OB showed a significant reduced performance in the inhibition response measured with the Stroop test (F(5.11); p<.001) compared with both AN and HC., Conclusions: These findings suggest that EWC subjects (namely AN and OB) have similar dysfunctional executive profile that may play a role in the development and maintenance of such disorders.

Background: Prevalence and clinical correlates of depersonalization symptoms have been associated with panic disorder. Personality traits might increase the likelihood of experiencing depersonalization symptoms or depersonalization disorder in panic patients., Aims: The objectives of this study are to establish the prevalence of depersonalization symptoms during the panic attack and in depersonalization disorder and to examine the personality factors associated with the presence of depersonalization in patients with panic disorder., Methods: The sample comprised 104 consecutive adult outpatients with panic disorder, diagnosed according to the Semistructured Clinical Interview for DSM-IV (Axis I/II disorders). Participants were assessed with the Cambridge Depersonalization Scales, the Temperament and Character Inventory, and the Panic and Agoraphobia Scale., Results: Forty-eight percent of the sample had depersonalization symptoms during the panic attack, whereas 20% of patients had a depersonalization disorder. Women presented more depersonalization disorders than did men (P = .036). Patients with panic disorder with depersonalization disorder had a more severe panic disorder (P = .002). Logistic regression analysis showed that self-transcendence trait (odds ratio, 1.089; 95% confidence interval, 1.021-1.162; P = .010) and severity of panic (odds ratio, 1.056; 95% confidence interval, 1.005-1.110; P = .032) were independently associated with depersonalization disorder., Conclusions: A high prevalence of depersonalization symptoms and depersonalization disorder was confirmed in patients with panic disorder, supporting a dosage effect model for understanding depersonalization pathology. Self-transcendence trait and severity of panic disorder were reported as risk factors for depersonalization disorder., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT), Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT), Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT). Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (>100 tablets lifetime use) interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy users.

Deficits in verbal fluency associated with ecstasy use have been well established; however, the mechanisms underlying this impairment have yet to be elucidated. In this study we investigated for the first time whether there was a disproportionate impairment in two cognitive subcomponents of verbal fluency: clustering (ability to generate words within the same subcategory) and switching (ability to change the subcategory). We also investigated a possible association between ecstasy use and verbal fluency in subjects genotyped for 5-HTT (5-HTTLPR and 5-HTTVNTR) and COMT (val(108/158)met, rs165599 and rs2097603) polymorphisms, in order to find a potential implication of genetic factors. Ecstasy polydrug users (n = 30) and non-ecstasy users (n = 41) were evaluated in both semantic and phonemic fluency. Results showed that ecstasy users had poorer semantic (but not phonemic) fluency performance than controls. Detailed analysis of clustering and switching performance revealed that this impairment was associated with poorer clustering mechanisms. Clustering was also modulated by the COMT rs165599 polymorphism independently of the group. A specific effect of the 5-HTTLPR polymorphism on switching performance was also found, with ss carriers performing significantly worse than ls and ll carriers, suggesting a serotonin modulation of frontal-executive flexibility. Based on the impaired clustering and switching strategies observed in ecstasy users, it might be proposed that both semantic knowledge and retrieval are impaired in this population. The verbal fluency deficit in ecstasy users may be attributable to a disruption of frontal-striatal circuits directly related with the serotonin function as well as a depletion of lexical-semantic stores mediated by temporal structures.

Background: We conducted a systematic review to assess the evidence for specific effects of cannabis on brain structure and function. The review focuses on the cognitive changes associated with acute and chronic use of the drug., Method: We reviewed literature reporting neuroimaging studies of chronic or acute cannabis use published up until January 2009. The search was conducted using Medline, EMBASE, LILACS and PsycLIT indexing services using the following key words: cannabis, marijuana, delta-9-tetrahydrocannabinol, THC, cannabidiol, CBD, neuroimaging, brain imaging, computerized tomography, CT, magnetic resonance, MRI, single photon emission tomography, SPECT, functional magnetic resonance, fMRI, positron emission tomography, PET, diffusion tensor MRI, DTI-MRI, MRS and spectroscopy., Results: Sixty-six studies were identified, of which 41 met the inclusion criteria. Thirty-three were functional (SPECT/PET/fMRI) and eight structural (volumetric/DTI) imaging studies. The high degree of heterogeneity across studies precluded a meta-analysis. The functional studies suggest that resting global and prefrontal blood flow are lower in cannabis users than in controls. The results from the activation studies using a cognitive task are inconsistent because of the heterogeneity of the methods used. Studies of acute administration of THC or marijuana report increased resting activity and activation of the frontal and anterior cingulate cortex during cognitive tasks. Only three of the structural imaging studies found differences between users and controls., Conclusions: Functional neuroimaging studies suggest a modulation of global and prefrontal metabolism both during the resting state and after the administration of THC/marijuana cigarettes. Minimal evidence of major effects of cannabis on brain structure has been reported.

Objective: The aims of the study are twofold: (1) to compare semantic fluency, clustering and switching performance among subjects with memory complaints, patients with Alzheimer Disease (AD), and healthy controls; and (2) to examine the clinical utility of the clustering/switching scoring system in the prediction of incident AD in subjects with memory complaints., Methods: A semantic fluency task was used to compare thirty eight subjects with memory complaints, forty two AD patients and twenty five healthy controls on the total number of words generated, clustering and switching performance. Subjects with memory complaints were followed-up for a maximum period of two years and re-evaluated. They remained in the memory complaints group (twenty eight subjects) or were defined as probable AD (ten subjects)., Results: AD patients generated fewer correct words (p < 0.001) and showed a reduction in clustering (p = 0.008) and switching (p < 0.001). Subjects with memory complaints showed a significant reduction in correct words (p < 0.001) and clustering performance (p = 0.008) compare to controls. In the first evaluation, the subgroup of patients who converted to AD at follow up produced less correct words (p < 0.01) and smaller clusters (p = 0.007) than the subgroup who did not become demented. There were no differences in switching between these two subgroups. AD development was better predicted by cluster size than by the total number of words generated or by switching., Conclusions: Subjects with memory complaints and AD patients have an alteration in both qualitative and quantitative aspects of semantic fluency. A clustering analysis could enhance the reliability of early AD diagnosis., (Copyright (c) 2008 John Wiley & Sons, Ltd.)