An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis.

INTRODUCTION: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. METHODS: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. RESULTS: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. CONCLUSION: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

Is Repetitive Transcranial Magnetic Stimulation (RTMS) a Promising Therapeutic Intervention for Eating Disorders and Obesity? Clinical Considerations Based on a Meta-Analytic Review.

Objective: Repetitive Transcranial Magnetic Stimulation (rTMS) has been introduced to treat eating disorders (EDs), especially Anorexia, Bulimia Nervosa (AN and BN) and other EDs not otherwise specified (NOS). Provisional rTMS single-case studies and clinical trials have been carried out for the treatment of binge eating disorder (BED) and obesity. However, it is still unclear whether and to what extent rTMS might be considered an effective intervention for these conditions. Method: This meta-analysis includes 15 independent studies examining the clinical effects of rTMS among different EDs and obesity (N = 402 patients). Several primary and secondary treatment outcomes have been considered. Cohen's d was used as an effect size measure. The analyses estimate heterogeneity across findings, sources of variability and publication bias together with an assessment of the quality of the studies. Results: The analyses show that rTMS induced large improvements in body mass index (BMI) among obese individuals. Null clinical effects have been detected for primary outcomes (i.e., BMI, binge eating and compensatory behaviors; urge to binge and to eat; severity of EDs symptoms) among individuals with AN, BN and other EDs-NOS. rTMS shows moderate therapeutic effects on the affective functioning (i.e., negative affectivity, depressive and anxious symptoms) of individuals with EDs. rTMS should be considered a promising intervention for the treatment of obesity. Conclusions: This evidence might provisionally support the hypothesis on the implementation of rTMS for BED. Furthermore, rTMS could be included as an ancillary intervention for the other EDs, especially considering secondary treatment outcomes. Future controlled trials are needed to clarify the clinical effects of rTMS for EDs.

Validation of the Italian version of the Power of Food Scale in the adult population.

PURPOSE: The Power of Food Scale (PFS) is designed to measure the personal susceptibility to highly processed and palatable foods. The purpose of this study was to validate the Italian version of PFS (PFS-It) in the adult population. METHODS: Data were obtained from 536 Italian adults aged between 18 and 86 years. The PFS-It and the Binge Eating Scale (BES) were administered to all participants. RESULTS: The factorial structure of the PFS-It was investigated using a CFA that returned excellent fit indices. The Cronbach's alpha coefficients for the PFS-It total score and for its subscales (Food Available, Food Present, and Food Tasted), as well as for the BES total score, revealed good to moderate reliability. Finally, PFS-It was positively and significantly correlated with BES. CONCLUSION: To our knowledge, this is the first study to propose the norms and psychometric characteristics of the Power of Food Scale in an Italian population. The results show that PFS-it is a valid and reliable instrument for the measurement of Hedonic Hunger in an adult Italian population. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Did i do that? Cognitive flexibility and self-agency in patients with obsessivecompulsive disorder.

Self-agency can be understood as the ability to infer causal relationships between actions and sensory events. Obsessive-Compulsive Disorder (OCD) patients with checking compulsions often report lack of "action-completion" sensations, possibly due to an altered sense of agency in these patients. The present study aimed to investigate whether self-agency was related to cognitive flexibility in OCD checkers. In 18 adult OCD checkers and 18 age- and gender-matched healthy controls, cognitive flexibility was assessed with the Intra-Extra Dimensional Set Shift Task (IED). Self-agency attribution was evaluated in two tasks that targeted the novel construct of "gaze-agency", the capability of an observer to identify his or her own eye movements as the cause of a concurrent event (here, an auditory beep). This technique allows sensitive measurement of agency under subtly varying investigator-controlled conditions. OCD checkers manifested significantly inferior performance correctly ascribing the beeps to their own ocular saccades than controls, even when after a hint was provided. Although cognitive inflexibility (errors on the IED) did not differ significantly between the two groups, within the OCD sample there were positive correlations between errors in self-agency attribution and total and extra-dimensional shift errors. These findings show that cognitive inflexibility is related to self-agency in OCD.

Binge Eating Disorder: What Is the Role of Physical Activity Associated with Dietary and Psychological Treatment?

Binge eating patients present lower physical activity levels, which could be associated with lower exercise capacity. Specific physical activity can ensure broad beneficial results relating to eating disorders, depression, and body mass index (BMI) in bulimia; however, research on binge eating disorder (BED) is scarce. Our study aimed to investigate the effects of specific training as an addition to conventional treatment of eating disorder symptoms, anthropometric characteristics, and physical performance. Nineteen women with BED were included in a dietary and cognitive-behavioral therapy program. After medical examination, 10 women carried out Combined Aerobic and Anaerobic Exercise Training in addition to conventional treatment (CAAET group), whereas the remaining 9 followed the conventional treatment alone (CTRL group). All of the measurements were assessed before and after six months of treatment. In both groups, we observed a significant decrease in binge episodes, weight, and body mass index, and an increase in exercise capacity. Moreover, the CAAET group presented a greater improvement in aerobic performance than that observed in the CTRL group. Our results suggest that both interventions similarly improved BED symptoms. The addition of physical activity could be important in the long-term maintenance of both weight loss and reduction in binge episodes in BED patients.

Eating disorders.

Twenty years have passed from the International Classification of Diseases, Tenth Revision (ICD-10) to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and, in the meanwhile, a lot of research data about eating disorders has been published. This article reviews the main modifications to the classification of eating disorders reported in the "Feeding and Eating Disorders" chapter of the DSM-5, and compares them with the ICD-10 diagnostic guidelines. Particularly, we will show that DSM-5 criteria widened the diagnoses of anorexia and bulimia nervosa to less severe forms (so decreasing the frequency of Eating Disorders, Not Otherwise Specified (EDNOS) diagnoses), introduced the new category of Binge Eating Disorder, and incorporated several feeding disorders that were first diagnosed in infancy, childhood, or adolescence. On the whole, the DSM-5 revision should allow the clinician to make more reliable and timely diagnoses for eating disorders.

Personality in women with endometriosis: temperament and character dimensions and pelvic pain.

STUDY QUESTION: Is pelvic pain due to endometriosis associated with temperament and character dimensions? SUMMARY ANSWER: Women with endometriosis and pelvic pain do not clearly exhibit a specific personality profile; however, personality is associated with pelvic pain perception. WHAT IS KNOWN ALREADY: There is research evidence suggesting that endometriosis patients with pelvic pain are more likely to present psychological disruption. Little is known about the association between subjective factors, such as personality traits, and pelvic pain. STUDY DESIGN, SIZE, DURATION: This cross-sectional study (N = 133) is part of a larger research on the association between endometriosis and several psychological variables carried out between 2012 and 2014. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: The participants were 82 endometriosis patients and 51 healthy controls. Endometriosis patients indicated on a dichotomous scale (yes/no) whether they were suffering from pelvic pain and were divided in two study groups: painful endometriosis group (N = 58) and pain-free endometriosis group (N = 24). The severity of pelvic pain (chronic pelvic pain, dysmenorrhoea, dyspareunia, and dyschezia) was rated on a 0-10 point numerical rating scale. All participants completed a 240-item psychometric test (TCI-R) evaluating personality in terms of temperament and character dimensions. MAIN RESULTS AND THE ROLE OF CHANCE: Women with painful endometriosis had lower novelty seeking compared with the control group (P = 0.017) and higher harm avoidance (P = 0.007) and lower exploratory excitability (P = 0.034) and responsibility (P = 0.027) compared with the pain-free endometriosis group, as well as higher fatigability compared with the pain-free endometriosis group (P = 0.001) and the control group (P = 0.032). Higher harm avoidance (B = 0.081; P = 0.002) and lower self-directedness (B = -0.053; P = 0.015) were associated with a greater severity of chronic pelvic pain. LIMITATIONS, REASONS FOR CAUTION: These study findings should be taken cautiously for several methodological reasons such as small sample size, differences in group sizes and cultural homogeneity. More research is needed to further investigate the association between personality and pelvic pain related to endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest new avenues for future research and treatment of endometriosis. The association between the severity of chronic pelvic pain and personality may help clarify the lack of a direct correlation between pain severity and the type and stage of endometriosis, as well as the inconsistencies in patients' response to medical and/or surgical treatment. Therapeutic strategies should be specifically targeted on individual women and involve an integrated approach to the treatment of chronic pelvic pain related to endometriosis. STUDY FUNDING/COMPETING INTERESTS: There was no external funding for this study and the authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable to this study.

Executive functioning in anorexia nervosa patients and their unaffected relatives.

Formal genetic studies suggested a substantial genetic influence for anorexia nervosa (AN), but currently results are inconsistent. The use of the neurocognitive endophenotype approach may facilitate our understanding of the AN pathophysiology. We investigated decision-making, set-shifting and planning in AN patients (n=29) and their unaffected relatives (n=29) compared to healthy probands (n=29) and their relatives (n=29). The Iowa Gambling Task (IGT), the Tower of Hanoi (ToH) and the Wisconsin Card Sorting Test (WCST) were administered. Concordance rates and heritability indices were also calculated in probands/relatives. Impaired performance on the IGT and the WCST were found in both AN probands and their relatives, although planning appeared to be preserved. The IGT heritability index suggested the presence of genetic effects that influence this measure. No evidence for genetic effects was found for the WCST. The results suggest the presence of a shared dysfunctional executive profile in women with AN and their unaffected relatives, characterized by deficient decision-making and set-shifting. Concordance analysis strongly suggests that these impairments aggregate in AN families, supporting the hypothesis that they may constitute biological markers for AN. Decision-making impairment presents a moderate heritability, suggesting that decision-making may be a candidate endophenotype for AN.

Fat mass and obesity-associated gene (FTO) in eating disorders: evidence for association of the rs9939609 obesity risk allele with bulimia nervosa and anorexia nervosa.

OBJECTIVE: The common single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity-associated gene (FTO) is associated with obesity. As genetic variants associated with weight regulation might also be implicated in the etiology of eating disorders, we evaluated whether SNP rs9939609 is associated with bulimia nervosa (BN) and anorexia nervosa (AN). METHODS: Association of rs9939609 with BN and AN was assessed in 689 patients with AN, 477 patients with BN, 984 healthy non-population-based controls, and 3,951 population-based controls (KORA-S4). Based on the familial and premorbid occurrence of obesity in patients with BN, we hypothesized an association of the obesity risk A-allele with BN. RESULTS: In accordance with our hypothesis, we observed evidence for association of the rs9939609 A-allele with BN when compared to the non-population-based controls (unadjusted odds ratio (OR) = 1.142, one-sided 95% confidence interval (CI) 1.001-∞; one-sided p = 0.049) and a trend in the population-based controls (OR = 1.124, one-sided 95% CI 0.932-∞; one-sided p = 0.056). Interestingly, compared to both control groups, we further detected a nominal association of the rs9939609 A-allele to AN (OR = 1.181, 95% CI 1.027-1.359, two-sided p = 0.020 or OR = 1.673, 95% CI 1.101-2.541, two-sided p = 0.015,). CONCLUSION: Our data suggest that the obesity-predisposing FTO allele might be relevant in both AN and BN.

Formal and informal help-seeking for mental health problems. A survey of preferences of italian students.

Help-seeking preferences for mental health are a crucial aspect to design strategies to support adolescents in an emotionally delicate life phase. Informal help-seeking is usually preferred but little was published about preferences in different cultures, and it is not clear whether informal and formal help are mutually exclusive or whether they are part of the same overall propensity to help-seeking. In a survey of 710 students in Milan, Italy, help-seeking propensity measured through an Italian version of the General Help-Seeking Questionnaire was high, similar in males and females (mean total score 3.8, DS 0.9); few (9%) tended not to seek help. The most-preferred source of help was a friend, then father or mother, partner, psychologist and psychiatrist. 355 students (55%) reported high propensity to seek both informal and formal help; 33 (5%) would only seek formal help. Help-seeking should be promoted in itself, rather than indicating professionals and professional settings as primary sources of help.

Motor inhibition and cognitive flexibility in eating disorder subtypes.

Anorexia Nervosa (AN) and Bulimia Nervosa (BN) are complex Eating Disorders (EDs). Even if are considered two different diagnostic categories, they share clinical relevant characteristics. The evaluation of neurocognitive functions, using standardized neuropsychological assessment, could be a interesting approach to better understand differences and similarities between diagnostic categories and clinical subtypes in EDs thus improving our knowledge of the pathophisiology of EDs spectrum. This study explored cognitive flexibility and motor inhibition in patients with AN considering both Restricter and Binge/Purge subtypes, patients with BN and healthy comparisons subjects (HC). Intra-Extra Dimentional Set shifting Test and Stop Signal Task, selected from CANTAB battery, were administered to analyzed set-shifting and motor inhibition respectively. AN patients showed a deficient motor inhibition compared to HC, while no evidence for impaired motor inhibition was found in BN patients; a significant relationship between commission errors in the Stop Signal Task and attentional impulsiveness was found. Moreover, no difference in set-shifting abilities was found comparing all clinician groups and HC. So our results indicated no cognitive impairment in these two cognitive functions in BN patients, while AN and BN showed different performances in motor inhibition. A similar cognitive profile was found in other obsessive compulsive spectrum disorders. Finally, the paper suggests a new interactive approach for the study of cognitive profile in psychiatric disorders; it might be more useful since it is more closely related to the executive functions complexity.

Self-injurious behavior and attempted suicide in purging bulimia nervosa: associations with psychiatric comorbidity.

BACKGROUND: Few studies, to date, have investigated the relationship between self-damaging behavior and the presence of comorbid psychiatric diagnoses in eating disorders. The aim of the present study was to investigate the axis I and II comorbidity in subjects with bulimia nervosa who report self-injurious behavior and/or suicide attempt. METHODS: The subjects were 95 patients with purging type bulimia nervosa who underwent a clinical evaluation assessing the presence of self-injurious behavior and suicide attempts, comorbidity for axis I and II psychiatric disorders and temperament. RESULTS: No axis I diagnosis was associated with any type of self-injurious behavior, whereas social phobia and bipolar disorder were linked to attempted suicide. Significant independent predictors of impulsive self-injurious behavior were the presence of childhood sexual abuse, high harm avoidance scores, and high self-transcendence scores, whereas childhood sexual abuse, the presence of a cluster B personality disorder, and a low self-directedness were predictors of suicide attempts. Compulsive self-injurious behavior was significantly associated with harm avoidance and cluster C personality disorders. Harm avoidance was also associated with skin picking. CONCLUSIONS: Personality disorders are a frequent correlate of the presence of SIB in purging bulimia nervosa. However, temperament seems to play a more important role. Further studies on larger samples are necessary to confirm our findings in bulimia nervosa and to extend them to other patient populations.

Investigation of the serotonin transporter regulatory region polymorphism in bulimia nervosa: relationships to harm avoidance, nutritional parameters, and psychiatric comorbidity.

OBJECTIVE: Genes involved in 5HT transmission have been supposed to contribute to the biologic vulnerability for bulimia nervosa (BN). Because a long (L) and a short (S) variant of the promoter region of the 5HT transporter gene have been identified, we tested whether the 5HTT gene-linked polymorphic region (5HTTLPR) could represent a susceptibility factor for BN and/or could be related to nutritional parameters, harm avoidance personality dimension, and psychiatric comorbidity. METHODS: A total of 219 white women (125 bulimics and 94 healthy control subjects) underwent a blood sample collection for 5HTTLPR genotyping and a clinical evaluation assessing comorbidity for axis I and II psychiatric disorders, harm avoidance personality dimension, and body composition (only patients). RESULTS: The distribution of the 5HTTLPR genotypes did not significantly differ between patients and control subjects, although the L allele was significantly more frequent in the former. Bulimic individuals carrying at least one copy of the S allele had significantly lower mean body mass index and body fat mass values and significantly higher mean harm avoidance score than patients with the LL genotype. No significant association was found between the 5HTTLPR genotype and comorbid axis I and II psychiatric disorders. CONCLUSIONS: These findings support the view that polymorphic variants of the 5HTT promoter region do not play a part in predisposing to BN, whereas they seem to predispose bulimic individuals to nutritional impairment and increased harm avoidance.

Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations.

Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case-control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the -270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI.

Low-dose risperidone augmentation of fluvoxamine treatment in obsessive-compulsive disorder: a double-blind, placebo-controlled study.

According to previous data, the addition of risperidone in obsessive-compulsive patients refractory to serotonin reuptake inhibitors (SRIs) is shown to be a safe and effective treatment strategy. The aims of our study were to evaluate the efficacy of risperidone addition, in comparison to placebo, in fluvoxamine-refractory obsessive-compulsive patients and to investigate whether risperidone could boost the efficacy of fluvoxamine in fluvoxamine-responder patients. Subjects were 45 obsessive-compulsive inpatients, consecutively recruited at the Department of Neurosciences at the San Raffaele Hospital, Milan. Thirty-nine patients completed the study. All patients received 12 weeks of a standardized open-label fluvoxamine monotherapy and then continued for 6 weeks with placebo or risperidone in a double-blind design. Results showed a significant effect of risperidone addition, at the end of the double-blind phase (18th week), only for fluvoxamine-refractory patients. Five patients on risperidone (50%) and two (20%) on placebo became responders, with a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) decrease > or =35%. Risperidone was generally well tolerated, except for a mild transient sedation and a mild increase in appetite. This preliminary study suggests that even very low (0.5 mg) risperidone doses are effective in OC patients who were nonresponders to a standardized treatment with fluvoxamine.

Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations.

Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates involved in the etiology of eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia nervosa (AN) or bulimia nervosa (BN) have been identified. Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of food intake and body weight in rodents. We previously reported a strong association of the Met66 allele of the Val66Met BDNF variant with restricting AN (ANR) and low minimum body mass index in Spanish patients. Another single nucleotide polymorphism located in the promoter region of the BDNF gene (-270C>T) showed lack of association with any ED phenotype. In order to replicate these findings in a larger sample, we performed a case-control study in 1142 Caucasian patients with ED consecutively recruited in six different centers from five European countries (France, Germany, Italy, Spain and UK) participating in the 'Factors in Healthy Eating' project. We have found that the Met66 variant is strongly associated to all ED subtypes (AN, ANR, binge-eating/purging AN and BN), and that the -270C BDNF variant has an effect on BN and late age at onset of weight loss. These are the first two variants associated with the pathophysiology of ED in different populations and support a role for BDNF in the susceptibility to aberrant eating behaviors.