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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-infinity; one-sided p = 0.049) and a trend in the population-based controls (OR = 1.124, one-sided 95% CI 0.932-infinity; 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. Copyright (C) 2012 S. Karger GmbH, Freiburg

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.

IntroductionSeveral studies recently investigated how Anorexia Nervosa patients (ANp) process multimodal information. Longo (2015) hypothesized that ANp might be less reliant on visual perception of bodies than healthy controls (HC). Case et al. showed that processing of multimodal information might be disrupted in ANp. Literature lacks of studies that measure precisely and compare directly the contributions of each sensory input.ObjectiveTo investigate the integration of visual and haptic inputs in ANp compared with HC and measure the weight of each input.MethodWe used a visuo-haptic integration task with a setup adapted from Gori et al. (2008) to measure each sensory input's when judging the size of a cube according to Maximum Likelihood Estimation theory which describes the optimal multimodal integration behaviour (Ernst and Banks, 2002). Fifteen ANp and 16 HCs were recruited.ResultsRegardless the group, we found considerable individual variability about the integration processes; moreover, many participants did not integrate optimally. Correlation analysis suggested that ANp rely less on visual information then HC.ConclusionsDespite using a setup previously validated with children, the observation that many HC did not integrate optimally is not in line with the results of previous studies, making it difficult the comparison with the AN group. The setup might not be adapted to adults and it needs to be improved. Our study shows for the first time how it might be possible to measure and compare directly the contribution of two different sensory modalities. This could provide precious information to deeply investigate the pathology.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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.

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. © D'Avanzo et al.; Licensee Bentham Open.

BackgroundStudies investigating neurocognitive impairment in subjects with eating disorders (EDs) have reported heterogeneous patterns of impairment and, in some instances, no dysfunction. The present study aimed to define the pattern of neurocognitive impairment in a large sample of bulimia nervosa (BN) patients and to demonstrate that neuroendocrine, personality and clinical characteristics influence neurocognitive performance in BN.MethodAttention/immediate memory, set shifting, perseveration, conditional and implicit learning were evaluated in 83 untreated female patients with BN and 77 healthy controls (HC). Cortisol and 17β-estradiol plasma levels were assessed. Cloninger's Temperament and Character Inventory – Revised (TCI-R), the Bulimic Investigation Test Edinburgh (BITE) and the Montgomery–Asberg Depression Rating Scale (MADRS) were administered.ResultsNo impairment of cognitive performance was found in subjects with BN compared with HC. Cortisol and ‘Self-directedness’ were associated with better performance on conditional learning whereas 17β-estradiol had a negative influence on this domain; ‘Reward dependence’ was associated with worse performance on implicit learning; and depressive symptomatology influenced performance on the Wisconsin Card Sorting Test (WCST) negatively.ConclusionsNo cognitive impairment was found in untreated patients with BN. Neuroendocrine, personality and clinical variables do influence neurocognitive functioning and might explain discrepancies in literature findings.

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. (c) 2007 Elsevier B.V. All rights reserved.

Anorexia nervosa (AN) has a complex pathophysiology, involving heterogeneous environmental and genetic factors, and is not associated to validated biomarkers for diagnosis and follow-up or outcome. Although the evaluation of changes of plasma biochemical markers, such as reproductive and thyroid hormones, adipokines and ghrelin, in AN may reflect the disnutritional condition rather than specific features of the disease [1], the combination of eating disorder and amenorrhea led to hypothesize the involvement of leptin or leptin-related mechanisms in the pathophysiology and the maintenance of this psychiatric syndrome [2, 3]. In AN patients, serum leptin levels are lower than in age-matched controls [4] and increase upon weight gain, together with a reduction of soluble leptin receptor [5]. The present study was aimed at evaluating the changes of plasma leptin in its free (FL) and soluble receptor-bound (BL) fractions and their relationship with body weight gain in AN patients undergoing a refeeding/ rehabilitation program. Materials and methods

We have studied fasting plasma tryptophan (TRP) levels and tryptophan/large neutral amino acid (TRP/LNAA) ratios in 12 patients with obsessive-compulsive disorder (OCD) and 12 patients with OCD and a coexisting current diagnosis of major depressive disorder (OCD-MDD). Assessments were made at baseline and after 6 weeks of treatment with fluvoxamine. OCD-MDD patients had significantly lower baseline TRP levels and TRP/LNAA ratios than OCD patients. After 6 weeks of fluvoxamine treatment, OCD-MDD patients had significant increases in plasma TRP and TRP/LNAA ratio, whereas OCD patients had non-significant decreases. Our data suggest that a major depressive syndrome could be a state variable affecting the changes in plasma TRP and TRP/LNAA ratio in OCD patients. (C) 1997 Elsevier Science Ireland Ltd. Z8 0 ZR 0 ZS 0 ZB 8

Previous reports have stressed the implication of Personality Disorders as predictors of a poorer treatment outcome in Obsessive-Compulsive Disorder (OCD). The aim of this study was to see whether or not Obsessive-Compulsive Personality Disorder in Obsessive-Compulsive Disorder may be predictive for a poorer outcome to antiobsessive pro-serotonergic pharmacological treatment. For this purpose, 30 OCD patients were divided into two groups according to the presence or absence of Obsessive-Compulsive Personality Disorder. Ten-week standardized treatments with oral SRI drugs were given to look for different outcomes between the two groups in Obsessive-Compulsive symptom severity. At the end of the study we found that the presence of Obsessive-Compulsive Personality Disorder, along with the total number of Personality Disorders, did predict poorer response to pharmacological treatment in OCD. (C) 1997 Elsevier Science B.V. Z8 0 ZR 0 ZS 1 ZB 23

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.

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. © 2005 Nature Publishing Group All rights reserved.

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.

Recently, a role for a functional polymorphism within the promoter region of the serotonin transporter gene (5-HTTLPR) in conferring susceptibility to Obsessive Compulsive Disorder (OCD) has been suggested. The aim of this study was to test the hypothesis that allelic variation of the 5-HTTLPR could be associated with OCD susceptibility or influence the drug response in OCD. One hundred and eighty-one OCD patients were recruited; 92 patients underwent a standardized treatment with fluvoxamine. No significant differences in allele/genotype distribution of the 5-HTTLPR were found between 191 controls and OCD. No differences in fluvoxamine response in the three genotypes groups in OCD were found, considering Yale-Brown Obsessive Compulsive Scale (YBOCS) total scores. Nevertheless, a significant time per genotype interaction was found for the YBOCS subtotal compulsion scores. Considering patients without tic disorder co-diagnosis, a significant time per genotype interaction for both YBOCS total scores and compulsion scores was found. Z8 0 ZR 0 ZS 2 ZB 32

In several reports, the acute oral administration of the partial serotonergic agonist meta-chlorophenylpiperazine (mCPP) in dose of 0.5 mg/kg induced a significant worsening of obsessive-compulsive (OC) symptoms in a number of patients. The aim of our study was to test the 0.25 mg/kg mCPP dose, which was hypothesized to be more specific for OC symptoms and was until now tested only on healthy subjects. In a double-blind, controlled crossover study, 12 OC patients participated on three test days, receiving one of the following on each day: oral 0.5 mg/kg mCPP (standard dose), 0.25 mg/kg mCPP (low dose), or placebo. Behavioral ratings were obtained by means of Visual Analogue Scale (VAS) ratings. The low dose mCPP induced a significant worsening of OC symptoms in 50% (6/12) of the patients, whereas 8.3% (1/12) of the patients showed a worsening after the standard dose. On the other hand, only the standard dose mCPP induced a worsening, although not statistically significant, of anxiety ratings. Our data show that the 0.25 mg/kg dose mCPP induces a specific response in OC symptoms, with little anxiogenic effect. To confirm these preliminary data, future studies will be needed on larger samples and with more sensitive rating settles. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. Z8 0 ZR 0 ZS 0 ZB 16

The aim of this study was to evaluate which clinical variables might influence the antiobsessional response to proserotonergic drugs in a sample of patients with obsessive-compulsive disorder (OCD). One hundred fifty-nine patients with DSM-IV OCD underwent a 12-week standardized treatment with fluvoxamine, clomipramine, citalopram, or paroxetine. According to treatment response, defined as a reduction of the Yale-Brown Obsessive Compulsive Scale total score > 35%, patients were divided into two groups. Ninety patients (56.6%) responded to treatment and 69 (43.4%) did not. Responders had a significantly higher frequency of positive family history for OCD (FH-OCD) in their first-degree relatives, whereas nonresponders had an earlier onset and a higher frequency of "poor insight" subtype and somatic obsessions. The predictive value of all these variables was tested by a stepwise logistic regression analysis that confirmed poor insight and FH-OCD to be the best predictors of poor and good drug treatment response, respectively. These preliminary findings need additional investigations toward a better definition of the genetic and biological heterogeneity of patients with OCD, and they underlie the importance of collecting the insight score and family history for psychiatric disorders in the pretreatment assessment. ZR 0 Z8 1

This study investigated the presence of obsessive-compulsive personality disorder (OCPD) in a group of 277 patients (88 with obsessive-compulsive disorder [OCD], 58 with major depressive disorder [MDD], and 131 with panic disorder [Panic]) to test the specificity of the relationship between OCPD and OCD. OCPD is statistically significantly more frequent in patients with OCD than in those with Panic and MDD. The distribution of single criteria of OCPD in the three groups does not differ significantly. Discriminant analysis selects a list of items that provide a correct classification rate of 66% based on OCPD criteria selected by canonical function. OCD patients with and without OCPD do not differ in sex, age of onset, duration of illness, positive family history for Tics disorder/Tourette syndrome (TS), or morbidity risk for OCD. Copyright (C) 1997 by W.B. Saunders Company ZR 0 ZS 0 Z8 1 ZB 13

Twelve patients with obsessive-compulsive disorder were studied after the administration of a mixture of amino acids devoid of tryptophan (TRP) or a mixture containing all the essential amino acids, in a double-blind, crossover design, The TRP-fi-ee mixture caused a marked depletion of plasma TRP, After TRP decrease, mean ratings of obsessions and compulsions, measured by Visual Analogue Scales (VAS) ratings, did not worsen. In contrast with other reports in literature, TRP depletion also failed to alter mood in our subjects. Z8 0 ZS 0 ZR 1 ZB 18

Levels of serum cholinesterase (PsChe) were measured in 32 drug-free patients with obsessive-compulsive disorder (OCD) and 32 sex- and age-matched healthy normal volunteers. No significant differences between OCD patients and normal subjects were found in PsChe levels. A significant positive correlation between patients' PsChe levels and the severity of anxiety, as measured by the Hamilton Rating Scale for Anxiety, was found, in agreement with the hypothesis of a relationship between state anxiety and PsChe activity. In contrast to findings in other reports, PsChe levels significantly increased after 10 weeks of antiobsessional pharmacological treatment, underscoring the potential influence of drugs on PsChe activity. ZB 0 Z8 0 ZR 0 ZS 0