Evaluating Proactive Strategy in Patients With OCD During Stop Signal Task.

OBJECTIVES: The aim of the present study was to investigate "Proactive-Adjustment hypothesis" (PA) during the Stop Signal Task (SST). The PA is implied in the highly inconsistent literature, and it deals with the role of response inhibition (RI) in obsessive-compulsive disorder (OCD). This hypothesis assumed that participants would balance stopping and going by adjusting the response threshold (RT) in the go task. We verified whether the PA strategy was also implemented in our clinical group. METHODS: To reach this goal, we analyzed SST performances in a group of 36 patients with OCD and 36 healthy controls (HCs). To identify different participants' behaviors during the task, without preconceived notions regarding the diagnosis, we performed a cluster analysis. Furthermore, we analyzed the influence of drug therapy and we investigated whether the rule and reversal acquisition investigated with the Intra-Extra Dimensional Set Shift, differed in the two clusters. RESULTS: We did not find any difference relative to the number of patients with OCD and HCs included in the two clusters. Furthermore, we found that only Not Proactive participants performed the task as fast as possible, while Proactive participants consistently slowed down their RTs and showed a lower number of Direction Errors, higher Stop Signal Delay, and worse cognitive flexibility. CONCLUSIONS: Our results show that among patients with OCD the use of PA is changeable and does not differ from HCs. This finding supports the idea that the RI heterogeneity concerning patients with OCD could be related to PA. (JINS, 2018, 24, 703-714).

Planning functioning and impulsiveness in obsessive-compulsive disorder.

Planning ability (PA) is a key aspect of cognitive functioning and requires subjects to identify and organise the necessary steps to achieve a goal. Despite the central role of executive dysfunction in patients with obsessive-compulsive disorder (OCD), deficits in PA have been investigated leading to contrasting results. Given these inconsistencies, the main aim of our work is to give a deeper and clearer understanding of PA in OCD patients. Moreover, we are interested in investigating the relationship between PAs and impulsivity traits and other clinical variables. Sixty-eight OCD patients and 68 healthy controls (HCs) matched for sex and age were assessed through the Stocking of Cambridge (SoC), a computerised version of the Tower of London. We examined planning sub-components for each difficulty levels (from 2 to 5 minimum moves). Our results showed that OCD patients needed longer initial thinking time than HCs during the execution of low demanding tasks (i.e. 2 and 3 moves), while the accuracy level between the two groups did not significantly differ. OCD patients required longer initial thinking time also during high demanding tasks (i.e., 4 and 5 moves), but in this case their accuracy was significantly worse than HCs' one. We did not find any association between impulsivity and PAs. Our results supported the hypothesis that OCD patients were not able to retain in memory the planned sequence and they had to reschedule their movements during the execution. Thus, future studies should deepen the interrelation between working memory and PA to better understand the influence between these two cognitive functions and their interaction with clinical variables in OCD 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.

Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.

A new social-family model for eating disorders: A European multicentre project using a case-control design.

OBJECTIVE: To examine a new socio-family risk model of Eating Disorders (EDs) using path-analyses. METHOD: The sample comprised 1264 (ED patients = 653; Healthy Controls = 611) participants, recruited into a multicentre European project. Socio-family factors assessed included: perceived maternal and parental parenting styles, family, peer and media influences, and body dissatisfaction. Two types of path-analyses were run to assess the socio-family model: 1.) a multinomial logistic path-model including ED sub-types [Anorexia Nervosa-Restrictive (AN-R), AN-Binge-Purging (AN-BP), Bulimia Nervosa (BN) and EDNOS)] as the key polychotomous categorical outcome and 2.) a path-model assessing whether the socio-family model differed across ED sub-types and healthy controls using body dissatisfaction as the outcome variable. RESULTS: The first path-analyses suggested that family and media (but not peers) were directly and indirectly associated (through body dissatisfaction) with all ED sub-types. There was a weak effect of perceived parenting directly on ED sub-types and indirectly through family influences and body dissatisfaction. For the second path-analyses, the socio-family model varied substantially across ED sub-types. Family and media influences were related to body dissatisfaction in the EDNOS and control sample, whereas perceived abusive parenting was related to AN-BP and BN. DISCUSSION: This is the first study providing support for this new socio-family model, which differed across ED sub-types. This suggests that prevention and early intervention might need to be tailored to diagnosis-specific ED profiles.

Evaluating effect of symptoms heterogeneity on decision-making ability in obsessive-compulsive disorder.

AIMS: Despite having a univocal definition, obsessive-compulsive disorder (OCD) shows a remarkably phenotypic heterogeneity. The published reports show impaired decision-making in OCD patients, using tasks such as the Iowa Gambling Task (IGT). We wanted to verify the hypothesis of an IGT worse performance in a large sample of OCD patients and healthy control (HC) subjects and to examine the relation between neuropsychological performance in IGT and the OCD symptoms heterogeneity. METHODS: Binary data from the Yale-Brown Obsessive Compulsive Scale collected on a large sample of OCD patients were analyzed using a multidimensional item response theory model to explore the underlying structure of data, thus revealing latent factors. Factor scores were categorized into quartiles. Then, for each factor, we identified patients respectively with the highest versus lowest score. We evaluated whether symptom dimensions affect the probability of a correct answer over time generalized, during IGT performance, fitting a generalized linear mixed model. RESULTS: We found a general deficit in ambiguous decision-making in OCD compared to HC. Moreover, our findings suggested that OCD symptoms heterogeneity affects decision-making learning abilities during IGT. In fact, while 'Symmetry' and 'Washing' patients showed a learning curve during the task, other subgroups did not. CONCLUSIONS: Our study confirmed previous findings suggesting that OCD is characterized by a deficit in decision-making under uncertainty. Moreover, our study gave evidence about biological specificity for each symptom dimension in OCD. Data were discussed in the context of the somatic marker hypothesis, which was hypothesized to be reduced in OCD patients.

The somatic marker affecting decisional processes in obsessive-compulsive disorder.

INTRODUCTION: Patients with obsessive-compulsive disorder (OCD) demonstrate impairment in decisional processes in which both cognition and emotion play a crucial role. METHODS: We investigated the connection between decision-making performances and choice-related skin conductance responses (SCRs), to identify a somatic marker impairment affecting decisional processes in these patients. We explored SCRs during the Iowa Gambling Task in 20 OCD and 18 control, measuring anticipatory and posticipatory psychophysiological reactions according to card choices and to the outcomes of each selection. RESULTS: Most patients exhibited weaker SCRs compared to HC, although there weren't substantial differences in magnitude between the two groups. In contrast with HC, patients with OCD showed no significant differences of SCRs activation according to card selections; they chose cards from neither favourable nor unfavourable decks. CONCLUSIONS: The main finding of the study were the evidence of a dysfunctional biological marker in OCD subjects, affecting decision-making process. Dysfunctional patterns of SCRs could partially explain OCDs' impairment in this ability. Decision-making deficits in OCDs could be influenced in part by the lack of somatic differences in discriminating between advantageous and disadvantageous behaviour. These findings could lead to a more complete understanding of OCD.

Temperament, character and anxiety sensitivity in panic disorder: a high-risk study.

BACKGROUND: Adult patients with panic disorder (PD) show high levels of harm avoidance and anxiety sensitivity. Peculiar temperament profiles and high anxiety sensitivity have been proposed as developmental risk factors for PD in adult age. Since familial-genetic influences play a role both in PD and in anxiety sensitivity and temperament profiles, this study aims to investigate the possible association between family history of PD and peculiar temperament-character profiles or high anxiety sensitivity in offspring of patients with PD. SAMPLING AND METHODS: Thirty-four children of patients with PD with/without agoraphobia and 30 children of healthy subjects were compared. Temperament and character dimensions and anxiety sensitivity levels of children were obtained by the Junior Temperament and Character Inventory and the Childhood Anxiety Sensitivity Index. RESULTS: Children of patients with PD and children of healthy subjects differed neither in temperament and character dimensions nor in anxiety sensitivity levels. CONCLUSIONS: Our results show that family history of PD is not associated with peculiar temperament and character profiles or high anxiety sensitivity in children, suggesting that these factors may not be early expressions of familial vulnerability to PD. Since the sample is small and the study has a cross-sectional design, longitudinal studies in larger samples are warranted to confirm these findings and to clarify the role of anxiety sensitivity and temperament-character dimensions in the development of PD.

Novel antidepressants and panic disorder: evidence beyond current guidelines.

AIM: The aim of the present review is to summarize available evidence about the efficacy and side effects of novel antidepressants for the treatment of panic disorder. METHODS: A literature search was undertaken using MEDLINE, ISI web of knowledge and references of retrieved articles. The search included articles published in English up to September 2009. Both controlled and uncontrolled trials were included. The quality of the reviewed articles was also assessed. RESULTS: Fourteen mainly poor-quality studies were included. Mirtazapine showed some efficacy in reducing the number and the severity of panic symptoms in many uncontrolled studies and was comparable to selective serotonin reputake inhibitors (SSRIs) in direct-comparison studies. Reboxetine was significantly more efficacious than placebo but less effective than SSRIs. Further uncontrolled studies suggested preliminary evidence for the use of milnacipran and duloxetine as well. All drugs were usually well tolerated. DISCUSSION: Current studies do not yet provide convincing evidence supporting the efficacy of mirtazapine, reboxetine, milnacipran and duloxetine for the treatment of panic disorder patients. However, on account of positive preliminary results, further research is warranted.

Factors of risk and maintenance for eating disorders: psychometric exploration of the cross-cultural questionnaire (CCQ) across five European countries.

OBJECTIVE: To explore the psychometric properties of the Cross-Cultural Questionnaire (CCQ), a new self-report tool for assessing factors of risk and maintenance for eating disorders (ED). METHOD: Data was collected during a multi-centre case-control study. The sample included 854 ED patients and 784 healthy participants from the UK, Spain, Austria, Slovenia and Italy. Exploratory factor analyses examined the factor structure of each section of the CCQ, and Cronbach's alpha coefficients valued the internal consistency of each derived scale score. Logistic regression and receiver operating characteristic (ROC) curve procedure assessed the screening accuracy and predictive validity of the empirical factors. RESULTS: Based on a total of 127 items, nine dimensions emerged, with satisfactory internal consistency and high congruence between countries. CCQ scores demonstrated satisfactory accuracy for discriminating between ED cases and controls (area under the ROC curve = 0.88). Most of the items achieved discriminative accuracy. CONCLUSIONS: This study offers preliminary evidence that the CCQ, available in five languages, is a useful and valid tool to assess factors of risk and maintenance for EDs.

Acoustic startle response in panic disorder.

The amygdala and the limbic system are important in inducing a fear reaction; if this "fear network" is involved in panic disorder, panic patients might be more sensitive to fear stimuli than healthy subjects. We compared the startle response with an aversive stimulus in a sample of 29 patients with panic disorder and a sample of 29 healthy controls. The intensity of the startle response, induced by a series of aversive loud (100 dB) sounds, was measured by skin conductance recording in each subject. No statistically significant differences between the two groups were found in either the baseline level of skin conductance or in the response to the stimuli. Nonetheless, panic patients reported significantly higher levels of baseline anxiety measured by the State-Trait Anxiety Inventory. In conclusion, our data do not support the hypothesis that patients with panic disorder are characterised by a hyperreactivity, as measured by the skin conductance response, to fearful sudden stimuli or, at least, to those delivered to the auditory system.

Emotional intelligence in panic disorder.

Panic attacks are psychopathological phenomena with a strong emotional activation that often induces subsequent anticipatory anxiety and phobic avoidance. Impairment in emotional processing in patients with Panic Disorder (PD) has been hypothesized. Emotional Intelligence (EI) involves the individual abilities to perceive, understand and manage emotions in order to cope with changes in internal and external environment. We examined EI in 42 patients with PD with Agoraphobia compared to 49 healthy controls and investigated if clinical severity of Agoraphobia is related to EI performance. We assessed EI by Mayer-Salovey-Caruso Emotional Intelligence Test and Agoraphobia by Mobility Inventory for Agoraphobia. Patients with PD and Agoraphobia showed lower Strategic EI ability than healthy controls, in both Understanding and Managing emotion abilities, and a general propensity to attribute negative emotional valence to different stimuli. These preliminary results suggest that impaired mechanisms of understanding and integrating emotions may be involved in the phenomenology of PD. These features might be the target of psychological interventions in PD. On the contrary, Emotional Intelligence did not appear to affect the clinical severity of Agoraphobia.

Artificial neural network model for the prediction of obsessive-compulsive disorder treatment response.

Several patients with obsessive-compulsive disorder (OCD) who are refractory to adequate treatment with first-line treatments are considered treatment-resistant. Further surveys were to be implemented to explore the outcome predictors of the antiobsessional response. Such study was aimed at building a model suitable to predict the final outcome of a mixed OCD pharmacologic and nonpharmacologic treatment approaches. We studied 130 subjects with OCD who underwent pharmacologic (with selective serotonin reuptake inhibitors alone or with selective serotonin reuptake inhibitors and risperidone at low dosage) and/or behavioral therapy (using exposure and response prevention techniques). The following variables were used as predictors: symptoms dimension, as resulting from the Yale-Brown Obsessive-Compulsive Scale items factor analysis; neuropsychologic performances; and epidemiologic variables. The treatment response arising from 3 to 6 months of therapy was used as dependent variable. A conventional logistic regression was used to define a previsional model of treatment response and multilayer perceptrons and to supervise an artificial neural network technique. The 46.9% of the sample resulted to be refractory to treatment. Results obtained with the logistic regression model showed that the only predictors of treatment outcome are hoarding symptoms, repeating rituals, and counting compulsions. Furthermore, using all the variables considered in the models, multilayer perceptrons showed highly better predictive performance as compared with the logistic regression models (93.3% vs 61.5%, respectively, of correct classification of cases). Complex interactions between different clinical and neuropsychologic variables are involved in defining OCD treatment response profile, and nonlinear and interactive modeling strategies, that is, supervised artificial neural networks, seem to be more suitable to investigate this complexity than linear techniques.

Associations of individual and family eating patterns during childhood and early adolescence: a multicentre European study of associated eating disorder factors.

The objective of this study was to examine whether there is an association between individual and family eating patterns during childhood and early adolescence and the likelihood of developing a subsequent eating disorder (ED). A total of 1664 participants took part in the study. The ED cases (n 879) were referred for assessment and treatment to specialized ED units in five different European countries and were compared to a control group of healthy individuals (n 785). Participants completed the Early Eating Environmental Subscale of the Cross-Cultural (Environmental) Questionnaire, a retrospective measure, which has been developed as part of a European multicentre trial in order to detect dimensions associated with ED in different countries. In the control group, also the General Health Questionnaire-28 (GHQ-28), the semi-structured clinical interview (SCID-I) and the Eating Attitudes Test (EAT-26) were used. Five individually Categorical Principal Components Analysis (CatPCA) procedures were adjusted, one for each theoretically expected factor. Logistic regression analyses indicated that the domains with the strongest effects from the CatPCA scores in the total sample were: food used as individualization, and control and rules about food. On the other hand, healthy eating was negatively related to a subsequent ED. When differences between countries were assessed, results indicated that the pattern of associated ED factors did vary between countries. There was very little difference in early eating behaviour on the subtypes of ED. These findings suggest that the fragmentation of meals within the family and an excessive importance given to food by the individual and the family are linked to the later development of an ED.

Common genetic, clinical, demographic and psychosocial predictors of response to pharmacotherapy in mood and anxiety disorders.

The aim of this study is to summarize available knowledge about common genetic, clinical, demographic and psychosocial predictors of response to pharmacotherapy in mood and anxiety disorders. A literature search was carried out by using MEDLINE and references of selected articles. The search included articles published up to March 2008. The main genetic finding concerns the serotonin transporter gene promoter polymorphisms, the long variant of which seems to be related to a positive response to therapy in mood disorders and could also have a role in the treatment of anxiety disorders. Among other predictors, the main factors common to both classes of disorder are comorbid axis II disorders and early onset of illness, which are related to a worse response to therapy and concomitant good physical conditions, absence of earlier treatments, early administration and response to therapies, and higher self- directedness, which is related to a better outcome. Many common predictors have been identified and these seem to be related to features covering the totality of patients that go beyond specific characteristics of single disorders. Possible limitations and suggestions for future research based on a more integrated vision of human complexity are discussed.

In vivo PET study of 5HT(2A) serotonin and D(2) dopamine dysfunction in drug-naive obsessive-compulsive disorder.

There are several lines of evidence, the majority indirect, suggesting that changes in serotonergic or dopaminergic neurotransmission may contribute to the pathogenesis of obsessive-compulsive disorder (OCD). We evaluated the co-occurrence of serotonergic and dopaminergic dysfunctions in OCD subjects, all drug-naive, with no co-morbidity and homogeneous for symptoms. Each subject underwent two positron emission tomography (PET) scans to measure in vivo both serotonin (5-HT(2A)) and dopamine (D(2)) receptor distribution. For this, we used [11C]MDL and [11C]Raclopride, highly selective antagonists of 5-HT(2A) and D(2) receptors, respectively. The comparison with a control group was carried out using both voxel-wise (SPM2) and regions of interest (ROI) approaches. There was a significant reduction of 5-HT(2A) receptor availability in frontal polar, dorsolateral, and medial frontal cortex, as well as in parietal and temporal associative cortex of OCD patients. We also found a significant correlation between 5-HT(2A) receptor availability in orbitofrontal and dorsolateral frontal cortex and clinical severity, suggesting a specific role for serotonin in determining the OCD symptoms. There was also a significant reduction of [11C]Raclopride uptake in the whole striatum, particularly in the ventral portion, possibly reflecting endogenous dopaminergic hyperactivity. The co-existence of serotonergic and dopaminergic dysfunction in the same homogeneous group of drug-naive OCD patients provides in vivo evidence for the complex molecular mechanisms of OCD, and represents the basis for further studies on the effect of therapeutic agents with specific modulatory effects on these neurotransmission systems.

Present and lifetime comorbidity of tobacco, alcohol and drug use in eating disorders: a European multicenter study.

OBJECTIVES: To assess the differences in comorbid lifetime and current substance use (tobacco, alcohol and drug use) between eating disorder (ED) patients and healthy controls in five different European countries. METHOD: A total of 1664 participants took part in the present study. ED cases (n=879) were referred to specialized ED units in five European countries. The ED cases were compared to a balanced control group of 785 healthy individuals. ASSESSMENT: Participants completed the Substance Use Subscale of the Cross Cultural (Environmental) Questionnaire (CCQ), a measure of lifetime tobacco, alcohol and drug use. In the control group, also the GHQ-28, the SCID-I interview and the EAT-26 were used. RESULTS: ED patients had higher lifetime and current tobacco and general drug use. The only non-significant result was obtained for lifetime and current alcohol use. Significant differences across ED subdiagnoses and controls also emerged, with BN and AN-BP generally presenting the highest and AN-R and controls the lowest rates. The only exception was detected for alcohol use where EDNOS demonstrated the highest values. Only a few cultural differences between countries emerged. CONCLUSIONS: With the exception of alcohol consumption, tobacco and drug use appear to be more prevalent in ED patients than healthy controls. The differential risk observed in patients with bulimic features might be related to differences in temperament or might be the result of increased sensitivity to reward.

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.

Fluvoxamine treatment and D2 receptors: a pet study on OCD drug-naïve patients.

Changes in D(2) receptors during antidepressant therapy have been reported in patients with major depressive disorder using PET/SPET. The aim of this study was to evaluate modifications in D(2) receptors that might occur in patients affected by obsessive-compulsive disorder (OCD) during serotonin reuptake sites inhibitors (SSRIs). To this purpose, we measured the in vivo binding of [(11)C]raclopride ([(11)C]Rac)in the brain of a group of OCD naïve patients before and after the repeated administration of the inhibitor SSRI fluvoxamine. Eight patients with a Diagnostic and Statistical Manual of Mental Disorders IVth edition diagnosis of OCD completed the study undergoing a PET scan and a complete clinical evaluation before and during treatment with fluvoxamine. Patients have been compared also with a group of nine age-matched normal volunteers. Fluvoxamine treatment significantly improved clinical symptoms and increased [(11)C]Rac binding potential (BP) in the basal ganglia of OCD patients (7.5+/-5.2, 6.9+/-6.9, and 9.9+/-9.3% in dorsal caudate, dorsal putamen, and ventral basal ganglia, respectively; p<0.01) to values closer to those observed in the group of normal subjects. Chronic treatment with fluvoxamine induces a slight but significant increase in striatal [(11)C]Rac BP of previously drug-naïve OCD patients. The modifications in D(2) receptor availability might be secondary to fluvoxamine effects on serotoninergic activity.