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.

Evaluation of Mother-Child Agreement and Factorial Structures of the SCARED Questionnaire in an Italian Clinical Sample.

Background: A great part of the literature has confirmed the importance of both child and parents reports as source of factual information, especially for childhood emotional syndromes. In our study we aimed at: (i) calculating mother-child agreement and (ii) evaluating factorial structure of the Screen for Child Anxiety Related Emotional Disorders (SCARED) questionnaire in an Italian clinical sample. The novelty of this contribution is two-fold: first, from a clinical point of view, we investigated the parent-child agreement level and examined separately the factorial structures of both parent and child versions of the SCARED for the first time in an Italian clinical sample. Second, unlike previous studies, we used statistical approaches specifically suited to account for the ordinal nature of the collected variables. Method: In a clinical sample of 171 children and adolescents aged 8-18 and their mothers we evaluated inter-rater agreement using weighted kappa indices to assess agreement for each item belonging to a certain SCARED subscale. Exploratory factor analysis for ordinal data was then performed on the polychoric correlation matrix calculated on SCARED items. Differences in the numbers of symptoms reported by children and parents were evaluated as well. Results and Conclusions: Our results reveal moderate to strong mother-child agreement. A significant age effect is present. Two different factorial solutions emerged for parent and child SCARED versions (a 5 factor structure for parents and a 6 factor solution in the child version, including a new factor "Worry about Parents"). This study confirmed the importance of evaluating both child and parent reports in assessment protocols for anxiety disorders. Our findings could help clinicians to determine which information, and from which rater, must be accounted for in evaluating treatment decisions. Moreover, we find that patients characteristics, such as gender and age, should be taken into account when assessing agreement.

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.

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.

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD. METHOD: The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders. RESULTS: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01). CONCLUSIONS: Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.

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.

Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.

OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. METHOD: The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. RESULTS: Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p = .09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p = .08 in the current study, p = .025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%). CONCLUSION: Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes.

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.

Smoking, physical activity and respiratory irregularities in patients with panic disorder.

BACKGROUND: In the past decades different evidences suggested a relationship between panic disorder (PD) and respiration, among which the presence of different respiratory irregularities at rest in PD patients. It has been hypothesized that PD could be characterized by a dysfunction of those areas involved in the central control of respiration. The aim of the present study was to elucidate possible differences in breath-by-breath respiratory function at rest between a sample of PD patients with agoraphobia and healthy controls (HC), with particular attention to smoking and physical activity as possible relevant factors in the understanding of respiratory dynamics in PD. METHODS: Respiratory physiology was assessed in 32 PD patients and 24 HC. Respiratory rate (RR), tidal volume (VT), minute ventilation (VE), and end-tidal CO2 (pCO2) have been assessed. RESULTS: A significant diagnosis-by-smoking interaction was found for mean RR and VT. Mean pCO2 was significantly higher in active than in sedentary patients. Anxiety state did not account for the results. CONCLUSIONS: Our findings suggest an abnormal regulation of the respiratory system as a key mechanism in PD. In future studies it should be useful t o stratify data taking into account level and intensity of physical activity and smoking behaviour, as well as to consider the cardiac profile and the effect of those variables able to modulate the homeostatic brain functioning. .

Low baseline startle in anorexia nervosa patients.

This study examined baseline startle magnitude, using eye blink response and skin conductance response in anorexia nervosa patients. Twenty female in-patients with anorexia nervosa and an equal number of female healthy controls were tested. Baseline startle response was assessed during blank screens while four startling loud sounds (a 116 dB, 1s, 250 Hz tone) were delivered with a time interval ranging from 35 to 55 s. It was investigated if BMI and state anxiety correlated with physiological responses. The clinical sample showed a lower baseline startle reflex measured with both indices, than healthy controls. Across the whole sample, a single regression model partially explained the relationship between BMI and baseline skin conductance response.

Low social interactions in eating disorder patients in childhood and adulthood: a multi-centre European case control study.

The objective of this article was to examine lifestyle behaviours in eating disorder (ED) patients and healthy controls. A total of 801 ED patients and 727 healthy controls from five European countries completed the questions related to lifestyle behaviours of the Cross-Cultural Questionnaire (CCQ). For children, the ED sample exhibited more solitary activities (rigorously doing homework [p<0.001] and watching TV [p<0.05] and less socializing with friends [p<0.05]) than the healthy control group and this continued in adulthood. There were minimal differences across ED sub-diagnoses and various cross-cultural differences emerged. Reduced social activities may be an important risk and maintaining factor for ED symptomatology.

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.

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.

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.

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.

Cardiorespiratory response to physical exercise and psychological variables in panic disorder.

OBJECTIVE: To investigate the possible influence of psychological variables on cardiorespiratory responses and perceived exertion of patients with Panic Disorder (PD) during a submaximal exercise test. METHOD: Ten outpatients with PD and 10 matched healthy subjects walked up on a treadmill slope at a speed of 4 km/h in order to reach 65% of their maximum heart rate. Cardiorespiratory variables were continuously recorded. Before the exercise, the state and trait anxiety (State-Trait Anxiety Inventory scores), fear of physical sensations (Body Sensation Questionnaire scores), and fear of autonomic arousal (Anxiety Sensitivity Index scores) were assessed; during the exercise, levels of anxiety (VAS-A) and exertion (Borg Scale CR 10) were measured. RESULTS: Compared to controls, patients reached earlier the target HR and the ventilatory threshold, showed lower oxygen consumption, higher HR and lower within-subject standard deviations of HR (a measure of cardiac variability). Exertion was also higher, and there was a significant correlation between breathing frequency, tidal volume and HR. No significant associations were found between cardiorespiratory response, perceived exertion, and psychological variables in patients with PD. CONCLUSION: Although patients with PD presented poor cardiorespiratory fitness and were required to spend more effort during physical exercise, this did not appear to be related to the psychological variables considered. Further studies with larger groups are warranted.