Search

Although the etiology of obsessive-compulsive disorder (OCD) is largely unknown, it is accepted that OCD is a complex disorder. There is a known bi-directional interaction between the gut microbiome and brain activity. Several authors have reported associations between changes in gut microbiota and neuropsychiatric disorders, including depression or autism. Furthermore, a pediatric-onset neuropsychiatric OCD-related syndrome occurs after streptococcal infection, which might indicate that exposure to certain microbes could be involved in OCD susceptibility. However, only one study has investigated the microbiome of OCD patients to date. We performed 16S ribosomal RNA gene-based metagenomic sequencing to analyze the stool and oropharyngeal microbiome composition of 32 OCD cases and 32 age and gender matched controls. We estimated different α- and β-diversity measures and performed LEfSe and Wilcoxon tests to assess differences in bacterial distribution. OCD stool samples showed a trend towards lower bacterial α-diversity, as well as an increase of the relative abundance of Rikenellaceae, particularly of the genus Alistipes, and lower relative abundance of Prevotellaceae, and two genera within the Lachnospiraceae: Agathobacer and Coprococcus. However, we did not observe a different Bacteroidetes to Firmicutes ratio between OCD cases and controls. Analysis of the oropharyngeal microbiome composition showed a lower Fusobacteria to Actinobacteria ratio in OCD cases. In conclusion, we observed an imbalance in the gut and oropharyngeal microbiomes of OCD cases, including, in stool, an increase of bacteria from the Rikenellaceae family, associated with gut inflammation, and a decrease of bacteria from the Coprococcus genus, associated with DOPAC synthesis. This project was supported by grants from the Spanish ministry of science and innovation (MICINN; SAF2013-49108-R); the Carlos III Health Institute (PI16/00950, PI18/00856, PI19/01184); FEDER funds (‘A way to build Europe’) and by the Agency of University and Research Funding Management of the Catalan Government (2014 SGR 1672 and 2017 SGR 738). We thank CERCA Programme / Generalitat de Catalunya for institutional support. LD was supported by a Severo Ochoa grant (SVP-2013-068066), MA was supported by the Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia Grant co-funded by the European Social Fund (ESF) “ESF, Investing in your future” (2017 FI_B 00327), DSC was supported by a grant from the MICINN (BES-2014-069814) and RR was supported by a fellowship from the Health Department of the Generalitat de Catalunya through the PERIS 2016-2020 program (SLT002/16/00310).

Cognitive behavioral therapy (CBT) including exposure and response prevention is a well-established treatment for obsessive-compulsive disorder (OCD) and is based on the principles of fear extinction. Fear extinction is linked to structural and functional variability in the ventromedial prefrontal cortex (vmPFC) and has been consistently associated with glutamate neurotransmission. The relationship between vmPFC glutamate and fear extinction and its effects on CBT outcome have not yet been explored in adults with OCD. We assessed glutamate levels in the vmPFC using 3T magnetic resonance spectroscopy, and fear extinction (learning and recall) using skin conductance responses during a 2-day experimental paradigm in OCD patients (n = 17) and in healthy controls (HC; n = 13). Obsessive-compulsive patients (n = 12) then received manualized CBT. Glutamate in the vmPFC was negatively associated with fear extinction recall and positively associated with CBT outcome (with higher glutamate levels predicting a better outcome) in OCD patients. Glutamate levels in the vmPFC in OCD patients were not significantly different from those in HC, and were not associated with OCD severity. Our results suggest that glutamate in the vmPFC is associated with fear extinction recall and CBT outcome in adult OCD patients.

Previous studies in non-clinical populations suggest that obsessive-compulsive symptoms are associated with hypothalamic-pituitary-adrenal (HPA) axis measures and that there are sex differences in these associations. We aimed to replicate these findings in a sample of 57 patients with obsessive-compulsive disorder (OCD) and 98 healthy subjects. Current and lifetime OCD symptom dimensions were assessed with the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS). Depressive symptoms and state and trait anxiety were also assessed. The following HPA axis measures were analysed in saliva: the diurnal cortisol slope (calculated using two formulas: [1] awakening to 11 p.m. [AWE diurnal slope] and [2] considering fixed time points [FTP diurnal slope] from 10 a.m. to 11 p.m.) and the dexamethasone suppression test ratio (DSTR) after 0.25 mg of dexamethasone. Multiple linear regression analyses were conducted to explore the contribution of OCD symptom dimensions to each HPA axis measure while adjusting for age, sex, BMI, smoking, trait anxiety and depressive symptoms. A sex-specific association between current ordering/symmetry symptoms and AWE diurnal cortisol slope (positive association [flattened slope] in men, inverse association [stepper slope] in women) was found. Two similar sex by OCD dimensions interactions were found for lifetime aggressive and ordering/symmetry symptoms and both (FTP, AWE) diurnal cortisol slopes. Current and lifetime hoarding symptoms were associated to a more flattened FTP diurnal cortisol slope in women. The DSTR was not associated with OCD symptoms. The lifetime interference in functionality was associated with a more flattened AWE diurnal cortisol slope. In conclusion, our study suggests that there are sex differences in the association between OCD subtypes and specific HPA axis measures.

Major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) have both been linked to abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. Polymorphisms in the genes involved in HPA axis activity, such as FKBP5, and their interactions with childhood trauma have been associated with stress-related mental disorders. Our goal was to study the role of FKBP5 genetic variants in HPA axis negative feedback regulation as a possible risk factor for different mental disorders such as MDD and OCD, while controlling for childhood trauma, anxiety and depressive symptoms. The sample included 266 participants divided into three groups: 1) MDD (n = 89 [n = 73 melancholic; n = 3 atypical]), 2) OCD (n = 51; 39% with comorbid MDD [n = 13 melancholic; n = 7 atypical]) and 3) healthy controls (n = 126). Childhood trauma, trait anxiety and depressive symptoms were assessed. HPA negative feedback was analyzed using the dexamethasone suppression test ratio (DSTR) after administration of 0.25 mg of dexamethasone. Twelve SNPs in the FKBP5 gene were selected for genotyping. Multiple linear regressions, after adjusting for the covariates considered, showed a reduced DSTR in individuals with the rs9470079-A variant that was significant after correction for multiple testing. Childhood trauma did not moderate the association between the rs9470079 and DSTR. Our results support the evidence that FKBP5 genetic variation could lead to abnormal HPA axis negative feedback independent of diagnosis. Therefore, this association can be identified as a transdiagnostic feature, offering an interesting opportunity to identify patients with higher stress vulnerability. Further studies focusing on the influence of FKBP5 on measurable biological endophenotypes are needed.

Major depressive disorder (MDD) is the most common psychiatric comorbidity in patients with obsessive–compulsive disorder (OCD). Hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been described in both disorders and might play a role in the association between them. We aimed to study the role of HPA axis activity in the comorbidity between OCD and MDD, while controlling for psychopathological dimensions such as anxiety and depressive symptoms. We studied 324 participants belonging to four diagnostic groups: 1) MDD (n = 101), 2) OCD with comorbid MDD (n = 33), 3) OCD without MDD (n = 52), and 4) healthy subjects (n = 138). State anxiety, trait anxiety and depressive symptoms were assessed. Three HPA axis measures were analyzed in saliva: cortisol awakening response (CAR), diurnal cortisol slope (calculated using two formulas: [1] awakening to 11 p.m. [AWE diurnal slope]; [2] considering fixed time points [FTP diurnal slope] from 10 a.m. to 11 p.m.), and dexamethasone suppression test ratio after 0.25 mg of dexamethasone (DSTR). Multiple linear regression analyses were conducted to explore the contribution of clinical diagnosis and symptom dimensions to each HPA axis measure. A more flattened FTP diurnal cortisol slope was observed for OCD patients with comorbid MDD. Regarding the CAR and DSTR, a significant interaction was found between trait anxiety and OCD, as OCD patients with greater trait anxiety showed an increased CAR and reduced cortisol suppression after dexamethasone administration. Our results suggest that trait anxiety plays an important role in the relationship between HPA axis measures and OCD/MDD comorbidity.

The rate of response to pharmacological treatment in Obsessive-compulsive disorder (OCD) oscillates between 40 and 70%. Genetic and environmental factors have been associated with treatment response in OCD. This study analyzes the predictive ability of a polygenic risk score (PRS) built from OCD-risk variants, for treatment response in OCD, and the modulation role of stressful life events (SLEs) at the onset of the disorder. PRSs were calculated for a sample of 103 patients. Yale–Brown Obsessive Compulsive Scale (YBOCS) scores were obtained before and after a 12-week treatment. Regression analyses were performed to analyze the influence of the PRS and SLEs at onset on treatment response. PRS did not predict treatment response. The best predictive model for post-treatment YBOCS (post YBOCS) included basal YBOCS and age. PRS appeared as a predictor for basal and post YBOCS. SLEs at onset were not a predictor for treatment response when included in the regression model. No evidence for PRS predictive ability for treatment response was found. The best predictor for treatment response was age, agreeing with previous literature specific for SRI treatment. Suggestions are made on the possible role of neuroplasticity as a mediator on this association. PRS significantly predicted OCD severity independent on pharmacological treatment. SLE at onset modulation role was not evidenced. Further research is needed to elucidate the genetic and environmental bases of treatment response in OCD. This study was supported in part by the Carlos III Health Institute (PI13/01958, PI13/00918, PI14/00413 and PI16/00950); FEDER funds (‘A way to build Europe’) and by the Agency of University and Research Funding Management of the Catalan Government (2014SGR1672). We also acknowledge support of the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2017-2021’, SEV-2016-0571 and of the Spanish MINECO SAF2013-49108-R Plan Estatal. M.A. was supported by the Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia. Grant co-funded by the European Social Fund (ESF) “ESF, Investing in your future” (2017 FI_B 00327). E.R. was supported by a Juan Rodés contract (JR14/00038) SI

BackgroundThe assessment of inter-regional functional connectivity (FC) has allowed for the description of the putative mechanism of action of treatments such as deep brain stimulation (DBS) of the nucleus accumbens in patients with obsessive–compulsive disorder (OCD). Nevertheless, the possible FC alterations of other clinically-effective DBS targets have not been explored. Here we evaluated the FC patterns of the subthalamic nucleus (STN) and the bed nucleus of the stria terminalis (BNST) in patients with OCD, as well as their association with symptom severity.MethodsEighty-six patients with OCD and 104 healthy participants were recruited. A resting-state image was acquired for each participant and a seed-based analysis focused on our two regions of interest was performed using statistical parametric mapping software (SPM8). Between-group differences in FC patterns were assessed with two-sample t test models, while the association between symptom severity and FC patterns was assessed with multiple regression analyses.ResultsIn comparison with controls, patients with OCD showed: (1) increased FC between the left STN and the right pre-motor cortex, (2) decreased FC between the right STN and the lenticular nuclei, and (3) increased FC between the left BNST and the right frontopolar cortex. Multiple regression analyses revealed a negative association between clinical severity and FC between the right STN and lenticular nucleus.ConclusionsThis study provides a neurobiological framework to understand the mechanism of action of DBS on the STN and the BNST, which seems to involve brain circuits related with motor response inhibition and anxiety control, respectively.

Background Familiality, stressful life events (SLE) and gender significantly affect the onset of obsessive-compulsive disorder (OCD). However, their combined impact on the probability of OCD chronicity is largely unknown. With the objective of clarifying their predictive value, we tested a model of interaction effects between these influences. Methods A sample of 449 patients with OCD was systematically assessed for familial loading, exposure to stressful life events, gender and course of the disease at the OCD referral unit at Bellvitge University Hospital. Multiple ordinal logistic regression was used to test interaction models. Results Familiality presented a main negative association with chronicity (OR=0.83, CI97.5%=0.70–0.98). This association was additively moderated by both exposure to SLE before onset and gender, and showed a positive slope among female patients not exposed to SLE before onset (Familiality*SLEbo: OR=0.69, CI97.5%=0.47–1; Familiality*gender: OR=1.30, CI97.5%=0.91–1.84). Limitations The findings are based on cross-sectional data. Assessment of course is based on a retrospective measure, which may imply the possibility of overestimation of chronicity. Conclusions The predictive value of familiality on the course of OCD is only partially informative as both SLEbo and gender modify the association. When other risk factors are included in the model, familiality may predict decreased chances of chronicity. The mediation effects identified could explain the discrepancies found in previous research on this topic. Increased chances of presenting a chronic course of OCD may be found in association with familial vulnerability among female patients not exposed to SLEbo.

Objectives Our main goal was to provide the psychometric properties of the Spanish version of the Dimensional Obsessive–Compulsive Scale (DOCS) in a non-clinical sample (n = 237) and in adult patients with Obsessive–Compulsive Disorder (OCD) (n = 110). We also examined the association between OC symptom dimensions and obsessive beliefs. Methods The psychometric properties involved four steps: reliability, structural validity, convergent and discriminant validity and diagnostic sensitivity. Linear regression analyses were used to assess the associations between OC symptoms and obsessive beliefs. Results Exploratory and confirmatory factor analyses replicated the original four-factor structure in both samples. The DOCS showed good performance in terms of internal consistency, test–retest reliability and convergent validity in both samples. The DOCS showed better diagnostic sensitivity than another self-report instrument of OC symptoms, the Obsessive–Compulsive Inventory Revised. Findings of the relationship between obsessive beliefs and OC symptoms revealed that certain obsessive beliefs predicted specific OC symptom dimensions. Conclusions The Spanish version of the DOCS has similar psychometric properties than the original English instrument, although its performance is somewhat better in OCD patients than in students. It will be important to ascertain its ability to discriminate OCD from other associated disorders.

BackgroundDespite knowledge of amygdala involvement in fear and anxiety, its contribution to the pathophysiology of obsessive–compulsive disorder (OCD) remains controversial. In the context of neuroimaging studies, it seems likely that the heterogeneity of the disorder might have contributed to a lack of consistent findings.AimsTo assess the influence of OCD symptom dimensions on amygdala responses to a well-validated emotional face-matching paradigm.MethodCross-sectional functional magnetic resonance imaging (fMRI) study of 67 patients with OCD and 67 age-, gender- and education-level matched healthy controls.ResultsThe severity of aggression/checking and sexual/religious symptom dimensions were significantly associated with heightened amygdala activation in those with OCD when responding to fearful faces, whereas no such correlations were seen for other symptom dimensions.ConclusionsAmygdala functional alterations in OCD appear to be specifically modulated by symptom dimensions whose origins may be more closely linked to putative amygdala-centric processes, such as abnormal fear processing.

Background: Cognitive behavioural therapy (CBT), including exposure and ritual prevention, is a first-line treatment for obsessive–compulsive disorder (OCD), but few reliable predictors of CBT outcome have been identified. Based on research in animal models, we hypothesized that individual differences in basolateral amygdala–ventromedial prefrontal cortex (BLA–vmPFC) communication would predict CBT outcome in patients with OCD. Methods: We investigated whether BLA–vmPFC resting-state functional connectivity (rs-fc) predicts CBT outcome in patients with OCD. We assessed BLA–vmPFC rs-fc in patients with OCD on a stable dose of a selective serotonin reuptake inhibitor who then received CBT and in healthy control participants. Results: We included 73 patients with OCD and 84 healthy controls in our study. Decreased BLA–vmPFC rs-fc predicted a better CBT outcome in patients with OCD and was also detected in those with OCD compared with healthy participants. Additional analyses revealed that decreased BLA–vmPFC rs-fc uniquely characterized the patients with OCD who responded to CBT. Limitations: We used a sample of convenience, and all patients were receiving pharmacological treatment for OCD. Conclusion: In this large sample of patients with OCD, BLA–vmPFC functional connectivity predicted CBT outcome. These results suggest that future research should investigate the potential of BLA–vmPFC pathways to inform treatment selection for CBT across patients with OCD and anxiety disorders.

Background Functional neuroimaging studies have provided consistent support for the idea that obsessive-compulsive disorder (OCD) is associated with disturbances of brain corticostriatal systems. However, in general, these studies have not sought to account for the disorder's prominent clinical heterogeneity. Methods To address these concerns, we investigated the influence of major OCD symptom dimensions on brain corticostriatal functional systems in a large sample of OCD patients (n = 74) and control participants (n = 74) examined with resting-state functional magnetic resonance imaging. We employed a valid method for mapping ventral and dorsal striatal functional connectivity, which supported both standard group comparisons and linear regression analyses with patients' scores on the Dimensional Yale-Brown Obsessive-Compulsive Scale. Results Consistent with past findings, patients demonstrated a common connectivity alteration involving the ventral striatum and orbitofrontal cortex that predicted overall illness severity levels. This common alteration was independent of the effect of particular symptom dimensions. Instead, we observed distinct anatomical relationships between the severity of symptom dimensions and striatal functional connectivity. Aggression symptoms modulated connectivity between the ventral striatum, amygdala, and ventromedial frontal cortex, while sexual/religious symptoms had a specific influence on ventral striatal-insular connectivity. Hoarding modulated the strength of ventral and dorsal striatal connectivity with distributed frontal regions. Conclusions Taken together, these results suggest that pathophysiological changes among orbitofrontal-striatal regions may be common to all forms of OCD. They suggest that a further examination of certain dimensional relationships will also be relevant for advancing current neurobiological models of the disorder.

Background Partial response and non-response to treatments are common problems in major depression. The identification of biological markers of clinical response may be of special interest for some adjunctive treatments, such as repetitive transcranial magnetic stimulation (rTMS), as it may ultimately improve their cost-effectiveness. Objective To identify pre-treatment functional imaging correlates of clinical response to rTMS in major depression. Methods We evaluated 21 depressed patients. They were randomized to receive 15 sessions of active or sham rTMS on the left dorsolateral prefrontal cortex. Functional magnetic resonance imaging (fMRI) was used to assess pre-treatment regional brain activity evoked by a word generation task. These regional activations were correlated (voxel-wise) with the Hamilton Rating Scale for Depression (HAM-D) reduction between baseline and end of treatment. A group of 13 healthy controls was also assessed using the same fMRI protocol to obtain reference imaging measurements. Results At the end of treatment, the percentage of patients with a HAM-D reduction greater than 50% was larger in the active than in the sham rTMS group (70% vs. 27.3%). In the active rTMS group, larger HAM-D reductions were significantly correlated with smaller deactivations during pre-treatment fMRI assessment in the anterior cingulate, the left medial orbitofrontal and the right middle frontal cortices, in addition to larger activations in the left ventral-caudal putamen. Conclusions These results suggest that brain activity in regions arguably relevant for major depression may predict clinical response to rTMS. This approach may help in identifying the most suitable candidates to undergo rTMS treatment.

The extent of functional abnormalities in frontal-subcortical circuits in obsessive-compulsive disorder (OCD) is still unclear. Although neuroimaging studies, in general, and resting-state functional Magnetic Resonance Imaging (rs-fMRI), in particular, have provided relevant information regarding such alterations, rs-fMRI studies have been typically limited to the analysis of between-region functional connectivity alterations at low-frequency signal fluctuations (i.e.

Genetic and environmental factors seem to interact and influence both the onset and the course of obsessive-compulsive disorder (OCD), but the role of glutamate transporter variants (SLC1A1) in pharmacological resistance is not known. We aimed to assess whether genetic variants in SLC1A1 and life stress at onset of the disorder interact and modulate pharmacological resistance in OCD. A single-marker association study of several single-nucleotide polymorphisms in the SLC1A1 genomic region was performed in a sample of 238 OCD patients. For the most strongly associated SNP (rs3087879), one copy of the risk allele increased the probability of higher treatment resistance (odds ratio=2.42; 95% confidence interval=1.39-4.21; P=0.0018), but only in OCD patients without life stress at onset of the disorder. These results suggest a gene-by-environment interaction effect on treatment resistance in OCD and strengthen the existing evidence of the role of the glutamatergic system in the phenomenology of OCD.

BackgroundRecent research suggests that the brain-derived neurotrophic factor (BDNF) may play a role in extinction learning. The goal of this study was to test whether variation in the BDNF Val66Met polymorphism is related to treatment response to exposure-based cognitive-behavior therapy (CBT), a form of extinction learning, in obsessive-compulsive disorder (OCD).MethodsOne hundred and six OCD patients from a specialized clinic, who underwent a standardized CBT treatment after partial or non-response to a 12-week pharmacological trial, were genotyped for the BDNF Val66Met and the relationship between genotype and treatment response was analyzed.ResultsAmong 98 CBT completers, 36% of those carrying the BDNF Met allele were rated as CBT responders compared to 60% of nonMet allele carriers (P = 0.027). When analyzing the different obsessive-compulsive symptom dimensions, in patients with contamination/cleaning symptoms, the Met allele was associated with a significantly worse CBT response (PP = 0.046).ConclusionGenetic variation in BDNF may be associated with treatment response in exposure-based CBT in OCD, especially in those patients exhibiting contamination/cleaning symptoms.

Background: Neuroimaging and neuropsychological data from patients with an obsessive-compulsive disorder (OCD) indicate the dysfunction of the orbitofrontal cortex (OFC). Olfactory processing has been associated with OFC function, although results from OCD studies regarding this sensory modality have been inconclusive. No previous study has analyzed both odor discrimination and identification capacity in OCD patients using “Sniffin' Sticks” tests. The aim of our study was to assess odor threshold, identification, discrimination, and nonverbal memory in OCD patients, in order to determine whether these functions were affected. Methods: Olfactory function was measured in 29 OCD patients and 29 healthy volunteers (HV) using the “Sniffin' Sticks” test and their nonverbal memory was scored with the Rey–Osterrieth Complex Figure Test. Results: OCD patients showed significant impairment in their odor performance and in their execution of the nonverbal memory task compared to HV. No statistical associations were found between the deficits in the two areas. The severity of depressive and obsessive-compulsive symptoms did correlate with olfactory identification. Conclusion: Our findings support the hypothesis that olfactory and memory dysfunctions in OCD reflect different neurobiological alterations of the disorder, and point to the modulation effect of depressive and obsessive-compulsive symptoms on odor performance. Depression and Anxiety, 2011. © 2011 Wiley-Liss, Inc.

Background: Environmental stressors are considered to play an important role in the triggering of mental disorders such as obsessive–compulsive disorder (OCD). Although there is extensive literature on traumatic life events, little is known about the role of nontraumatic but nonetheless stressful life events (SLEs) in OCD. The aim of this study was to establish whether OCD preceded by an SLE presents a different clinical pattern compared to non-SLE-preceded OCD. Methods: We interviewed 412 OCD patients to assess both SLEs at onset of OCD and other clinical variables, including OCD symptom dimensions. Logistic regression was then applied to explore the relationship between clinical variables and OCD preceded by an SLE. Results: The SLE-preceded OCD group showed a later onset of the disorder (OR = 1.04, P = .015), a history of complicated birth (OR = 5.54, P

Although clinical and genetic data for obsessive-compulsive disorder (OCD) support the hypothesis of sexual dimorphism, the neuropsychological findings remain inconclusive. The aim of our study was to determine whether there are differences in cognitive performance between men and women with OCD as compared with healthy controls (HCs). A neuropsychological battery was administered to 50 patients with OCD (31 men and 19 women) and 50 HCs matched by sex, age, and educational level with patients. We evaluated intelligence, attention, episodic memory, and use of organizational strategies during encoding of verbal and nonverbal information. Male patients scored worse than controls did in measures of nonverbal memory tasks, whereas the cognitive performance of women with OCD was consistent with that of their HC counterparts. These results suggest a distinct pattern of cognitive dysfunction specific to the patients' sex.

Background Several clinical and genetic studies have focused on the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of various mental disorders. Recent lines of evidence regarding the network hypothesis of treatment outcome point towards the involvement of BDNF variants in the pharmacologic response in mood disorders (MD). Furthermore, there is strong evidence of a role for the serotonergic system in the pathophysiology and treatment of OCD, and upregulation of BDNF has been observed with various classes of antidepressants, including selective serotonin reuptake inhibitors (SSRI). Thus, we hypothesized that the BDNF gene might also be associated with treatment outcome in OCD. Methods We performed a single-marker and haplotype association study of eight tag single nucleotide polymorphisms in the BDNF genomic region and related this to pharmacologic response in a sample of 131 OCD patients. Results We found an association for a haplotype containing two single nucleotide polymorphisms that have previously been reported to be associated with treatment outcome in MD (rs908867 and rs1491850). Conclusions Our results support the hypothesis that the BDNF gene is involved in the response to psychopharmacologic treatment even though these preliminary findings await replication in a follow-up sample.

Ninety female outpatients with obsessive-compulsive disorder (OCD) completed a semistructured interview to assess the relationship between different OCD symptom dimensions and the onset of OCD at menarche or during the perinatal period. Patients with hoarding symptoms had an earlier age at menarche than non-hoarders (12.1 +/- 1.3 vs 13.0 +/- 1.5 years, p = 0.019) and were more likely to report OCD onset at menarche (OR = 4.1, p = 0.034). Patients with symptoms of the contamination/cleaning dimension were more likely to report the onset of their disorder during pregnancy or postpartum (OR = 9.3, p = 0.048).

Aim: To compare the effectiveness of two forms of cognitive behavioral treatment (CBT; group and individual) in a sample of patients with obsessive–compulsive disorder (OCD) at 6-month and 12-month follow up. Method: Thirty-eight subjects meeting DSM-IV-TR OCD criteria completed 20 sessions of individual and group CBT. They were assessed using the Yale–Brown Obsessive–Compulsive Scale and the Hamilton Anxiety and Depression Scales at baseline, after treatment and at 6-month and 12-month follow up. Results: The clinical improvement obtained at the end of the treatment was maintained at 6-month and 12-month follow up. The clinical outcome of the individual treatment (IT) and the group treatment (GT) was the same. The dropout rates were significantly higher in women than in men, but were similar for IT and GT. Conclusions: CBT was effective in a sample of OCD patients. Individual and group CBT had similar results at 6-month and 12-month follow up. The clinical implications of these findings are discussed.

The aim of our study was to assess the role of gender in OCD symptom dimensions with a multivariate analysis while controlling for history of tic disorders and age at onset of OCD. One hundred and eighty-six consecutive outpatients with a DSM-IV diagnosis of OCD were interviewed. Yale-Brown Obsessive-Compulsive Scale (YBOC-S), YBOC-S Symptom Checklist, and Hamilton Depression and Anxiety Scales were administered to all patients. Lifetime history of tic disorders was assessed with the tic inventory section of the Yale Global Tic Severity Scale. Age at onset of OCD was assessed by direct interview. Statistical analysis was carried out through logistic regression to calculate adjusted female:male odds ratios (OR) for each dimension. A relationship was found between gender and two main OCD dimensions: contamination/cleaning (higher in females; female:male OR=2.02, P=0.03) and sexual/religious (lower in females; female:male OR=0.41, P=0.03). We did not find gender differences in the aggressive/checking, symmetry/ordering, or hoarding dimensions. We also found a greater history of tic disorders in those patients with symptoms from the symmetry/ordering, dimension (P

This study sought to examine the effectiveness of group and individual cognitive-behavioral treatment (CBT) and to compare the results with those of a wait-list control group among a sample of patients with obsessive-compulsive disorder (OCD). Fifty-seven individuals diagnosed with OCD were evaluated pre- and posttreatment with the Yale-Brown Obsessive Compulsive Scale and the Hamilton Rating Scales for Anxiety and Depression. Both group and individual CBT obtained statistically significant reductions in anxiety and depressive symptoms. Patients in individual treatment achieved a statistically significant reduction in OCD symptoms compared with those in group treatment, but their dropout rate was twice as high. Patients with symmetry and order rituals presented less improvement in anxiety symptoms than those with other rituals. Associated general symptoms were lower in patients receiving either mode of CBT compared with wait-list participants. The authors found that individual treatment is more effective in reducing obsessive-compulsive symptoms than group treatment.

Poor insight has been reported in 15% to 36% of patients with obsessive-compulsive disorder (OCD), but little is known about its clinical correlations. This study examines insight among patients with OCD using a standardized instrument, the Brown Assessment of Beliefs Scale, and analyzes its relationship with clinical factors. Insight was assessed in 132 patients with OCD, before and after pharmacologic treatment, using the Brown Assessment of Beliefs Scale. Differences between patients with good and poor insight on sociodemographic variables, OCD severity, comorbidity, and treatment response were studied. Stability of insight after pharmacologic treatment was also examined. Thirty-nine patients (29.5%) exhibited poor insight. They showed more depressive symptoms (P = .001) and personality disorders (P = .001), especially the schizotypal form, than did good insight subjects, but there were no significant differences in treatment response. Insight significantly improves after treatment (P < .001). Our results suggest that insight in OCD varies widely and constitutes a dynamic phenomenon that can improve after treatment and is influenced by clinical conditions such as affective status or personality.

Memory deficits have been reported in several neuropsychological studies of obsessive-compulsive disorder (OCD). Dysfunction in nonverbal memory has been consistently reported, whereas findings on verbal memory are more heterogeneous. The authors studied 50 patients with OCD who were matched for sex, age, educational level, and hand dominance with 50 healthy controls (HC). Cognitive performance in both groups was assessed on verbal and nonverbal memory tasks, and several clinical variables were also assessed in the patient group. Patients with OCD showed a pattern of cognitive dysfunction with alterations in areas of nonverbal memory (recall and recognition), and verbal memory (learning and recall). Older age at onset of OCD was associated with poorer performance on verbal memory tasks. Low scores on some verbal memory tasks were associated with severity of OCD, and nonverbal memory was influenced by depressive symptoms. The study suggests the existence of dysfunction in the execution of verbal and nonverbal memory tasks in OCD; the influence of clinical variables depends on the specific neuropsychological function.

Background Mental health problems are very common and often lead to prolonged sickness absence, having serious economic repercussions for most European countries. Periods of economic crisis are important social phenomena that are assumed to increase sickness absence due to mental disorders, although research on this topic remains scarce. The aim of this study was to gather data on long-term sickness absence (and relapse) due to mental disorders in Spain during a period of considerable socio-economic crisis. Methods Relationships were analyzed (using chi-squared tests and multivariate modelling via binary logistic regression) between clinical, social/employment-related and demographic factors associated and long-term sickness absence (>60 consecutive days) due to mental disorders in a cohort of 7112 Spanish patients during the period 2008–2012. Results Older age, severe mental disorders, being self-employed, having a non-permanent contract, and working in the real estate and construction sector were associated with an increased probability of long-term sickness absence (gender had a mediating role with respect to some of these variables). Relapses were associated with short-term sick leave (return to work due to ‘improvement’) and with working in the transport sector and public administration. Conclusions Aside from medical factors, other social/employment-related and demographic factors have a significant influence on the duration of sickness absence due to mental disorders.

Objectives There is growing evidence supporting a role for stressful life events (SLEs) at obsessive–compulsive disorder (OCD) onset, but neurobiological correlates of such effect are not known. We evaluated regional grey matter (GM) changes associated with the presence/absence of SLEs at OCD onset. Methods One hundred and twenty-four OCD patients and 112 healthy controls were recruited. Patients were split into two groups according to the presence (n = 56) or absence (n = 68) of SLEs at disorder’s onset. A structural magnetic resonance image was acquired for each participant and pre-processed with Statistical Parametric Mapping software (SPM8) to obtain a volume-modulated GM map. Between-group differences in sociodemographic, clinical and whole-brain regional GM volumes were assessed. Results SLEs were associated with female sex, later age at disorder’s onset, more contamination/cleaning and less hoarding symptoms. In comparison with controls, patients without SLEs showed GM volume increases in bilateral dorsal putamen and the central tegmental tract of the brainstem. By contrast, patients with SLEs showed specific GM volume increases in the right anterior cerebellum. Conclusions Our findings support the idea that neuroanatomical alterations of OCD patients partially depend on the presence of SLEs at disorder’s onset.

Common single-nucleotide polymorphisms (SNPs) account for a large proportion of the heritability of obsessive-compulsive disorder (OCD). Co-ocurrence of OCD and schizophrenia is commoner than expected based on their respective prevalences, complicating the clinical management of patients. This study addresses two main objectives: to identify particular genes associated with OCD by SNP-based and gene-based tests; and to test the existence of a polygenic risk shared with schizophrenia. The primary analysis was an exon-focused genome-wide association study of 370 OCD cases and 443 controls from Spain. A polygenic risk model based on the Psychiatric Genetics Consortium schizophrenia data set (PGC-SCZ2) was tested in our OCD data. A polygenic risk model based on our OCD data was tested on previous data of schizophrenia from our group. The most significant association at the gene-based test was found at DNM3 (P=7.9 × 10(-5)), a gene involved in synaptic vesicle endocytosis. The polygenic risk model from PGC-SCZ2 data was strongly associated with disease status in our OCD sample, reaching its most significant value after removal of the major histocompatibility complex region (lowest P=2.3 × 10(-6), explaining 3.7% of the variance). The shared polygenic risk was confirmed in our schizophrenia data. In conclusion, DNM3 may be involved in risk to OCD. The shared polygenic risk between schizophrenia and OCD may be partially responsible for the frequent comorbidity of both disorders, explaining epidemiological data on cross-disorder risk. This common etiology may have clinical implications. The study was supported by Fundación María José Jove, Fondo Europeo de Desarrollo Regional (FEDER), Xunta de Galicia; and by grants from the Instituto de Salud Carlos III FIS PI13/01136 to AC, CP11/00163 to JC, PI13/00918 to JMM, PI14/00413 to PA; the Generalitat de Catalunya AGAUR 2014 SGR-1138; the Spanish MINIECO SAF2013-49108- R Plan Estatal; and the European Commission 7th Framework Program, Project N. 262055 (ESGI) to XE. LD is supported by a Severo Ochoa fellowship of the Spanish MINIECO.

Background: Sensory phenomena (SP) are uncomfortable feelings, including bodily sensations, sense of inner tension, “just-right” perceptions, feelings of incompleteness, or “urge-only” phenomena, which have been described to precede, trigger or accompany repetitive behaviours in individuals with obsessive–compulsive disorder (OCD). Sensory phenomena are also observed in individuals with tic disorders, and previous research suggests that sensorimotor cortex abnormalities underpin the presence of SP in such patients. However, to our knowledge, no studies have assessed the neural correlates of SP in patients with OCD. Methods: We assessed the presence of SP using the University of Sao Paulo Sensory Phenomena Scale in patients with OCD and healthy controls from specialized units in Sao Paulo, Brazil, and Barcelona, Spain. All participants underwent a structural magnetic resonance examination, and brain images were examined using DARTEL voxel-based morphometry. We evaluated grey matter volume differences between patients with and without SP and healthy controls within the sensorimotor and premotor cortices. Results: We included 106 patients with OCD and 87 controls in our study. Patients with SP (67% of the sample) showed grey matter volume increases in the left sensorimotor cortex in comparison to patients without SP and bilateral sensorimotor cortex grey matter volume increases in comparison to controls. No differences were observed between patients without SP and controls. Limitations Most patients were medicated. Participant recruitment and image acquisition were performed in 2 different centres. Conclusion: We have identified a structural correlate of SP in patients with OCD involving grey matter volume increases within the sensorimotor cortex; this finding is in agreement with those of tic disorder studies showing that abnormal activity and volume increases within this region are associated with the urges preceding tic onset.

BackgroundThe size of particular sub-regions within the ventromedial prefrontal cortex (vmPFC) has been associated with fear extinction in humans. Exposure therapy is a form of extinction learning widely used in the treatment of obsessive-compulsive disorder (OCD). Here we investigated the relationship between morphometric measurements of different sub-regions of the vmPFC and exposure therapy outcome in OCD.MethodA total of 74 OCD patients and 86 healthy controls underwent magnetic resonance imaging (MRI). Cortical thickness and volumetric measurements were obtained for the rostral anterior cingulate cortex (rACC), the medial orbital frontal cortex and the subcallosal cortex. After MRI acquisition, patients were enrolled in an exposure therapy protocol, and we assessed the relationship between MRI-derived measurements and treatment outcome. Baseline between-group differences for such measurements were also assessed.ResultsCompared with healthy controls, OCD patients showed a thinner left rACC (p = 0.008). Also, left rACC thickness was inversely associated with exposure therapy outcome (r – 0.32, p = 0.008), and this region was significantly thinner in OCD patients who responded to exposure therapy than in those who did not (p = 0.006). Analyses based on regional volumetry did not yield any significant results.ConclusionsOCD patients showed cortical thickness reductions in the left rACC, and these alterations were related to exposure therapy outcome. The precise characterization of neuroimaging predictors of treatment response derived from the study of the brain areas involved in fear extinction may optimize exposure therapy planning in OCD and other anxiety disorders.

There have been few attempts to integrate neurobiological and cognitive models of obsessive-compulsive disorder (OCD), although this might constitute a key approach to clarify the complex etiology of the disorder. Our study aimed to explore the neural correlates underlying dysfunctional beliefs hypothesized by cognitive models to be involved in the development and maintenance of OCD. We obtained a high-resolution magnetic resonance image from fifty OCD patients and 30 healthy controls, and correlated them, voxel-wise, with the severity of OC-related dysfunctional beliefs assessed by the Obsessive Beliefs Questionnaire-44. In healthy controls, significant negative correlations were observed between anterior temporal lobe (ATL) volume and scores on perfectionism/intolerance of uncertainty and overimportance/need to control thoughts. No significant correlations between OBQ-44 domains and regional gray matter volumes were observed in OCD patients. A post-hoc region-of-interest analysis detected that the ATLs was bilaterally smaller in OCD patients. On splitting subjects into high- and low-belief subgroups, we observed that such brain structural differences between OCD patients and healthy controls were explained by significantly larger ATL volumes among healthy subjects from the low-belief subgroup. Our results suggest a significant correlation between OC-related dysfunctional beliefs and morphometric variability in the anterior temporal lobe, a brain structure related to socio-emotional processing. Future studies should address the interaction of these correlations with environmental factors to fully characterize the bases of OC-related dysfunctional beliefs and to advance in the integration of biological and cognitive models of OCD.

Olfactory dysfunction has been described in obsessive-compulsive disorder (OCD). Brain regions involved in smell processing partially overlap with structures included in the neurobiological models of OCD, although no previous studies have analyzed the neuroanatomical correlates of olfactory dysfunction in this disorder. The aim of our study was to examine the association between regional gray matter volume, as assessed by a voxel-based morphometry analysis of magnetic resonance images (MRI), and olfactory function, as assessed by the Sniffin' Sticks test (SST). Olfactory function was assessed in 19 OCD patients and 19 healthy volunteers. All participants were also scanned in a 1.5-T magnet to obtain T1-weighted anatomical MRIs, which were pre-processed and analyzed with SPM8. Three different correlation models were used to study the association between regional gray matter volumes and olfactory function in the domains assessed by the SST: detection threshold, discrimination, and identification. OCD patients showed a significant impairment in all the domains assessed by the SST. Voxel-based mapping revealed a positive association in healthy controls between detection threshold and the gray matter content of a left anterior cingulate cortex cluster. In OCD patients, a positive correlation was observed between identification errors and the gray matter volume of the left medial orbital gyrus. In a post hoc analysis, these two gray matter regions were shown to be enlarged in OCD patients. Our findings support the idea that olfactory dysfunction in OCD is associated with volumetric changes in brain areas typically implicated in the neurobiology of the disorder.

Context: heightened moral sensitivity seems to characterize patients with obsessive-compulsive disorder (OCD). Recent advances in social cognitive neuroscience suggest that a compelling relationship may exist between this disorder-relevant processing bias and the functional activity of brain regions implicated in OCD. Objective: to test the hypothesis that patients with OCD demonstrate an increased response of relevant ventromedial prefrontal and orbitofrontal cortex regions in a functional magnetic resonance imaging study of difficult moral decision making. Design: case-control cross-sectional study. Setting: hospital referral OCD unit and magnetic resonance imaging facility. Participants: seventy-three patients with OCD (42 men and 31 women) and 73 control participants matched for age, sex, and education level. Main outcome measures: functional magnetic resonance imaging activation maps representing significant changes in blood oxygenation level-dependent signal in response to 24 hypothetical moral dilemma vs nondilemma task vignettes and additional activation maps representing significant linear associations between patients' brain responses and symptom severity ratings. Results: in both groups, moral dilemma led to robust activation of frontal and temporoparietal brain regions. Supporting predictions, patients with OCD demonstrated significantly increased activation of the ventral frontal cortex, particularly of the medial orbitofrontal cortex. In addition, the left dorsolateral prefrontal cortex and left middle temporal gyrus were more robustly activated in patients with OCD. These results were unexplained by group differences in comorbid affective symptoms. Patients' global illness severity predicted the relative magnitude of orbitofrontal-striatal activation. The severity of 'harm/checking' symptoms and 'sexual/religious' obsessions predicted the magnitude of posterior temporal and amygdala-paralimbic activation, respectively. Conclusions: the neural correlates of moral sensitivity in patients with OCD partly coincide with brain regions that are of general interest to pathophysiologic models of this disorder. In particular, these findings suggest that the orbitofrontal cortex together with the left dorsolateral prefrontal cortex may be relevant for understanding the link between neurobiological processes and certain maladaptive cognitions in OCD.

Background: Recent data from neuroimaging, genetic and clinical trials and animal models suggest a role for altered glutamatergic neurotransmission in the pathogenesis of obsessive–compulsive disorder (OCD). The aim of this study was to investigate whether variants in the GRIN2B gene, the gene encoding the NR2 subunit of the N-methyl-d-aspartate (NMDA) glutamate receptor, may contribute to genetic susceptibility to OCD or to different OCD subphenotypes. Methods: Between 2003 and 2008, we performed a case–control association study in which we genotyped 10 tag single-nucleotide polymorphisms (SNPs) in the 3′ untranslated region (3′ UTR) of GRIN2B. We performed SNP association and haplotype analysis considering the OCD diagnosis and different OCD subphenotypes: early-onset OCD, comorbid tic disorders and OCD clinical symptom dimensions. Results: We enrolled 225 patients with OCD and 279 controls recruited from the OCD Clinic at Bellvitge Hospital (Barcelona, Spain). No significant difference in the distribution of alleles or genotypes was detected between patients with OCD and controls. Nonetheless, on analyzing OCD subphenotypes, the rs1805476 SNP in male patients (95% confidence interval [CI] 1.37–4.22, p = 0.002) and a 4-SNP haplotype in the whole sample (rs1805476, rs1805501, rs1805502 and rs1805477; odds ratio 1.92, 95% CI 1.22–3.01; permutation p = 0.023) were significantly associated with the presence of contamination obsessions and cleaning compulsions. Limitations: Study limitations included the risk of population stratification associated with the case–control design, use of psychiatrically unscreened blood donors as the control group, reduced sample size of participants with certain OCD subphenotypes and tested polymorphisms limited to 3′ UTR and exon 13 of GRIN2B. Conclusion: Our results converge with recent data suggesting a possible contribution of glutamatergic variants to the genetic vulnerability to OCD or at least to certain OCD manifestations. The dissection of OCD into more homogeneous subphenotypes may constitute a useful tool to disentangle the complex genetic basis of the disorder.

Cognitive models emphasize the importance of dysfunctional beliefs as overimportance/need to control thoughts, perfectionism, intolerance of uncertainty, responsibility, and overestimation of threat in obsessive-compulsive disorder (OCD). Twin studies suggest that these beliefs are significantly heritable, but candidate genes associated with them have not been analyzed. We genotyped the Val158Met in the COMT gene and Val66Met variant in the BDNF gene in 141 OCD patients and analyzed their single and interactive effects on the obsessive beliefs questionnaire (OBQ-44). Variability in dysfunctional beliefs was not affected by the COMT or BDNF genotype in isolation, but we detected a significant COMT×BDNF interaction effect on responsibility/overestimation of threat and overimportance/need to control thoughts scores. Subjects with the BDNF Met-present and the COMT Met-present genotype showed higher scores on responsibility/overestimation of threat. An interaction between dopaminergic and neurotrophic functional gene variants may influence dysfunctional beliefs hypothesized to contribute to the development of OCD.

BackgroundThe same executive dysfunctions and alterations in neuroimaging tests (both functional and structural) have been found in obsessive-compulsive patients and their first-degree relatives. These neurobiological findings are considered to be intermediate markers of the disease. The aim of our study was to assess verbal and non-verbal memory in unaffected first-degree relatives, in order to determine whether these neuropsychological functions constitute a new cognitive marker for obsessive-compulsive disorder (OCD).MethodRecall and use of organizational strategies in verbal and non-verbal memory tasks were measured in 25 obsessive-compulsive patients, 25 unaffected first-degree relatives and 25 healthy volunteers.ResultsFirst-degree relatives and healthy volunteers did not show differences on most measures of verbal memory. However, during the recall and processing of non-verbal information, deficits were found in first-degree relatives and patients compared with healthy volunteers.ConclusionsThe presence of the same deficits in the execution of non-verbal memory tasks in OCD patients and unaffected first-degree relatives suggests the influence of certain genetic and/or familial factors on this cognitive function in OCD and supports the hypothesis that deficits in non-verbal memory tasks could be considered as cognitive markers of the disorder.

Compelling data from animal and clinical studies suggest that sex steroids may play a role in the etiopathology of obsessive-compulsive disorder (OCD). The aim of this study was to investigate whether variants in estrogen receptor genes ESR1 and ESR2 may contribute to the genetic susceptibility to OCD, through a case-control association study using an extensive linkage disequilibrium-mapping approach. Twenty tag single-nucleotide polymorphisms (tagSNPs) covering the ESR2 region and nine tagSNPS from regions of ESR1 reported to be related to transcriptional control were genotyped in 229 OCD patients and 279 controls. SNP association and haplotype analysis were performed. The association of these genes and OCD subphenotypes was tested, considering early-onset OCD, comorbid tic and affective disorders, and OCD symptom dimensions. No significant difference in the distribution of alleles or genotypes was detected between controls and OCD subjects. Nevertheless, on analyzing OCD subphenotypes, SNP rs34535804 in ESR1 and a five SNPs haplotype, located at the 5' end of intron 1 of ESR1, were associated with the presence of contamination obsessions and cleaning compulsions. Specifically, carriers of the ACCCG haplotype, a combination of functional alleles related to higher ER alpha expression, showed a reduced risk of suffering from these symptoms. Our results suggest that the ESR1 gene may contribute to the genetic vulnerability to certain OCD manifestations. The dissection of OCD into more homogeneous subphenotypes may well help to identify susceptibility genes for the disorder.

Background The Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS) is a promising new instrument that allows patient and clinician ratings of dimension-specific symptom severity, as well as estimates of global symptom severity in patients with obsessive-compulsive disorder (OCD). The goal of this study was to further explore the psychometric properties of the DY-BOCS in a Spanish sample. Methods The internal consistency, reliability, and convergent and divergent validity of the Spanish adaptation of the DY-BOCS were assessed in a sample of 51 Spanish adult patients with OCD. Results All the subscales of the Spanish DY-BOCS showed high internal consistency. The interrater reliability was excellent for all component scores, and the level of agreement between self-report and expert ratings was high for most symptom dimensions. The subscales of the DY-BOCS were largely independent from one another and from global OCD severity. The convergent and divergent validities of the DY-BOCS subscales were adequate. Conclusions The Spanish version of the DY-BOCS is a reliable and valid clinical tool for the assessment of obsessive-compulsive symptom dimensions.

BACKGROUND The aim of our study was to assess whether there is a relationship between reproductive cycle events and the initiation or changes in symptoms of obsessive-compulsive disorder (OCD). METHOD Forty-six female outpatients meeting DSM-IV criteria for OCD completed a semistructured interview at our OCD unit to assess the relationship between reproductive cycle events and OCD. Dates of data collection were from January 2001 to December 2003. RESULTS In our sample, OCD onset occurred in the same year as menarche in 22% (N = 10), at pregnancy in 2% (N = 1), at postpartum in 7% (N = 3), and at menopause in 2% (N = 1). Worsening of preexisting OCD was reported by 20% of patients (9/45) at premenstruum, 8% (1/12) at pregnancy, 50% (6/12) at postpartum, and 8% (1/12) at menopause. The number of premenstrual mood symptoms, which included anxiety, irritability, mood lability and depressed mood, was associated with both premenstrual worsening of OCD (OR = 5.1, p < .01) and onset or worsening of OCD at postpartum (OR = 2.7, p < .05). Patients with an onset or worsening of OCD at postpartum also more frequently reported pre-menstrual worsening of OCD and previous history of major depressive disorder, including postpartum depression (p < or =.05 for all). CONCLUSION In a substantial number of patients, the onset or worsening of OCD was related to reproductive cycle events, especially at menarche and postpartum. Certain women with OCD seem to be vulnerable to worsening of OCD at different reproductive periods that imply hormonal fluctuations, and premenstruum and post-partum were the 2 reproductive events with a greater vulnerability. Those patients whose OCD symptoms appeared to be related to reproductive events also exhibited a greater history of mood symptoms (premenstrual depression and major depressive episodes).

BackgroundNeurological soft signs (NSS) have been inconsistently reported in obsessive-compulsive disorder (OCD) but may make an impact on treatment response.MethodThe current study examined the presence of NSS in two independent European samples of OCD patients (combined 85 patients and 88 matched healthy controls) using a standardized instrument and conducted a meta-analysis of all published studies identified in the literature with the aim to provide a more definitive answer to the question of whether OCD patients are characterized by increased NSS.ResultsBoth empirical studies found elevated NSS scores in patients compared with matched controls. The results of the meta-analysis, which included 15 studies (combined 498 patients and 520 controls) showed large effect sizes (Hedges' g=1.27, 95% confidence interval 0.80–1.75), indicating that OCD patients have significantly higher rates of NSS than matched controls on both sides of the body and in multiple domains (motor coordination, sensory integration and primitive reflexes). The results were robust and remained largely unchanged in our reliability analyses, which controlled for possible outliers. Meta-regression was employed to examine the role of potential variables of interest including sociodemographic variables, symptom severity, medication effects and the use of different instruments, but none of these variables was clearly associated with NSS.ConclusionsAs a group, OCD patients are characterized by increased rates of NSS, compared with healthy controls. However, their origins and potential clinical importance remain to be clarified. Future directions for research are discussed.

Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. Although structural brain alterations have been consistently reported in OCD, their interaction with particular clinical subtypes deserves further examination. Among other approaches, a two-group classification in patients with autogenous and reactive obsessions has been proposed. The purpose of the present study was to assess, by means of a voxel-based morphometry analysis, the putative brain structural correlates of this classification scheme in OCD patients. Ninety-five OCD patients and 95 healthy controls were recruited. Patients were divided into autogenous (n = 30) and reactive (n = 65) sub-groups. A structural magnetic resonance image was acquired for each participant and pre-processed with SPM8 software to obtain a volume-modulated gray matter map. Whole-brain and voxel-wise comparisons between the study groups were then performed. In comparison to the autogenous group, reactive patients showed larger gray matter volumes in the right Rolandic operculum. When compared to healthy controls, reactive patients showed larger volumes in the putamen (bilaterally), while autogenous patients showed a smaller left anterior temporal lobe. Also in comparison to healthy controls, the right middle temporal gyrus was smaller in both patient subgroups. Our results suggest that autogenous and reactive obsessions depend on partially dissimilar neural substrates. Our findings provide some neurobiological support for this classification scheme and contribute to unraveling the neurobiological basis of clinical heterogeneity in OCD.