Is glutamate associated with fear extinction and cognitive behavior therapy outcome in OCD? A pilot study.

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.

Regionally selective knockdown of astroglial glutamate transporters in infralimbic cortex induces a depressive phenotype in mice.

Elevation of energy metabolism and disturbance of astrocyte number/function in the ventral anterior cingulate cortex (vACC) contributes to the pathophysiology of major depressive disorder (MDD). Functional hyperactivity of vACC may result from reduced astrocytic glutamate uptake and increased neuronal excitation. Here we tested this hypothesis by knocking-down astrocytic glutamate transporter GLAST/GLT-1 expression in mouse infralimbic (IL, rodent equivalent of vACC) or prelimbic (PrL) cortices using RNAi strategies. Unilateral siRNA (small interfering RNA) microinfusion targeting GLAST or GLT-1 in mouse IL induced a moderate (20-30%) and long-lasting (7 days) decrease in their expression. Intra-IL GLAST-/GLT-1 siRNA microinfusion reduced the number of glial fibrillary acidic protein (GFAP)-positive and glutamine synthetase (GS)-positive astrocytes and evoked a depressive-like phenotype reversed by citalopram and ketamine. Intra-IL GLAST or GLT-1 knockdown markedly reduced serotonin (5-HT) release in the dorsal raphe nucleus (DR) and induced an overall reduction of brain-derived neurotrophic factor (BDNF) expression in ipsilateral and contralateral hemispheres. Egr-1 (early growth response protein-1) labeling suggests that both siRNAs enhance the GABAergic tone onto DR 5-HT neurons, leading to an overall decrease of 5-HT function, likely related to the widespread reduction on BDNF expression. Conversely, similar reductions of GLAST and GLT-1 expression in PrL did not induce a depressive-like phenotype. These results suggest that a focal glial change in IL translates into global change of brain activity by virtue of the descending projections from IL to DR and the subsequent attenuation of serotonergic function in forebrain, an effect perhaps related to the varied symptomatology of MDD.

Impact and risk factors of non-adherence to 5-aminosalicylates in quiescent ulcerative colitis evaluated by an electronic management system.

BACKGROUND AND OBJECTIVE: To determine the impact of non-adherence to 5-Aminosalicylates (5-ASA) on the risk of flares and to identify risk factors of non-adherence. METHODS: Observational, cohort study of ulcerative colitis (UC) patients in clinical remission at least 6 months on 5-ASA monotherapy maintenance prescribed by an electronic management program. Adherence was considered when 80% of the prescribed 5-ASA had been dispensed at the pharmacy. The study analyzed the existence and degree of 5-ASA adherence, disease course, UC phenotypic expression, and 5-ASA dose and regimen, and consumption of non-UC chronic drugs during 2-year follow-up. RESULTS: The study included 274 patients, 49% males with a median age of 38 (27-49) years old. Overall, 41% of patients were non-adherent to 5-ASA. Risk of flares was reduced in the adherent group (36% vs 54%; OR = 0,484; p = 0,004), mainly the mild ones (26% vs 38%; OR = 0,559; p = 0,031). Non-adherence was associated with younger age at diagnosis (32 (26-45) vs 41.5 (21-50), p = 0.000) and no-consumption of other chronic treatments (1.1 vs 2.1; OR = 1709; p = 0,048). CONCLUSION: Non-adherence to 5-ASA evaluated by the pharmaceutical management system was at 41% with a higher risk of relapse. Younger patients and patients who do not receive non-UC chronic treatments showed lower adherence rate.

Ventromedial prefrontal cortex activity and pathological worry in generalised anxiety disorder.

BACKGROUND: Pathological worry is a hallmark feature of generalised anxiety disorder (GAD), associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of such processes, but the link between vmPFC emotional responses and pathological v. adaptive worry has not yet been examined.AimsTo study the association between worry and vmPFC activity evoked by the processing of learned safety and threat signals. METHOD: In total, 27 unmedicated patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging. RESULTS: Compared to HC, the GAD group demonstrated reduced vmPFC activation to safety signals and no safety-threat processing differentiation. This response was positively correlated with worry severity in GAD, whereas the same variables showed a negative and weak correlation in HC. CONCLUSIONS: Poor vmPFC safety-threat differentiation might characterise GAD, and its distinctive association with GAD worries suggests a neural-based qualitative difference between healthy and pathological worries.Declaration of interestNone.

Neural signatures of human fear conditioning: an updated and extended meta-analysis of fMRI studies.

Classical Pavlovian fear conditioning remains the most widely employed experimental model of fear and anxiety, and continues to inform contemporary pathophysiological accounts of clinical anxiety disorders. Despite its widespread application in human and animal studies, the neurobiological basis of fear conditioning remains only partially understood. Here we provide a comprehensive meta-analysis of human fear-conditioning studies carried out with functional magnetic resonance imaging (fMRI), yielding a pooled sample of 677 participants from 27 independent studies. As a distinguishing feature of this meta-analysis, original statistical brain maps were obtained from the authors of 13 of these studies. Our primary analyses demonstrate that human fear conditioning is associated with a consistent and robust pattern of neural activation across a hypothesized genuine network of brain regions resembling existing anatomical descriptions of the 'central autonomic-interoceptive network'. This finding is discussed with a particular emphasis on the neural substrates of conscious fear processing. Our associated meta-analysis of functional deactivations-a scarcely addressed dynamic in fMRI fear-conditioning studies-also suggests the existence of a coordinated brain response potentially underlying the 'safety signal' (that is, non-threat) processing. We attempt to provide an integrated summary on these findings with the view that they may inform ongoing studies of fear-conditioning processes both in healthy and clinical populations, as investigated with neuroimaging and other experimental approaches.

Predicting response to cognitive behavioral therapy in contamination-based obsessive-compulsive disorder from functional magnetic resonance imaging.

BACKGROUND: Although cognitive behavioral therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD), few reliable predictors of treatment outcome have been identified. The present study examined the neural correlates of symptom improvement with CBT among OCD patients with predominantly contamination obsessions and washing compulsions, the most common OCD symptom dimension. METHOD: Participants consisted of 12 OCD patients who underwent symptom provocation with contamination-related images during functional magnetic resonance imaging (fMRI) scanning prior to 12 weeks of CBT. RESULTS: Patterns of brain activity during symptom provocation were correlated with a decrease on the Yale-Brown Obsessive Compulsive Scale (YBOCS) after treatment, even when controlling for baseline scores on the YBOCS and the Beck Depression Inventory (BDI) and improvement on the BDI during treatment. Specifically, activation in brain regions involved in emotional processing, such as the anterior temporal pole and amygdala, was most strongly associated with better treatment response. By contrast, activity in areas involved in emotion regulation, such as the dorsolateral prefrontal cortex, correlated negatively with treatment response mainly in the later stages within each block of exposure during symptom provocation. CONCLUSIONS: Successful recruitment of limbic regions during exposure to threat cues in patients with contamination-based OCD may facilitate a better response to CBT, whereas excessive activation of dorsolateral prefrontal regions involved in cognitive control may hinder response to treatment. The theoretical implications of the findings and their potential relevance to personalized care approaches are discussed.

Brain regions related to fear extinction in obsessive-compulsive disorder and its relation to exposure therapy outcome: a morphometric study.

BACKGROUND: The 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. METHOD: A 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. RESULTS: Compared 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. CONCLUSIONS: OCD 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.

Ketamine triggers rapid antidepressant effects by modulating synaptic plasticity in a new depressive-like mouse model based on astrocyte glutamate transporter GLT-1 knockdown in infralimbic cortex.

OBJECTIVE: Recently, we reported on a new MDD-like mouse model based on a regionally selective knockdown of astroglial glutamate transporters, GLAST/GLT-1, in infralimbic cortex (IL) which evokes widespread changes in mouse brain associated with the typical alterations found in MDD patients. To further characterize this new MDD-like mouse model, here we examine some transcriptional elements of glutamatergic/GABAergic neurotransmission and neuroplasticity in forebrain regions in the GLT-1 knockdown mice. Furthermore, we assess the acute ketamine effects on these transcriptional processes. MATERIAL AND METHODS: We used a small interfering RNA (siRNA) pool targeting GLT-1 mRNA to disrupt the GLT-1 transcription in mouse IL. Histological assays were performed to examine postsynaptic density protein-95 (PSD95), neuritin (NRN), glutamine acid descarboxilase-65 (GAD65), and GLT-1 mRNA expression in IL and hippocampus. RESULTS: Knockdown of GLT-1 in mouse IL leads to decreased expression of PSD95 and NRN neuroplasticity mRNAs in IL and hippocampus, which was reversed by an acute dose of ketamine antidepressant. Likewise, a single dose of ketamine also increased the mRNA levels of GAD65 and GLT-1 in IL of GLT-1 knockdown mice, reaching the basal values of control mice. CONCLUSIONS: The glutamatergic neuronal hyperactivity and deficits in the GABA system resulting from siRNA-induced astroglial glutamate transporter knockdown in IL can compromise the integrity/plasticity of neurocircuits affected in MDD. Suitable depressive-like animal models to address the neurobiological changes in MDD are an unmet need and the development of the GLAST/GLT-1 knockdown mouse model may represent a better option to understand the rapid-acting antidepressant effects of ketamine.

Risk factors prospectively associated with adult obsessive-compulsive symptom dimensions and obsessive-compulsive disorder.

BACKGROUND: Very few longitudinal studies have evaluated prospective neurodevelopmental and psychosocial risk factors for obsessive-compulsive disorder (OCD). Furthermore, despite the heterogeneous nature of OCD, no research has examined risk factors for its primary symptom dimensions, such as contamination/washing. METHOD: Potential risk factors for symptoms or diagnosis of OCD in adulthood and for specific adult obsessive-compulsive (OC) symptom dimensions were examined in the Dunedin Study birth cohort. The presence of obsessions and compulsions and psychological disorders was assessed using the Diagnostic Interview Schedule (DIS) at ages 26 and 32 years. Individuals with a diagnosis of OCD at either age (n=36) were compared to both a healthy control group (n=613) and an anxious control group (n=310) to determine whether associations between a risk factor and an OCD diagnosis were specific. RESULTS: Childhood neurodevelopmental, behavioral, personality and environmental risk factors were associated with a diagnosis of OCD and with OC symptoms at ages 26 and 32. Social isolation, retrospectively reported physical abuse and negative emotionality were specific predictors of an adult OCD diagnosis. Of note, most risk factors were associated with OC symptoms in adulthood and several risk factors predicted specific OCD dimensions. Perinatal insults were linked to increased risk for symmetry/ordering and shameful thoughts dimensions, whereas poor childhood motor skills predicted the harm/checking dimension. Difficult temperament, internalizing symptoms and conduct problems in childhood also predicted specific symptom dimensions and lower IQ non-specifically predicted increased risk for most dimensions. CONCLUSIONS: The current findings underscore the need for a dimensional approach in evaluating childhood risk factors for obsessions and compulsions.

Human fear conditioning: From neuroscience to the clinic.

Both clinicians and neuroscientists have been long interested in the topic of fear conditioning, with recent advances in neuroscience, in particular, igniting a shared interest in further translation between these domains. Here, we review some historical aspects of this relationship and the progress that has been made in translating the neuroscientific study of fear conditioning to the conceptualization and treatment of mental disorders, especially anxiety-related disorders. We also address some conceptual and methodological challenges faced by this research, and offer some suggestions to support future progress in the field.

Prefrontal-amygdala connectivity in trait anxiety and generalized anxiety disorder: Testing the boundaries between healthy and pathological worries.

BACKGROUND: Current brain-based theoretical models of generalized anxiety disorder (GAD) suggest a dysfunction of amygdala-ventromedial prefrontal cortex emotional regulatory mechanisms. These alterations might be reflected by an altered resting state functional connectivity between both areas and could extend to vulnerable non-clinical samples such as high worriers without a GAD diagnosis. However, there is a lack of information in this regard. METHODS: We investigated differences in resting state functional connectivity between the basolateral amygdala and the ventromedial prefrontal cortex (amygdala-vmPFC) in 28 unmedicated participants with GAD, 28 high-worriers and 28 low-worriers. We additionally explored selected clinical variables as predictors of amygdala-vmPFC connectivity, including anxiety sensitivity. RESULTS: GAD participants presented higher left amygdala-vmPFC connectivity compared to both groups of non-GAD participants, and there were no differences between the latter two groups. In our exploratory analyses, concerns about the cognitive consequences of anxiety (the cognitive dimension of anxiety sensitivity) were found to be a significant predictor of the left amygdala-vmPFC connectivity. LIMITATIONS: The cross-sectional nature of our study preclude us from assessing if functional connectivity measures and anxiety sensitivity scores entail an increased risk of GAD. CONCLUSIONS: These results suggest a neurobiological qualitative distinction at the level of the amygdala-vmPFC emotional-regulatory system in GAD compared to non-GAD participants, either high- or low-worriers. At this neural level, they question previous hypotheses of continuity between high worries and GAD development. Instead, other anxiety traits such as anxiety sensitivity might confer a greater proneness to the amygdala-vmPFC connectivity alterations observed in GAD.

Common and distinct neural correlates of fear extinction and cognitive reappraisal: A meta-analysis of fMRI studies.

Cognitive reappraisal and fear extinction learning represent two different approaches to emotion regulation. While their respective neural correlates have been widely studied with functional magnetic resonance imaging (fMRI), few direct comparisons between these processes have been conducted. We conducted a meta-analysis of fMRI studies of reappraisal and fear extinction, with the aim of examining both commonalities and differences in their neural correlates. We also conducted independent analyses that focused on specific reappraisal strategies (reinterpretation, distancing). Overall, we observed that the dorsal anterior cingulate cortex (dACC) and the bilateral anterior insular cortex (AIC) were similarly consistently engaged by reappraisal and extinction. Extinction was more consistently linked to activation of sensory and emotion processing regions, whereas reappraisal was more consistently associated with activation of a dorsal fronto-parietal network. Interestingly, the amygdala was preferentially deactivated by distancing. These results suggest that the dACC and the AIC are involved in domain-general regulatory networks. Differences between extinction and reappraisal could be explained by their relative processing demands on visual perceptual versus higher cognitive neural systems.

Selective Knockdown of TASK3 Potassium Channel in Monoamine Neurons: a New Therapeutic Approach for Depression.

Current pharmacological treatments for major depressive disorder (MDD) are severely compromised by both slow action and limited efficacy. RNAi strategies have been used to evoke antidepressant-like effects faster than classical drugs. Using small interfering RNA (siRNA), we herein show that TASK3 potassium channel knockdown in monoamine neurons induces antidepressant-like responses in mice. TASK3-siRNAs were conjugated to cell-specific ligands, sertraline (Ser) or reboxetine (Reb), to promote their selective accumulation in serotonin (5-HT) and norepinephrine (NE) neurons, respectively, after intranasal delivery. Following neuronal internalization of conjugated TASK3-siRNAs, reduced TASK3 mRNA and protein levels were found in the brainstem 5-HT and NE cell groups. Moreover, Ser-TASK3-siRNA induced robust antidepressant-like behaviors, enhanced the hippocampal plasticity, and potentiated the fluoxetine-induced increase on extracellular 5-HT. Similar responses, yet of lower magnitude, were detected for Reb-TASK3-siRNA. These findings provide substantial support for TASK3 as a potential target, and RNAi-based strategies as a novel therapeutic approach to treat MDD.

CRTC1 Function During Memory Encoding Is Disrupted in Neurodegeneration.

BACKGROUND: Associative memory impairment is an early clinical feature of dementia patients, but the molecular and cellular mechanisms underlying these deficits are largely unknown. In this study, we investigated the functional regulation of the cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) by associative learning in physiological and neurodegenerative conditions. METHODS: We evaluated the activation of CRTC1 in the hippocampus of control mice and mice lacking the Alzheimer's disease-linked presenilin genes (presenilin conditional double knockout [PS cDKO]) after one-trial contextual fear conditioning by using biochemical, immunohistochemical, and gene expression analyses. PS cDKO mice display classical features of neurodegeneration occurring in Alzheimer's disease including age-dependent cortical atrophy, neuron loss, dendritic degeneration, and memory deficits. RESULTS: Context-associative learning, but not single context or unconditioned stimuli, induces rapid dephosphorylation (Ser151) and translocation of CRTC1 from the cytosol/dendrites to the nucleus of hippocampal neurons in the mouse brain. Accordingly, context-associative learning induces differential CRTC1-dependent transcription of c-fos and the nuclear receptor subfamily 4 (Nr4a) genes Nr4a1-3 in the hippocampus through a mechanism that involves CRTC1 recruitment to CRE promoters. Deregulation of CRTC1 dephosphorylation, nuclear translocation, and transcriptional function are associated with long-term contextual memory deficits in PS cDKO mice. Importantly, CRTC1 gene therapy in the hippocampus ameliorates context memory and transcriptional deficits and dendritic degeneration despite ongoing cortical degeneration in this neurodegeneration mouse model. CONCLUSIONS: These findings reveal a critical role of CRTC1 in the hippocampus during associative memory, and provide evidence that CRTC1 deregulation underlies memory deficits during neurodegeneration.

Influence of individual differences in the Behavioral Inhibition System and stimulus content (fear versus blood-disgust) on affective startle reflex modulation.

Inconsistencies among affective startle reflex modulation studies may be due to differences in the startle potentiation produced by the specific content of the images used, to individual differences in sensitivity to negative stimuli, or to the interaction of both factors. To explore this interaction, 52 undergraduates obtaining extreme scores on a self-report measure of the Behavioral Inhibition System (BIS) participated in an affective startle reflex modulation paradigm. A significant interaction between BIS group (high versus low) and image content emerged from the MANOVA. Comparing startle magnitude between fear and pleasant images, low BIS participants did not seem to show startle potentiation, whereas high BIS participants did. Both groups displayed potentiated startle during blood-disgust images. The present results suggest the importance of considering personality variables and their interaction with image content in the affective startle modulation paradigm.

[Potential validity of thermolabile drugs outside the preservation conditions recommended by the manufacturer]. / Posible validez de medicamentos termolábiles fuera de las condiciones de conservación recomendadas por el fabricante.

Hospital pharmacists, according to the Ley del Medicamento 25/1990 of 20th December, should ensure appropriate drug preservation within the Pharmacy Department and in hospital stocks. The storage and preservation of thermolabile drugs according to manufacturer recommendations guarantees stability and optimal use conditions until the expiration date. Cold chain disruption may significantly affect the activity and toxicity of these drugs. Pharmacists should make quick decisions in case of cold chain-related events, hence the relevance of up-to-date information on stability under temperatures differing from those recommended. A review of the information available on the stability of drugs commonly used in the hospital setting that require a fridge for storage has been carried out.

Variation in the BDNF Val66Met polymorphism and response to cognitive-behavior therapy in obsessive-compulsive disorder.

BACKGROUND: Recent 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). METHODS: One 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. RESULTS: Among 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 (P<0.0001) and a lower obsessions severity decrease from pre- to posttreatment (P=0.046). CONCLUSION: Genetic variation in BDNF may be associated with treatment response in exposure-based CBT in OCD, especially in those patients exhibiting contamination/cleaning symptoms.

Prevalence and correlates of respiratory and non-respiratory panic attacks in the general population.

BACKGROUND: Panic attacks are heterogeneous with regards to symptom profile. Subtypes of panic attacks have been proposed, of which the most investigated is respiratory panic attacks (RPA). Limited information exists about RPA in the general population. METHOD: The prevalence and correlates of RPA and non-respiratory panic attacks (NRPA) were examined in a subsample (n=8.796) of individuals participating in a cross-sectional survey of the adult general population of six European countries. Panic attacks, mental disorders, and chronic physical conditions were assessed with the Composite International Diagnostic Interview (CIDI) 3.0. Data on use of health services and disability were obtained. RESULTS: The lifetime prevalence of RPA was 6.77 and the 12-month prevalence was 2.26. No robust associations of RPA with sociodemographic characteristics, mental disorders or physical conditions were found as compared to NRPA. RPA were associated with increased use of health services but similar disability in comparison to NRPA. LIMITATIONS: Few direct data are available on the validity of the CIDI to assess RPA. Other definitions of RPA exist in the literature. CONCLUSIONS: Our findings suggest that there are very few differences between RPA and NRPA and do not support the need of subtyping panic attacks in current classification systems.

Obsessive-compulsive symptom dimensions in the general population: results from an epidemiological study in six European countries.

BACKGROUND: The prevalence of obsessive-compulsive symptom dimensions and their sociodemographic and psychopathological correlates at the population level are unknown. METHOD: Obsessive-compulsive symptom dimensions and mental disorders were assessed with the Composite International Diagnostic Interview 3.0 in a random subsample (n=2804) of individuals participating in a cross-sectional survey of the adult general population of six European countries. RESULTS: The lifetime prevalence of any obsessive-compulsive symptom dimension was 13%. Harm/Checking was the most prevalent dimension (8%) followed by Somatic obsessions (5%) and Symmetry/Ordering (3%). Females were more likely to have symptoms in Contamination/Cleaning (OR=3, 95%CI=1.06-8.51) and Somatic obsessions (OR=1.88, 95%CI=1.05-3.37). All symptom dimensions were associated with an increased risk of most mental (but not physical) disorders. There were some differences in prevalence between countries. LIMITATIONS: The interference associated with each symptom dimension could not be assessed. Few direct data are available on the validity of the CIDI to assess obsessive-compulsive symptom dimensions. CONCLUSIONS: Obsessive-compulsive symptom dimensions are relatively frequent in the general population. Their sociodemographic and psychopathological correlates may be slightly different in clinical and community samples. They are associated with an increased risk of most mental disorders.