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Hospital de Órbigo, Spain

Alonso P.,OCD Clinical and Research Unit | Alonso P.,Carlos III Health Institute | Alonso P.,University of Barcelona | Alonso P.,Institute Dinvestigacio Biomedica Of Bellvitge Idibell | And 27 more authors.
Journal of Anxiety Disorders

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. © 2013 Elsevier Ltd. Source

Lopez-Sola C.,OCD Clinical and Research Unit | Lopez-Sola C.,Carlos III Health Institute | Lopez-Sola C.,Bellvitge Biomedical Research Institute IDIBELL | Lopez-Sola C.,University of Barcelona | And 16 more authors.
Comprehensive Psychiatry

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. © 2014 Elsevier Inc. Source

Alonso P.,OCD Clinical and Research Unit | Alonso P.,Bellvitge Biomedical Research Institute IDIBELL | Alonso P.,Carlos III Health Institute | Alonso P.,University of Barcelona | And 23 more authors.

Background. Deep brain stimulation (DBS) has been proposed as an alternative to ablative neurosurgery for severe treatment-resistant Obsessive-Compulsive Disorder (OCD), although with partially discrepant results probably related to differences in anatomical targetting and stimulation conditions. We sought to determine the efficacy and tolerability of DBS in OCD and the existence of clinical predictors of response using meta-analysis. Methods. We searched the literature on DBS for OCD from 1999 through January 2014 using PubMed/MEDLINE and PsycINFO. We performed fixed and random-effect meta-analysis with score changes (pre-post DBS) on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) as the primary-outcome measure, and the number of responders to treatment, quality of life and acceptability as secondary measures. Findings. Thirty-one studies involving 116 subjects were identified. Eighty-three subjects were implanted in striatal areas-anterior limb of the internal capsule, ventral capsule and ventral striatum, nucleus accumbens and ventral caudate-27 in the subthalamic nucleus and six in the inferior thalamic peduncle. Global percentage of Y-BOCS reduction was estimated at 45.1% and global percentage of responders at 60.0%. Better response was associated with older age at OCD onset and presence of sexual/religious obsessions and compulsions. No significant differences were detected in efficacy between targets. Five patients dropped out, but adverse effects were generally reported as mild, transient and reversible. Conclusions. Our analysis confirms that DBS constitutes a valid alternative to lesional surgery for severe, therapy-refractory OCD patients. Well-controlled, randomized studies with larger samples are needed to establish the optimal targeting and stimulation conditions and to extend the analysis of clinical predictors of outcome. © 2015 Alonso et al. Source

Alonso P.,OCD Clinical and Research Unit | Alonso P.,Bellvitge Biomedical Research Institute IDIBELL | Alonso P.,Carlos III Health Institute | Alonso P.,University of Barcelona | And 12 more authors.
Neuropsychiatric Disease and Treatment

Obsessive–compulsive disorder (OCD) is a disabling and common neuropsychiatric condition of poorly known etiology. Many attempts have been made in the last few years to develop animal models of OCD with the aim of clarifying the genetic, neurochemical, and neuroanatomical basis of the disorder, as well as of developing novel pharmacological and neurosurgical treatments that may help to improve the prognosis of the illness. The latter goal is particularly important given that around 40% of patients with OCD do not respond to currently available therapies. This article summarizes strengths and limitations of the leading animal models of OCD including genetic, pharmacologically induced, behavioral manipulation-based, and neurodevelopmental models according to their face, construct, and predictive validity. On the basis of this evaluation, we discuss that currently labeled “animal models of OCD” should be regarded not as models of OCD but, rather, as animal models of different psychopathological processes, such as compulsivity, stereotypy, or perseverance, that are present not only in OCD but also in other psychiatric or neurological disorders. Animal models might constitute a challenging approach to study the neural and genetic mechanism of these phenomena from a trans-diagnostic perspective. Animal models are also of particular interest as tools for developing new therapeutic options for OCD, with the greatest convergence focusing on the glutamatergic system, the role of ovarian and related hormones, and the exploration of new potential targets for deep brain stimulation. Finally, future research on neurocognitive deficits associated with OCD through the use of analogous animal tasks could also provide a genuine opportunity to disentangle the complex etiology of the disorder. © 2015 Alonso et al. Source

Real E.,Neuroscience Group Idibell Institute Dinvestigacio Biomedica Of Bellvitge | Real E.,OCD Clinical and Research Unit | Real E.,Obsessive Compulsive Disorder Clinical and Research Unit | Gratacos M.,CIBER ISCIII | And 14 more authors.
Pharmacogenomics Journal

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. © 2013 Macmillan Publishers Limited All rights reserved. Source

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