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De Wit S.J.,VU University Amsterdam | Alonso P.,University of Barcelona | Schweren L.,Carlos III Health Institute | Mataix-Cols D.,Stellenbosch University | And 7 more authors.
American Journal of Psychiatry | Year: 2014

Objective: Results from structural neuroimaging studies of obsessive-compulsive disorder (OCD) have been only partially consistent. The authors sought to assess regional gray and white matter volume differences between large samples of OCD patients and healthy comparison subjects and their relation with demographic and clinical variables. Method: A multicenter voxel-based morphometry mega-analysis was performed on 1.5-T structural T1-weighted MRI scans derived from the International OCD Brain Imaging Consortium. Regional gray and white matter brain volumes were compared between 412 adult OCD patients and 368 healthy subjects. Results: Relative to healthy comparison subjects, OCD patients had significantly smaller volumes of frontal gray and white matter bilaterally, including the dorsomedial prefrontal cortex, the anterior cingulate cortex, and the inferior frontal gyrus extending to the anterior insula. Patients also showed greater cerebellar gray matter volume bilaterally compared with healthy subjects. Group differences in frontal gray and white matter volume were significant after correction for multiple comparisons. Additionally, group-by-age interactions were observed in the putamen, insula, and orbitofrontal cortex (indicating relative preservation of volume in patients compared with healthy subjects with increasing age) and in the temporal cortex bilaterally (indicating a relative loss of volume in patients compared with healthy subjects with increasing age). Conclusions: These findings partially support the prevailing fronto-striatalmodels of OCD and offer additional insights into the neuroanatomy of the disorder that were not apparent from previous smaller studies. The group-by-age interaction effects in orbitofrontal-striatal and (para)limbic brain regions may be the result of altered neuroplasticity associated with chronic compulsive behaviors, anxiety, or compensatory processes related to cognitive dysfunction. Source


Pagonabarraga J.,Autonomous University of Barcelona | Pagonabarraga J.,CIBER ISCIII | Soriano-Mas C.,CRC Hospital Del Mar | Soriano-Mas C.,University of Barcelona | And 7 more authors.
Parkinsonism and Related Disorders | Year: 2014

Background: Hallucinations are a frequent and severe complication in Parkinson's disease (PD). Minor hallucinations are generally not disturbing, but likely progress to well-structured hallucinations with loss of insight and a great impact on quality of life. Knowledge on the neural bases of minor hallucinations may help to describe those systems associated with the early development of psychotic phenomena in PD.In this study, we aimed to identify the pattern of structural brain alterations associated with minor hallucinations in PD by using voxel-based morphometry (VBM). Methods: We prospectively collected a sample of 46 non-demented PD patients, with (N=17) and without (n=29) minor hallucinations (passage and/or presence hallucinations), and 15 healthy controls. Groups were matched for age, education and global cognitive function. Presence and type of minor psychotic phenomena was assessed by the new MDS-UPDRS. Three dimensional T1-weighted MRI images were acquired with a 1.5T magnet, and analyzed using optimized VBM. Results: Compared to controls, PD with minor hallucinations (PD-mH) showed reduced gray matter volume bilaterally in different areas of the dorsal visual stream, and in functionally related midbrain and cerebellar structures. Additionally, bilateral gray matter volume increases were observed in the PD-mH group in limbic and paralimbic regions. Conclusions: Our data support a major role of the dorsal visual stream in the genesis of minor hallucinations in PD, reinforcing the importance of posterior cortical regions for the development of cognitive and psychiatric complications in PD. © 2013 Elsevier Ltd. Source


Hernandez-Ribas R.,University of Barcelona | Hernandez-Ribas R.,Carlos III Health Institute | Deus J.,Autonomous University of Barcelona | Pujol J.,CRC Hospital Del Mar | And 10 more authors.
Brain Stimulation | Year: 2013

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. © 2013 Elsevier Inc. All rights reserved. Source


Lopez-Sola C.,Bellvitge Biomedical Research Institute IDIBELL | Lopez-Sola C.,University of Barcelona | Lopez-Sola C.,Carlos III Health Institute | Fontenelle L.F.,Federal University of Rio de Janeiro | And 19 more authors.
American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics | Year: 2014

While past twin studies indicate moderate levels of heritability of "obsessive-compulsive related" and anxiety disorder symptoms, no single study has reported such estimates in the same twin population nor examined potential genetic sex differences. We assessed symptoms of obsessive-compulsive disorder, body dysmorphic disorder, hoarding disorder, hypochondriasis, panic disorder, social phobia and generalized anxiety disorder in 2,495 adult twins (1,468 female). Prevalence estimates for the corresponding symptom measures were determined using empirically derived cut-off scores. Twin resemblance was assessed by Pearson correlations and biometrical model-fitting analyses, incorporating sex-specific effects, using OpenMx. Prevalence estimates ranged from 1.6% in the symptoms of generalized anxiety to 16.9% for social phobia. Female twins demonstrated significantly higher prevalence rates across all domains with the exception of obsessive-compulsive symptoms. Additive genetic factors accounted for a moderate proportion of the total liability to each symptom domain. Evidence suggesting qualitative genetic sex differences (i.e., distinct genetic influences between genders) was observed for body dysmorphic concern and panic symptoms, while quantitative differences were observed for hoarding and social phobia symptoms, indicating stronger heritability in females. Novel findings in this study include the observation of probable genetic sex differences in liability towards hoarding symptoms and dysmorphic concern, as well as the lack of such differences in hypochondriasis. The trend towards qualitative sex differences in panic symptoms has some intuitive appeal with regard to biological-experimental models of panic. © 2014 Wiley Periodicals, Inc. Source


Parrado-Hernandez E.,Charles III University of Madrid | Gomez-Verdejo V.,Charles III University of Madrid | Martinez-Ramon M.,University of New Mexico | Shawe-Taylor J.,University College London | And 9 more authors.
Medical Image Analysis | Year: 2014

In the present study we applied a multivariate feature selection method based on the analysis of the sign consistency of voxel weights across bagged linear Support Vector Machines (SVMs) with the aim of detecting brain regions relevant for the discrimination of subjects with obsessive-compulsive disorder (OCD, n = 86) from healthy controls (n = 86). Each participant underwent a structural magnetic resonance imaging (sMRI) examination that was pre-processed in Statistical Parametric Mapping (SPM8) using the standard pipeline of voxel-based morphometry (VBM) studies. Subsequently, we applied our multivariate feature selection algorithm, which also included an L2 norm regularization to account for the clustering nature of MRI data, and a transduction-based refinement to further control overfitting. Our approach proved to be superior to two state-of-the-art feature selection methods (i.e., mass-univariate t-Test selection and recursive feature elimination), since, following the application of transductive refinement, we obtained a lower test error rate of the final classifier. Importantly, the regions identified by our method have been previously reported to be altered in OCD patients in studies using traditional brain morphometry methods. By contrast, the discrimination patterns obtained with the t-Test and the recursive feature elimination approaches extended across fewer brain regions and included fewer voxels per cluster. These findings suggest that the feature selection method presented here provides a more comprehensive characterization of the disorder, thus yielding not only a superior identification of OCD patients on the basis of their brain anatomy, but also a discrimination map that incorporates most of the alterations previously described to be associated with the disorder. © 2014 Elsevier B.V. Source

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