CRC Hospital Del Mar

Barcelona, Spain

CRC Hospital Del Mar

Barcelona, Spain

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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.


Domingo L.,Hospital Del Mar IMIM | Domingo L.,CIBER ISCIII | Domingo L.,Autonomous University of Barcelona | Sala M.,Hospital Del Mar IMIM | And 13 more authors.
Cancer Causes and Control | Year: 2010

Objective: To analyze phenotypic classification and other risk factors for interval breast cancer, focusing on true interval and false negative cancers. Methods: A nested case-control study was performed among 115 cancers detected between two screening mammograms (interval cancers) and 115 screen-detected cancers diagnosed between 1995 and 2008 in a population-based breast cancer screening program in Barcelona (Spain). Bivariate and multivariate analyses were performed to compare patient and tumor molecular characteristics among all interval cancers, true intervals and false negatives, and screen-detected cancers. Results: A total of 42.5% of interval cancers were true interval tumors and 16.2% were false negatives. High breast density and triple negative phenotype were more frequent in true interval cancers than in screen-detected cancers (57.6 and 34.1%, respectively for breast density, p = 0.023; 28.1 and 7.5%, respectively for triple negative phenotype, p = 0.028), while no statistically significant differences were observed between false negatives and screen-detected cancers. The main adjusted factors associated with true interval cancers compared with screen-detected cancers were high breast density and triple negative phenotype (OR = 3.1, 95% CI, 1.03-9.24 and OR = 8.9, 95% CI, 2.03-38.62, respectively). Conclusion: A more aggressive molecular phenotype and high breast density were identified in breast tumors that truly arise in the interval between screenings. © 2010 Springer Science+Business Media B.V.


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.


Lopez-Sola M.,CRC Hospital Del Mar | Lopez-Sola M.,University of Barcelona | Pujol J.,CRC Hospital Del Mar | Pujol J.,CIBER ISCIII | And 17 more authors.
Neuropsychopharmacology | Year: 2010

Major depressive disorder (MDD) is characterized by a constellation of affective, cognitive, and somatic symptoms associated with functional abnormalities in relevant brain systems. Painful stimuli are primarily stressful and can trigger consistent responses in brain regions highly overlapping with the regions altered in MDD patients. Duloxetine has proven to be effective in treating both core emotional symptoms and somatic complaints in depression. This study aimed to assess the effects of duloxetine treatment on brain response to painful stimulation in MDD patients. A total of 13 patients and a reference group of 20 healthy subjects were assessed on three occasions (baseline, treatment week 1, and week 8) with functional magnetic resonance imaging (fMRI) during local application of painful heat stimulation. Treatment with duloxetine was associated with a significant reduction in brain responses to painful stimulation in MDD patients in regions generally showing abnormally enhanced activation at baseline. Clinical improvement was associated with pain-related activation reductions in the pregenual anterior cingulate cortex, right prefrontal cortex, and pons. Pontine changes were specifically related to clinical remission. Increased baseline activations in the right prefrontal cortex and reduced deactivations in the subgenual anterior cingulate cortex predicted treatment responders at week 8. This is the first fMRI study addressed to assess the effect of duloxetine in MDD. As a novel approach, the application of painful stimulation as a basic neural stressor proved to be effective in mapping brain response changes associated with antidepressant treatment and brain correlates of symptom improvement in regions of special relevance to MDD pathophysiology. © 2010 Nature Publishing Group All rights reserved.


Cardoner N.,University of Barcelona | Cardoner N.,Carlos III Health Institute | Soria V.,University of Barcelona | Soria V.,Carlos III Health Institute | And 15 more authors.
Depression and Anxiety | Year: 2013

Background A brain-derived neurotrophic factor (BDNF) prodomain single-nucleotide polymorphism resulting in a valine to methionine substitution (Val66Met) has been associated with depression-related phenotypes and brain alterations involving regions consistently associated with major depressive disorder (MDD). The aim of our study was to evaluate the association of regional gray matter (GM) volume within the hippocampus and other unpredicted regions at the whole-brain level with the BDNF Val66Met polymorphism in MDD patients with melancholic features and their impact on treatment outcome. Methods A sample of 37 MDD inpatients was assessed with three-dimensional magnetic resonance imaging (1.5-T scanner). GM volume was analyzed with voxel-based morphometry (VBM) using Statistical Parametric Mapping (SPM5). The BDNF Val66Met variant was genotyped using SNPlex technology. MDD patients were classified according to genotype distribution under a dominant model of inheritance and thus comparing Val66 homozygotes (n = 22) versus Met66 carriers (n = 15). Results A significant GM volume reduction in the left hippocampus was observed in Met66 carriers. Conversely, in the same group, a volume increase in the right orbitofrontal cortex was detected. Moreover, a significant negative correlation between left hippocampal volume and days to remission was found in Val66 homozygotes, whereas right orbitofrontal volume was inversely correlated to days to remission in Met66 carriers. Conclusions Our results suggest that the Val66Met BDNF variant may have a differential impact on the brain structure of melancholic patients with possible treatment outcome implications. © 2012 Wiley Periodicals, Inc.


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.


PubMed | University of Barcelona, CRC Hospital del Mar, University of New Mexico, University Institute of Mental Health and 2 more.
Type: Journal Article | Journal: 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.


Hernandez-Ribas R.,University of Barcelona | Hernandez-Ribas R.,Carlos III Health Institute | Deus J.,Autonomous University of Barcelona | Deus J.,CRC Hospital Del Mar | And 11 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.


Soriano-Mas C.,University of Barcelona | Soriano-Mas C.,Carlos III Health Institute | Harrison B.J.,University of Melbourne | Pujol J.,CRC Hospital Del Mar | And 15 more authors.
Brain Structure and Function | Year: 2013

The caudate and putamen nuclei have been traditionally divided into dorsal and ventral territories based on their segregated patterns of functional and anatomical connectivity with distributed cortical regions. Activity-dependent structural plasticity may potentially lead to the development of regional volume correlations, or structural covariance, between the different components of each cortico-striatal circuit. Here, we studied the whole-brain structural covariance patterns of four neostriatal regions belonging to distinct cortico-striatal circuits. We also assessed the potential modulating influence of laterality, age and gender. T1-weighted three-dimensional magnetic resonance images were obtained from ninety healthy participants (50 females). Following data pre-processing, the mean signal value per hemisphere was calculated for the 'seed' regions of interest, located in the dorsal and ventral caudate and the dorsal-caudal and ventral-rostral putamen. Statistical parametric mapping was used to estimate whole-brain voxel-wise structural covariance patterns for each striatal region, controlling for the shared anatomical variance between regions in order to obtain maximally specific structural covariance patterns. As predicted, segregated covariance patterns were observed. Age was found to be a relevant modulator of the covariance patterns of the right caudate regions, while laterality effects were observed for the dorsal-caudal putamen. Gender effects were only observed via an interaction with age. The different patterns of structural covariance are discussed in detail, as well as their similarities with the functional and anatomical connectivity patterns reported for the same striatal regions in other studies. Finally, the potential mechanisms underpinning the phenomenon of volume correlations between distant cortico-striatal structures are also discussed. © 2012 Springer-Verlag.


PubMed | CRC Hospital del Mar, University of the Sea and Autonomous University of Barcelona
Type: Journal Article | Journal: Parkinsonism & related disorders | Year: 2014

Hallucinations are a frequent and severe complication in Parkinsons 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).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 1.5 T magnet, and analyzed using optimized VBM.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.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.

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