Center for Biomedical Research Network on Mental Health

Madrid, Spain

Center for Biomedical Research Network on Mental Health

Madrid, Spain
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Besga A.,Center for Biomedical Research Network on Mental Health | Chyzhyk D.,University of the Basque Country | Gonzalez-Ortega I.,University of Santiago de Compostela | Gonzalez-Ortega I.,University of the Basque Country | And 6 more authors.
Frontiers in Aging Neuroscience | Year: 2017

Background: Late Onset Bipolar Disorder (LOBD) is the development of Bipolar Disorder (BD) at an age above 50 years old. It is often difficult to differentiate from other aging dementias, such as Alzheimer's Disease (AD), because they share cognitive and behavioral impairment symptoms. Objectives: We look for WM tract voxel clusters showing significant differences when comparing of AD vs. LOBD, and its correlations with systemic blood plasma biomarkers (inflammatory, neurotrophic factors, and oxidative stress). Materials: A sample of healthy controls (HC) (n = 19), AD patients (n = 35), and LOBD patients (n = 24) was recruited at the Alava University Hospital. Blood plasma samples were obtained at recruitment time and analyzed to extract the inflammatory, oxidative stress, and neurotrophic factors. Several modalities of MRI were acquired for each subject, Methods: Fractional anisotropy (FA) coefficients are obtained from diffusion weighted imaging (DWI). Tract based spatial statistics (TBSS) finds FA skeleton clusters of WM tract voxels showing significant differences for all possible contrasts between HC, AD, and LOBD. An ANOVA F-test over all contrasts is carried out. Results of F-test are used to mask TBSS detected clusters for the AD > LOBD and LOBD > AD contrast to select the image clusters used for correlation analysis. Finally, Pearson's correlation coefficients between FA values at cluster sites and systemic blood plasma biomarker values are computed. Results: The TBSS contrasts with by ANOVA F-test has identified strongly significant clusters in the forceps minor, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and cingulum gyrus. The correlation analysis of these tract clusters found strong negative correlation of AD with the nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) blood biomarkers. Negative correlation of AD and positive correlation of LOBD with inflammation biomarker IL6 was also found. Conclusion: TBSS voxel clusters tract atlas localizations are consistent with greater behavioral impairment and mood disorders in LOBD than in AD. Correlation analysis confirms that neurotrophic factors (i.e., NGF, BDNF) play a great role in AD while are absent in LOBD pathophysiology. Also, correlation results of IL1 and IL6 suggest stronger inflammatory effects in LOBD than in AD. © 2017 Besga, Chyzhyk, Gonzalez-Ortega, Echeveste, Graña-Lecuona, Graña and Gonzalez-Pinto.


Ugarte A.U.,University of Santiago de Compostela | Ugarte A.U.,Center for Biomedical Research Network on Mental Health | Lopez-Pena P.,University of Santiago de Compostela | Lopez-Pena P.,Center for Biomedical Research Network on Mental Health | And 11 more authors.
BMC Psychiatry | Year: 2017

Background: Postpartum depression is a disease with a prevalence of 20% that has deleterious consequences not only for the mother but also for the baby and can cause delays in physical, social and cognitive development. In this context, the European Union Committee on Public Health has declared it essential that preventative measures are taken by centres providing care for women with a multidisciplinary approach. PROGEA is a multicentre, single-blind randomized, 3-year, longitudinal clinical trial aiming to evaluate the efficacy of a psychoeducational programme in preventing postpartum depression in at-risk women, based on a range of clinical variables, and explore prognostic factors. This paper describes the methods and rationale behind the study. Methods: We will study women receiving treatment as usual plus a psychoeducation cognitive behavioural therapy (CBT)-based intervention and a control group receiving only treatment as usual. The sample will be recruited from an incidental sampling of pregnant women in two health regions. We will recruit 600 women in the third trimester of pregnancy who consent to take part in the study. Almost half of the women, about 280, would be expected to have some risk factors for postpartum depression. All those found to have risk factors will be evaluated, and we estimate that a quarter will be classified as at-risk of developing postpartum depression as measured with the Edinburgh Postnatal Depression Scale. This subset will be randomly allocated to receive treatment as usual with or without the CBT intervention. Six sessions of CBT (1 individual and 5 group) will be offered by a psychologist. Discussion: Findings from this study will be used to design a definitive study that will examine the clinical and cost-effectiveness of the CBT-based intervention in improving the mood of women in the postpartum period. Trial Registration: ClinicalTrials.gov Identifier: NCT02323152 ; Date: December 2014. © 2017 The Author(s).


Besga A.,Hospital Universitario La Paz | Besga A.,Center for Biomedical Research Network on Mental Health | Cedazo-Minguez A.,Karolinska Institutet | Kareholt I.,Karolinska Institutet | And 12 more authors.
Neuroscience Letters | Year: 2012

Investigate possible associations of white matter hyperintensities (WMHs) with the metabolism of cholesterol and insulin in two subgroups of patients with memory complaints and different CSF Aβ42 and CSF tau levels. 59 patients from the memory clinic at Karolinska Hospital were included. Degree of WMHs was rated using the ARWMC scale and the following biomarkers were measured in CSF and plasma: insulin, cholesterol, lanosterol, lathosterol, and oxidized cholesterol metabolites. The WMHs in CSF control-like group correlated with increased brain cholesterol synthesis and reduced efflux of oxysterols and insulin in CSF. In the CSF AD-like group, the WMHs correlated with increased peripheral cholesterol metabolism. Despite having similar appearance on FLAIR images, the pathogenic mechanisms of WMHS are likely to be different in the two groups investigated. © 2012 Elsevier Ireland Ltd.


Besga A.,Hospital Santiago Apostol | Besga A.,Center for Biomedical Research Network on Mental Health | Termenon M.,University of the Basque Country | Grana M.,University of the Basque Country | And 3 more authors.
Neuroscience Letters | Year: 2012

The aim of this study is to look for differential effects in white matter (WM) of bipolar disorder (BD) and Alzheimer's disease (AD) patients. We proceed by investigating the feasibility of discriminating between BD and AD patients, and from healthy controls (HC), using multivariate data analysis based on diffusion tensor imaging (DTI) data features. Specifically, support vector machine (SVM) classifiers were trained and tested on fractional anisotropy (FA). Voxel sites are selected as features for classification if their Pearson's correlation between FA values at voxel site across subjects and the indicative variable specifying the subject class is above the threshold set by a percentile of its empirical distribution. To avoid double dipping, selection was performed only on training data in a leave one out cross-validation study. Classification results show that FA features and a linear SVM classifier achieve perfect accuracy, sensitivity and specificity in AD vs. HC, BD vs. HC, and AD vs. BD leave-one-out cross-validation studies. The localization of the discriminant voxel sites on a probabilistic tractography atlas shows effects on seven major WM tracts in each hemisphere and two commissural tracts. © 2012 Elsevier Ireland Ltd.


Besga A.,University of Santiago de Compostela | Besga A.,Center for Biomedical Research Network on Mental Health | Besga A.,University of the Basque Country | Chyzhyk D.,University of the Basque Country | And 11 more authors.
Current Alzheimer Research | Year: 2016

Background: Late Onset Bipolar Disorder (LOBD) is the arousal of Bipolar Disorder (BD) at old age (>60) without any previous history of disorders. LOBD is often difficult to distinguish from degenerative dementias, such as Alzheimer Disease (AD), due to comorbidities and common cognitive symptoms. Moreover, LOBD prevalence is increasing due to population aging. Biomarkers extracted from blood plasma are not discriminant because both pathologies share pathophysiological features related to neuroinflammation, therefore we look for anatomical features highly correlated with blood biomarkers that allow accurate diagnosis prediction. This may shed some light on the basic biological mechanisms leading to one or another disease. Moreover, accurate diagnosis is needed to select the best personalized treatment. Objective: We look for white matter features which are correlated with blood plasma biomarkers (inflammatory and neurotrophic) discriminating LOBD from AD. Materials: A sample of healthy controls (HC) (n=19), AD patients (n=35), and BD patients (n=24) has been recruited at the Alava University Hospital. Plasma biomarkers have been obtained at recruitment time. Diffusion weighted (DWI) magnetic resonance imaging (MRI) are obtained for each subject. Methods: DWI is preprocessed to obtain diffusion tensor imaging (DTI) data, which is reduced to fractional anisotropy (FA) data. In the selection phase, eigenanatomy finds FA eigenvolumes maximally correlated with plasma biomarkers by partial sparse canonical correlation analysis (PSCCAN). In the analysis phase, we take the eigenvolume projection coefficients as the classification features, carrying out cross-validation of support vector machine (SVM) to obtain discrimination power of each biomarker effects. The John Hopkins Universtiy white matter atlas is used to provide anatomical localizations of the detected feature clusters. Results: Classification results show that one specific biomarker of oxidative stress (malondialdehyde MDA) gives the best classification performance (accuracy 85%, F-score 86%, sensitivity, and specificity 87%,) in the discrimination of AD and LOBD. Discriminating features appear to be localized in the posterior limb of the internal capsule and superior corona radiata. Conclusion: It is feasible to support contrast diagnosis among LOBD and AD by means of predictive classifiers based on eigenanatomy features computed from FA imaging correlated to plasma biomarkers. In addition, white matter eigenanatomy localizations offer some new avenues to assess the differential pathophysiology of LOBD and AD. © 2016 Bentham Science Publishers. All Rights Reserved.


Salazar A.,University of Cádiz | Duenas M.,University of Cádiz | Mico J.A.,University of Cádiz | Mico J.A.,Center for Biomedical Research Network on Mental Health | And 6 more authors.
Pain Medicine (United States) | Year: 2013

Objective: The study aims to determine the prevalence of undiagnosed comorbid mood disorders in patients suffering chronic musculoskeletal pain in a primary care setting and to identify sleep disturbances and other associated factors in these patients, and to compare the use of health services by chronic musculoskeletal pain patients with and without comorbid mood disorders. Design: Cross-sectional study. Subjects: A total of 1,006 patients with chronic musculoskeletal pain from a representative sample of primary care centers were evaluated. Outcome Measures: Pain was measured using a visual analog scale and the Primary Care Evaluation of Mental Disorders questionnaire was used to measure mood disorders. Results: We observed a high prevalence of undiagnosed mood disorders in chronic musculoskeletal pain patients (74.7%, 95% confidence interval [CI] 71.9-77.4%), with greater comorbidity in women (adjusted odds ratio [OR]=1.91, 95% CI 1.37-2.66%) and widow(er)s (adjusted OR=1.87, 95% CI 1.19-2.91%). Both sleep disturbances (adjusted OR=1.60, 95% CI 1.17-2.19%) and pain intensity (adjusted OR=1.02, 95% CI 1.01-1.02%) displayed a direct relationship with mood disorders. Moreover, we found that chronic musculoskeletal pain patients with comorbid mood disorders availed of health care services more frequently than those without (P<0.001). Conclusions: The prevalence of undiagnosed mood disorders in patients with chronic musculoskeletal pain is very high in primary care settings. Our findings suggest that greater attention should be paid to this condition in general practice and that sleep disorders should be evaluated in greater detail to achieve accurate diagnoses and select the most appropriate treatment. © 2013 American Academy of Pain Medicine.


Gutierrez-Galve L.,University College London | Gutierrez-Galve L.,University of Zaragoza | Gutierrez-Galve L.,Center for Biomedical Research Network on Mental Health | Flugel D.,National Hospital for Neurology and Neurosurgery | And 5 more authors.
Epilepsia | Year: 2012

Purpose: To determine whether cortical abnormalities are more severe and widespread in patients with temporal lobe epilepsy (TLE) and interictal psychosis (IP) compared to those with TLE only (NIP) and healthy controls (HC), and to explore the associations between cortical parameters (area, thickness and volume), psychotic symptoms, and cognitive performance. Methods: Twenty-two patients with IP (9 male; 10 hippocampal sclerosis, HS), 23 TLE nonpsychotic (NIP) patients (11 male; 13 HS) matched for duration of epilepsy and 20 HC participated. Surface-based morphometry (SBM) was used to measure cortical parameters. Cognition was examined in IP and NIP patients. Associations between cortical parameters and cognition were examined using linear mixed models adjusted by age, gender, and brain volume. Key Findings: IP patients had an earlier onset of epilepsy, more status epilepticus, and worse cognitive performance than NIP patients. In IP patients, cortical thickness was reduced in the inferior frontal gyrus (IFG), and their current IQ was associated with decreases in area, but not thickness, in regions of the frontotemporal cortex. Significance: IP likely reflects the interplay of psychosis-related genetic factors and the cumulative effects of seizure activity on the brain. Cortical thinning in the IFG, a region implicated in schizophrenia, is likely to be related to seizure activity, whereas changes in IQ, associated with reductions in area of frontotemporal cortex, may be related to the presence of psychosis. © Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.


Alemany S.,University of Barcelona | Alemany S.,Center for Biomedical Research Network on Mental Health | Ayesa-Arriola R.,Center for Biomedical Research Network on Mental Health | Ayesa-Arriola R.,University of Cantabria | And 10 more authors.
European Psychiatry | Year: 2015

Goal: The present study aimed to examine the prevalence of child abuse across the continuum of psychosis. Patients and methods: The sample consisted of 198individuals divided in three groups: (1) 48FEP patients, (2) 77individuals scoring high in Community Assessment of Psychic Experiences (CAPE), classified as "High CAPE" group and (3) 73individuals scoring low, classified as "Low CAPE" group. Childhood abuse was assessed using self-report instruments. Chi2 tests and logistic regression models controlling by sex, age and cannabis were used to perform three comparisons: (i) FEP vs. Low CAPE; (ii) FEP vs. High CAPE and (iii) High CAPE vs. Low CAPE. Results: The frequency of individuals exposed to childhood abuse for FEP, High CAPE and Low CAPE groups were 52.1%, 41.6% and 11%, respectively. FEP and High CAPE group presented significantly higher rates of childhood abuse compared to Low CAPE group, however, no significant differences were found between FEP and High CAPE groups regarding the frequency of childhood abuse. Conclusion: There is an increasing frequency of childhood abuse from low subclinical psychosis to FEP patients. However, childhood abuse is equally common in FEP and at risk individuals. © 2014 Elsevier Masson SAS.


Alemany S.,University of Barcelona | Alemany S.,Center for Biomedical Research Network on Mental Health | Goldberg X.,University of Barcelona | Goldberg X.,Center for Biomedical Research Network on Mental Health | And 7 more authors.
European Psychiatry | Year: 2013

Purpose: To test whether the association between childhood adversity and positive and negative psychotic experiences is due to genetic confounding. Method: Childhood adversity and psychotic experiences were assessed in an ongoing sample of 226 twins from the general population. A monozygotic (MZ) twin differences approach was used to assess possible genetic confounding. Results: In the whole sample, childhood adversity was significantly associated with positive (β. =. 45; SE. =. 0.16; P=. 0.008) and negative psychotic experiences (β. =. 0.77; SE. =. 0.18; P<. 0.01). Within-pair MZ twin differences in exposure to childhood adversity were significantly associated with differences in positive (β. =. 71; SE. =. 0.29; P=. 0.016) and negative psychotic experiences (β. =. 98; SE. =. 0.38; P=. 0.014) in a subsample of 85 MZ twin pairs. Conclusions: Individuals exposed to childhood adversity are more likely to report psychotic experiences. Furthermore, our findings indicate that this association is not due to genetic confounding. © 2012 Elsevier Masson SAS.


Besga A.,Santiago Apostol Hospital | Besga A.,Center for Biomedical Research Network on Mental Health | Besga A.,Basque Foundation for Health Innovation and Research BIOEF | Martinez-Cengotitabengoa M.,Santiago Apostol Hospital | And 14 more authors.
Maturitas | Year: 2011

Bipolar disorder in elderly is probably heterogenous and the age of onset has been considered to be a potential clinical marker of heterogeneity for this disease. Early- and late-onset bipolar disorders share symptoms, but it is not clear whether they have different aetiologies and vulnerabilities. In bipolar disorder one of the most frequent neuroimaging finding is the white matter hyperintensities (WMHs). The disruption caused by WMHs in the connectivity between structures related to mood regulation and cognition in elderly may be responsible for the affective symptomatology seen in these patients. White matter hyperintensities are found both in late onset patients and in early age onset bipolar patients. It is likely that the aetiology of the white matter hyperintensities in late-onset bipolar disorder be multifactorial, although cardiovascular changes in particular seem to contribute to their physiopathology. In early life onset the aetiology of these lesions is less clear, although probably genetic factors are more important than cardiovascular factors. Understanding the aetiopathogenesis is of key importance when dealing with this disease. © 2011 Elsevier Ireland Ltd. All rights reserved.

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