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.,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.


Besga A.,University of Santiago de Compostela | Besga A.,Center for Biomedical Research Network on Mental Health | Besga A.,University of the Basque Country | Gonzalez I.,University of Santiago de Compostela | And 17 more authors.
Frontiers in Aging Neuroscience | Year: 2015

Background: Late onset bipolar disorder (LOBD) is often difficult to distinguish from degenerative dementias, such as Alzheimer disease (AD), due to comorbidities and common cognitive symptoms. Moreover, LOBD prevalence in the elder population is not negligible and it is increasing. Both pathologies share pathophysiological neuroinflammation features. Improvements in differential diagnosis of LOBD and AD will help to select the best personalized treatment. Objective: The aim of this study is to assess the relative significance of clinical observations, neuropsychological tests, and specific blood plasma biomarkers (inflammatory and neurotrophic), separately and combined, in the differential diagnosis of LOBD versus AD. It was carried out evaluating the accuracy achieved by classification-based computer-aided diagnosis (CAD) systems based on these variables. Materials: A sample of healthy controls (HC) (n = 26), AD patients (n = 37), and LOBD patients (n = 32) was recruited at the Alava University Hospital. Clinical observations, neuropsychological tests, and plasma biomarkers were measured at recruitment time. Methods: We applied multivariate machine learning classification methods to discriminate subjects from HC, AD, and LOBD populations in the study. We analyzed, for each classification contrast, feature sets combining clinical observations, neuropsychological measures, and biological markers, including inflammation biomarkers. Furthermore, we analyzed reduced feature sets containing variables with significative differences determined by a Welch's t-test. Furthermore, a battery of classifier architectures were applied, encompassing linear and non-linear Support Vector Machines (SVM), Random Forests (RF), Classification and regression trees (CART), and their performance was evaluated in a leave-one-out (LOO) cross-validation scheme. Post hoc analysis of Gini index in CART classifiers provided a measure of each variable importance. Results: Welch's t-test found one biomarker (Malondialdehyde) with significative differences (p < 0.001) in LOBD vs. AD contrast. Classification results with the best features are as follows: discrimination of HC vs. AD patients reaches accuracy 97.21% and AUC 98.17%. Discrimination of LOBD vs. AD patients reaches accuracy 90.26% and AUC 89.57%. Discrimination of HC vs LOBD patients achieves accuracy 95.76% and AUC 88.46%. Conclusion: It is feasible to build CAD systems for differential diagnosis of LOBD and AD on the basis of a reduced set of clinical variables. Clinical observations provide the greatest discrimination. Neuropsychological tests are improved by the addition of biomarkers, and both contribute significantly to improve the overall predictive performance. © 2015 Besga, Gonzalez, Echeburua, Savio, Ayerdi, Chyzhyk, Madrigal, Leza, Graña and Gonzalez-Pinto.


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.


Ibarra P.,University of Barcelona | Alemany S.,University of Barcelona | Alemany S.,Center for Biomedical Research Network on Mental Health | Fatjo-Vilas M.,University of Barcelona | And 14 more authors.
European Psychiatry | Year: 2014

Purpose: To test whether firstly, different parental rearing components were associated with different dimensions of psychiatric symptoms in adulthood, secondly BDNF-Val66Met polymorphism moderated this association and thirdly, this association was due to genetic confounding. Method: Perceived parental rearing according to Parental Bonding Instrument (PBI), psychiatric symptoms evaluated with the Brief Symptom Inventory (BSI) and the BDNF-Val66Met polymorphism were analyzed in a sample of 232 adult twins from the general population. Results: In the whole sample, paternal care was negatively associated with depression. Maternal overprotection was positively associated with paranoid ideation, obsession-compulsion and somatization. Gene-environment interaction effects were detected between the BDNF-Val66Met polymorphism and maternal care on phobic anxiety, paternal care on hostility, maternal overprotection on somatization and paternal overprotection also in somatization. In the subsample of MZ twins, intrapair differences in maternal care were associated with anxiety, paranoid ideation and somatization. Conclusions: Met carriers were, in general, more sensitive to the effects of parental rearing compared to Val/Val carriers in relation to anxiety and somatization. Contra-intuitively, our findings suggest that high rates of maternal care might be of risk for Met carriers regarding anxiety. Results from analyses controlling for genetic confounding were in line with this finding. © 2014 Elsevier Masson SAS.


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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