Publications by authors named "Jose L Ayuso-Mateos"

32 Publications

Genetic underpinnings of sociability in the general population.

Neuropsychopharmacology 2021 08 30;46(9):1627-1634. Epub 2021 May 30.

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Levels of sociability are continuously distributed in the general population, and decreased sociability represents an early manifestation of several brain disorders. Here, we investigated the genetic underpinnings of sociability in the population. We performed a genome-wide association study (GWAS) of a sociability score based on four social functioning-related self-report questions from 342,461 adults in the UK Biobank. Subsequently we performed gene-wide and functional follow-up analyses. Robustness analyses were performed in the form of GWAS split-half validation analyses, as well as analyses excluding neuropsychiatric cases. Using genetic correlation analyses as well as polygenic risk score analyses we investigated genetic links of our sociability score to brain disorders and social behavior outcomes. Individuals with autism spectrum disorders, bipolar disorder, depression, and schizophrenia had a lower sociability score. The score was significantly heritable (SNP h of 6%). We identified 18 independent loci and 56 gene-wide significant genes, including genes like ARNTL, DRD2, and ELAVL2. Many associated variants are thought to have deleterious effects on gene products and our results were robust. The sociability score showed negative genetic correlations with autism spectrum, disorders, depression, schizophrenia, and two sociability-related traits-loneliness and social anxiety-but not with bipolar disorder or Alzheimer's disease. Polygenic risk scores of our sociability GWAS were associated with social behavior outcomes within individuals with bipolar disorder and with major depressive disorder. Variation in population sociability scores has a genetic component, which is relevant to several psychiatric disorders. Our findings provide clues towards biological pathways underlying sociability.
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http://dx.doi.org/10.1038/s41386-021-01044-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280100PMC
August 2021

Effects of transient and chronic loneliness on major depression in older adults: A longitudinal study.

Int J Geriatr Psychiatry 2021 01 10;36(1):76-85. Epub 2020 Sep 10.

Department of Psychiatry, Universidad Autónoma de Madrid, Madrid, Spain.

Objectives: The number of older adults is rapidly rising globally. Loneliness is a common problem that can deteriorate health. The aims of this work were to identify different types of loneliness (transient and chronic) and to assess their association with depression over time.

Methods: A nationally representative sample from the Spanish population comprising 1190 individuals aged 50+ years was interviewed on three evaluations over a 7-year period. The UCLA Loneliness Scale was used to measure loneliness. While chronic loneliness was defined as the presence of loneliness across all three waves, transient loneliness expressed the presence of loneliness in one wave only. A 12-month major depressive episode was assessed at each interview. After confirming the cross-sectional relationship, a multilevel mixed-effects model was used to examine the association between loneliness and depression.

Results: Almost a quarter of individuals felt lonely and one out of 10 presented depression at baseline. Of the sample, 22.78% showed transient loneliness, while 6.72% presented the chronic type. People experiencing chronic loneliness were at a higher risk of presenting major depression (OR = 6.11; 95% CI = 2.62, 14.22) than those presenting transient loneliness (OR = 2.22; 95% CI = 1.19, 4.14). This association varied over time and was stronger at the first follow-up than at the second one.

Conclusions: Focusing on loneliness prevention could reduce the risk of depression. Chronic loneliness is a public health problem that should be addressed through the full participation of the political, social, and medical sectors.
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http://dx.doi.org/10.1002/gps.5397DOI Listing
January 2021

Pain rates in general population for the period 1991-2015 and 10-years prediction: results from a multi-continent age-period-cohort analysis.

J Headache Pain 2020 May 13;21(1):52. Epub 2020 May 13.

Neurology, Public Health and Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133, Milan, Italy.

Background: Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people. The aims of this study are to evaluate the temporal variations of pain rates among general populations for the period 1991-2015 and to project 10-year pain rates.

Methods: We used the harmonized dataset of ATHLOS project, which included 660,028 valid observations in the period 1990-2015 and we applied Bayesian age-period-cohort modeling to perform projections up to 2025. The harmonized Pain variable covers the content "self-reported pain experienced at the time of the interview", with a dichotomous (yes or no) modality.

Results: Pain rates were higher among females, older subjects, in recent periods, and among observations referred to cohorts of subjects born between the 20s and the 60s. The 10-year projections indicate a noteworthy increase in pain rates in both genders and particularly among subjects aged 66 or over, for whom a 10-20% increase in pain rate is foreseen; among females only, a 10-15% increase in pain rates is foreseen for those aged 36-50.

Conclusions: Projected increase in pain rates will require specific interventions by health and welfare systems, as pain is responsible for limited quality of subjective well-being, reduced employment rates and hampered work performance. Worksite and lifestyle interventions will therefore be needed to limit the impact of projected higher pain rates.
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http://dx.doi.org/10.1186/s10194-020-01108-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218619PMC
May 2020

Diagnostic classification of irritability and oppositionality in youth: a global field study comparing ICD-11 with ICD-10 and DSM-5.

J Child Psychol Psychiatry 2021 03 12;62(3):303-312. Epub 2020 May 12.

Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

Background: Severe irritability has become an important topic in child and adolescent mental health. Based on the available evidence and on public health considerations, WHO classified chronic irritability within oppositional defiant disorder (ODD) in ICD-11, a solution markedly different from DSM-5's (i.e. the new childhood mood diagnosis, disruptive mood dysregulation disorder [DMDD]) and from ICD-10's (i.e. ODD as one of several conduct disorders without attention to irritability). In this study, we tested the accuracy with which a global, multilingual, multidisciplinary sample of clinicians were able to use the ICD-11 classification of chronic irritability and oppositionality as compared to the ICD-10 and DSM-5 approaches.

Methods: Clinicians (N = 196) from 48 countries participated in an Internet-based field study in English, Spanish, or Japanese and were randomized to review and use one of the three diagnostic systems. Through experimental manipulation of validated clinical vignettes, we evaluated how well clinicians in each condition could identify chronic irritability versus nonirritable oppositionality, episodic bipolar disorder, dysthymic depression, and normative irritability.

Results: Compared to ICD-10 and DSM-5, ICD-11 led to more accurate identification of severe irritability and better differentiation from boundary presentations. Participants using DSM-5 largely failed to apply the DMDD diagnosis when it was appropriate, and they more often applied psychopathological diagnoses to developmentally normative irritability.

Conclusions: The formulation of irritability and oppositionality put forth in ICD-11 shows evidence of clinical utility, supporting accurate diagnosis. Global mental health clinicians can readily identify ODD both with and without chronic irritability.
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http://dx.doi.org/10.1111/jcpp.13244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657976PMC
March 2021

Cross-cultural comparison of symptom networks in late-life major depressive disorder: Yoruba Africans and the Spanish Population.

Int J Geriatr Psychiatry 2020 09 22;35(9):1060-1068. Epub 2020 Jun 22.

Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain.

Background: The concept of European psychologisation of depression versus somatisation in non-European populations has been the basis of several studies of cultural psychopathology in the general population. Little is currently known about cross-cultural differences and similarities in late-life depression symptom reporting. We cross-culturally compared symptom reporting in the context of Major Depressive Disorder (MDD) among community-dwelling older adults from Spain and Nigeria.

Methods: We relied on data from two household multistage probability samples comprising 3,715 persons aged 65 years or older in the Spanish and Nigerian populations. All participants underwent assessments for MDD using the World Mental Health Survey version of the Composite International Diagnostic Interview. Cross-cultural comparison of broad somatic and psychological categories as well as relationship and influence of individual symptoms were analysed using the Symptom Network Analysis approach.

Results: Current MDD was diagnosed in 232 and 195 older persons from Spain and Nigeria, respectively. The symptom network of the two samples were invariant in terms of global strength, S(G , G ) = 7.56, P = .06, with psychological and somatic symptoms demonstrating centrality in both countries. However, country-specific relationships and influence of individual symptoms were found in the network structure of both samples, M(G , G ) = 2.95, P < .01.

Conclusion: Broad somatic and psychological symptoms categories contributed to the structural network of older Africans and their peers from the Spanish population. Variations in the relationship and influence of individual symptoms suggests that the functional and "communicative" role of individual symptoms may be differentiated by context specific imperatives. J Am Geriatr Soc 68:-, 2020.
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http://dx.doi.org/10.1002/gps.5329DOI Listing
September 2020

Predictors of pain in general ageing populations: results from a multi-country analysis based on ATHLOS harmonized database.

J Headache Pain 2020 May 6;21(1):45. Epub 2020 May 6.

National Research Council, Neuroscience Institute, Padova, Italy.

Background: Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people, and with increasing trends in general populations. Different risk factors for pain have been identified, but generally from studies with limited samples and a limited number of candidate predictors. The aim of this study is to evaluate the predictors of pain from a large set of variables and respondents.

Methods: We used part of the harmonized dataset of ATHLOS project, selecting studies and waves with a longitudinal course, and in which pain was absent at baseline and with no missing at follow-up. Predictors were selected based on missing distribution and univariable association with pain, and were selected from the following domains: Socio-demographic and economic characteristics, Lifestyle and health behaviours, Health status and functional limitations, Diseases, Physical measures, Cognition, personality and other psychological measures, and Social environment. Hierarchical logistic regression models were then applied to identify significant predictors.

Results: A total of 13,545 subjects were included of whom 5348 (39.5%) developed pain between baseline and the average 5.2 years' follow-up. Baseline risk factors for pain were female gender (OR 1.34), engaging in vigorous exercise (OR 2.51), being obese (OR 1.36) and suffering from the loss of a close person (OR 1.88) whereas follow-up risk factors were low energy levels/fatigue (1.93), difficulties with walking (1.69), self-rated health referred as poor (OR 2.20) or average to moderate (OR 1.57) and presence of sleep problems (1.80).

Conclusions: Our results showed that 39.5% of respondents developed pain over a five-year follow-up period, that there are proximal and distal risk factors for pain, and that part of them are directly modifiable. Actions aimed at improving sleep, reducing weight among obese people and treating fatigue would positively impact on pain onset, and avoiding vigorous exercise should be advised to people aged 60 or over, in particular if female or obese.
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http://dx.doi.org/10.1186/s10194-020-01116-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201730PMC
May 2020

Strengthening mental health systems in low- and middle-income countries: recommendations from the Emerald programme.

BJPsych Open 2019 Aug 6;5(5):e73. Epub 2019 Aug 6.

Professor of Community Psychiatry, Centre for Global Mental Health and Centre for Implementation Science, Institute of Psychiatry, Psychology and Psychiatry, King's College London, UK.

Background: There is a large treatment gap for mental, neurological or substance use (MNS) disorders. The 'Emerging mental health systems in low- and middle-income countries (LMICs)' (Emerald) research programme attempted to identify strategies to work towards reducing this gap through the strengthening of mental health systems.

Aims: To provide a set of proposed recommendations for mental health system strengthening in LMICs.

Method: The Emerald programme was implemented in six LMICs in Africa and Asia (Ethiopia, India, Nepal, Nigeria, South Africa and Uganda) over a 5-year period (2012-2017), and aimed to improve mental health outcomes in the six countries by building capacity and generating evidence to enhance health system strengthening.

Results: The proposed recommendations align closely with the World Health Organization's key health system strengthening 'building blocks' of governance, financing, human resource development, service provision and information systems; knowledge transfer is included as an additional cross-cutting component. Specific recommendations are made in the paper for each of these building blocks based on the body of data that were collected and analysed during Emerald.

Conclusions: These recommendations are relevant not only to the six countries in which their evidential basis was generated, but to other LMICs as well; they may also be generalisable to other non-communicable diseases beyond MNS disorders.

Declaration Of Interest: None.
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http://dx.doi.org/10.1192/bjo.2018.90DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700480PMC
August 2019

Effective methods for knowledge transfer to strengthen mental health systems in low- and middle-income countries.

BJPsych Open 2019 Aug 6;5(5):e72. Epub 2019 Aug 6.

Professor of Community Psychiatry, Centre for Global Mental Health and Centre for Implementation Science, Institute of Psychiatry, Psychology and Psychiatry, King's College London, UK.

Background: The Emerald project's focus is on how to strengthen mental health systems in six low- and middle-income countries (LMICs) (Ethiopia, India, Nepal, Nigeria, South Africa and Uganda). This was done by generating evidence and capacity to enhance health system performance in delivering mental healthcare.A common problem in scaling-up interventions and strengthening mental health programmes in LMICs is how to transfer research evidence, such as the data collected in the Emerald project, into practice.

Aims: To describe how core elements of Emerald were implemented and aligned with the ultimate goal of strengthening mental health systems, as well as their short-term impact on practices, policies and programmes in the six partner countries.

Method: We focused on the involvement of policy planners, managers, patients and carers.

Results: Over 5 years of collaboration, the Emerald consortium has provided evidence and tools for the improvement of mental healthcare in the six LMICs involved in the project. We found that the knowledge transfer efforts had an impact on mental health service delivery and policy planning at the sites and countries involved in the project.

Conclusions: This approach may be valid beyond the mental health context, and may be effective for any initiative that aims at implementing evidence-based health policies for health system strengthening.
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http://dx.doi.org/10.1192/bjo.2019.50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688465PMC
August 2019

Innovations and changes in the ICD-11 classification of mental, behavioural and neurodevelopmental disorders.

World Psychiatry 2019 Feb;18(1):3-19

Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.

Following approval of the ICD-11 by the World Health Assembly in May 2019, World Health Organization (WHO) member states will transition from the ICD-10 to the ICD-11, with reporting of health statistics based on the new system to begin on January 1, 2022. The WHO Department of Mental Health and Substance Abuse will publish Clinical Descriptions and Diagnostic Guidelines (CDDG) for ICD-11 Mental, Behavioural and Neurodevelopmental Disorders following ICD-11's approval. The development of the ICD-11 CDDG over the past decade, based on the principles of clinical utility and global applicability, has been the most broadly international, multilingual, multidisciplinary and participative revision process ever implemented for a classification of mental disorders. Innovations in the ICD-11 include the provision of consistent and systematically characterized information, the adoption of a lifespan approach, and culture-related guidance for each disorder. Dimensional approaches have been incorporated into the classification, particularly for personality disorders and primary psychotic disorders, in ways that are consistent with current evidence, are more compatible with recovery-based approaches, eliminate artificial comorbidity, and more effectively capture changes over time. Here we describe major changes to the structure of the ICD-11 classification of mental disorders as compared to the ICD-10, and the development of two new ICD-11 chapters relevant to mental health practice. We illustrate a set of new categories that have been added to the ICD-11 and present the rationale for their inclusion. Finally, we provide a description of the important changes that have been made in each ICD-11 disorder grouping. This information is intended to be useful for both clinicians and researchers in orienting themselves to the ICD-11 and in preparing for implementation in their own professional contexts.
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http://dx.doi.org/10.1002/wps.20611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313247PMC
February 2019

Understanding the direct and indirect costs of a first episode of psychosis program: Insights from PAFIP of Cantabria, Spain, during the first year of intervention.

Early Interv Psychiatry 2019 10 12;13(5):1182-1190. Epub 2018 Oct 12.

School of Medicine, University of Cantabria, Santander, Spain.

Aim: Early intervention psychiatric services for patients with psychosis aim to limit the most damaging outcomes and reduce the patient's risk of social drift, decreasing illness severity and thus containing healthcare costs. There is a scarcity of studies that focus on first-episode psychosis (FEP), and those few that have been published only looked at direct health costs, but not at indirect costs, which make up the bulk of the budget. Our study aims to explore the short-term (1-year follow-up) economic cost of a FEP Program, including both direct and indirect costs.

Methods: Data were collected retrospectively from the clinical records of 157 patients included in the Programa Atención Fases Iniciales de Psicosis, from Marqués de Valdecilla University Hospital, Santander. Our data collection sheet collated data from direct and indirect costs associated with the illness. Data were also extracted from the Cantabria Health Service Records. STATA 15.0 was used for statistical analysis.

Results: On average, the total costs during the first year were €48 353.51 per patient, with direct healthcare costs being €13 729.47 (28.39%), direct non-medical costs €108.6 (0.22%), and indirect costs €34 515.44 (71.39%). We found that hospitalization costs were higher in males (p = 0.081) and in cannabis users (p = 0.032). The number of relapses increased both, hospitalization and treatment costs (r = 0.40 p = 0.000; r = 0.24 p = 0.067, respectively).

Conclusions: Intensive Early Intervention in Psychosis Services may result in cost savings by decreasing hospitalization, premature mortality, disability, unemployment, and legal problems; however, the first year after diagnosis would represent the one with the highest costs.
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http://dx.doi.org/10.1111/eip.12752DOI Listing
October 2019

Working definitions, subjective and objective assessments and experimental paradigms in a study exploring social withdrawal in schizophrenia and Alzheimer's disease.

Neurosci Biobehav Rev 2019 02 24;97:38-46. Epub 2018 Jun 24.

Department of Biomedical and Neuromotor Science, University of Bologna, Bologna, Italy.

Social withdrawal is one of the first and common signs of early social dysfunction in a number of important neuropsychiatric disorders, likely because of the enormous amount and complexity of brain processes required to initiate and maintain social relationships (Adolphs, 2009). The Psychiatric Ratings using Intermediate Stratified Markers (PRISM) project focusses on the shared and unique neurobiological basis of social withdrawal in schizophrenia, Alzheimer and depression. In this paper, we discuss the working definition of social withdrawal for this study and the selection of objective and subjective rating scales to assess social withdrawal chosen or adapted for this project. We also discuss the MRI and EEG paradigms selected to study the systems and neural circuitry thought to underlie social functioning and more particularly to be involved in social withdrawal in humans, such as the social perception and the social affiliation networks. A number of behavioral paradigms were selected to assess complementary aspects of social cognition. Also, a digital phenotyping method (a smartphone application) was chosen to obtain real-life data.
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http://dx.doi.org/10.1016/j.neubiorev.2018.06.020DOI Listing
February 2019

Research Recommendations for Improving Measurement of Treatment Effectiveness in Depression.

Front Psychol 2017 9;8:356. Epub 2017 Mar 9.

Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red, CIBERMadrid, Spain; Department of Psychiatry, Universidad Autónoma de MadridMadrid, Spain; Instituto de Investigación de La Princesa (IIS-IP), Hospital Universitario de La PrincesaMadrid, Spain.

Despite the steadily escalating psychological and economic burden of depression, there is a lack of evidence for the effectiveness of available interventions on functioning areas beyond symptomatology. Therefore, the main objective of this study was to give an insight into the current measurement of treatment effectiveness in depression and to provide recommendations for its improvement. The study was based on a multi-informant approach, comparing data from a systematic literature review, an expert survey with representatives from clinical practice (130), and qualitative interviews with patients (11) experiencing depression. Current literature places emphasis on symptomatic outcomes and neglects other domains of functioning, whereas clinicians and depressed patients highlight the importance of both. Interpersonal relationships, recreation and daily activities, communication, social participation, work difficulties were identified as being crucial for recovery. Personal factors, neglected by the literature, such as self-efficacy were introduced by experts and patients. Furthermore, clinicians and patients identified a number of differences regarding the areas improved by psychotherapeutic or pharmacological interventions that were not addressed by the pertinent literature. Creation of a new cross-nationally applicable measure of psychosocial functioning, broader remission criteria, report of domain-specific information, and a personalized approach in treatment decision-making are the first crucial steps needed for the improvement of the measurement of treatment effectiveness in depression. A better measurement will facilitate the clinical decision making and answer the escalating burden of depression.
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http://dx.doi.org/10.3389/fpsyg.2017.00356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343004PMC
March 2017

Financial crisis, austerity, and health in Europe.

Lancet 2013 Aug;382(9890):391-392

Centro de Estudos de Doenças Crónicas, Departamento de Saúde Mental, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Portugal.

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http://dx.doi.org/10.1016/S0140-6736(13)61663-3DOI Listing
August 2013

Development of the International Classification of Functioning, Disability and Health core sets for bipolar disorders: results of an international consensus process.

Disabil Rehabil 2013 15;35(25):2138-46. Epub 2013 Apr 15.

Department of Psychiatry, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Princesa , Madrid , Spain .

Purpose: The International Classification of Functioning, Disability and Health (ICF) is a tool of the World Health Organization (WHO) designed to be a guide to identify and classify relevant domains of human experience affected by health conditions. The purpose of this article is to describe the process for the development of two Core Sets for bipolar disorder (BD) in the framework of the ICF. The Comprehensive ICF Core Set for BD intends to be a guide for multidisciplinary assessment of patients diagnosed with this condition, while the Brief ICF Core Set for BD will be useful when rating aspects of patient's experience for clinical practice or epidemiological studies.

Methods: An international consensus conference involving a sample of experts with different professional backgrounds was performed using the nominal group technique. Various preparatory studies identified a set of 743 potential ICF categories to be included in the Core Sets.

Results: A total of 38 ICF categories were selected to be included in the Comprehensive Core Set for BD. A total of 19 ICF categories from the Comprehensive Core Set were chosen as the most significant to constitute the Brief Core Set for BD.

Conclusions: The formal consensus process integrating evidence and expert opinion on the ICF led to the formal adoption of the ICF Core Sets for BD. The most important categories included are representative of the characteristics usually associated with BD. The next phase of this ICF project is to conduct a formal validation process to establish its applicability in clinical settings. Implications for Rehabilitation Bipolar disorder (BD) is a prevalent condition that has a great impact on people who suffer it, not only in health but also in daily functioning and quality of life. No standard has been defined so far regarding the problems in functioning of persons with BDs. The process described in this article defines the set of areas of functioning to be addressed in clinical assessments of persons with BD and establish the starting point for the development of condition-specific outcome measures.
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http://dx.doi.org/10.3109/09638288.2013.771708DOI Listing
April 2014

Predictors of neurocognitive impairment at 3 years after a first episode non-affective psychosis.

Prog Neuropsychopharmacol Biol Psychiatry 2013 Jun 7;43:23-8. Epub 2012 Dec 7.

Department of Psychiatry, Marqués de Valdecilla University Hospital, IFIMAV, School of Medicine, University of Cantabria, Santander, Spain.

Background: Neurocognitive impairment is a core component of schizophrenia. However, patients show great variability in the level and course of deficits. The goal of the present longitudinal study was to identify predictors of neurocognitive impairment in first episode psychosis patients.

Methods: Neurocognitive performance was analyzed in a cohort of 146 patients 3 years after a first episode non-affective psychosis. Subgroups, impaired vs. unimpaired, were compared on baseline clinical, neuropsychological, premorbid and sociodemographic characteristics.

Results: Fifty-nine percent of participants presented general neurocognitive impairment and regression analyses demonstrated that clinical and sociodemographic characteristics were not predictive variables. A model composed of premorbid IQ, verbal memory and motor dexterity correctly classified 79.6% of the individuals.

Conclusions: The present study gives information on frequency and neurocognitive profile of subtypes of patients showing impairment. Our results suggest general neurocognitive impairment is a trait dimension of the disorder related to specific cognitive dysfunctions.
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http://dx.doi.org/10.1016/j.pnpbp.2012.11.012DOI Listing
June 2013

Towards a clinical staging for bipolar disorder: defining patient subtypes based on functional outcome.

J Affect Disord 2013 Jan 3;144(1-2):65-71. Epub 2012 Aug 3.

Bipolar Disorders Program, Institute of Neurosciences, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.

Background: The functional outcome of Bipolar Disorder (BD) is highly variable. This variability has been attributed to multiple demographic, clinical and cognitive factors. The critical next step is to identify combinations of predictors that can be used to specify prognostic subtypes, thus providing a basis for a staging classification in BD.

Methods: Latent Class Analysis was applied to multiple predictors of functional outcome in a sample of 106 remitted adults with BD.

Results: We identified two subtypes of patients presenting "good" (n=50; 47.6%) and "poor" (n=56; 52.4%) outcome. Episode density, level of residual depressive symptoms, estimated verbal intelligence and inhibitory control emerged as the most significant predictors of subtype membership at the p<0.05 level. Their odds ratio (OR) and confidence interval (CI) with reference to the "good" outcome group were: episode density (OR=4.622, CI 1.592-13.418), level of residual depressive symptoms (OR=1.543, CI 1.210-1.969), estimated verbal intelligence (OR=0.969; CI 0.945-0.995), and inhibitory control (OR=0.771, CI 0.656-0.907). Age, age of onset and duration of illness were comparable between prognostic groups.

Limitations: The longitudinal stability or evolution of the subtypes was not tested.

Conclusions: Our findings provide the first empirically derived staging classification of BD based on two underlying dimensions, one for illness severity and another for cognitive function. This approach can be further developed by expanding the dimensions included and testing the reproducibility and prospective prognostic value of the emerging classes. Developing a disease staging system for BD will allow individualised treatment planning for patients and selection of more homogeneous patient groups for research purposes.
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http://dx.doi.org/10.1016/j.jad.2012.06.005DOI Listing
January 2013

Towards a clinical staging for bipolar disorder: defining patient subtypes based on functional outcome.

J Affect Disord 2013 Jan 3;144(1-2):65-71. Epub 2012 Aug 3.

Bipolar Disorders Program, Institute of Neurosciences, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.

Background: The functional outcome of Bipolar Disorder (BD) is highly variable. This variability has been attributed to multiple demographic, clinical and cognitive factors. The critical next step is to identify combinations of predictors that can be used to specify prognostic subtypes, thus providing a basis for a staging classification in BD.

Methods: Latent Class Analysis was applied to multiple predictors of functional outcome in a sample of 106 remitted adults with BD.

Results: We identified two subtypes of patients presenting "good" (n=50; 47.6%) and "poor" (n=56; 52.4%) outcome. Episode density, level of residual depressive symptoms, estimated verbal intelligence and inhibitory control emerged as the most significant predictors of subtype membership at the p<0.05 level. Their odds ratio (OR) and confidence interval (CI) with reference to the "good" outcome group were: episode density (OR=4.622, CI 1.592-13.418), level of residual depressive symptoms (OR=1.543, CI 1.210-1.969), estimated verbal intelligence (OR=0.969; CI 0.945-0.995), and inhibitory control (OR=0.771, CI 0.656-0.907). Age, age of onset and duration of illness were comparable between prognostic groups.

Limitations: The longitudinal stability or evolution of the subtypes was not tested.

Conclusions: Our findings provide the first empirically derived staging classification of BD based on two underlying dimensions, one for illness severity and another for cognitive function. This approach can be further developed by expanding the dimensions included and testing the reproducibility and prospective prognostic value of the emerging classes. Developing a disease staging system for BD will allow individualised treatment planning for patients and selection of more homogeneous patient groups for research purposes.
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http://dx.doi.org/10.1016/j.jad.2012.06.005DOI Listing
January 2013

A systematic review of cognitive remediation for schizo-affective and affective disorders.

J Affect Disord 2012 Dec 25;142(1-3):13-21. Epub 2012 Jul 25.

Department of Psychiatry, Universidad Autónoma de Madrid, Instituto de Investigación Sanitaria Hospital de la Princesa, Madrid, Spain.

Background: Cognitive remediation is accepted as an important therapeutic intervention in schizophrenia, but few studies provide data on whether the benefits extend to affective disorders.

Objectives: To review quantitatively studies of cognitive remediation with samples that included cases of schizoaffective disorder, affective psychosis, unipolar and/or bipolar disorders.

Methods: Twenty one studies met preliminary inclusion criteria, comprising a total of 940 participants of which 35% had an affective or schizoaffective disorder. Effect sizes (ES) for pre- to post-intervention change in cognitive performance were estimated.

Results: A meta-analysis of 16 studies gave a pooled ES for change in cognitive function of 0.32 (95% Confidence Intervals 0.20 to 0.43) and produced statistical homogeneity. Overall, ES were significantly positively correlated with higher proportion of schizo-affective and affective cases (r=0.61; p=0.007), even when age, gender and duration of therapy were included as covariates in the analysis (r=.59, p=0.017).

Limitations: The quality of and small number of affective disorder only studies mean the findings must be treated with caution.

Conclusions: The estimated ES reflect those reported in the literature on cognitive remediation for schizophrenia. As such a conservative interpretation is that cognitive remediation has at least equivalent benefits in affective and schizo-affective disorder as demonstrated in schizophrenia. Further studies are urgently required to examine the durability of any gains with cognitive remediation in affective populations and to determine if any changes in cognitive deficits lead to improvements in symptoms or functioning and/or whether post-intervention cognitive changes differ in character or magnitude from those reported in schizophrenia.
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http://dx.doi.org/10.1016/j.jad.2012.04.020DOI Listing
December 2012

Prototype diagnosis of psychiatric syndromes and the ICD-11.

World Psychiatry 2012 Feb;11(1):30-1

Universidad Autonoma de Madrid, Instituto de Investigacion Sanitaria Princesa, CIBERSAM, Madrid, Spain.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266759PMC
http://dx.doi.org/10.1016/j.wpsyc.2012.01.026DOI Listing
February 2012

The Madrid Declaration: why we need a coordinated Europe-wide effort in mental health research.

Br J Psychiatry 2011 Apr;198(4):253-5

The Madrid Declaration is being promoted by representatives from seven nationally funded mental health research networks, along with leaders of ongoing European Union-funded mental health projects. It advocates the creation of a Network of Excellent Networks, based on a dynamic and adaptive cross-European network of distinctly qualified research centres.
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http://dx.doi.org/10.1192/bjp.bp.110.082511DOI Listing
April 2011

The Madrid Declaration: why we need a coordinated Europe-wide effort in mental health research.

Br J Psychiatry 2011 Apr;198(4):253-5

The Madrid Declaration is being promoted by representatives from seven nationally funded mental health research networks, along with leaders of ongoing European Union-funded mental health projects. It advocates the creation of a Network of Excellent Networks, based on a dynamic and adaptive cross-European network of distinctly qualified research centres.
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http://dx.doi.org/10.1192/bjp.bp.110.082511DOI Listing
April 2011

Efficacy of antidepressants and benzodiazepines in minor depression: systematic review and meta-analysis.

Br J Psychiatry 2011 Jan;198(1):11-6, sup 1

Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, University of Verona, Policlinico GB Rossi, 37134 Verona, Italy.

Background: Depression is a common condition that has been frequently treated with psychotropics.

Aims: To review systematically the evidence of efficacy and acceptability of antidepressant and benzodiazepine treatments for patients with minor depression.

Method: A systematic review and meta-analysis of double-blind randomised controlled trials comparing antidepressants or benzodiazepines v. placebo in adults with minor depression. Data were obtained from MEDLINE, CINAHL, EMBASE, PsycInfo, Cochrane Controlled Trials Register and pharmaceutical company websites. Risk of bias was assessed for the generation of the allocation sequence, allocation concealment, masking, incomplete outcome data, and sponsorship bias.

Results: Six studies met inclusion criteria. Three studies compared paroxetine with placebo; fluoxetine, amitriptyline and isocarboxazid were studied in one study each. No studies compared benzodiazepines with placebo. In terms of failures to respond to treatment (6 studies, 234 patients treated with antidepressants and 234 with placebo) no significant difference between antidepressants and placebo was found (relative risk (RR) 0.94, 95% CI 0.81-1.08). In terms of acceptability, data extracted from two studies (93 patients treated with antidepressants and 93 with placebo) showed no statistically significant difference between antidepressants and placebo (RR=1.06, 95% CI 0.65-1.73). There was no statistically significant between-study heterogeneity for any of the reported analyses.

Conclusions: There is evidence showing there is unlikely to be a clinically important advantage for antidepressants over placebo in individuals with minor depression. For benzodiazepines, no evidence is available, and thus it is not possible to determine their potential therapeutic role in this condition.
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http://dx.doi.org/10.1192/bjp.bp.109.076448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014462PMC
January 2011

Efficacy of antidepressants and benzodiazepines in minor depression: systematic review and meta-analysis.

Br J Psychiatry 2011 Jan;198(1):11-6, sup 1

Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, University of Verona, Policlinico GB Rossi, 37134 Verona, Italy.

Background: Depression is a common condition that has been frequently treated with psychotropics.

Aims: To review systematically the evidence of efficacy and acceptability of antidepressant and benzodiazepine treatments for patients with minor depression.

Method: A systematic review and meta-analysis of double-blind randomised controlled trials comparing antidepressants or benzodiazepines v. placebo in adults with minor depression. Data were obtained from MEDLINE, CINAHL, EMBASE, PsycInfo, Cochrane Controlled Trials Register and pharmaceutical company websites. Risk of bias was assessed for the generation of the allocation sequence, allocation concealment, masking, incomplete outcome data, and sponsorship bias.

Results: Six studies met inclusion criteria. Three studies compared paroxetine with placebo; fluoxetine, amitriptyline and isocarboxazid were studied in one study each. No studies compared benzodiazepines with placebo. In terms of failures to respond to treatment (6 studies, 234 patients treated with antidepressants and 234 with placebo) no significant difference between antidepressants and placebo was found (relative risk (RR) 0.94, 95% CI 0.81-1.08). In terms of acceptability, data extracted from two studies (93 patients treated with antidepressants and 93 with placebo) showed no statistically significant difference between antidepressants and placebo (RR=1.06, 95% CI 0.65-1.73). There was no statistically significant between-study heterogeneity for any of the reported analyses.

Conclusions: There is evidence showing there is unlikely to be a clinically important advantage for antidepressants over placebo in individuals with minor depression. For benzodiazepines, no evidence is available, and thus it is not possible to determine their potential therapeutic role in this condition.
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http://dx.doi.org/10.1192/bjp.bp.109.076448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014462PMC
January 2011

The 12-item World Health Organization Disability Assessment Schedule II (WHO-DAS II): a nonparametric item response analysis.

BMC Med Res Methodol 2010 May 20;10:45. Epub 2010 May 20.

Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain.

Background: Previous studies have analyzed the psychometric properties of the World Health Organization Disability Assessment Schedule II (WHO-DAS II) using classical omnibus measures of scale quality. These analyses are sample dependent and do not model item responses as a function of the underlying trait level. The main objective of this study was to examine the effectiveness of the WHO-DAS II items and their options in discriminating between changes in the underlying disability level by means of item response analyses. We also explored differential item functioning (DIF) in men and women.

Methods: The participants were 3615 adult general practice patients from 17 regions of Spain, with a first diagnosed major depressive episode. The 12-item WHO-DAS II was administered by the general practitioners during the consultation. We used a non-parametric item response method (Kernel-Smoothing) implemented with the TestGraf software to examine the effectiveness of each item (item characteristic curves) and their options (option characteristic curves) in discriminating between changes in the underliying disability level. We examined composite DIF to know whether women had a higher probability than men of endorsing each item.

Results: Item response analyses indicated that the twelve items forming the WHO-DAS II perform very well. All items were determined to provide good discrimination across varying standardized levels of the trait. The items also had option characteristic curves that showed good discrimination, given that each increasing option became more likely than the previous as a function of increasing trait level. No gender-related DIF was found on any of the items.

Conclusions: All WHO-DAS II items were very good at assessing overall disability. Our results supported the appropriateness of the weights assigned to response option categories and showed an absence of gender differences in item functioning.
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http://dx.doi.org/10.1186/1471-2288-10-45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881065PMC
May 2010

From depressive symptoms to depressive disorders: the relevance of thresholds.

Br J Psychiatry 2010 May;196(5):365-71

Department of Psychiatry, Hospital Universitario de la Princesa, Universidad Autonoma de Madrid and Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain.

Background: Nosological boundaries for depressive disorders as well as the prevalence and impact of 'subsyndromal' depression remain unclear.

Aims: To examine the impact of subsyndromal depressive disorders on health status and to assess if depressive disorders lie on a continuum of severity.

Method: The sample was composed of randomly selected respondents from the general population in 68 countries from across the world participating in the World Health Organization's World Health Survey.

Results: The pattern of risk factors for depressive disorders was consistent across all types of depression (subsyndromal, brief depressive episode and depressive episode): odds ratios for females ranged between 1.49 and 1.80, and for the unemployed from 1.19 to 1.25. All types of depression produced a significant decrement in health status compared with no depression after controlling for demographic variables, income and country.

Conclusions: Subthreshold depressive disorders occur commonly all across the world and are associated with the same risk factors everywhere. They produce significant decrements in health and do not qualitatively differ from full-blown episodes of depression as currently defined, and lie on a continuum with more severe forms of depressive episodes but are distinct from normal mood changes.
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http://dx.doi.org/10.1192/bjp.bp.109.071191DOI Listing
May 2010

Utility of the twelve-item World Health Organization Disability Assessment Schedule II (WHO-DAS II) for discriminating depression "caseness" and severity in Spanish primary care patients.

Qual Life Res 2010 Feb 18;19(1):97-101. Epub 2009 Dec 18.

Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain.

Purpose: The 12-item WHO-DAS II was developed to assess the activity limitations and participation restrictions experienced by individuals irrespective of medical diagnosis. In this paper we examine the known-groups' validity of the instrument by evaluating its ability to discriminate between patients with/without major depression, patients with depression with/without medical comorbidity, and patients with depression with different depression severity.

Method: The participants were 3,615 PC patients from 17 regions of Spain, with a first-time diagnosis of major depressive episode according to the general practitioner. The 12-item WHO-DAS II, the PHQ-9, and a chronic medical conditions checklist were administered during the consultation.

Results: The statistical analyses indicated that the 12-item WHO-DAS II was able to discriminate between patients with/without depression and between those with different depression severity. The ROC analysis revealed that with a cutoff score >or=50, the instrument correctly classified 70.4% of the sample (area under the ROC curve = .76; sensitivity = 71.4%; specificity = 67.6%).

Conclusions: Overall, our results support the discriminant validity of the 12-item WHO-DAS II for major depression, being quite recommendable its use in epidemiological research.
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http://dx.doi.org/10.1007/s11136-009-9566-zDOI Listing
February 2010

Psychometric properties of the twelve item World Health Organization Disability Assessment Schedule II (WHO-DAS II) in Spanish primary care patients with a first major depressive episode.

J Affect Disord 2010 Feb 22;121(1-2):52-8. Epub 2009 May 22.

Sant Joan de Déu, Servicios de Salud Mental, Sant Boi de Llobregat, Barcelona, Spain.

Background: Psychometric information on the World Health Organization Disability Assessment Schedule II (WHO-DAS II) in depressive primary care (PC) patients is scarce and has been obtained with the 36-item version of the instrument. The main objective of this study was to analyse the dimensionality, internal consistency and construct validity of the 12-item WHO-DAS II in a large sample of Spanish PC patients with a first diagnosed major depressive episode.

Method: Data were collected between December 2006 and July 2007. A total of 3615 adult (18 years or older) PC patients from 17 regions of Spain with a first diagnosed major depressive episode participated in the study. The 12-item WHO-DAS II and a battery of instruments assessing sociodemographic characteristics, depression severity (PHQ-9), quality of life (EQ-5D) and chronic health conditions were administered by the family physician during the consultation.

Results: The principal component analysis and the subsequent confirmatory factor analysis indicated that the 12-item WHO-DAS II is one-dimensional. The instrument showed adequate internal consistency (alpha=0.89) and construct validity because it was significantly associated with quality of life and depression severity (convergent validity) and was able to discriminate between patients on sick leave and those that were working (discriminative validity).

Limitations: The test-retest reliability and sensitivity to change of the instrument was not examined due to the cross-sectional design of the study.

Conclusions: The 12-item WHO-DAS II is a reliable, valid and useful tool for assessing overall disability in PC patients with depression.
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http://dx.doi.org/10.1016/j.jad.2009.05.008DOI Listing
February 2010
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