Publications by authors named "Roberto Rodriguez-Jimenez"

88 Publications

CIBERSAM: Ten years of collaborative translational research in mental disorders.

Rev Psiquiatr Salud Ment (Engl Ed) 2019 Jan - Mar;12(1):1-8. Epub 2018 Nov 9.

Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, España; Servicio de Psiquiatría y Psicología, Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España. Electronic address:

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http://dx.doi.org/10.1016/j.rpsm.2018.10.001DOI Listing
January 2020

Influence of emotional contexts on facial emotion attribution in schizophrenia.

Psychiatry Res 2018 12 12;270:554-559. Epub 2018 Oct 12.

Complutense University of Madrid, Spain; Department of Psychiatry, Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain; Biomedical Research Networking Centre in Mental Health (CIBERSAM), Spain.

Recent emotion recognition studies in schizophrenia have reported misattribution of emotional content to emotionally neutral faces. While in these studies faces are presented in the absence of any contextual reference, in daily life facial expressions are typically perceived within a specific situational context. However, there is no evidence on the possible modulatory role of contextual aids on emotion attribution to neutral faces. We address this issue in the present study. Thirty schizophrenia patients and thirty paired controls performed an emotion categorization task (by choosing one among six labels of emotions) with neutral target faces that were superimposed on affectively positive, negative or neutral scenes. In presence of positive contexts, patients categorized neutral faces as happy and fearful more frequently than controls. When negative contexts were present, patients also categorized neutral faces as fearful more frequently than controls. However, in the presence of neutral contexts patients and controls did not differ in their categorization pattern. These results suggest that explicit presence of a neutral context seems to compensate for the bias showed by patients. With the purpose of correcting emotion misattribution in schizophrenia, emotionally neutral contexts might be incorporated to treatments aimed at improving social cognition performance in this patient population.
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http://dx.doi.org/10.1016/j.psychres.2018.10.034DOI Listing
December 2018

Pharmacological interventions in social cognition deficits: A systematic mapping review.

Psychiatry Res 2018 12 11;270:57-67. Epub 2018 Sep 11.

Department of Psychiatry, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain; CIBERSAM (Biomedical Research Networking Centre in Mental Health), Spain; CogPsy-Group, Universidad Complutense de Madrid (UCM), Madrid, Spain. Electronic address:

Social cognition is an important research field in psychiatry due to its relevance in the functioning and quality of life of patients. The objective of this work is to conduct a systematic mapping review of pharmacological strategies for improving social cognition deficits. Publications from 2006 to 2016 were reviewed in Scopus, PsycINFO, PubMed, and Embase. From the initial 1059 publications obtained, a final number of 110 were selected. The results show an increasing interest in pharmacological approaches in different medical fields (especially psychiatry, pharmacology, and endocrinology, with schizophrenia and autism as the most studied disorders), as can be observed in the progressive increase in the number of publications, the high degree of scientific evidence, and the high impact factor of publications. However, it is also observed that most studies were conducted with oxytocin, psychostimulants, and antipsychotics (mainly risperidone and olanzapine), with few studies using other drugs. In the different social cognition domains, the majority of publications were focused on emotional processing or theory of mind, with few studies in other domains. Thus, this systematic mapping review shows that, even though there are increasing research activities, there are some important gaps to cover in future investigation.
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http://dx.doi.org/10.1016/j.psychres.2018.09.012DOI Listing
December 2018

Neutrophil Count Is Associated With Reduced Gray Matter and Enlarged Ventricles in First-Episode Psychosis.

Schizophr Bull 2019 06;45(4):846-858

Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain.

Although there is recent evidence that cells from the peripheral immune system can gain access to the central nervous system in certain conditions such as multiple sclerosis, their role has not been assessed in psychosis. Here, we aimed to explore whether blood cell count was associated with brain volume and/or clinical symptomatology. A total of 218 participants (137 first-episode psychosis patients [FEP] and 81 healthy controls [HC]) were included in the study. For each participant, a T1 structural image was acquired, from which brain tissue volumes were calculated. We found that, in FEP, neutrophil count was associated with reduced gray matter (GM) volume (β = -0.117, P < .001) and increased cerebrospinal fluid volume (β = 0.191, P = .007). No associations were observed in HC. GM reduction was generalized but more prominent in certain regions, notably the thalamus, the anterior insula, and the left Heschl's gyrus, among many others. Neutrophil count was also associated with the total PANSS score (β = 0.173, P = .038), including those items assessing hallucinations (β = 0.182, P = .028) and avolition (β = 0.197, P = .018). Several confounders, such as antipsychotic medication, body mass index, and smoking, were controlled for. Overall, the present study may represent the first indirect evidence of brain tissue loss associated with neutrophils in psychosis, and lends support to the hypothesis of a dysregulated immune system. Higher neutrophil count was also associated with more severe clinical symptomatology, which renders it a promising indicator of schizophrenia severity and could even give rise to new therapies.
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http://dx.doi.org/10.1093/schbul/sby113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581126PMC
June 2019

Impact of number of episodes on neurocognitive trajectory in bipolar disorder patients: a 5-year follow-up study.

Psychol Med 2019 06 25;49(8):1299-1307. Epub 2018 Jul 25.

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

Background: The neurocognitive trajectory in bipolar disorder (BD) is variable, with controversial findings, and most evidence come from cross-sectional studies. We aimed to examine the course of neurocognitive functioning in a sample of euthymic BD patients in comparison with a control group during a 5-year follow-up.

Methods: Ninety-nine euthymic bipolar patients and 40 healthy controls were assessed using a comprehensive neurocognitive battery (six neurocognitive domains) at baseline (T1) and then at 5-year follow-up (T2) in a longitudinal study.

Results: No evidence of a progression in neurocognitive dysfunction was found either in cognitive composite index or in any of the neurocognitive domains for the whole cohort. However, there was a negative correlation between number of manic episodes and hospitalisations due to manic episodes and change in neurocognitive composite index (NCI) during the follow-up. Moreover, patients with higher number of manic and hypomanic episodes have a greater decrease in NCI, working memory and visual memory. History of psychotic symptoms was not related to the trajectory of neurocognitive impairment.

Conclusions: Our results suggest that, although the progression of cognitive decline is not a general rule in BD, BD patients who have a greater number of manic or hypomanic episodes may constitute a subgroup characterised by the progression of neurocognitive impairment. Prevention of manic and hypomanic episodes could have a positive impact on the trajectory of cognitive function.
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http://dx.doi.org/10.1017/S0033291718001885DOI Listing
June 2019

Long-acting injectable antipsychotics for the treatment of schizophrenia in Spain.

Rev Psiquiatr Salud Ment (Engl Ed) 2019 Apr - Jun;12(2):92-105. Epub 2018 Jun 25.

Universidad de Cantabria, IDIVAL, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Santander, España.

Antipsychotics are an essential component in the treatment of schizophrenia. Long-acting injectable formulations (LAI) arose to improve adherence with the associated potential of reducing the risk of relapse. The objective of this article is to analyze the use of LAI antipsychotics in Spain, which is similar to other European countries but with a predominance of the use of second generation LAI, to discuss the possible causes of prescribing differences with respect to other countries (including organizational aspects, attitudes of psychiatrists, patients and family members, and clinical practice guidelines), and to discuss their use in acute psychiatric units, first episode, and in children and adolescents. In our view, while it is necessary to increase existing evidence regarding the advantages of LAI antipsychotics and the differentiation between LAI antipsychotics currently available, their use will likely continue to grow driven by clinical experience.
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http://dx.doi.org/10.1016/j.rpsm.2018.03.006DOI Listing
January 2020

A greater birthweight increases the risk of acute leukemias in Mexican children-experience from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia (MIGICCL).

Cancer Med 2018 04 13;7(4):1528-1536. Epub 2018 Mar 13.

Pediatric ER, HGZ No. 47, IMSS, Mexico City, Mexico.

In Mexico, due to the high rates of diabetes, overweight, and obesity, there has also been noted an increased newborn weight, which may be contributing to the elevated incidence rate of childhood acute leukemia (AL). We conducted a case-control study in public hospitals of Mexico City aimed to know whether a greater weight at birth is associated with a higher risk of developing leukemia. We included incident cases with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) diagnosed between 2010 and 2015. Controls were frequency-matched to the cases by age, sex, and health institution. Logistic regression analysis was performed adjusting risks by child's sex, overcrowding index, birth order, and mother's age at the time of pregnancy. Adjusted odds ratios (aORs) and 95% confidence intervals were calculated. A total of 1455 cases and 1455 controls were included. An evident association between ALL and child's birthweight ≥2500 g was found (aOR 2.06; 95% CI: 1.59, 2.66) and also, in those with birthweight ≥3500 g (aOR 1.19; 95% CI: 1.00, 1.41). In AML patients with birthweight ≥2500 g and ≥3500 g, an aOR of 1.77 (95% CI: 1.07, 2.94) and 1.42 (95% CI: 1.03-1.95) was observed, respectively. No association was noticed with either type of AL and a birthweight ≥4000 g. To sum up, we found a moderate association between not having a low birthweight and an increased risk of acute leukemias. Birthweight ≥3500 g was also a risk factor for both types of leukemia. This suggests that a greater birthweight may increase the risk of acute leukemias in Mexican children.
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http://dx.doi.org/10.1002/cam4.1414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911591PMC
April 2018

Psychosocial functioning in patients with psychotic and non-psychotic bipolar I disorder. A comparative study with individuals with schizophrenia.

J Affect Disord 2018 03 2;229:177-185. Epub 2018 Jan 2.

Department of Psychiatry, Hospital Virgen de La Luz, Cuenca, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain. Electronic address:

Background: More than 50% of individuals with bipolar disorder (BD) do not reach full psychosocial functioning, even during periods of euthymia. It has been suggested that history of psychotic symptoms is one of the factors which are associated with a worse functional outcome. The objective was to compare psychosocial functioning between patients with BD, with (BD-P), and without (BD-NP) a history of psychotic symptoms, and to examine whether the history of psychotic symptoms, or other clinical or neurocognitive variables predict psychosocial functioning.

Methods: Psychosocial functioning and neurocognition were examined in 100 euthymic patients with bipolar I disorder (50 BD-P, and 50 BD-NP), compared to 50 stabilised patients with schizophrenia (SZ), and 51 healthy controls (HC).

Results: 1) There were no differences between BD-P and BD-NP in the GAF-F score or in the FAST total score. 2) The two groups of patients with BD had better scores than SZ both in the GAF-F, and in all measures of the FAST, except for the subscale leisure time. 3) The neurocognitive composite index, verbal memory and subclinical depressive symptoms were the variables which explained a higher percentage of the variance of functional outcome.

Limitations: The cross-sectional design, and the relatively small sample size are the main limitations.

Conclusions: A history of psychotic symptoms has no relevant impact on the level of psychosocial functioning in BD. Neurocognitive dysfunction and subclinical depressive symptoms are the variables that best explain the functional impairment. These findings have important clinical implications.
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http://dx.doi.org/10.1016/j.jad.2017.12.094DOI Listing
March 2018

Human-Avatar Symbiosis for the Treatment of Auditory Verbal Hallucinations in Schizophrenia through Virtual/Augmented Reality and Brain-Computer Interfaces.

Front Neuroinform 2017 21;11:64. Epub 2017 Nov 21.

Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.

This perspective paper faces the future of alternative treatments that take advantage of a social and cognitive approach with regards to pharmacological therapy of auditory verbal hallucinations (AVH) in patients with schizophrenia. AVH are the perception of voices in the absence of auditory stimulation and represents a severe mental health symptom. Virtual/augmented reality (VR/AR) and brain computer interfaces (BCI) are technologies that are growing more and more in different medical and psychological applications. Our position is that their combined use in computer-based therapies offers still unforeseen possibilities for the treatment of physical and mental disabilities. This is why, the paper expects that researchers and clinicians undergo a pathway toward human-avatar symbiosis for AVH by taking full advantage of new technologies. This outlook supposes to address challenging issues in the understanding of non-pharmacological treatment of schizophrenia-related disorders and the exploitation of VR/AR and BCI to achieve a real human-avatar symbiosis.
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http://dx.doi.org/10.3389/fninf.2017.00064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702358PMC
November 2017

Neurocognition in patients with psychotic and non-psychotic bipolar I disorder. A comparative study with individuals with schizophrenia.

J Affect Disord 2017 11 8;222:169-176. Epub 2017 Jul 8.

Department of Psychiatry, Hospital Virgen de La Luz, Cuenca, Spain; Biomedical Research Networking Centre in Mental Health (CIBERSAM), Madrid, Spain. Electronic address:

Background: It has been suggested that patients with bipolar disorder with psychotic symptoms (BD-P) have larger neurocognitive impairment than patients with bipolar disorder without a history of psychotic symptoms (BD-NP). The objective of this study was to compare neurocognitive performance of BD-P and BD-NP relative to a group of patients with schizophrenia (SZ), and healthy controls (HC).

Methods: Neurocognitive function was examined in 100 subjects with bipolar I disorder (50 BD-P, 50 BD-NP), 50 SZ, and 51 HC. All patients with BD fulfilled criteria for euthymia, while all SZ patients were stabilised for at least the previous 3 months.

Results: Patients with BD-P and BD-NP performed worse than HC in all neurocognitive measures, except for sustained attention. Differences between BD-P and BD-NP were subtle and circumscribed to the working memory domain (effect size: 0.29). SZ performed worse than BD-NP in the neurocognitive composite index (NCI) and in the working memory domain. There were no differences between SZ and BD-P in any neurocognitive measure.

Limitations: The relatively small sample size, the cross-sectional design and, that patients were receiving pharmacological treatment are the main limitations of this study.

Conclusions: Our findings show that the three groups of patients have a large neurocognitive impairment. Differences are quantitative and only present in some neurocognitive domains, such as working memory. These results suggest that patients with BD and SZ can benefit from the same strategies of cognitive remediation.
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http://dx.doi.org/10.1016/j.jad.2017.07.014DOI Listing
November 2017

Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial.

BMC Psychiatry 2017 07 14;17(1):250. Epub 2017 Jul 14.

Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Av. Monforte de Lemos, 3-5, Madrid, Spain.

Background: A 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) was conducted to evaluate the effectiveness of pharmacogenetic (PGx) testing for drug therapy guidance.

Methods: Patients with a CGI-S ≥ 4 and requiring antidepressant medication de novo or changes in their medication regime were recruited at 18 Spanish public hospitals, genotyped with a commercial PGx panel (Neuropharmagen®), and randomized to PGx-guided treatment (n = 155) or treatment as usual (TAU, control group, n = 161), using a computer-generated random list that locked or unlocked psychiatrist access to the results of the PGx panel depending on group allocation. The primary endpoint was the proportion of patients achieving a sustained response (Patient Global Impression of Improvement, PGI-I ≤ 2) within the 12-week follow-up. Patients and interviewers collecting the PGI-I ratings were blinded to group allocation. Between-group differences were evaluated using χ2-test or t-test, as per data type.

Results: Two hundred eighty patients were available for analysis at the end of the 12-week follow-up (PGx n = 136, TAU n = 144). A difference in sustained response within the study period (primary outcome) was not observed (38.5% vs 34.4%, p = 0.4735; OR = 1.19 [95%CI 0.74-1.92]), but the PGx-guided treatment group had a higher responder rate compared to TAU at 12 weeks (47.8% vs 36.1%, p = 0.0476; OR = 1.62 [95%CI 1.00-2.61]), and this difference increased after removing subjects in the PGx-guided group when clinicians explicitly reported not to follow the test recommendations (51.3% vs 36.1%, p = 0.0135; OR = 1.86 [95%CI 1.13-3.05]). Effects were more consistent in patients with 1-3 failed drug trials. In subjects reporting side effects burden at baseline, odds of achieving a better tolerability (Frequency, Intensity and Burden of Side Effects Rating Burden subscore ≤2) were higher in the PGx-guided group than in controls at 6 weeks and maintained at 12 weeks (68.5% vs 51.4%, p = 0.0260; OR = 2.06 [95%CI 1.09-3.89]).

Conclusions: PGx-guided treatment resulted in significant improvement of MDD patient's response at 12 weeks, dependent on the number of previously failed medication trials, but not on sustained response during the study period. Burden of side effects was also significantly reduced.

Trial Registration: European Clinical Trials Database 2013-002228-18 , registration date September 16, 2013; ClinicalTrials.gov NCT02529462 , retrospectively registered: August 19, 2015.
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http://dx.doi.org/10.1186/s12888-017-1412-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513031PMC
July 2017

Evolution of metabolic risk factors over a two-year period in a cohort of first episodes of psychosis.

Schizophr Res 2018 03 26;193:188-196. Epub 2017 Jun 26.

Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPs), Barcelona, Spain; Barcelona Clínic Schizophrenia Unit, Neuroscience Institute, Hospital Clínic of Barcelona, Barcelona, Spain; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), G04, Barcelona, Spain. Electronic address:

Patients with a first episode of psychosis (FEP) display a broad range of metabolic risk factors related to the development of diverse medical comorbidities. Initial stages of these disorders are essential in understanding the increased vulnerability of developing cardiometabolic disturbances, associated with a reduced life expectancy. This study aimed to evaluate the metabolic profile of a cohort of patients with a FEP and its evolution during a two year follow-up, as well as the factors that influence the changes in their metabolic status. 16 participating centers from the PEPs Project recruited 335 subjects with a FEP and 253 matched healthy controls, aged 9-35years. We investigated a set of anthropometric measures, vital signs and laboratory data obtained from each participant over two years in a prospective, naturalistic study. From the beginning of the study the FEP group showed differences in the metabolic profile compared to the control group, together with a progressive worsening in the major part of the analyzed variables during the follow-up period, with higher rates of obesity and metabolic syndrome. Certain risk factors were related to determinate clinical variables such as male gender, the presence of affective symptoms or an early onset or to treatment variables such as the use of antipsychotic polypharmacy, antidepressants or mood stabilizers. Our results highlight the extremely high risk of patients at early phases of schizophrenia and other psychotic disorders of developing cardiovascular comorbidity and the fast worsening of the metabolic profile during the first two years.
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http://dx.doi.org/10.1016/j.schres.2017.06.032DOI Listing
March 2018

Psychological symptomatology and impaired prepulse inhibition of the startle reflex are associated with cannabis-induced psychosis.

J Psychopharmacol 2017 08 26;31(8):1035-1045. Epub 2017 Jun 26.

2 Research Institute 12-i, Madrid, Spain.

Background: Cannabis-induced psychotic disorder (CIPD) is a psychiatric disorder induced by cannabis consumption. The psychological and psychophysiological features of this disorder are still unknown. We aimed to examine the psychological, personality and psychophysiological features of patients with CIPD. This study is an analytical extension of our previously published data, which previously found prepulse inhibition (PPI) deficits in the CIPD group used in this current paper.

Methods: We used a sample of 45 patients with CIPD. After 9 months of follow up, these patients were assessed with a Symptom Checklist-90-R (SCL-90-R) questionnaire of psychopathology, with the Eysenck Personality Questionnaire, and with a psychophysiological paradigm of inhibition of the startle reflex (PPI). These results were compared with a group of patients with schizophrenia and cannabis abuse (SCHZ) ( n = 54); patients with cannabis dependence (CD) ( n = 21); and healthy controls ( n = 50).

Results: CIPD patients obtained significant higher scores in the SCL-90-R subscale of neuroticism. These patients showed PPI percentages similar to SCHZ patients within early attentional levels (30 ms). The variables with greater correlation, and that appeared in the CIPD group were interpersonal sensitivity, depression and phobia.

Conclusions: Neurotic symptomatology and difficulties in inhibition of the startle reflex might be risk factors for developing CIPD.
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http://dx.doi.org/10.1177/0269881117711920DOI Listing
August 2017

Intuitive pharmacogenetic dosing of risperidone according to CYP2D6 phenotype extrapolated from genotype in a cohort of first episode psychosis patients.

Eur Neuropsychopharmacol 2017 07 5;27(7):647-656. Epub 2017 Apr 5.

Dept. Pathological Anatomy, Pharmacology and Microbiology, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain; Psychiatry Department, Hospital General Universitario Gregorio Marañón, Spain; Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain; Department of Psychiatry, Hospital de Sant Pau, Barcelona, Spain; BIOARABA Health Research Institute, OSI Araba. University Hospital, University of the Basque Country, CIBERSAM, Vitoria, Spain; Instituto de Investigación Sanitaria Aragón (IIS Aragón), Dept. of Medicine and Psychiatry, University Zaragoza, CIBERSAM, Spain; Clinic Hospital Valencia, INCLIVA, Valencia University, CIBERSAM, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Universitat Autonoma de Barcelona, Barcelona. CIBERSAM, Spain; Institute of Neuroscience, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; Department of Child and Adolescent Psychiatry and Psychology, SGR489, Institute of Neuroscience, Hospital Clínic of Barcelona, IDIBAPS, CIBERSAM, Spain; Psychiatry Department, Bellvitge University Hospital-IDIBELL, Barcelona, Spain; Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain; Psychiatry Department, University of Oviedo, Oviedo, Spain; Araba University Hospital, Bioaraba Research Institute, Vitoria, Spain; University of the Basque Country (UPV/EHU), Department of Neurosciences. CIBERSAM, Spain; Cruces University Hospital, Department of Psychiatry, BioCruces Health Research Institute, Vizcaya, Spain; Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain; CIBERSAM, Barcelona, Spain; Research Unit, Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain; FIDMAG Hermanas Hospitalarias Research Foundation, Barcelona, Spain; Neuroscience Research Australia, Sydney, NSW, Australia; School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia; ARC Centre of Excellence in Cognition and its Disorders, Sydney, NSW, Australia; Hospital Ramon y Cajal, Universidad de Alcala, IRYCIS, CIBERSAM, Madrid, Spain; Department of Psychiatry, Complejo Hospitalario de Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Spain; Mental Health Centre of Catarroja, University of Valencia, CIBERSAM, Spain.

Risperidone (R) is the most prescribed antipsychotic drug for patients with a first episode of psychosis (FEP). In a naturalistic cohort of chronic psychiatric inpatients, we demonstrated that clinicians adjust R dosage by CYP2D6 activity, despite being blinded to the genotype, which we described as an "intuitive pharmacogenetic" process. The aim of the present study is to replicate our previous findings of intuitive pharmacogenetic in a cohort of FEP patients using CYP2D6 phenotype extrapolated from genotypes. 70 FEP patients, under baseline treatment with R monotherapy were genotyped using the iPLEX® ADME PGx multiplex panel and TaqMan® Genotyping and Copy Number Assays. Plasma concentrations of R and its metabolite, 9-hydroxyrisperidone (9-OH), were determined. The predictive properties of those variables associated with R dosage were tested using a multiple linear regression model as well as regression trees. Significant differences in the mean daily dosage of R among CYP2D6 phenotypes were observed (Kruskal-Wallis test p=0.02): PM (4.00±2.3mg/mL), IM (4.56±2.44), EM (6.22±4.0mg/day) and UM (10.20±4.91mg/day). However, non-significant differences were observed in the R/9-OH ratio or in the Concentration/Dose ratio. Regression tree provided better estimations of R dosage than the multiple linear regression model (MAE=0.958 and R=0.871). We confirm the "intuitive pharmacogenetic" dosing of R according to the CYP2D6 phenotype in a FEP cohort. The results presented provides a rationale for the clinical use of CYP2D6 genotyping in personalized medicine.
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http://dx.doi.org/10.1016/j.euroneuro.2017.03.012DOI Listing
July 2017

Cognitive impairments in patients with first episode psychosis: The relationship between neurophysiological and neuropsychological assessments.

J Clin Neurosci 2017 Feb 4;36:80-87. Epub 2016 Nov 4.

Department of Psychiatry, Hospital 12 de Octubre, Madrid, Spain; Department of Psychiatry, Complutense University of Madrid, Madrid, Spain.

Cognitive deficits in schizophrenia have been widely reported. Neurophysiological and neuropsychological assessments have been conducted to study these impairments. Event-related potentials (ERPs) are relevant markers of cognitive deficits in schizophrenia, and reductions in specific ERP components have been found. The MATRICS Consensus Cognitive Battery (MCCB) was developed to obtain a consensus battery for the assessment of cognitive deficits in schizophrenia. Here, we aimed to study modulations of several ERP components in first episode psychosis (FEP). We also examined neuropsychological deficits using the MCCB, and correlations between ERP and MCCB impairments. Thirty-eight FEP patients were compared to thirty-eight healthy controls. The following ERP components were examined: P1, N1, MMN, P2, early-P3 and late-P3. We used an auditory three-stimulus oddball paradigm, with standard (60%), target (20%) and distractor (20%) stimuli. FEP patients showed significantly lower amplitudes of P2, early-P3 and late-P3 components. FEP patients also showed significant deficits in all the MCCB cognitive domains. Finally, correlational analyses found strong associations between amplitudes of P2, early-P3 and late-P3 components and MCCB tests for attention and speed of processing. These findings indicate that deficits in late auditory ERP components are present in FEP, whereas early components are preserved. These reductions in late ERP components were related to attentional deficits in FEP as assessed by MCCB. These findings indicate that MCCB is a valid battery for studying cognitive impairments in the initial stages of schizophrenia, and highlight the utility of converging neurophysiological and neuropsychological measures to examine attentional impairments in schizophrenia.
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http://dx.doi.org/10.1016/j.jocn.2016.10.023DOI Listing
February 2017

Sensory Gating Deficits in First-Episode Psychosis: Evidence From Neurophysiology, Psychophysiology, and Neuropsychology.

J Nerv Ment Dis 2016 Dec;204(12):877-884

*Neuroscience Center, University of Helsinki, Helsinki, Finland; †Laboratory of Clinical Psychophysiology and ‡Department of Psychiatry, Hospital 12 de Octubre, Madrid; §Department of Basic Psychology II (Cognitive Processes), Complutense University of Madrid; ∥Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid; ¶Department of Psychiatry, Complutense University of Madrid, Madrid, Spain; and #Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA.

Sensory gating deficits are commonly found in patients with schizophrenia. However, there is still scarce research on this issue. Thirty-eight patients with first-episode psychosis (FEP) were compared to thirty-eight controls. A condition-test paradigm of event-related potentials (ERP), prepulse inhibition (PPI), and some specific tasks of the MATRICS Consensus Cognitive Battery (MCCB) were used (i.e., TMT, BACS-SC, and Fluency for processing speed and CPT-IP for attention and vigilance). The ERP components measured were P50, N1, and P2. The PPI intervals examined were 30, 60, and 120 msec. Regarding the MCCB, processing speed and attention/vigilance cognitive domains were selected. FEP patients showed significant deficits in N1 and P2 components, at 30 and 60 PPI levels and in all the MCCB subtests selected. We obtained significant relationships in N1 with PPI-60, and with one MCCB subtest for processing speed. In addition, this same subtest showed significant association with P2. Therefore, sensory gating functioning is widely impaired since the very early stages of schizophrenia.
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http://dx.doi.org/10.1097/NMD.0000000000000572DOI Listing
December 2016

Facial affect recognition in early and late-stage schizophrenia patients.

Schizophr Res 2016 Apr 10;172(1-3):177-83. Epub 2016 Feb 10.

Department of Psychiatry, Hospital Infantil Universitario Niño Jesús, Avda. Menéndez Pelayo, N° 65, 28009 Madrid, Spain; The National University of Distance Education, Spain.

Prior studies have shown deficits in social cognition and emotion perception in first-episode psychosis (FEP) and multi-episode schizophrenia (MES) patients. These studies compared patients at different stages of the illness with only a single control group which differed in age from at least one clinical group. The present study provides new evidence of a differential pattern of deficit in facial affect recognition in FEP and MES patients using a double age-matched control design. Compared to their controls, FEP patients only showed impaired recognition of fearful faces (p=.007). In contrast to this, the MES patients showed a more generalized deficit compared to their age-matched controls, with impaired recognition of angry, sad and fearful faces (ps<.01) and an increased misattribution of emotional meaning to neutral faces. PANSS scores of FEP patients on Depressed factor correlated positively with the accuracy to recognize fearful expressions (r=.473). For the MES group fear recognition correlated positively with negative PANSS factor (r=.498) and recognition of sad and neutral expressions was inversely correlated with disorganized PANSS factor (r=-.461 and r=-.541, respectively). These results provide evidence that a generalized impairment of affect recognition is observed in advanced-stage patients and is not characteristic of the early stages of schizophrenia. Moreover, the finding that anomalous attribution of emotional meaning to neutral faces is observed only in MES patients suggests that an increased attribution of salience to social stimuli is a characteristic of social cognition in advanced stages of the disorder.
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http://dx.doi.org/10.1016/j.schres.2016.02.010DOI Listing
April 2016

Elevated midline-parietal gamma band noise power in schizophrenia but not in bipolar patients.

Eur Arch Psychiatry Clin Neurosci 2016 Dec 1;266(8):743-753. Epub 2016 Feb 1.

Psychiatry Department, Faculty of Medicine, University of Valladolid, Valladolid, Spain.

Gamma oscillations are key in coordinating brain activity and seem to be altered in schizophrenia. In previous work, we studied the spatial distribution of a noise power measure (scalp-recorded electroencephalographic activity unlocked to stimuli) and found higher magnitudes in the gamma band related to symptoms and cognition in schizophrenia. In the current study, we sought to replicate those findings and to study its specificity for schizophrenia in a completely independent sample. A principal component analysis (PCA) was used to determine the factorial structure of gamma noise power acquired with an electroencephalographic recording during an odd-ball P300 paradigm in the 250- to 550-ms window in 70 patients with schizophrenia (16 patients with first episode), 45 bipolar patients and 65 healthy controls. Clinical and cognitive correlates of the resulting factors were also assessed. Three factors arose from the PCA. The first displayed a midline-parietal distribution (roughly corresponding to the default mode network), the second was centro-temporal and the third anterior-frontal. Schizophrenia but not bipolar patients showed higher gamma noise power loadings in the first factor in comparison with controls. Scores for this factor were significantly and directly associated with positive and total symptoms in patients and inversely associated with global cognition in all participants. The results of this study replicate those of our previous publication and suggest an elevated midline-parietal gamma noise power specific to schizophrenia. The gamma noise power measure seems to be a useful tool for studying background oscillatory activity during performance of cognitive tasks.
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http://dx.doi.org/10.1007/s00406-016-0673-xDOI Listing
December 2016

Are negative symptoms really related to cognition in schizophrenia?

Psychiatry Res 2015 Dec 14;230(2):377-82. Epub 2015 Sep 14.

Department of Psychiatry, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain; Department of Psychiatry, Faculty of Medicine, Universidad Complutense de Madrid, Spain. Electronic address:

Previous studies have generally found a relationship between negative and cognitive symptoms in schizophrenia. The present study investigated the relationship between the 5 PANSS factors of a recent consensus model developed by NIMH researchers, and cognitive performance as assessed with the MATRICS Consensus Cognitive Battery (MCCB) in 80 patients with schizophrenia using correlation and regression analyses. The PANSS Cognitive factor showed a small to moderate significant association with MCCB Speed of processing, Working memory, Verbal learning, the Neurocognitive composite score, and the Overall composite score. Notably, however, no relationship was found between the PANSS Negative factor and any of the MCCB scores. The Positive, Excited and Depressed factors also did not show associations with the MCCB. These results highlight the need for refined assessment instruments and support the relative independence of cognition from other domains of psychopathology, including negative symptoms, in patients with schizophrenia.
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http://dx.doi.org/10.1016/j.psychres.2015.09.022DOI Listing
December 2015

Patterns of Emotion Attribution are Affected in Patients with Schizophrenia.

Span J Psychol 2015 Aug 10;18:E59. Epub 2015 Aug 10.

Instituto de Investigación Hospital 12 de octubre (i+12), Madrid/CIBERSAM (Spain).

Deficits in facial affect recognition have been repeatedly reported in schizophrenia patients. The hypothesis that this deficit is caused by poorly differentiated cognitive representation of facial expressions was tested in this study. To this end, performance of patients with schizophrenia and controls was compared in a new emotion-rating task. This novel approach allowed the participants to rate each facial expression at different times in terms of different emotion labels. Results revealed that patients tended to give higher ratings to emotion labels that did not correspond to the portrayed emotion, especially in the case of negative facial expressions (p < .001, η 2 = .131). Although patients and controls gave similar ratings when the emotion label matched with the facial expression, patients gave higher ratings on trials with "incorrect" emotion labels (p s < .05). Comparison of patients and controls in a summary index of expressive ambiguity showed that patients perceived angry, fearful and happy faces as more emotionally ambiguous than did the controls (p < .001, η 2 = .135). These results are consistent with the idea that the cognitive representation of emotional expressions in schizophrenia is characterized by less clear boundaries and a less close correspondence between facial configurations and emotional states.
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http://dx.doi.org/10.1017/sjp.2015.60DOI Listing
August 2015

Retinal nerve fiber layer and macular thickness in patients with schizophrenia: Influence of recent illness episodes.

Psychiatry Res 2015 Sep 15;229(1-2):230-6. Epub 2015 Jul 15.

Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain; Department of Medicine and Psychiatry, University of Zaragoza, Spain.

Optical coherence tomography (OCT) has been recently used to investigate neuropsychiatric disorders. We aimed to study retinal OCT measures of patients with schizophrenia with respect to healthy controls, and to evaluate possible differences between recent illness episode (RIE) and non-recent illness episode (NRIE) patients. Thirty schizophrenia patients were classified as RIE (n=10) or NRIE (n=20), and compared with 30 matched controls. Statistical analyses included linear mixed-effects models to study the association between OCT measures and group membership. Multivariate models were used to control for potential confounders. In the adjusted linear mixed-effects regression model, patients had a significantly thinner retinal nerve fiber layer (RNFL) in overall measurements, and in the nasal, superior and inferior quadrants. Macular inner ring thickness and macular volume were also significantly smaller in patients than controls. Compared with controls, in the adjusted model only NRIE (but not RIE) patients had significantly reduced RNFL overall measures, superior RNFL, nasal RNFL, macular volume, and macular inner ring thickness. No significant correlation was found between illness duration and retinal measurements after controlling for age. In conclusion, retinal parameters observed using OCT in schizophrenia patients could be related to clinical status and merit attention as potential state biomarkers of the disorder.
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http://dx.doi.org/10.1016/j.psychres.2015.07.028DOI Listing
September 2015

Stress induced by the socially evaluated cold-pressor test cause equivalent deficiencies of sensory gating in male subjects with schizophrenia and healthy controls.

Psychiatry Res 2015 Aug 26;228(3):283-8. Epub 2015 Jun 26.

"Hospital 12 de Octubre" Research Institute, Madrid, Spain; Biomedical Research Center Network for Mental Health (CIBERSAM), Madrid, Spain; Department of Pharmacology, Complutense University, Madrid, Spain.

It is known that patients with schizophrenia show a deficiency in the prepulse inhibition reflex (PPI). These patients display abnormalities in autonomic nervous system and hypothalamic-pituitary-adrenal function and may have an altered sensitivity to stress. To date, no studies have been carried out to determine the effect of acute stress on the PPI. We investigated whether there was a differential response in reactivity to acute stress caused by the socially evaluated cold-pressor test (SECPT) in a sample of 58 chronic male patients with schizophrenia and 28 healthy control subjects. PPI, salivary cortisol and heart rate (HR) were measured. The patients were evaluated in two sessions (with and without the SECPT) 72 h apart and basal measurements were carried out and 30 min post-startle probe. We found an increase in salivary cortisol levels and the HR with SECPT condition in both groups and a significantly lower PPI% in patients with schizophrenia. The most relevant findings of this study are that the impairment of the PPI is increased by stress. Stress-induced increase in cortisol in both groups, mainly in healthy control group which allows us to hypothesize that at least such deterioration may be due to the hypercortisolemia caused by the SECPT.
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http://dx.doi.org/10.1016/j.psychres.2015.05.097DOI Listing
August 2015

Maintenance Electroconvulsive Therapy: Cost-effectiveness and Patient/Family Satisfaction.

J ECT 2015 Dec;31(4):279

Department of Psychiatry Instituto de Investigación Hospital 12 de Octubre Madrid, Spain Centro de Investigación Biomédica en Red de Salud Mental Madrid, Spain Instituto de Investigación Hospital 12 de Octubre Madrid, Spain Centro de Investigación Biomédica en Red de Salud Mental Madrid, Spain The Zucker Hillside Hospital North Shore-LIJ Health System Hofstra North Shore-LIJ School of Medicine Glen Oaks, NY.

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http://dx.doi.org/10.1097/YCT.0000000000000249DOI Listing
December 2015

Cannabis abuse effects on prepulse inhibition in patients with first episode psychosis in schizophrenia.

J Neuropsychiatry Clin Neurosci 2015 ;27(1):48-53

From the Laboratory of Clinical Psychophysiology. Dept. of Psychiatry, Hospital Universitario 12 de Octubre, Madrid, Spain (IM-M); Dept. of Psychiatry, Hospital Universitario 12 de Octubre, Madrid, Spain (RJ-B); Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Madrid, Spain (MC); Dept. of Psychiatry, School of Medicine, Complutense University of Madrid, Madrid, Spain (SF-G); and Dept. of Basic Psychology II (Cognitive Processes), School of Psychology, Complutense University of Madrid, Madrid, Spain (GR).

Deficits in prepulse inhibition (PPI) and cannabis abuse are consistently found in schizophrenia. The authors studied PPI deficits in first episode psychosis (FEP) with schizophrenia and cannabis abuse influence. Thirty-five patients with FEP and 22 control subjects were examined. Patients were divided into cannabis use disorder (CUD) (N=21) and non-CUD (N=14). Startle measures were as follows: PPI at 30, 60, and 120 msec. Patients with CUD and patients without CUD showed lower PPI at 30 msec than control subjects. At 60 msec, patients with CUD obtained higher %PPI than patients without CUD, and patients without CUD obtained lower levels than control subjects. These findings show that cannabis abuse may improve PPI in patients with FEP at some levels.
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http://dx.doi.org/10.1176/appi.neuropsych.12120398DOI Listing
November 2015

Clinical usefulness and economic implications of continuation/maintenance electroconvulsive therapy in a Spanish National Health System public hospital: A case series.

Rev Psiquiatr Salud Ment 2015 Apr-Jun;8(2):75-82. Epub 2015 Jan 22.

Servicio de Psiquiatría, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, España; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, España.

Introduction: Continuation/maintenance electroconvulsive therapy has been shown to be effective for prevention of relapse in affective and psychotic disorders. However, there is a limited nubber of studies that investigate clinical management, associated costs, and perceived quality variables.

Material And Methods: A series of 8 cases included during the first 18 months of the Continuation/Maintenance Electroconvulsive Therapy Program of the Psychiatry Department at 12 de Octubre University Hospital is presented. Clinical variables (Clinical Global Impression-Improvement Scale, length of hospitalization, number of Emergency Department visits, number of urgent admissions) before and after inclusion in the continuation/maintenance electroconvulsive therapy program were compared for each patient, as well as associated costs and perceived quality.

Results: After inclusion in the program, 50.0% of patients reported feeling « much better » and 37.5% « moderately better » in the Clinical Global Impression-Improvement Scale. In addition, after inclusion in the continuation/maintenance electroconvulsive therapy program, patients were hospitalized for a total of 349 days, visited the Emergency Department on 3 occasions, and had 2 urgent admissions, compared to 690 days of hospitalization (P = .012), 26 Emergency Department visits (P = .011) and 22 urgent admissions (P = .010) during the same period before inclusion in the program. Associated direct costs per day of admission were reduced to 50.6% of the previous costs, and costs associated with Emergency Department visits were reduced to 11.5% of the previous costs. As regards perceived quality, 87.5% of patients assessed the care and treatment received as being « very satisfactory », and 12.5% as « satisfactory ».

Conclusions: This continuation/maintenance electroconvulsive therapy program has shown to be clinically useful and to have a favourable economic impact, as well as high perceived quality.
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http://dx.doi.org/10.1016/j.rpsm.2014.10.002DOI Listing
December 2016

Reduced visual surround suppression in schizophrenia shown by measuring contrast detection thresholds.

Front Psychol 2014 10;5:1431. Epub 2014 Dec 10.

Department of Psychiatry, Instituto de Investigación Hospital 12 de Octubre (i+12) Madrid, Spain ; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) Madrid, Spain.

Visual perception in schizophrenia is attracting a broad interest given the deep knowledge that we have about the visual system in healthy populations. One example is the class of effects known collectively as visual surround suppression. For example, the visibility of a grating located in the visual periphery is impaired by the presence of a surrounding grating of the same spatial frequency and orientation. Previous studies have suggested abnormal visual surround suppression in patients with schizophrenia. Given that schizophrenia patients have cortical alterations including hypofunction of NMDA receptors and reduced concentration of GABA neurotransmitter, which affect lateral inhibitory connections, then they should be relatively better than controls at detecting visual stimuli that are usually suppressed. We tested this hypothesis by measuring contrast detection thresholds using a new stimulus configuration. We tested two groups: 21 schizophrenia patients and 24 healthy subjects. Thresholds were obtained using Bayesian staircases in a four-alternative forced-choice detection task where the target was a grating within a 3∘ Butterworth window that appeared in one of four possible positions at 5∘ eccentricity. We compared three conditions, (a) target with no-surround, (b) target embedded within a surrounding grating of 20∘ diameter and 25% contrast with same spatial frequency and orthogonal orientation, and (c) target embedded within a surrounding grating with parallel (same) orientation. Previous results with healthy populations have shown that contrast thresholds are lower for orthogonal and no-surround (NS) conditions than for parallel surround (PS). The log-ratios between parallel and NS thresholds are used as an index quantifying visual surround suppression. Patients performed poorly compared to controls in the NS and orthogonal-surround conditions. However, they performed as well as controls when the surround was parallel, resulting in significantly lower suppression indices in patients. To examine whether the difference in suppression was driven by the lower NS thresholds for controls, we examined a matched subgroup of controls and patients, selected to have similar thresholds in the NS condition. Patients performed significantly better in the PS condition than controls. This analysis therefore indicates that a PS raised contrast thresholds less in patients than in controls. Our results support the hypothesis that inhibitory connections in early visual cortex are impaired in schizophrenia patients.
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http://dx.doi.org/10.3389/fpsyg.2014.01431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261701PMC
December 2014

Is it possible to combine different psychotic symptom scales in bipolar disorder?

Psychiatry Res 2014 Dec;220(3):1090-3

It has been suggested that data on positive and negative psychotic symptoms in patients with schizophrenia as assessed using different scales may be combined. For the first time, we assessed correlations between the positive syndrome subscale of the Positive and Negative Syndrome Scale (PANSS-P) and the Scale for the Assessment of Positive Symptoms (SAPS), and between the negative syndrome subscale of the Positive and Negative Syndrome Scale (PANSS-N) and the Scale for the Assessment of Negative Symptoms (SANS) in patients with bipolar disorder. We also aimed to confirm these correlations in patients with schizophrenia. This cross-sectional study was conducted with a group of 94 patients (40 diagnosed with bipolar disorder, 54 with schizophrenia). Assessments were carried out using the PANSS, SAPS and SANS. Large significant correlations were found between the PANSS-P and SAPS, and between the PANSS-N and SANS, in both the bipolar disorder group and the schizophrenia group. These results confirm previous findings regarding correlations between these scales in schizophrenia, and support the hypothesis that similar correlations exist in bipolar disorder. Therefore, our data support the potential usefulness in collaborative research of combining results from different scales for the assessment of psychotic symptoms in patients with bipolar disorder.
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http://dx.doi.org/10.1016/j.psychres.2014.10.018DOI Listing
December 2014

Pharmacogenetic study of second-generation antipsychotic long-term treatment metabolic side effects (the SLiM Study): rationale, objectives, design and sample description.

Rev Psiquiatr Salud Ment 2014 Oct-Dec;7(4):166-78. Epub 2014 Oct 19.

CIBER del área de Salud Mental (CIBERSAM), España; Servicio de Psiquiatría del Niño y del Adolescente, Departamento de Psiquiatría, Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, IiSGM, Madrid, España.

Aim: Weight gain is an important and common side effect of second generation antipsychotics (SGAs). Furthermore, these drugs can induce other side effects associated with higher cardiovascular morbidity and mortality, such as insulin resistance, diabetes or metabolic syndrome. Preliminary studies show that inter-individual genetic differences produce varying degrees of vulnerability to the different SGA-induced side effects. The Second-generation antipsychotic Long-term treatment Metabolic side effects (SLiM) study aims to identify clinical, environmental and genetic factors that explain inter-individual differences in weight gain and metabolic changes in drug-naïve patients after six months of treatment with SGAs.

Materials And Methods: The SLIM study is a multicenter, observational, six-month pharmacogenetic study where a cohort of 307 drug-naïve paediatric and adult patients (age range 8.8-90.1 years) and a cohort of 150 age- and sex- matched healthy controls (7.8-73.2 years) were recruited.

Results: This paper describes the rationale, objectives and design of the study and provides a description of the sample at baseline.

Conclusions: Results from the SLiM study will provide a better understanding of the clinical, environmental, and genetic factors involved in weight gain and metabolic disturbances associated with SGA treatment.
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http://dx.doi.org/10.1016/j.rpsm.2014.05.004DOI Listing
October 2016

Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain.

Schizophr Res 2014 Oct 12;159(1):107-13. Epub 2014 Aug 12.

CIBERSAM, Spain; Hospital Clinic, University of Valencia, INCLIVA, Valencia, Spain. Electronic address:

Genome wide association studies (GWAS) has allowed the discovery of some interesting risk variants for schizophrenia (SCZ). However, this high-throughput approach presents some limitations, being the most important the necessity of highly restrictive statistical corrections as well as the loss of statistical power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis approach. These problems can be partially solved through the use of a polygenic approach. We performed a genotyping study in SCZ using 86 previously associated SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum disorder (ASD) patients. The sample consisted of 3063 independent cases with DSM-IV-TR diagnosis of SCZ and 2847 independent controls of European origin from Spain. A polygenic score analysis was also used to test the overall effect on the SCZ status. One SNP, rs12290811, located in the ODZ4 gene reached statistical significance (p=1.7×10(-4), Allelic odds ratio=1.21), a value very near to those reported in previous GWAS of BPD patients. In addition, 4 SNPs were close to the significant threshold: rs3850333, in the NRXN1 gene; rs6932590, at MHC; rs2314398, located in an intergenic region on chromosome 2; and rs1006737, in the CACNA1C gene. We also found that 74% of the studied SNPs showed the same tendency (risk or protection alleles) previously reported in the original GWAS (p<0.001). Our data strengthen the polygenic component of susceptibility to SCZ. Our findings show ODZ4 as a risk gene for SCZ, emphasizing the existence of common vulnerability in psychosis.
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http://dx.doi.org/10.1016/j.schres.2014.07.004DOI Listing
October 2014

Double-blind, placebo-controlled study of the efficacy of reboxetine and citalopram as adjuncts to atypical antipsychotics for negative symptoms of schizophrenia.

J Clin Psychiatry 2014 Jun;75(6):608-15

Pare Sanitari Sant Joan de Deu C/Antoni Pujadas, 42 Sant Boi de Llobregat 08830, Barcelona, Spain

Objective: In this study, we assessed the efficacy of 2 pharmacodynamically different antidepressants, citalopram (a selective serotonin reuptake inhibitor) and reboxetine (a norepinephrine reuptake inhibitor), as adjunctive therapy to risperidone and olanzapine for the treatment of negative symptoms in schizophrenia.

Method: We performed a 6-month, multicenter, double-blind, randomized, placebo-controlled clinical trial. The recruitment period was from November 2008 to December 2011.The sample comprised 90 patients with a diagnosis of schizophrenia (DSM-IV criteria) who exhibited negative symptoms. The patients were recruited from 10 centers in different cities of the Spanish State. The primary efficacy measure was change in score on the negative subscale of the Positive and Negative Syndrome Scale (PANSS) between baseline and 6-month assessment. Other efficacy measures were changes in the PANSS subscales and total score, as well as the Scale for the Assessment of Negative Symptoms (SANS) subscales and total score.

Results: For statistical analysis, we employed mixed-effects models. We did not find statistically significant differences between the placebo group and the 2 treatment groups at 6-month assessments for the PANSS total (P=.6511), any PANSS subscale (negative [P=.5533], positive [P=.1723], or general psychopathology [P=.2083]), or the SANS (P= .5884). Cohen d measure showed a small effect size below the 0.5 threshold for all comparisons.

Conclusions: In conclusion, our results do not support adjunctive use of citalopram or reboxetine with risperidone or olanzapine for the treatment of negative symptoms in schizophrenia.

Trial Registration: ClinicalTrials.gov identifier: NCT01300364.
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http://dx.doi.org/10.4088/JCP.13m08551DOI Listing
June 2014
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