Publications by authors named "Miquel Bernardo"

130 Publications

Premorbid Characteristics as Predictors of Early Onset Versus Adult Onset in Patients With a First Episode of Psychosis.

J Clin Psychiatry 2021 09 14;82(6). Epub 2021 Sep 14.

Members of the PEPs Group are listed at the end of the article.

To study the differences in early-life characteristics between patients with an early onset of psychotic disorders (EOP, aged < 18 years) versus adult onset of psychotic disorders (AOP, aged ≥ 18 years) and to identify predictors of earlier onset.

278 patients with a first episode of psychosis between the ages of 7 and 35 years were recruited as part of a multicenter prospective longitudinal study conducted in Spain between January 1, 2009, and December 31, 2011, with diagnoses made for AOP using the Structured Clinical Interview for Axis I Disorders (SCID-I) and for EOP using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS). Early-stage factors such as prenatal, perinatal, and other premorbid factors were registered and compared between EOP and AOP patients. To analyze the association between baseline variables and outcome, univariate and multivariate logistic regression models were used, and the association or odds ratios (ORs) for significant risk factors were calculated.

224 patients with AOP (mean ± SD age = 25.6 ± 5.0 years; 65.6% male) and 54 patients with EOP (16.1 ± 1.7 years; 68.5% male) were included. Univariate analysis revealed significant differences between the groups. Specifically, compared to AOP subjects, EOP patients had more frequent obstetric complications (OCs) ( < .001), birth weight < 2.500 g ( < .028), a background of any personal psychiatric disorder ( < .001), a previous diagnosis of attention-deficit/hyperactivity disorder ( = .001), and premorbid IQ < 85 ( < .001). In the multivariate model, only OCs (OR = 5.44), personal psychiatric background (OR = 4.05), and IQ < 85 (OR = 3.96) predicted an onset of the first episode of psychosis before age 18 years.

Premorbid factors such as OCs, personal psychiatric background, and IQ < 85 could help predict which patients are more likely to have an early onset of psychosis. Awareness of these factors could help clinicians work to prevent the early transition to psychosis in children and adolescents.
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http://dx.doi.org/10.4088/JCP.21m13907DOI Listing
September 2021

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.

Transl Psychiatry 2021 Aug 10;11(1):423. Epub 2021 Aug 10.

Department of Psychiatry, Early Psychosis Section, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03-0.33) and positive (B = 0.19; 95%CI 0.03-0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11-0.52) and in controls (B = 0.26; 95%CI 0.06-0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.
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http://dx.doi.org/10.1038/s41398-021-01526-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355107PMC
August 2021

Interindividual variability of functional connectome in schizophrenia.

Schizophr Res 2021 Sep 27;235:65-73. Epub 2021 Jul 27.

Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.

Schizophrenia is a complex psychiatric disorder that displays an outstanding interindividual variability in clinical manifestation and neurobiological substrates. A better characterization and quantification of this heterogeneity could guide the search for both common abnormalities (linked to lower intersubject variability) and the presence of biological subtypes (leading to a greater heterogeneity across subjects). In the current study, we address interindividual variability in functional connectome by means of resting-state fMRI in a large sample of patients with schizophrenia and healthy controls. Among the different metrics of distance/dissimilarity used to assess variability, geodesic distance showed robust results to head motion. The main findings of the current study point to (i) a higher between subject heterogeneity in the functional connectome of patients, (ii) variable levels of heterogeneity throughout the cortex, with greater variability in frontoparietal and default mode networks, and lower variability in the salience network, and (iii) an association of whole-brain variability with levels of clinical symptom severity and with topological properties of brain networks, suggesting that the average functional connectome overrepresents those patients with lower functional integration and with more severe clinical symptoms. Moreover, after performing a graph theoretical analysis of brain networks, we found that patients with more severe clinical symptoms had decreased connectivity at both whole-brain level and within the salience network, and that patients with higher negative symptoms had large-scale functional integration deficits.
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http://dx.doi.org/10.1016/j.schres.2021.07.010DOI Listing
September 2021

The Role of Premorbid IQ and Age of Onset as Useful Predictors of Clinical, Functional Outcomes, and Recovery of Individuals with a First Episode of Psychosis.

J Clin Med 2021 Jun 2;10(11). Epub 2021 Jun 2.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Gregorio Marañón Health Research Institute (IiSGM), Hospital General Universitario Gregorio Marañón, Research Networking Center for Mental Health Network (CIBERSAM), School of Medicine, Complutense University of Madrid (UCM), 28007 Madrid, Spain.

Background: premorbid IQ (pIQ) and age of onset are predictors of clinical severity and long-term functioning after a first episode of psychosis. However, the additive influence of these variables on clinical, functional, and recovery rates outcomes is largely unknown.

Methods: we characterized 255 individuals who have experienced a first episode of psychosis in four a priori defined subgroups based on pIQ (low pIQ < 85; average pIQ ≥ 85) and age of onset (early onset < 18 years; adult onset ≥ 18 years). We conducted clinical and functional assessments at baseline and at two-year follow-up. We calculated symptom remission and recovery rates using the Positive and Negative Symptoms of Schizophrenia Schedule (PANSS) and the Global Assessment Functioning (GAF or Children-GAF). We examined clinical and functional changes with pair-wise comparisons and two-way mixed ANOVA. We built hierarchical lineal and logistic regression models to estimate the predictive value of the independent variables over functioning or recovery rates.

Results: early-onset patients had more severe positive symptoms and poorer functioning than adult-onset patients. At two-year follow-up, only early-onset with low pIQ and adult-onset with average pIQ subgroups differed consistently, with the former having more negative symptoms ( = 0.59), poorer functioning ( = 0.82), lower remission (61% vs. 81.1%), and clinical recovery (34.1% vs. 62.2%).

Conclusions: early-onset individuals with low pIQ may present persistent negative symptoms, lower functioning, and less recovery likelihood at two-year follow-up. Intensive cognitive and functional programs for these individuals merit testing to improve long-term recovery rates in this subgroup.
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http://dx.doi.org/10.3390/jcm10112474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199787PMC
June 2021

Clinical practice guideline on pharmacological and psychological management of adult patients with attention deficit and hyperactivity disorder and comorbid substance use.

Adicciones 2021 Jun 14;0(0):1569. Epub 2021 Jun 14.

Parc Sanitari Sant Joan de Deu, CIBERSAM, Barcelona.

Substantial evidence has confirmed the high comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and a substance use disorder (SUD). This review synthesizes the pharmacological and psychosocial interventions conducted in ADHD and SUDs, and provides clinical recommendations using the GRADE approach. Our results suggest: 1) In patients with ADHD and alcohol use, atomoxetine is recommended to reduce ADHD symptoms (weak recommendation) and alcohol craving (weak recommendation). 2) In patients with ADHD and cannabis use disorder, atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to reduce cannabis use (weak recommendation). 3) In patients with ADHD and cocaine use disorder, methylphenidate is not recommended to improve ADHD symptoms or to reduce cocaine use (weak recommendation). 4) In patients with ADHD and comorbid nicotine use disorder, methylphenidate is recommended to improve ADHD symptoms (weak recommendation). Psychoestimulants, such as methylphenidate or lisdexamfetamine dimesylate, are not recommended to reduce nicotine use (weak recommendation). 5) Regarding patients with ADHD and any SUD, the use of psychostimulants is recommended to improve ADHD symptoms (weak recommendation), not to reduce substance use (weak recommendation) or to improve retention to treatment (strong recommendation). In these patients, the use of atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to decrease substance use (weak recommendation) or to improve retention to treatment (strong recommendation). Atomoxetine and psychostimulants appear to be safe in patients with any SUD (strong recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite and conclusive evidence.
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http://dx.doi.org/10.20882/adicciones.1569DOI Listing
June 2021

Clinical practice guideline on pharmacological and psychological management of adult patients with an Anxiety Disorder and comorbid substance use.

Adicciones 2021 Jun 14;0(0):1548. Epub 2021 Jun 14.

Universidad de Oviedo, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Servicio de Salud del Principado de Asturias (SESPA) (Oviedo).

This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid anxiety disorders and SUDs while also providing clinical recommendations about which intervention elements are helpful for addressing substance use versus anxiety symptoms in patients with these co-occurring conditions. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Clinical trials are only available for posttraumatic stress disorder (PTSD) and for social anxiety. Concerning the comorbid substance use, all the studies have included patients with alcohol use, none of them have dealt with cocaine, cannabis or nicotine use. Although some treatments have shown benefit for anxiety symptoms without benefits for alcohol or other substance use, only limited pharmacological approaches have been assayed (sertraline, desipramine, paroxetine, buspirone, naltrexone and disulfiram). Our results suggest that 1) we can (weakly) recommend the use of desipramine over paroxetine to alleviate symptoms of anxiety in patients with a PTSD and alcohol use; 2) In these patients, the use of naltrexone to reduce symptoms of anxiety is also recommended (weak strength); and 3) SSRI antidepressants vs placebo can be recommended to reduce alcohol use (weak recommendation). Our review highlights the need for more research in this area and for larger, multisite studies with generalizable samples to provide more definite guidance for clinical practice.
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http://dx.doi.org/10.20882/adicciones.1548DOI Listing
June 2021

Clinical practice guideline on pharmacological and psychological management of adult patients with bipolar disorder and comorbid substance use.

Adicciones 2021 Jun 14;0(0):1528. Epub 2021 Jun 14.

Instituto de Investigación Sanitaria BIOARABA. OSI Araba. Hospital Universitario. CIBERSAM, UPV/EHU. Vitoria.

This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid bipolar disorder (BD) and substance use disorders (SUDs) while also providing clinical recommendations about which intervention elements are helpful for addressing substance use versus mood symptoms in patients with these co-occurring conditions. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Very few of the randomized trials performed so far have provided consistent evidence for the management of both mood symptoms and substance use in patients with a BD. No clinical trials are available for bipolar patients using cannabis. Some treatments have shown benefit for mood symptoms without benefits for alcohol or illicit substance use. Our results suggest that 1) we can (weakly) recommend the use of adjuvant valproate or naltrexone to improve symptoms of alcohol use disorder; 2) Lamotrigine add-on therapy seems to reduce cocaine-related symptoms and is therefore recommended (moderate strength); and 3) Varenicline is (weakly) recommended to improve nicotine abstinence. Integrated group therapy is the most-well validated and efficacious approach on substance use outcomes if substance use is targeted in an initial treatment phase.
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http://dx.doi.org/10.20882/adicciones.1528DOI Listing
June 2021

Real-World Data on the Adverse Metabolic Effects of Second-Generation Antipsychotics and Their Potential Determinants in Adult Patients: A Systematic Review of Population-Based Studies.

Adv Ther 2021 05 7;38(5):2491-2512. Epub 2021 Apr 7.

Internal Medicine Department, Instituto de Investigación Biomedica de Malaga-IBIMA, Regional University Hospital of Malaga, Malaga, Spain.

Introduction: To assess the risk of occurrence and potential determinants of metabolic disorders in adult patients treated with second-generation antipsychotics (SGAs) under real-world practice conditions.

Methods: MEDLINE, EMBASE, and PsycInfo were searched in July 2019 from database inception. We included population-based, longitudinal, comparative studies that report the results of the outcomes of interest for adult participants, including diabetes, ketoacidosis, hyperosmolar hyperglycemic state, weight gain/obesity, dyslipidemia, hypertension, and metabolic syndrome. Two reviewers independently extracted data on the study design, study quality, and study outcomes.

Results: We included 40 studies. Most studies showed that clozapine and olanzapine were associated with an increased likelihood of developing diabetes, while the results for risperidone and quetiapine were mixed. Although less well studied, ziprasidone and aripiprazole appeared to not be associated with the occurrence of diabetes. Information on antipsychotic-induced weight gain/obesity is extremely scarce. Regarding dyslipidemia, aripiprazole was not associated with an increased likelihood of developing dyslipidemia, clozapine was associated with an increased likelihood of developing dyslipidemia, and risperidone, olanzapine, quetiapine, and ziprasidone showed mixed results. Two studies suggested an association between ziprasidone and the occurrence of hypertension. Several studies found that the occurrence of a metabolic disorder acted as a risk factor for the development of other metabolic disorders. We did not find information on brexpiprazole, cariprazine, or lurasidone, and data on any long-acting SGA were lacking.

Conclusion: Although there are relevant differences among SGAs concerning the risk of metabolic disorders, it appears that none of the SGAs included in our review are fully devoid of these disturbances.
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http://dx.doi.org/10.1007/s12325-021-01689-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107077PMC
May 2021

Clinical practice guideline on pharmacological and psychological management of adult patients with depression and a comorbid substance use disorder.

Adicciones 2021 Mar 12;0(0):1559. Epub 2021 Mar 12.

IMIM-Institut Hospital del Mar d'Investigacions Mèdiques.

Co-occurrence of depression and a substance use disorder (SUD) in patients who present dual diagnoses has been long recognized as an important consideration in clinical practice. This review synthesizes the evidence of pharmacological and psychosocial interventions for comorbid depressive disorders and SUDs while providing clinical recommendations about the best interventions to address these patients. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Our results suggest that 1) In patients with depression and alcohol consumption, the administration of non-selective serotonin reuptake inhibitor (SSRI) antidepressants instead of SSRI is recommended for improvement of depressive symptoms (strong recommendation). Neither SSRI (strong recommendation) nor non-SSRI (weak recommendation) antidepressants are recommended for reduction in alcohol consumption. 2) In patients with depression and cannabis use, the use of venlafaxine is not recommended (weak recommendation). 3) In patients with depression and cocaine consumption, the use of SSRI antidepressants for improving depressive symptoms (weak recommendation) or to reduce cocaine use is not recommended (strong recommendation). The use of non-SSRI antidepressants is only recommended for improving depressive symptoms (strong recommendation). 4) The administration of bupropion to reduce nicotine consumption is not recommended (strong recommendation). 5) Regarding psychological treatment, in patients with depression and co-occurring alcohol disorder, both pharmacotherapy and cognitive behavioural therapy have positive effects on internalizing symptoms and in reducing alcohol consumption (weak recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite evidence.
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http://dx.doi.org/10.20882/adicciones.1559DOI Listing
March 2021

Clinical Practice Guideline on Pharmacological and Psychological management of adult patients with Schizophrenia Spectrum Disorders and a comorbid substance use.

Adicciones 2021 Mar 11;0(0):1504. Epub 2021 Mar 11.

CIBERSAM. Universitat de Barcelona.

Although correct diagnosis and management of patients with schizophrenia and a comorbid substance use disorder (SUD) would determine a decrease in morbidity and mortality in these patients, development of efficient therapeutic strategies is still pending. We present recommendations on the pharmacological and psychological management of these patients following the 'PICO' structure (Patient-Intervention-Comparison-Outcomes). Evaluation of the quality of studies and summary of the evidence for each question was performed following the recommendations of the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) working group. Our results suggest: 1) In patients with schizophrenia and cannabis use disorder, it is not possible to recommend one antipsychotic drug over another (between olanzapine, risperidone or haloperidol) for improving psychotic symptoms, reducing cannabis use, or improving pragmatic variables (weak recommendation). Clozapine cannot be recommended to reduce cannabis use (weak recommendation). 2) In patients with schizophrenia and cocaine use disorder we recommend haloperidol over olanzapine to reduce craving (moderate recommendation), and olanzapine over haloperidol to improve motor side effects in these patients (moderate recommendation). 3) In patients with schizophrenia and alcohol use disorder while naltrexone is recommended to reduce alcohol use (in terms of reducing alcohol craving) (weak recommendation), there is insufficient evidence to make any recommendation on the use of adjuvant acamprosate (weak recommendation). 4) In patients with schizophrenia and nicotine use disorder, adjuvant bupropion and varenicline are recommended for reducing nicotine use and nicotine abstinence (strong/moderate recommendation). 5) In patients with schizophrenia and polydrug use disorder, second-generation over first-generation antipsychotic drugs and olanzapine over other second-generation antipsychotics are recommended to improve psychotic symptoms (moderate/weak recommendation).
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http://dx.doi.org/10.20882/adicciones.1504DOI Listing
March 2021

Clinical Practice Guideline on Pharmacological and Psychological management of adult patients with Schizophrenia Spectrum Disorders and a comorbid substance use.

Adicciones 2021 Mar 11;0(0):1504. Epub 2021 Mar 11.

CIBERSAM. Universitat de Barcelona.

Although correct diagnosis and management of patients with schizophrenia and a comorbid substance use disorder (SUD) would determine a decrease in morbidity and mortality in these patients, development of efficient therapeutic strategies is still pending. We present recommendations on the pharmacological and psychological management of these patients following the 'PICO' structure (Patient-Intervention-Comparison-Outcomes). Evaluation of the quality of studies and summary of the evidence for each question was performed following the recommendations of the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) working group. Our results suggest: 1) In patients with schizophrenia and cannabis use disorder, it is not possible to recommend one antipsychotic drug over another (between olanzapine, risperidone or haloperidol) for improving psychotic symptoms, reducing cannabis use, or improving pragmatic variables (weak recommendation). Clozapine cannot be recommended to reduce cannabis use (weak recommendation). 2) In patients with schizophrenia and cocaine use disorder we recommend haloperidol over olanzapine to reduce craving (moderate recommendation), and olanzapine over haloperidol to improve motor side effects in these patients (moderate recommendation). 3) In patients with schizophrenia and alcohol use disorder while naltrexone is recommended to reduce alcohol use (in terms of reducing alcohol craving) (weak recommendation), there is insufficient evidence to make any recommendation on the use of adjuvant acamprosate (weak recommendation). 4) In patients with schizophrenia and nicotine use disorder, adjuvant bupropion and varenicline are recommended for reducing nicotine use and nicotine abstinence (strong/moderate recommendation). 5) In patients with schizophrenia and polydrug use disorder, second-generation over first-generation antipsychotic drugs and olanzapine over other second-generation antipsychotics are recommended to improve psychotic symptoms (moderate/weak recommendation).
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http://dx.doi.org/10.20882/adicciones.1504DOI Listing
March 2021

Exploring Risk and Resilient Profiles for Functional Impairment and Baseline Predictors in a 2-Year Follow-Up First-Episode Psychosis Cohort Using Latent Class Growth Analysis.

J Clin Med 2020 Dec 28;10(1). Epub 2020 Dec 28.

Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic of Barcelona, Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Department of Medicine, Institut de Neurociències, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain.

Being able to predict functional outcomes after First-Episode Psychosis (FEP) is a major goal in psychiatry. Thus, we aimed to identify trajectories of psychosocial functioning in a FEP cohort followed-up for 2 years in order to find premorbid/baseline predictors for each trajectory. Additionally, we explored diagnosis distribution within the different trajectories. A total of 261 adults with FEP were included. Latent class growth analysis identified four distinct trajectories: Mild impairment-Improving trajectory (Mi-I) (38.31% of the sample), Moderate impairment-Stable trajectory (Mo-S) (18.39%), Severe impairment-Improving trajectory (Se-I) (12.26%), and Severe impairment-Stable trajectory (Se-S) (31.03%). Participants in the Mi-I trajectory were more likely to have higher parental socioeconomic status, less severe baseline depressive and negative symptoms, and better premorbid adjustment than individuals in the Se-S trajectory. Participants in the Se-I trajectory were more likely to have better baseline verbal learning and memory and better premorbid adjustment than those in the Se-S trajectory. Lower baseline positive symptoms predicted a Mo-S trajectory vs. Se-S trajectory. Diagnoses of Bipolar disorder and Other psychoses were more prevalent among individuals falling into Mi-I trajectory. Our findings suggest four distinct trajectories of psychosocial functioning after FEP. We also identified social, clinical, and cognitive factors associated with more resilient trajectories, thus providing insights for early interventions targeting psychosocial functioning.
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http://dx.doi.org/10.3390/jcm10010073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796026PMC
December 2020

Effects of the COVID-19 pandemic and lockdown in Spain: comparison between community controls and patients with a psychiatric disorder. Preliminary results from the BRIS-MHC STUDY.

J Affect Disord 2021 02 24;281:13-23. Epub 2020 Nov 24.

Bipolar and Depressive Disorders Unit, Hospital Clinic, Institute of Neurosciences, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.

Background: The aim of this study was to evaluate potential differences about the effects of the COVID-19 pandemic and lockdown between community controls (CC) and patients with a mental illness (MI) in a Spanish population during the state of emergency.

Methods: Individuals with a psychiatric condition and the general population were invited to complete an anonymous online survey. Bivariate analyses were used to compare them in a broad range of measures: sociodemographic, clinical variables, behavioral changes related to the lockdown and coping strategies to face it. Two groups of different psychiatric disorders were compared: depression or anxiety disorders (D+A) versus bipolar disorder and schizophrenia related disorders (BD+SCZ).

Results: 413 CC and 206 MI were included in the study. CC reported to use more adaptive coping strategies as following a routine, talking to friends/relatives, practicing physical exercise and maintaining a balanced diet. MI reported significantly more anxiety and depression symptoms during the lockdown when compared to CC. Gaining weight, sleep changes, and tobacco consumption were more prevalent in the MI group. The D+A group showed significantly more psychological distress and negative expectations about the future, suffered more sleep disturbances when compared to BD+SCZ, whilst reported to practice more exercise.

Limitations: psychiatric disorders were self-reported.

Conclusions: Imposed restrictions and uncertainty during confinement had a higher psychological impact in individuals with a psychiatric illness, with less healthy behavior strategies to face the situation. Developing interventions to mitigate negative mental health outcomes among this vulnerable population will be essential in the coming months.
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http://dx.doi.org/10.1016/j.jad.2020.11.099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683299PMC
February 2021

Predictors of Bipolar Disorder Versus Schizophrenia Diagnosis in a Multicenter First Psychotic Episode Cohort: Baseline Characterization and a 12-Month Follow-Up Analysis.

J Clin Psychiatry 2020 11 3;81(6). Epub 2020 Nov 3.

PEPs Group members are listed at the end of the article.

Objective: The aim of this study was to identify predisposing factors and clinical features at baseline that might help predict diagnosis of bipolar disorder vs schizophrenia in a first-episode psychosis (FEP) cohort.

Methods: In this prospective, naturalistic study, we evaluated a cohort of 335 subjects with FEP recruited from April 2009 to April 2012. Baseline features were compared between subjects with a final DSM-IV diagnosis of bipolar disorder and schizophrenia at 12-month follow-up. A binary logistic regression model was used to assess predictors of diagnosis of bipolar disorder at follow-up.

Results: At 12-month follow-up, 47 of the 335 subjects included in the study received the diagnosis of bipolar disorder and 105, of schizophrenia. Subjects with a final diagnosis of bipolar disorder had a higher prevalence of family history of mood disorders (38.2% vs 18.0%, P = .02), better baseline premorbid adjustment (Premorbid Adjustment Scale [PAS]: 38.4 vs 50.6, P < .01) and psychosocial functioning (Functional Assessment Short Test [FAST]: 23.6 vs 33.7, P = .001), better cognitive flexibility (number of perseverative errors on the Wisconsin Card Sorting Test [WCST]: 14.2 vs 19.7, P = .01), more manic symptoms (Young Mania Rating Scale [YMRS]: 14.1 vs 7.3, P < .01), lesser negative symptoms (Positive and Negative Syndrome Scale negative scale [PANSS-N]: 15.0 vs 22.3, P < .001), and shorter duration of untreated psychosis (144.2 vs 194.7 days, P < .01) than subjects with a schizophrenia diagnosis. Binary logistic regression model revealed that lower FAST scores (odds ratio [OR] = 0.956; P = .015), lower PANSS-N scores (OR = 0.93; P = .048), and lower number of perseverative errors on the WCST (OR = 0.946; P = .035) were significantly related to diagnosis of bipolar disorder at follow-up.

Conclusions: In our FEP cohort, better psychosocial functioning, lesser negative symptoms, and better cognitive flexibility were related to diagnosis of bipolar disorder at 12-month follow-up.
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http://dx.doi.org/10.4088/JCP.19m12996DOI Listing
November 2020

Influence of BDNF and MTHFR polymorphisms on hippocampal volume in first-episode psychosis.

Schizophr Res 2020 09 26;223:345-352. Epub 2020 Sep 26.

Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Spain; Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, Madrid, Spain.

Background: The BDNF and MTHFR genes are independently linked to the pathogenesis of schizophrenia and its neuroimaging correlates. The aim of this study was to explore, for the first time, the individual and interactional effects of the Val66Met and C677T polymorphisms on hippocampal atrophy in first-episode psychosis (FEP).

Method: Multi-site case-control study based on clinical, genetic (rs 6265, rs 1801133) and structural magnetic resonance imaging data from 98 non-affective FEP patients and 117 matched healthy controls (HC). Hippocampal volume was estimated using FreeSurfer software and this volume was compared between diagnostic (FEP vs HC) and genotype (Val66Met, C677T) groups. The BDNF Val66Met x MTHFR C677T effect on hippocampal volume was further evaluated through stratified analyses.

Results: After applying Bonferroni correction, diagnosis showed a significant effect for adjusted left and right hippocampal volume (FEP < HC). Stratified analyses showed that the interactive effect contributed to adjusted hippocampal size in both the HC (left and right hippocampus) and FEP groups (right hippocampus); among BDNF Met carriers, those with the CT-TT genotype exhibited decreased hippocampal volume compared to individuals with the homozygous normal CC genotype.

Conclusions: Our results provide preliminary evidence indicating that the Val66Met x C677T interaction may be a potential genetic risk factor for reduced hippocampal size in both healthy controls and in patients with FEP. Further research in independent samples including different ethnic groups is warranted to confirm this new finding.
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http://dx.doi.org/10.1016/j.schres.2020.08.002DOI Listing
September 2020

Electroconvulsive therapy protocol adaptation during the COVID-19 pandemic.

J Affect Disord 2020 Nov 15;276:241-248. Epub 2020 Jul 15.

Bipolar and Depressive Disorders Unit, Hospital Clínic de Barcelona, Catalonia, Spain; Department of Psychiatry and Psychology, Hospital Clínic de Barcelona, Catalonia, Spain; Institute of Neuroscience (ICN), Hospital Clínic de Barcelona, Catalonia, Spain; Hospital Clínic de Barcelona, 170 Villarroel St., 08036 Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red Salud Mental (CIBERSAM), 28029 Madrid, Spain; University of Barcelona, 08036 Barcelona, Catalonia, Spain. Electronic address:

Background: During the COVID-19 pandemic, electroconvulsive therapy units have had to confront challenges such as the infectious hazard due to aerosol-generating ventilation, or the lack of staff and material resources. Our objective was to elaborate a protocol to make ECT during the COVID-19 pandemic a safer procedure for patients and professionals.

Methods: A multidisciplinary workgroup (including mental health, anesthesia, preventive medicine, and occupational risk professionals) was formed in the Hospital Clínic de Barcelona, in March 2020. A core group conducted a review of the scientific literature and healthcare organizations' guidelines and wrote a protocol draft. Then, a discussion with the workgroup was made until consensus was reached. The protocol has been continuously updated. Discussions were made by group e-mailing and video conferencing.

Results: The protocol includes the following main areas: (1) ECT unit's structural and functional considerations; (2) SARS-CoV-2 screening protocol; (3) ECT clinical practice adaptation (personal protective equipment, airway management, recovery room, and maintenance of the facilities); (4) management of COVID-19 cases; and (5) protocol assessment.

Limitations: The literature review was not systematic; the consensus was not based on a structured methodology. For other ECT units, local advisories may not be valid, and resource shortages (such as anesthetist availability, or the lack of respirators and PCR tests) may impede or prevent their implementation.

Conclusions: During the COVID-19 pandemic, ECT should continue to be advocated as an essential medical procedure. It is recommended that each ECT unit develop its own protocol. This proposal may be used as a reference.
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http://dx.doi.org/10.1016/j.jad.2020.06.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361096PMC
November 2020

Cognitive remediation and brain connectivity: A resting-state fMRI study in patients with schizophrenia.

Psychiatry Res Neuroimaging 2020 09 15;303:111140. Epub 2020 Jul 15.

Medical Psychology Unit, Department of Medicine. Institute of Neuroscience, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic de Barcelona, Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Cognitive remediation is able to improve activation patterns in the frontal lobe but only few data on neuroconnectivity has been reported yet. Resting-state approach is a neuroimaging methodology with potentiality for testing neuroconnectivity in the context of cognitive remediation in schizophrenia. A resting-state fMRI data was acquired in part of the sample (n = 26 patients, n = 10 healthy controls) of a partner study (NCT02341131) testing the effects of cognitive remediation. A data-driven approach using independent component analysis (ICA) was used to identify functional brain networks, which were compared between groups and group per time using a dual-regression approach. ICA results revealed reduced functional connectivity between patients and controls in sensorimotor, basal ganglia, default mode and visual networks at baseline (p<0.05 FWE-corrected). After treatment, time per group analyses evidenced increased connectivity in sensorimotor network. Furthermore, group comparison at follow-up showed similar connectivity patterns between patients and healthy controls in sensorimotor network, but also in default mode and basal ganglia networks. No differences between treatment groups were found. Our results add some evidence to the hypothesis of altered connectivity in schizophrenia, and the possibility to modify some aspects of brain connectivity networks after psychological interventions.
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http://dx.doi.org/10.1016/j.pscychresns.2020.111140DOI Listing
September 2020

Acute effects of a session of electroconvulsive therapy on brain-derived neurotrophic factor plasma levels.

Rev Psiquiatr Salud Ment (Engl Ed) 2020 Jul 13. Epub 2020 Jul 13.

Barcelona Clínic Schizophrenia Unit, Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en red en salud Mental (CIBERSAM), Departament de Medicina, Universitat de Barcelona, Spain.

Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are neurotrophins that play critical roles in brain neuronal function. Previous studies have established the association between BDNF and NGF signaling and severe mental disorders, but changes in BDNF plasma levels and electroconvulsive therapy (ECT) response are controversial. The aim of his study was to explore the acute effects of a single session of ECT on these neurotrophins signaling. Plasma levels of BDNF and NGF and their tyrosine kinase-type receptors expression in peripheral blood mononuclear cells (PBMCs) were determined before and two hours after a single ECT session in 30 subjects with a severe mental disorder. Two hours after an ECT session we found a statistically significant decrease of BDNF plasma levels (p=0.007). We did not find significant acute effects on NGF plasma levels or receptors expression in PBMCs. We found a significant inverse correlation between the time of convulsion and BDNF plasma levels decrease (r=-0.041, p=0.024). We have identified a decrease in BDNF plasma levels after 2h of a single ECT session. These results indicate the interest for future research in the role of neurotrophins in the response and safety of ECT.
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http://dx.doi.org/10.1016/j.rpsm.2020.05.011DOI Listing
July 2020

Clozapine and paliperidone palmitate antipsychotic combination in treatment-resistant schizophrenia and other psychotic disorders: A retrospective 6-month mirror-image study.

Eur Psychiatry 2020 07 16;63(1):e71. Epub 2020 Jul 16.

Barcelona Clínic Schizophrenia Unit (BCSU), Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain.

Background: Around 30% of patients with schizophrenia are considered treatment resistant (TRS). Only around 40% of TRS patients respond to clozapine. Long acting injectable antipsychotics could be a useful augmentation strategy for nonresponders.

Methods: We conducted a multicenter, observational, naturalistic, retrospective, 6-month mirror-image study to evaluate the efficacy and tolerability of clozapine and paliperidone palmitate association in 50 patients with TRS and other psychotic disorders. Clinical outcomes and side effects were systematically assessed.

Results: Six months after starting the combined treatment, participants showed a significant relief of symptoms, decreasing the Brief Psychiatric Rating Scale total score from 18.32 ± 7.71 to 7.84 ± 5.16 (p < 0.001). The number of hospitalizations, the length of hospital stays and the number of visits to emergency services also decreased, while an increase of the functionality was observed (Personal and Social Performance total score increased from 46.06 ± 118.7 to 60.86 ± 18.68, p < 0.001). There was also a significant decrease in the number and severity of side effects with the combination therapy, decreasing the Udvalg for Kliniske Undersogelser total score from 10.76 ± 8.04 to 8.82 ± 6.63 (p = 0.004).

Conclusions: This study provides the first evidence that combining clozapine with paliperidone palmitate in patients with TRS and other psychotic disorders could be effective and safe, suggesting further research with randomized controlled trials of augmentation strategies for clozapine nonresponder patients.

Policy Significance Statement: Patients with psychotic disorders such as schizophrenia show a variable response to antipsychotic treatments. Around 30% of patients are considered treatment resistant, indicated by insufficient symptom control to at least two different drugs. In these resistant cases, clozapine should be indicated, as it has shown to be superior to other options. However, only 40% of patients respond to clozapine, being necessary to establish which treatments could best potentiate clozapine action. Combining clozapine with long acting injectable antipsychotics, and particularly paliperidone palmitate, could be a useful strategy. We conducted a multicenter study of 50 patients with treatment-resistant schizophrenia and other psychotic disorders comparing the efficacy and tolerability in the 6 month-period prior and after starting the clozapine and paliperidone palmitate association. Our study suggests that this combination could be effective and safer, laying the groundwork for future clinical trials with this combination.
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http://dx.doi.org/10.1192/j.eurpsy.2020.72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443780PMC
July 2020

Identifying key transcription factors for pharmacogenetic studies of antipsychotics induced extrapyramidal symptoms.

Psychopharmacology (Berl) 2020 Jul 7;237(7):2151-2159. Epub 2020 May 7.

Dept. Clinical Foundations, Pharmacology Unit, University of Barcelona, Barcelona, Spain.

Introduction: We explore the transcription factors involved in the molecular mechanism of antipsychotic (AP)-induced acute extrapyramidalsymptoms (EPS) in order to identify new candidate genes for pharmacogenetic studies.

Methods: Protein-protein interaction (PPI) networks previously created from three pharmacogenomic models (in vitro, animal, and peripheral blood inhumans) were used to, by means of several bioinformatic tools; identify key transcription factors (TFs) that regulate each network. Once the TFs wereidentified, SNPs disrupting the binding sites (TFBS) of these TFs in the genes of each network were selected for genotyping. Finally, SNP-basedassociations with EPS were analyzed in a sample of 356 psychiatric patients receiving AP.

Results: Our analysis identified 33 TFs expressed in the striatum, and 125 SNPs disrupting TFBS in 50 genes of our initial networks. Two SNPs (rs938112,rs2987902) in two genes (LSMAP and ABL1) were significantly associated with AP induced EPS (p < 0.001). These SNPs disrupt TFBS regulated byPOU2F1.

Conclusion: Our results highlight the possible role of the disruption of TFBS by SNPs in the pharmacological response to AP.
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http://dx.doi.org/10.1007/s00213-020-05526-8DOI Listing
July 2020

Daily use of high-potency cannabis is associated with more positive symptoms in first-episode psychosis patients: the EU-GEI case-control study.

Psychol Med 2020 Mar 18:1-9. Epub 2020 Mar 18.

Department of Psychiatry, Early Psychosis Section, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

Background: Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients.

Method: We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses.

Results: In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14-0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = -0.22; 95% CI -0.37 to -0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use.

Conclusions: Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.
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http://dx.doi.org/10.1017/S0033291720000082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223239PMC
March 2020

Examining Gene-Environment Interactions Using Aggregate Scores in a First-Episode Psychosis Cohort.

Schizophr Bull 2020 07;46(4):1019-1025

Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPs), Barcelona, Spain.

Gene-environment (GxE) interactions have been related to psychosis spectrum disorders, involving multiple common genetic variants in multiple genes with very small effect sizes, and several environmental factors that constitute a dense network of exposures named the exposome. Here, we aimed to analyze GxE in a cohort of 310 first-episode psychotic (FEP) and 236 healthy controls, by using aggregate scores estimated in large populations such as the polygenic risk score for schizophrenia and (PRS-SCZ) and the Maudsley environmental risk score (ERS). In contrast to previous findings, in our study, the PRS-SCZ did not discriminate cases from controls, but the ERS score explained a similar percentage of the variance as in other studies using similar approaches. Our study supports a positive additive interaction, indicating synergy between genetic susceptibility to schizophrenia (PRS-SCZ dichotomized according to the highest quartile distribution of the control population) and the exposome (ERS > 75% of the controls). This additive interaction showed genetic and environmental dose dependence. Our study shows that the use of aggregate scores derived from large and powered studies instead of statistics derived from specific sample characteristics is a powerful tool for the study of the effects of GxE on the risk of psychotic spectrum disorders. In conclusion, by using a genetic risk score and an ERS we have provided further evidence for the role of GxE in psychosis.
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http://dx.doi.org/10.1093/schbul/sbaa012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342095PMC
July 2020

The role of genetics in cognitive remediation in schizophrenia: A systematic review.

Schizophr Res Cogn 2020 Mar 1;19:100146. Epub 2019 May 1.

Barcelona Clinic Schizophrenia Unit, Hospital Clinic Barcelona, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.

The role of genetics in cognitive remediation therapies in schizophrenia has not been completely understood yet. Different genes involved in neurotrophic, dopaminergic and serotonin systems have reported to influence cognitive functioning in schizophrenia. These genetic factors could also be contributing to the variability in responsiveness to cognitive treatments. No comprehensive synthesis of the literature of the role of genetics in the context of cognitive remediation has been conducted until now. We aimed to systematically review the published works through three electronic database searches: PubMed, Scopus, and the Cochrane Library. Eligible studies revealed a rising interest in the field although the number of published studies was rather small (n = 10). Eventually, promising results showing a relationship between some phenotypic variations based on different polymorphisms and different levels of responsivity to cognitive remediation therapies have been described although results are still inconclusive. In case those findings will be replicated, they could be guiding future research and informing clinical decision-making in the next future.
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http://dx.doi.org/10.1016/j.scog.2019.100146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889757PMC
March 2020

Premorbid Adjustment and IQ in Patients With First-Episode Psychosis: A Multisite Case-Control Study of Their Relationship With Cannabis Use.

Schizophr Bull 2020 04;46(3):517-529

Department of Addiction, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Psychotic patients with a lifetime history of cannabis use generally show better cognitive functioning than other psychotic patients. Some authors suggest that cannabis-using patients may have been less cognitively impaired and less socially withdrawn in their premorbid life. Using a dataset comprising 948 patients with first-episode psychosis (FEP) and 1313 population controls across 6 countries, we examined the extent to which IQ and both early academic (Academic Factor [AF]) and social adjustment (Social Factor [SF]) are related to the lifetime frequency of cannabis use in both patients and controls. We expected a higher IQ and a better premorbid social adjustment in psychotic patients who had ever used cannabis compared to patients without any history of use. We did not expect such differences in controls. In both patients and controls, IQ was 3 points higher among occasional-users than in never-users (mean difference [Mdiff] = 2.9, 95% CI = [1.2, 4.7]). Both cases and control daily-users had lower AF compared to occasional (Mdiff = -0.3, 95% CI = [-0.5; -0.2]) and never-users (Mdiff = -0.4, 95% CI = [-0.6; -0.2]). Finally, patient occasional (Mdiff = 0.3, 95% CI = [0.1; 0.5]) and daily-users (Mdiff = 0.4, 95% CI = [0.2; 0.6]) had better SF than their never-using counterparts. This difference was not present in controls (Fgroup*frequency(2, 2205) = 4.995, P = .007). Our findings suggest that the better premorbid social functioning of FEP with a history of cannabis use may have contributed to their likelihood to begin using cannabis, exposing them to its reported risk-increasing effects for Psychotic Disorders.
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http://dx.doi.org/10.1093/schbul/sbz077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147569PMC
April 2020

Effects of electroconvulsive therapy in the systemic inflammatory balance of patients with severe mental disorder.

Psychiatry Clin Neurosci 2019 Oct 15;73(10):628-635. Epub 2019 Jul 15.

Barcelona Clínic Schizophrenia Unit, Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain.

Aim: There is a great interest in the role of the immune system and the inflammatory balance as key mechanisms involved in the pathophysiology of severe mental disorders. Previous studies have indicated that electroconvulsive therapy (ECT) produces changes in certain inflammatory mediators or in the immune system response. This study aimed to explore the effects of ECT on the nuclear transcription factor κB (NFκB) pathway, a main regulatory pathway of the inflammatory/immune response.

Methods: Thirty subjects with a severe mental disorder receiving treatment with ECT in our center were included. Thirteen systemic biomarkers related to the NFκB pathway were analyzed right before and 2 h after a single ECT session.

Results: An ECT session significantly decreased the expression of NFκB (P = 0.035) and of the inducible nitric oxide synthase (P = 0.012), and the plasma levels of nitrites (P = 0.027), prostaglandin E (P = 0.049), and 15-deoxy-PGJ (P < 0.001). Decrease in plasmatic levels of nitrites was greater in females than in males (P = 0.021). A positive correlation between the ECT stimulus load and changes in the expression of NFkB was found (P = 0.036). Thiobarbituric acid reactive substance levels were decreased in treatment responders and increased in non-responders (P = 0.047).

Conclusion: Our study shows the effects that a single session of ECT produces on a canonical regulatory pathway of the inflammatory/innate immune system and the inflammatory balance. These biomarkers could be useful as treatment response targets and could help to clarify the biological basis of ECT action. These findings warrant greater attention in future investigations and in the translational significance of these data.
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http://dx.doi.org/10.1111/pcn.12906DOI Listing
October 2019

Food craving and consumption evolution in patients starting treatment with clozapine.

Psychopharmacology (Berl) 2019 Nov 13;236(11):3317-3327. Epub 2019 Jun 13.

Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.

Background: Antipsychotic-induced weight gain has been especially related to clozapine and olanzapine. Underlying mechanisms in relation to food preferences with an increased food craving and consumption of specific nutrients have not been extensively studied in patients with serious mental illness (SMI). We aim to describe specific food preferences (craving) and subsequent food consumption in SMI patients starting clozapine, as well as their possible relation to weight and body mass index (BMI).

Methods: An observational prospective follow-up study (18 weeks) was conducted in a cohort of 34 SMI patients who started clozapine due to resistant-psychotic symptoms. Anthropometric measures, Food Craving Inventory (FCI), and a food consumption frequency questionnaire were evaluated at baseline, weeks 8 and 18 of treatment. Statistical analysis included generalized estimating equations models with adjustment for potential confounding factors.

Results: No longitudinal changes over time were found across the different food craving scores after 18 weeks of treatment. However, adjusted models according to BMI status showed that the normal weight (NW) group presented an increased score for the "complex carbohydrates/proteins" food cravings (- 0.67; 95% CI [- 1.15, - 0.19]; P = 0.010), while baseline scores for "fast-food fats" cravings were significantly higher in the overweight/obese (OWO) group in comparison with NW patients (NW, 2.05; 95% CI [1.60, 2.49]; OWO, 2.81, 95% CI [2.37, 3.25]; P = 0.016). When considering if food craving could predict weight gain, only increments in "fast-food fats" cravings were associated (β = - 5.35 ± 1.67; 95% CI [- 8.64, - 2.06]; P = 0.001).

Conclusions: No longitudinal differences were found for any of the food craving scores evaluated; however, in the NW group, food craving for "complex carbohydrates/proteins" changed. Thus, changes in "fast-food fats" cravings predicted weight increase in this sample. Interventions targeting food preferences may help to mitigate weight gain in patients starting treatment with clozapine.
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http://dx.doi.org/10.1007/s00213-019-05291-3DOI Listing
November 2019

Auditory hallucinations in first-episode psychosis: A voxel-based morphometry study.

Schizophr Res 2019 07 18;209:148-155. Epub 2019 May 18.

Department of Psychiatry, Hospital Clinic, University of Valencia, INCLIVA, Valencia, Spain; Faculty of Medicine, Universitat de València, Avda. Blasco Ibáñez, 15, 46010 Valencia, Spain; Ciber del Área de Salud Mental (CIBERSAM), Spain.

Background: Auditory hallucinations (AH) are a core symptom of psychosis. The brain abnormalities responsible for AH remain controversial due to inconsistent and conflicting findings across studies, with substantial confounding factors, such as chronicity. Few studies have examined the pathological changes that occur in the gray matter (GM) of patients with first-episode psychosis (FEP) and AH. The present study aims to validate the presence and characteristics of these structural abnormalities in relation to the intensity of psychotic symptoms and AH in a larger homogeneous sample than those of previous studies.

Methods: A magnetic resonance voxel-based morphometric analysis was applied to a group of 215 patients with FEP (93 patients with AH and 122 patients without AH) and 177 healthy controls. The patients were evaluated using the PANSS scale.

Results: Patients with FEP exhibited greater reductions in GM concentrations in the temporal, frontal, cingulate and insular areas than the healthy controls did. No specific differences were found between the patients with FEP and AH and the patients without AH. In addition, total scores on the PANSS were negatively correlated with GM reductions in the FEP group. No correlations were found between the severity of the AH and the GM volumes.

Conclusions: As in previous studies, reductions in the GM concentrations in patients with FEP suggest that alterations are present in the early stages of psychosis, and these alterations are correlated with the severity of the illness. The GM reductions were not found to be related to the presence or severity of AH.
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http://dx.doi.org/10.1016/j.schres.2019.05.001DOI Listing
July 2019

One decade of the first episodes project (PEPs): Advancing towards a precision psychiatry.

Rev Psiquiatr Salud Ment (Engl Ed) 2019 Jul - Sep;12(3):135-140. Epub 2019 May 16.

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.

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http://dx.doi.org/10.1016/j.rpsm.2019.03.001DOI Listing
May 2020

Antipsychotic-induced weight gain and birth weight in psychosis: A fetal programming model.

J Psychiatr Res 2019 08 4;115:29-35. Epub 2019 May 4.

Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic, Barcelona, Spain; Institute of Biomedical Research Agusti Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain; Department of Medicine, University of Barcelona. Barcelona, Spain. Electronic address:

Antipsychotic induced weight gain is a frequent reason for treatment discontinuation in psychosis, subsequently increasing the risk of relapse and negatively affecting patient well-being. The metabolic effect of weight gain and the subsequent risk of obesity constitute a major medical problem on the long term. Despite its consequences, to date few risk factors have been identified (age, gender, body mass index at baseline), with some authors suggesting the implication of early life stressful events, such as perinatal conditions. We aim to describe if a surrogate marker of intrauterine environment (birth weight) might predict weight gain in a cohort of 23 antipsychotic naïve patients at the onset of the psychotic disease evaluated during 16 weeks with olanzapine treatment and in another cohort of 24 psychosis-resistant patients initiating clozapine assessed for 18 weeks. Two independent linear mixed model analyses were performed in each cohort of patients, with prospective weight gain as the dependent variable, age, gender, body mass index, duration of treatment and time as independent variables. Only in naïve patients, weight gain due to antipsychotics was significantly associated with birth weight, while male gender and body mass index at baseline were associated in both cohorts of patients. Treatment-resistant psychotic patients under clozapine were older, had previous antipsychotic treatment and more years of disease, confounders that might have influence a non significant association. Our results suggest that early environmental events might be playing a role in weight evolution in naïve patients treated with antipsychotics.
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http://dx.doi.org/10.1016/j.jpsychires.2019.05.004DOI Listing
August 2019
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