Publications by authors named "Celso Arango"

360 Publications

Examining facial emotion recognition as an intermediate phenotype for psychosis: Findings from the EUGEI study.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Sep 15:110440. Epub 2021 Sep 15.

Biomedical Research Networking Centre in Mental Health (CIBERSAM), Spain; Department of Psychiatry, Hospital Clínico Universitario de Valencia, INCLIVA, School of Medicine, Universidad de Valencia, Valencia, Spain.

Background: Social cognition impairments, such as facial emotion recognition (FER), have been acknowledged since the earliest description of schizophrenia. Here, we tested FER as an intermediate phenotype for psychosis using two approaches that are indicators of genetic risk for schizophrenia: the proxy-genetic risk approach (family design) and the polygenic risk score for schizophrenia (PRS-SCZ).

Methods: The sample comprised 2039 individuals with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). The Degraded Facial Affect Recognition Task (DFAR) was applied to measure the FER accuracy. Schizotypal traits in siblings and HC were assessed using the Structured Interview for Schizotypy-Revised (SIS-R). The PRS-SCZ was trained using the Psychiatric Genomics Consortium results. Regression models were applied to test the association of DFAR with psychosis risk, SIS-R, and PRS-SCZ.

Results: The DFAR-total scores were lower in individuals with schizophrenia than in siblings (RR = 0.97 [95% CI 0.97, 0.97]), who scored lower than HC (RR = 0.99 [95% CI 0.99-1.00]). The DFAR total score was negatively associated with SIS-R total scores in siblings (B = -2.04 [95% CI -3.72, -0.36]) and HC (B = -2.93 [95% CI -5.50, -0.36]). Different patterns of association were observed for individual emotions. No significant associations were found between DFAR scores and PRS-SCZ.

Conclusions: Our findings based on a proxy genetic risk approach suggest that FER deficits may represent an intermediate phenotype for schizophrenia. However, a significant association between FER and PRS-SCZ was not found. In the future, genetic mechanisms underlying FER phenotypes should be investigated trans-diagnostically.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110440DOI Listing
September 2021

Risk and protective factors for mental disorders beyond genetics: an evidence-based atlas.

World Psychiatry 2021 Oct;20(3):417-436

Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remain uncer-tain. We conducted a "meta-umbrella" systematic synthesis of umbrella reviews, which are systematic reviews of meta-analyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on non-purely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convincing), class II (highly suggestive), class III (suggestive), class IV (weak). Sensitivity analyses were conducted on prospective studies to test for temporality (reverse causation), TRANSD criteria were applied to test transdiagnosticity of factors, and A Measurement Tool to Assess Systematic Reviews (AMSTAR) was employed to address the quality of meta-analyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 meta-analyses and 1,180 associations between putative risk or protective factors and mental disorders. We included 176 class I to III evidence associations, relating to 142 risk/protective factors. The most robust risk factors (class I or II, from prospective designs) were 21. For dementia, they included type 2 diabetes mellitus (risk ratio, RR from 1.54 to 2.28), depression (RR from 1.65 to 1.99) and low frequency of social contacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For non-organic psychotic disorders, the most robust risk factors were clinical high risk state for psychosis (OR=9.32), cannabis use (OR=3.90), and childhood adversities (OR=2.80). For depressive disorders, they were widowhood (RR=5.59), sexual dysfunction (OR=2.71), three (OR=1.99) or four-five (OR=2.06) metabolic factors, childhood physical (OR=1.98) and sexual (OR=2.42) abuse, job strain (OR=1.77), obesity (OR=1.35), and sleep disturbances (RR=1.92). For autism spectrum disorder, the most robust risk factor was maternal overweight pre/during pregnancy (RR=1.28). For attention-deficit/hyperactivity disorder (ADHD), they were maternal pre-pregnancy obesity (OR=1.63), maternal smoking during pregnancy (OR=1.60), and maternal overweight pre/during pregnancy (OR=1.28). Only one robust protective factor was detected: high physical activity (hazard ratio, HR=0.62) for Alzheimer's disease. In all, 32.9% of the associations were of high quality, 48.9% of medium quality, and 18.2% of low quality. Transdiagnostic class I-III risk/protective factors were mostly involved in the early neurodevelopmental period. The evidence-based atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expanding early intervention and preventive strategies for mental disorders.
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http://dx.doi.org/10.1002/wps.20894DOI Listing
October 2021

A Phase II Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Arbaclofen Administered for the Treatment of Social Function in Children and Adolescents With Autism Spectrum Disorders: Study Protocol for AIMS-2-TRIALS-CT1.

Front Psychiatry 2021 24;12:701729. Epub 2021 Aug 24.

Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Autism Spectrum Disorder (ASD or autism) is characterized by difficulties in social communication and interaction, which negatively impact on individuals and their families' quality of life. Currently no pharmacological interventions have been shown to be effective for improving social communication in autism. Previous trials have indicated the potential of arbaclofen for improving social function among autistic children and adolescents with fluent speech. The AIMS2TRIALS-Clinical Trial 1 (AIMS-CT1) will examine whether arbaclofen is superior to placebo in improving social function and other secondary outcomes over 16 weeks, along with safety and tolerability profiles. AIMS-CT1 is an international, multi-site, double-blind, parallel group Phase II randomized clinical trial. It will include 130 males and females aged 5:0-17:11 years, with a diagnosis of ASD and fluent speech. Eligible participants will be randomized on a ratio of 1:1 for a 16-week treatment period. Medication will be titrated over 5 weeks. The primary outcome is the effect on social function from weeks 0 to 16 measured on the Socialization domain of the Vineland Adaptive Behavior Scales, 3rd edition. Secondary outcome measures include the CGI-S (Clinical Global Impression-Severity), CGI-I (Clinical Global Impression-Improvement), other areas of adaptive function, social communication and other autism symptoms, co-occurring behavior problems and health-related quality of life. Genetic and electrophysiological markers will be examined as potential stratifiers for treatment response. Exploratory novel digital technologies will also be used to measure change, examining simultaneously the validity of digital biomarkers in natural environments. The safety and tolerability of the drug will also be examined. Our protocol is very closely aligned with a parallel Canadian trial of 90 participants (ARBA Study, US NCT number: NCT03887676) to allow for secondary combined analyses. Outcomes will be compared using both an Intent-to-reat and Per Protocol approach. The outcomes of this trial, combined with the parallel Canadian trial, will contribute to the evidence base for medications used to help social difficulties among young autistic individuals; demonstrate the capabilities of the AIMS-2-TRIALS network of academic centers to deliver clinical trials; and support future drug development. EudraCT number: 2018-000942-21 and ClinicalTrials.gov registry number: NCT03682978. Currently under protocol v.7.2, dated 20.11.2020.
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http://dx.doi.org/10.3389/fpsyt.2021.701729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421761PMC
August 2021

Fronto-Parietal Gray Matter Volume Loss Is Associated with Decreased Working Memory Performance in Adolescents with a First Episode of Psychosis.

J Clin Med 2021 Aug 31;10(17). Epub 2021 Aug 31.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, 28040 Madrid, Spain.

Cognitive maturation during adolescence is modulated by brain maturation. However, it is unknown how these processes intertwine in early onset psychosis (EOP). Studies examining longitudinal brain changes and cognitive performance in psychosis lend support for an altered development of high-order cognitive functions, which parallels progressive gray matter (GM) loss over time, particularly in fronto-parietal brain regions. We aimed to assess this relationship in a subsample of 33 adolescents with first-episode EOP and 47 matched controls over 2 years. Backwards stepwise regression analyses were conducted to determine the association and predictive value of longitudinal brain changes over cognitive performance within each group. Fronto-parietal GM volume loss was positively associated with decreased working memory in adolescents with psychosis (frontal left (B = 0.096, = 0.008); right (B = 0.089, = 0.015); parietal left (B = 0.119, = 0.007), right (B = 0.125, = 0.015)) as a function of age. A particular decrease in frontal left GM volume best predicted a significant amount (22.28%) of the variance of decreased working memory performance over time, accounting for variance in age (14.9%). No such association was found in controls. Our results suggest that during adolescence, EOP individuals seem to follow an abnormal neurodevelopmental trajectory, in which fronto-parietal GM volume reduction is associated with the differential age-related working memory dysfunction in this group.
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http://dx.doi.org/10.3390/jcm10173929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432087PMC
August 2021

Humanization in mental health plans in Spain.

Rev Psiquiatr Salud Ment 2021 Sep 4. Epub 2021 Sep 4.

Servicio del Niño y el Adolescente, Instituto de Psiquiatría y Salud Mental, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, Facultad de Medicina, Universidad Complutense, Madrid, España.

Introduction: Mental health (MH) care has important challenges, especially in the field of humanization. Our objectives were to identify the humanization measures in MH plans of the Spanish autonomous communities (CCAA) and the priorities to be developed in this area.

Material And Methods: A large and multidisciplinary group of people involved in MH care participated in a consensus, according to a modified Delphi method, based on «design thinking», in three phases: (1) identification of humanization measures in MH plans of CCAA; (2) analysis of the implementation of these measures; and (3) identification of humanization priorities in MH.

Results: Fourteen of the 17 CCAA have current MH plans. They contained four types of humanization measures: (1) improvement of the quality of care; (2) promotion of user participation; (3) campaigns against stigma and discrimination; (4) caring for especially vulnerable people. Implementation of measures ranged from 6.3% (i.e.: specific budget) to 100%, with an average of 64.1%. We identified priority issues, operationalized in 5 proposals: (1) information campaigns; (2) multidisciplinary meeting forums; (3) platforms of support entities; (4) strategies on MH education; (5) humanization in study plans.

Conclusions: Some MH plans include humanization among their objectives, but partially. The implementation of humanization proposals such as those identified in this study is essential to achieve a high-quality MH care.
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http://dx.doi.org/10.1016/j.rpsm.2021.08.003DOI Listing
September 2021

The impact of COVID-19 lockdown on child and adolescent mental health: systematic review.

Eur Child Adolesc Psychiatry 2021 Aug 18. Epub 2021 Aug 18.

Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

COVID-19 was declared a pandemic in March 2020, resulting in many countries worldwide calling for lockdowns. This study aimed to review the existing literature on the effects of the lockdown measures established as a response to the COVID-19 pandemic on the mental health of children and adolescents. Embase, Ovid, Global Health, PsycINFO, Web of Science, and pre-print databases were searched in this PRISMA-compliant systematic review (PROSPERO: CRD42021225604). We included individual studies reporting on a wide range of mental health outcomes, including risk and protective factors, conducted in children and adolescents (aged ≤ 19 years), exposed to COVID-19 lockdown. Data extraction and quality appraisal were conducted by independent researchers, and results were synthesised by core themes. 61 articles with 54,999 children and adolescents were included (mean age = 11.3 years, 49.7% female). Anxiety symptoms and depression symptoms were common in the included studies and ranged 1.8-49.5% and 2.2-63.8%, respectively. Irritability (range = 16.7-73.2%) and anger (range = 30.0-51.3%), were also frequently reported by children and adolescents. Special needs and the presence of mental disorders before the lockdown, alongside excessive media exposure, were significant risk factors for anxiety. Parent-child communication was protective for anxiety and depression. The COVID-19 lockdown has resulted in psychological distress and highlighted vulnerable groups such as those with previous or current mental health difficulties. Supporting the mental health needs of children and adolescents at risk is key. Clinical guidelines to alleviate the negative effects of COVID-19 lockdown and public health strategies to support this population need to be developed.
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http://dx.doi.org/10.1007/s00787-021-01856-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371430PMC
August 2021

The relationship of symptom dimensions with premorbid adjustment and cognitive characteristics at first episode psychosis: Findings from the EU-GEI study.

Schizophr Res 2021 Aug 14;236:69-79. Epub 2021 Aug 14.

Department of Psychiatry, Early Psychosis Section, Amsterdam UMC, University of Amsterdam, Meibergdreef 5, 1105 AZ Amsterdam, the Netherlands; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.

Premorbid functioning and cognitive measures may reflect gradients of developmental impairment across diagnostic categories in psychosis. In this study, we sought to examine the associations of current cognition and premorbid adjustment with symptom dimensions in a large first episode psychosis (FEP) sample. We used data from the international EU-GEI study. Bifactor modelling of the Operational Criteria in Studies of Psychotic Illness (OPCRIT) ratings provided general and specific symptom dimension scores. Premorbid Adjustment Scale estimated premorbid social (PSF) and academic adjustment (PAF), and WAIS-brief version measured IQ. A MANCOVA model examined the relationship between symptom dimensions and PSF, PAF, and IQ, having age, sex, country, self-ascribed ethnicity and frequency of cannabis use as confounders. In 785 patients, better PSF was associated with fewer negative (B = -0.12, 95% C.I. -0.18, -0.06, p < 0.001) and depressive (B = -0.09, 95% C.I. -0.15, -0.03, p = 0.032), and more manic (B = 0.07, 95% C.I. 0.01, 0.14, p = 0.023) symptoms. Patients with a lower IQ presented with slightly more negative and positive, and fewer manic, symptoms. Secondary analysis on IQ subdomains revealed associations between better perceptual reasoning and fewer negative (B = -0.09, 95% C.I. -0.17, -0.01, p = 0.023) and more manic (B = 0.10, 95% C.I. 0.02, 0.18, p = 0.014) symptoms. Fewer positive symptoms were associated with better processing speed (B = -0.12, 95% C.I. -0.02, -0.004, p = 0.003) and working memory (B = -0.10, 95% C.I. -0.18, -0.01, p = 0.024). These findings suggest that the negative and manic symptom dimensions may serve as clinical proxies of different neurodevelopmental predisposition in psychosis.
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http://dx.doi.org/10.1016/j.schres.2021.08.008DOI Listing
August 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

Primary prevention of depression: An umbrella review of controlled interventions.

J Affect Disord 2021 Nov 31;294:957-970. Epub 2021 Jul 31.

Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK; OASIS service, South London and Maudsley NHS Foundation Trust, London, UK; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. Electronic address:

Background: Primary prevention has the potential to modify the course of depression, but the consistency and magnitude of this effect are currently undetermined.

Methods: PRISMA and RIGHT compliant (PROSPERO:CRD42020179659) systematic meta-review, PubMed/Web of Science, up to June 2020. Meta-analyses of controlled interventions for the primary prevention of depressive symptoms [effect measures: standardized mean difference (SMD)] or depressive disorders [effect measure: relative risk (RR)] were carried out. Results were stratified by: (i) age range; (ii) target population (general and/or at-risk); (iii) intervention type. Quality (assessed with AMSTAR/AMSTAR-PLUS content) and credibility (graded as high/moderate/low) were assessed. USPSTF grading system was used for recommendations.

Results: Forty-six meta-analyses (k=928 individual studies, n=286,429 individuals, mean age=22.4 years, 81.1% female) were included. Effect sizes were: SMD=0.08-0.53; for depressive symptoms; RR=0.90-0.28 for depressive disorders. Sensitivity analyses including only RCTs did not impact the findings. AMSTAR median=9 (IQR=8-9); AMSTAR-PLUS content median=4.25 (IQR=4-5). Credibility of the evidence was insufficient/low in 43 (93.5%) meta-analyses, moderate in two (4.3%), and high in one (2.2%): reduction of depressive symptoms using psychosocial interventions for young adults only, and a combination of psychological and educational interventions in primary care had moderate credibility; preventive administration of selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in individuals with a stroke had high credibility.

Limitations: Intervention heterogeneity and lack of long-term efficacy evaluation.

Conclusions: Primary preventive interventions for depression might be effective. Among them, clinicians may offer SSRIs post-stroke to prevent depressive disorders, and psychosocial interventions for children/adolescents/young adults with risk factors or during the prenatal/perinatal period.
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http://dx.doi.org/10.1016/j.jad.2021.07.101DOI Listing
November 2021

Imputing the Number of Responders from the Mean and Standard Deviation of CGI-Improvement in Clinical Trials Investigating Medications for Autism Spectrum Disorder.

Brain Sci 2021 Jul 9;11(7). Epub 2021 Jul 9.

Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, 81675 Munich, Germany.

Introduction: Response to treatment, according to Clinical Global Impression-Improvement (CGI-I) scale, is an easily interpretable outcome in clinical trials of autism spectrum disorder (ASD). Yet, the CGI-I rating is sometimes reported as a continuous outcome, and converting it to dichotomous would allow meta-analysis to incorporate more evidence.

Methods: Clinical trials investigating medications for ASD and presenting both dichotomous and continuous CGI-I data were included. The number of patients with at least much improvement (CGI-I ≤ 2) were imputed from the CGI-I scale, assuming an underlying normal distribution of a latent continuous score using a primary threshold θ = 2.5 instead of θ = 2, which is the original cut-off in the CGI-I scale. The original and imputed values were used to calculate responder rates and odds ratios. The performance of the imputation method was investigated with a concordance correlation coefficient (CCC), linear regression, Bland-Altman plots, and subgroup differences of summary estimates obtained from random-effects meta-analysis.

Results: Data from 27 studies, 58 arms, and 1428 participants were used. The imputation method using the primary threshold (θ = 2.5) had good performance for the responder rates (CCC = 0.93 95% confidence intervals [0.86, 0.96]; β of linear regression = 1.04 [0.95, 1.13]; bias and limits of agreements = 4.32% [-8.1%, 16.74%]; no subgroup differences χ = 1.24, -value = 0.266) and odds ratios (CCC = 0.91 [0.86, 0.96]; β = 0.96 [0.78, 1.14]; bias = 0.09 [-0.87, 1.04]; χ = 0.02, -value = 0.894). The imputation method had poorer performance when the secondary threshold (θ = 2) was used.

Discussion: Assuming a normal distribution of the CGI-I scale, the number of responders could be imputed from the mean and standard deviation and used in meta-analysis. Due to the wide limits of agreement of the imputation method, sensitivity analysis excluding studies with imputed values should be performed.
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http://dx.doi.org/10.3390/brainsci11070908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305379PMC
July 2021

Manifesto for an ECNP Neuromodulation Thematic Working Group (TWG): Non-invasive brain stimulation as a new Super-subspecialty.

Eur Neuropsychopharmacol 2021 Aug 1;52:72-83. Epub 2021 Aug 1.

Sheba Medical Center at Tel Hashomer, Israel, Sackler Faculty of Medicine, Tel Aviv.

Non-Invasive Brain Stimulation (NIBS) techniques and in particular, repetitive Transcranial Magnetic Stimulation (rTMS), are developing beyond mere clinical application. Although originally purposed for the treatment of resistant neuropsychiatric disorders, NIBS is also contributing to a deeper understanding of psychiatric disorders. rTMS is also changing the model of the disorder itself, from "mental" to one of neural connectivity. TMS allows the assessment of brain circuit excitability and eventually, of plastic changes affecting these circuits. While a clinical translational approach is, at the present time, the most adequate to meet the dimensional-circuit base model of the disorder, it refines the standard categorical classification of psychiatric disorders. The discovery of the fundamental importance of the balance between neuroplasticity and inflammation is also now explored through neuro-modulation findings consistently with the evidence of anti-inflammatory actions of the magnetic pulses. rTMS may activate, inhibit, or otherwise interfere with the activity of neuronal cortical networks, depending on stimulus frequency and intensity of brain-induced electric field. Of particular interest, yet still unclear, is how the relatively unspecific nature of TMS stimulation may lead to specific neuronal reorganization, as well as a definition of the TMS-triggered reorganization of functional brain modules, raising attention on the importance of the active participation of the patient to the treatment.. Configuration and state of consciousness of the subject have made subjective experience under treatment regain importance in the neuro-scientific Psychiatry based on the requirement of United States National Institute of Health (NIH) and the substantial importance of the consciousness state in the efficacy of the TMS treatment. By focusing on the subjective experience, a renaissance of the phenomenology offers Psychiatry an opportunity to become proficient and to distinguish itself from other disciplines. For all these reasons, TMS should be included in the cluster of the sub-specialties as a new "Super-Specialty" and an appropriate training course has to be inaugurated. Psychiatrists are nowadays multi-specialists, moving from a specialty to another, vs super-specialist. The cultivation of a properly trained cohort of TMS psychiatrists will better meet the challenges of treatment-resistant psychiatric conditions (disorders of connectivity), through appropriate and ethical practice, meanwhile facilitating an informed development and integration of additional emerging neuro-modulation techniques. The aim of this consensus paper is to underline the interdisciplinary nature of NIBS, that also encompasses the subjective experience and to point out the necessity of a neuroscience-applied approach to NIBS in the context of the European College of Neuro-psychopharmacology (ECNP).
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http://dx.doi.org/10.1016/j.euroneuro.2021.07.002DOI Listing
August 2021

Building up resilience in an uncertain world: mental health challenges in the aftermath of the first modern pandemic.

Eur Arch Psychiatry Clin Neurosci 2021 09;271(6):1001-1003

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.

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http://dx.doi.org/10.1007/s00406-021-01313-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8334334PMC
September 2021

Trends in utilisation of hypnotics among Scandinavian young people.

Acta Psychiatr Scand 2021 08;144(2):97-99

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, CIBERSAM, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain.

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http://dx.doi.org/10.1111/acps.13341DOI Listing
August 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

Longitudinal outcome of attenuated positive symptoms, negative symptoms, functioning and remission in people at clinical high risk for psychosis: a meta-analysis.

EClinicalMedicine 2021 Jun 16;36:100909. Epub 2021 Jun 16.

Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.

Background: Little is known about clinical outcomes other than transition to psychosis in people at Clinical High-Risk for psychosis (CHR-P). Our aim was to comprehensively meta-analytically evaluate for the first time a wide range of clinical and functional outcomes beyond transition to psychosis in CHR-P individuals.

Methods: PubMed and Web of Science were searched until November 2020 in this PRISMA compliant meta-analysis (PROSPERO:CRD42020206271). Individual longitudinal studies conducted in individuals at CHR-P providing data on at least one of our outcomes of interest were included. We carried out random-effects pairwise meta-analyses, meta-regressions, and assessed publication bias and study quality. Analyses were two-tailed with α=0.05.

Findings: 75 prospective studies were included (n=5,288, age=20.0 years, females=44.5%). Attenuated positive symptoms improved at 12 (Hedges' g=0.753, 95%CI=0.495-1.012) and 24 (Hedges' g=0.836, 95%CI=0.463-1.209), but not ≥36 months (Hedges' g=0.315. 95%CI=-0.176-0.806). Negative symptoms improved at 12 (Hedges' g=0.496, 95%CI=0.315-0.678), but not 24 (Hedges' g=0.499, 95%CI=-0.137-1.134) or ≥36 months (Hedges' g=0.033, 95%CI=-0.439-0.505). Depressive symptoms improved at 12 (Hedges' g=0.611, 95%CI=0.441-0.782) and 24 (Hedges' g=0.583, 95%CI=0.364-0.803), but not ≥36 months (Hedges' g=0.512 95%CI=-0.337-1.361). Functioning improved at 12 (Hedges' g=0.711, 95%CI=0.488-0.934), 24 (Hedges' g=0.930, 95%CI=0.553-1.306) and ≥36 months (Hedges' g=0.392, 95%CI=0.117-0.667). Remission from CHR-P status occurred in 33.4% (95%CI=22.6-44.1%) at 12 months, 41.4% (95%CI=32.3-50.5%) at 24 months and 42.4% (95%CI=23.4-61.3%) at ≥36 months. Heterogeneity across the included studies was significant and ranged from I=53.6% to I=96.9%. The quality of the included studies (mean±SD) was 4.6±1.1 (range=2-8).

Interpretation: CHR-P individuals improve on symptomatic and functional outcomes over time, but these improvements are not maintained in the longer term, and less than half fully remit. Prolonged duration of care may be needed for this patient population to optimize outcomes.

Funding: None.
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http://dx.doi.org/10.1016/j.eclinm.2021.100909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219991PMC
June 2021

Sex Differences in Lifespan Trajectories and Variability of Human Sulcal and Gyral Morphology.

Cereb Cortex 2021 Jun 26. Epub 2021 Jun 26.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Calle Ibiza, 43, 28009, Madrid, Spain.

Sex differences in the development and aging of human sulcal morphology have been understudied. We charted sex differences in trajectories and inter-individual variability of global sulcal depth, width, and length, pial surface area, exposed (hull) gyral surface area, unexposed sulcal surface area, cortical thickness, gyral span, and cortex volume across the lifespan in a longitudinal sample (700 scans, 194 participants 2 scans, 104 three scans, age range: 16-70 years) of neurotypical males and females. After adjusting for brain volume, females had thicker cortex and steeper thickness decline until age 40 years; trajectories converged thereafter. Across sexes, sulcal shortening was faster before age 40, while sulcal shallowing and widening were faster thereafter. Although hull area remained stable, sulcal surface area declined and was more strongly associated with sulcal shortening than with sulcal shallowing and widening. Males showed greater variability for cortex volume and lower variability for sulcal width. Our findings highlight the association between loss of sulcal area, notably through sulcal shortening, with cortex volume loss. Studying sex differences in lifespan trajectories may improve knowledge of individual differences in brain development and the pathophysiology of neuropsychiatric conditions.
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http://dx.doi.org/10.1093/cercor/bhab145DOI Listing
June 2021

Drug development for Autism Spectrum Disorder (ASD): Progress, challenges, and future directions.

Eur Neuropsychopharmacol 2021 Jul 19;48:3-31. Epub 2021 Jun 19.

Department of Psychiatry, Columbia University, New York, NY, United States.

In 2017, facing lack of progress and failures encountered in targeted drug development for Autism Spectrum Disorder (ASD) and related neurodevelopmental disorders, the ISCTM with the ECNP created the ASD Working Group charged to identify barriers to progress and recommending research strategies for the field to gain traction. Working Group international academic, regulatory and industry representatives held multiple in-person meetings, teleconferences, and subgroup communications to gather a wide range of perspectives on lessons learned from extant studies, current challenges, and paths for fundamental advances in ASD therapeutics. This overview delineates the barriers identified, and outlines major goals for next generation biomedical intervention development in ASD. Current challenges for ASD research are many: heterogeneity, lack of validated biomarkers, need for improved endpoints, prioritizing molecular targets, comorbidities, and more. The Working Group emphasized cautious but unwavering optimism for therapeutic progress for ASD core features given advances in the basic neuroscience of ASD and related disorders. Leveraging genetic data, intermediate phenotypes, digital phenotyping, big database discovery, refined endpoints, and earlier intervention, the prospects for breakthrough treatments are substantial. Recommendations include new priorities for expanded research funding to overcome challenges in translational clinical ASD therapeutic research.
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http://dx.doi.org/10.1016/j.euroneuro.2021.05.010DOI Listing
July 2021

Calling for the integration of children's mental health and protection into COVID-19 responses.

Rev Psiquiatr Salud Ment (Engl Ed) 2021 Apr-Jun;14(2):113-116

Department of Medicine, University of Barcelona, Barcelona, Spain; Department of Child and Adolescent Psychiatry, Institute of Neuroscience, Hospital Clínic de Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.

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http://dx.doi.org/10.1016/j.rpsmen.2021.02.002DOI Listing
January 2021

Mental health services during the first wave of the COVID-19 pandemic in Europe: Results from the EPA Ambassadors Survey and implications for clinical practice.

Eur Psychiatry 2021 06 9;64(1):e41. Epub 2021 Jun 9.

INSERM, U1266 (Institute of Psychiatry and Neuroscience of Paris), Université de Paris, Paris, France.

Background: The COVID-19 pandemic caused an unprecedented worldwide crisis affecting several sectors, including health, social care, economy and society at large. The World Health Organisation has emphasized that mental health care should be considered as one of the core sectors within the overall COVID-19 health response. By March 2020, recommendations for the organization of mental health services across Europe have been developed by several national and international mental health professional associations.

Methods: The European Psychiatric Association (EPA) surveyed a large European sample of psychiatrists, namely the "EPA Ambassadors", on their clinical experience of the impact of COVID-19 pandemic on the treatment of psychiatric patients during the month of April 2020 in order to: a) identify and report the views and experiences of European psychiatrists; and b) represent and share these results with mental health policy makers at European level. Based on the recommendations issued by national psychiatric associations and on the results of our survey, we identified important organisational aspects of mental health care during the peak of the first wave of the COVID-19.

Results: While most of the recommendations followed the same principles, significant differences between countries emerged in service delivery, mainly relating to referrals to outpatients and for inpatient admission, assessments and treatment for people with mental disorders. Compared to previous months, the mean number of patients treated by psychiatrists in outpatient settings halved in April 2020. In the same period, the number of mentally ill patients tested for, or developing, COVID-19 was low. In most of countries, traditional face-to-face visits were replaced by online remote consultations.

Conclusions: Based on our findings we recommend: 1) to implement professional guidelines into practice and harmonize psychiatric clinical practice across Europe; 2) to monitor the treatment outcomes of patients with COVID-19 and pre-existing mental disorders; 3) to keep psychiatric services active by using all available options (for example telepsychiatry); 4) to increase communication and cooperation between different health care providers.
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http://dx.doi.org/10.1192/j.eurpsy.2021.2215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314055PMC
June 2021

Genetic underpinnings of sociability in the general population.

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

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

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

Affective symptom dimensions in early-onset psychosis over time: a principal component factor analysis of the Young Mania Rating Scale and the Hamilton Depression Rating Scale.

Eur Child Adolesc Psychiatry 2021 May 30. Epub 2021 May 30.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, C/Ibiza, 43, 28009, Madrid, Spain.

Early-onset psychosis (EOP) is a complex disorder characterized by a wide range of symptoms, including affective symptoms. Our aim was to (1) examine the dimensional structure of affective symptoms in EOP, (2) evaluate the predominance of the clinical dimensions and (3) assess the progression of the clinical dimensions over a 2-year period. STROBE-compliant prospective principal component factor analysis of Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale-21 (HDRS-21) at baseline, 6-months, 1-year and 2-year follow-up. We included 108 EOP individuals (mean age = 15.5 ± 1.8 years, 68.5% male). The factor analysis produced a four-factor model including the following dimensions: mania, depression/anxiety, sleep and psychosis. It explained 47.4% of the total variance at baseline, 60.6% of the total variance at 6-months follow-up, 54.5% of the total variance at 1-year follow-up and 49.5% of the total variance at 2-year follow-up. According to the variance explained, the mania factor was predominant at baseline (17.4%), 6-month follow-up (23.5%) and 2-year follow-up (26.1%), while the depression/anxiety factor was predominant at 1-year follow-up (23.1%). The mania factor was the most stable; 58.3% items that appeared in this factor (with a load > 0.4) at any time point appeared in the same factor at ≥ 3/4 time points. Affective symptoms are frequent and persistent in EOP. Mania seems to be the most predominant and stable affective dimension. However, depression and anxiety may gain predominance with time. A comprehensive evaluation of the dimensional structure and the progression of affective symptoms may offer clinical and therapeutic advantages.
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http://dx.doi.org/10.1007/s00787-021-01815-5DOI Listing
May 2021

The Independent Effects of Psychosocial Stressors on Subclinical Psychosis: Findings From the Multinational EU-GEI Study.

Schizophr Bull 2021 May 19. Epub 2021 May 19.

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.

The influence of psychosocial stressors on psychosis risk has usually been studied in isolation and after the onset of the disorder, potentially ignoring important confounding relationships or the fact that some stressors that may be the consequence of the disorder rather than preexisting. The study of subclinical psychosis could help to address some of these issues. In this study, we investigated whether there was (i) an association between dimensions of subclinical psychosis and several psychosocial stressors including: childhood trauma, self-reported discrimination experiences, low social capital, and stressful life experiences, and (ii) any evidence of environment-environment (ExE) interactions between these factors. Data were drawn from the EUGEI study, in which healthy controls (N = 1497) and siblings of subjects with a psychotic disorder (N = 265) were included in six countries. The association between psychosocial stressors and subclinical psychosis dimensions (positive, negative and depressive dimension as measured by the Community Assessment of Psychic Experiences (CAPE) scale) and possible ExE interactions were assessed using linear regression models. After adjusting for sex, age, ethnicity, country, and control/sibling status, childhood trauma (β for positive dimension: 0.13, negative: 0.49, depressive: 0.26) and stressful life events (positive: 0.08, negative: 0.16, depressive: 0.17) were associated with the three dimensions. Lower social capital was associated with the negative and depression dimensions (negative: 0.26, depressive: 0.13), and self-reported discrimination experiences with the positive dimension (0.06). Our findings are in favor of independent, cumulative and non-specific influences of social adversities in subclinical psychosis in non-clinical populations, without arguments for E × E interactions.
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http://dx.doi.org/10.1093/schbul/sbab060DOI Listing
May 2021

Preventive psychiatry: a blueprint for improving the mental health of young people.

World Psychiatry 2021 Jun;20(2):200-221

Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, CA, USA.

Preventive approaches have latterly gained traction for improving mental health in young people. In this paper, we first appraise the conceptual foundations of preventive psychiatry, encompassing the public health, Gordon's, US Institute of Medicine, World Health Organization, and good mental health frameworks, and neurodevelopmentally-sensitive clinical staging models. We then review the evidence supporting primary prevention of psychotic, bipolar and common mental disorders and promotion of good mental health as potential transformative strategies to reduce the incidence of these disorders in young people. Within indicated approaches, the clinical high-risk for psychosis paradigm has received the most empirical validation, while clinical high-risk states for bipolar and common mental disorders are increasingly becoming a focus of attention. Selective approaches have mostly targeted familial vulnerability and non-genetic risk exposures. Selective screening and psychological/psychoeducational interventions in vulnerable subgroups may improve anxiety/depressive symptoms, but their efficacy in reducing the incidence of psychotic/bipolar/common mental disorders is unproven. Selective physical exercise may reduce the incidence of anxiety disorders. Universal psychological/psychoeducational interventions may improve anxiety symptoms but not prevent depressive/anxiety disorders, while universal physical exercise may reduce the incidence of anxiety disorders. Universal public health approaches targeting school climate or social determinants (demographic, economic, neighbourhood, environmental, social/cultural) of mental disorders hold the greatest potential for reducing the risk profile of the population as a whole. The approach to promotion of good mental health is currently fragmented. We leverage the knowledge gained from the review to develop a blueprint for future research and practice of preventive psychiatry in young people: integrating universal and targeted frameworks; advancing multivariable, transdiagnostic, multi-endpoint epidemiological knowledge; synergically preventing common and infrequent mental disorders; preventing physical and mental health burden together; implementing stratified/personalized prognosis; establishing evidence-based preventive interventions; developing an ethical framework, improving prevention through education/training; consolidating the cost-effectiveness of preventive psychiatry; and decreasing inequalities. These goals can only be achieved through an urgent individual, societal, and global level response, which promotes a vigorous collaboration across scientific, health care, societal and governmental sectors for implementing preventive psychiatry, as much is at stake for young people with or at risk for emerging mental disorders.
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http://dx.doi.org/10.1002/wps.20869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129854PMC
June 2021

Efficacy of a Web-Enabled, School-Based, Preventative Intervention to Reduce Bullying and Improve Mental Health in Children and Adolescents: Study Protocol for a Cluster Randomized Controlled Trial.

Front Pediatr 2021 26;9:628984. Epub 2021 Apr 26.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Centro de Investigación Biomédica en Red (CIBER) de Salud Mental (CIBERSAM), School of Medicine, Universidad Complutense, Madrid, Spain.

Bullying is a major preventable risk factor for mental disorders. Available evidence suggests school-based interventions reduce bullying prevalence rates. This study aims to test the efficacy of a web-enabled, school-based, multicomponent anti-bullying intervention to prevent school bullying and to assess its effects on mental health and quality of life. Cluster randomized controlled trial conducted in 20 publicly funded primary and secondary schools in Madrid, Spain. Schools are randomly allocated to either the intervention arm ( = 10) or conventional practices arm ( = 10). The web-enabled intervention (LINKlusive) lasts ~12 weeks and consists of three main components: (i) an online training program for teachers and parents, (ii) a web-guided educational program for students, focusing on promoting respect for diversity, empathy, and social skill development, and (iii) a web-guided, teacher-delivered, targeted intervention program for bullying situations identified based on peer-support strategies and individual intervention for those involved (i.e., bullying victims and perpetrators). The primary objective is to compare differences between peer-reported bullying victimization in the intervention and control arms at the end of the intervention. Secondary outcome measures are additional measures of bullying victimization and perpetration, mental health symptoms, self-esteem, and quality of life. A follow-up assessment is conducted 1 year after the end of the intervention. Treatment effects will be tested using multilevel mixed models, adjusting for school-, classroom-, and student-related covariates. Considering the increased bullying rates in children with special educational needs, a specific subgroup analysis will test the efficacy of the intervention on bullying prevalence, mental health, and quality of life in this particularly vulnerable population. The Deontology Commission of the School of Psychology, Universidad Complutense in Madrid, Spain reviewed the study protocol and granted ethical approval on 21st January 2019. The results of the trial will be disseminated in relevant peer-reviewed journals and at conferences in the field. ISRCTN15719015.
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http://dx.doi.org/10.3389/fped.2021.628984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107271PMC
April 2021

Universal and Selective Interventions to Prevent Poor Mental Health Outcomes in Young People: Systematic Review and Meta-analysis.

Harv Rev Psychiatry 2021 May-Jun 01;29(3):196-215

From the Early Psychosis: Interventions and Clinical-Detection (EPIC) Laboratory, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London (Drs. Salazar de Pablo, De Micheli, Catalan, Verdino, Di Maggio, Radua, Provenzani, Montealegre, Signorini, and Fusar-Poli, and Mr. Oliver); Departments of Child and Adolescent Psychiatry (Dr. Salazar de Pablo) and of Psychosis Studies (Drs. Bonoldi and Baccaredda Boy), Institute of Psychiatry, Psychology & Neuroscience, King's College London; Institute of Psychiatry and Mental Health. Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, Madrid (Drs. Salazar de Pablo and Arango); National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London (Drs. De Micheli and Fusar-Poli); Department of Brain and Behavioral Sciences, University of Pavia (Drs. Di Maggio, Provenzani, Ruzzi, Calorio, Nosari, Di Marco, Famularo, Molteni, Filosi, Mensi, Balottin, Politi, and Fusar-Poli); Neurosciences Department, University of Padova (Dr. Solmi); Mental Health Department, Biocruces Bizkaia Health Research Institute, Basurto University Hospital, Facultad de Medicina y Odontología, Campus de Leioa, University of the Basque Country, UPV/EHU, Barakaldo, Bizkaia, Spain (Dr. Catalan); Department of Molecular and Developmental Medicine, Division of Psychiatry, University of Siena (Dr. Verdino); Imaging of Mood- and Anxiety-Related Disorders (IMARD) group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, Barcelona (Dr. Radua); Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm (Dr. Radua); Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Mondino Foundation, Child and Adolescent Neuropsychiatric Unit (Dr. Mensi); Department of Paediatrics, Yonsei University College of Medicine, Seoul (Dr. Shin); Zucker Hillside Hospital, Department of Psychiatry, Northwell Health, Glen Oaks, NY (Dr. Correll); Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY (Dr. Correll); Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY (Dr. Correll); Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin (Dr. Correll); OASIS service, South London and Maudsley NHS Foundation Trust, London (Dr. Fusar-Poli).

Background: Much is not known about the efficacy of interventions to prevent poor mental health outcomes in young people by targeting either the general population (universal prevention) or asymptomatic individuals with high risk of developing a mental disorder (selective prevention).

Methods: We conducted a PRISMA/MOOSE-compliant systematic review and meta-analysis of Web of Science to identify studies comparing post-test efficacy (effect size [ES]; Hedges' g) of universal or selective interventions for poor mental health outcomes versus control groups, in samples with mean age <35 years (PROSPERO: CRD42018102143). Measurements included random-effects models, I2 statistics, publication bias, meta-regression, sensitivity analyses, quality assessments, number needed to treat, and population impact number.

Results: 295 articles (447,206 individuals; mean age = 15.4) appraising 17 poor mental health outcomes were included. Compared to control conditions, universal and selective interventions improved (in descending magnitude order) interpersonal violence, general psychological distress, alcohol use, anxiety features, affective symptoms, other emotional and behavioral problems, consequences of alcohol use, posttraumatic stress disorder features, conduct problems, tobacco use, externalizing behaviors, attention-deficit/hyperactivity disorder features, and cannabis use, but not eating-related problems, impaired functioning, internalizing behavior, or sleep-related problems. Psychoeducation had the highest effect size for ADHD features, affective symptoms, and interpersonal violence. Psychotherapy had the highest effect size for anxiety features.

Conclusion: Universal and selective preventive interventions for young individuals are feasible and can improve poor mental health outcomes.
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http://dx.doi.org/10.1097/HRP.0000000000000294DOI Listing
May 2021

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated With Common Genetic Variants for Major Psychiatric Conditions: Results From the Multi-Center EU-GEI Study.

Schizophr Bull 2021 May 8. Epub 2021 May 8.

Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy.

Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.
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http://dx.doi.org/10.1093/schbul/sbab055DOI Listing
May 2021

The pediatric psychopharmacology of autism spectrum disorder: A systematic review - Part I: The past and the present.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Aug 20;110:110326. Epub 2021 Apr 20.

Child and Adolescent Psychiatry Department, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, School of Medicine Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.

Autism Spectrum Disorder (ASD) is a severe and lifelong neurodevelopmental disorder, with high social costs and a dramatic burden on the quality of life of patients and family members. Despite its high prevalence, reaching 1/54 children and 1/45 adults in the United States, no pharmacological treatment is still directed to core symptoms of ASD, encompassing social and communication deficits, repetitive behaviors, restricted interests, and abnormal sensory processing. The purpose of this review is to provide an overview of the state-of-the-art of psychopharmacological therapy available today for ASD in children and adolescents, in order to foster best practices and to organize new strategies for future research. To date, atypical antipsychotics such as risperidone and aripiprazole represent the first line of intervention for hyperactivity, impulsivity, agitation, temper outbursts or aggression towards self or others. Tricyclic antidepressants are less prescribed because of uncertain efficacy and important side effects. SSRIs, especially fluoxetine and sertraline, may be effective in treating repetitive behaviors (anxiety and obsessive-compulsive symptoms) and irritability/agitation, while mirtazapine is more helpful with sleep problems. Low doses of buspirone have shown some efficacy on restrictive and repetitive behaviors in combination with behavioral interventions. Stimulants, and to a lesser extent atomoxetine, are effective in reducing hyperactivity, inattention and impulsivity also in comorbid ASD-ADHD, although with somewhat lower efficacy and greater incidence of side effects compared to idiopathic ADHD. Clonidine and guanfacine display some efficacy on hyperactivity and stereotypic behaviors. For several other drugs, case reports and open-label studies suggest possible efficacy, but no randomized controlled trial has yet been performed. Research in the pediatric psychopharmacology of ASD is still faced with at least two major hurdles: (a) Great interindividual variability in clinical response and side effect sensitivity is observed in the ASD population. This low level of predictability would benefit from symptom-specific treatment algorithms and from biomarkers to support drug choice; (b) To this date, no psychoactive drug appears to directly ameliorate core autism symptoms, although some indirect improvement has been reported with several drugs, once the comorbid target symptom is abated.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110326DOI Listing
August 2021

The role of depression in the prediction of a "late" remission in first-episode psychosis: An analysis of the OPTiMiSE study.

Schizophr Res 2021 05 7;231:100-107. Epub 2021 Apr 7.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, School of Medicine, Universidad Complutense, Madrid, Spain.

Objective: The identification of predictors of psychosis remission could guide early clinical decision-making for treatment of first-episode schizophrenia (FES).

Methods: We analyzed two non-independent subsamples of patients with FES ages 18-40 years from the OPTiMiSE study dataset to investigate the demographic and clinical factors that might help to differentiate "late" remitters (i.e., not in remission at week 2 or 4, but achieving remission within a 10-week follow-up period) from non-remitters within the same period.

Results: Subsample 1 included 216 individuals (55 females, mean age 25.9 years) treated with amisulpride in an open-label design who were not in remission at week 2. Early symptomatic response between baseline and week 2 (odds ratio (OR) = 4.186, 95% confidence interval (CI) = 2.082-8.416, p < 0.001) and older age (OR = 1.081, 95% CI = 1.026-1.138, p = 0.003) were the only variables significantly associated with a higher probability of psychosis remission at week 4. Subsample 2 was composed of the 72 participants (19 females, mean age 25.1 years) who were not in remission at week 4 and completed a 6-week double-blind randomized trial comparing continuation of amisulpride with switch to olanzapine. Depression at baseline (as measured with the Calgary Depression Scale for Schizophrenia) was significantly associated with a nearly 3-fold lower likelihood of psychosis remission during the 10-week follow-up (hazard ratio = 2.865, 95% CI = 1.187-6.916, p = 0.019).

Conclusion: Our results reinforce the importance of assessing depressive symptoms in people with FES and support the relevance of an early response (as early as 2 weeks) as a predictor of clinical outcome in this population.

Clinical Trials Registration: ClinicalTrials.gov identifier: NCT01248195, https://clinicaltrials.gov/ct2/show/NCT01248195.
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http://dx.doi.org/10.1016/j.schres.2021.03.010DOI Listing
May 2021

Drug development in ASD, an ISCTM-ECNP joint adventure.

Authors:
Celso Arango

Eur Neuropsychopharmacol 2021 Jul 5;48:1-2. Epub 2021 Apr 5.

Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, CIBERSAM, IiSGM, Universidad Complutense, School of Medicine, Madrid, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.euroneuro.2021.03.018DOI Listing
July 2021
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