Benedicto Crespo-Facorro

Benedicto Crespo-Facorro
Universidad de Sevilla | US · Psychiatry

MD PhD

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625
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Publications

Publications (625)
Article
Background Cardiometabolic disorders are largely responsible for excess mortality in schizophrenia. Non-alcoholic fatty liver disease (NAFLD) is increasingly relevant in the development of metabolic risk factors that have been associated with antipsychotic treatment. We aimed to assess the incidence of NAFLD and metabolic disturbances during the fi...
Article
Background Few investigations have been carried out on metabolic syndrome in antipsychotic- naïve patients with schizophrenia. Methods Our primary objective was to compare the prevalence of Metabolic Syndrome (MetS), as defined by the National Cholesterol Education Program, Adult Treatment Panel III in 2001 (NCEP-ATP III), between a Spanish cohort...
Article
Background Antipsychotic choice for the acute phase of a first episode of psychosis (FEP) is of the utmost importance since it may influence long-term outcome. However, head-to-head comparisons between second generation antipsychotics remain scarce. The aim of this study was to compare the effectiveness in the short-term of aripiprazole and risperi...
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Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and brain diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization meth...
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Clozapine is seldom prescribed in treatment-resistant schizophrenia (TRS) patients during early phases of the illness. We aimed to examine the pathway and patterns and the impact of clozapine use in patients with TRS who were followed up for 10 years after the first outbreak of the illness. Data were obtained retrospectively from an epidemiological...
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A c c e p t e d M a n u s c r i p t 2 Statement of interest: Antipsychotics are the first-line pharmacological treatment in patients suffering from a First Episode of Psychosis (FEP). However, its value transcends the acute phase, since they may influence the long-term functional and clinical outcomes for these patients. Thus, the early stages afte...
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Autism spectrum disorder (ASD) is associated with high structural heterogeneity in magnetic resonance imaging (MRI). This work uncovers three neuroanatomical dimensions of ASD ( N = 307) using machine learning methods and constructs their characteristic MRI signatures. The presence of these signatures, along with their clinical profiles and genetic...
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Schizophrenia is frequently associated with obesity, which is linked with neurostructural alterations. Yet, we do not understand how the brain correlates of obesity map onto the brain changes in schizophrenia. We obtained MRI-derived brain cortical and subcortical measures and body mass index (BMI) from 1260 individuals with schizophrenia and 1761...
Article
Background Attention deficits have been considered to be a central characteristic of schizophrenia-spectrum disorders. However, the specific interactions with, and longitudinal effects of, cannabis use at the different stages of the disorder remain unknown. Due to the high percentage of patients who are cannabis users at the onset of the disease, o...
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Treatment-resistant schizophrenia (TRS) will affect about one in three patients with schizophrenia. Clozapine is the only treatment approved for TRS, and patients should be treated as soon as possible to improve their chances of achieving remission. Despite its effectiveness, concern over side effects, monitoring requirements, and inexperience with...
Article
Objective Aripiprazole and risperidone are two of the most used second-generation antipsychotics (SGAs) worldwide. Previous evidence shows a similar effect of these SGAs on weight and metabolic changes at short-term. However, a longer period of time is necessary for a better assessment of their metabolic profile. We aimed to compare the long-term (...
Preprint
Mechanisms underpinning neurotypical age-related variations in cortical thickness in the human brain remain insufficiently specified. Here we used cell-specific marker genes, followed by gene ontology and enrichment analyses, to quantify the association between gene-expression levels and inter-regional age-related variations in neurotypical cortica...
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Background: Latest studies in patients with first episode psychosis (FEP) have shown alterations in cardiovascular, immune and endocrinological systems. These findings could indicate a systemic onset alteration in the metabolic disease as opposed to justifying these findings exclusively by antipsychotics´ side effects and long-term lifestyle conseq...
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Objective: The prevalence and significance of schizophrenia-related phenotypes at the population level is debated in the literature. Here, the authors assessed whether two recently reported neuroanatomical signatures of schizophrenia-signature 1, with widespread reduction of gray matter volume, and signature 2, with increased striatal volume-could...
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Women present a second peak of incidence of psychosis during the menopausal transition, partially explained by the loss of estrogen protection conferred during the reproductive years. In view of the lack of studies comparing sociodemographic, biological, and clinical variables and neurocognitive performance between women with early onset of psychos...
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Despite being a major cause of disability worldwide, the pathophysiology of schizophrenia and molecular basis of treatment response heterogeneity continue to be unresolved. Recent evidence suggests that multiple aspects of pathophysiology, including genetic risk factors, converge on key cell signaling pathways and that exploration of peripheral blo...
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Objective Neurological correlates of impaired insight in non-affective psychosis remain unclear. This study aimed to review and meta-analyze the studies assessing the grey matter volumetric correlates of impaired insight in non-affective psychosis. Methods This study consisted of a systematic review of 23 studies, and a meta-analysis with SDM-PSI...
Article
Objective: Obesity and metabolic diseases such as metabolic syndrome (MetS) are more prevalent in people with type 2 diabetes mellitus (T2DM), major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). MetS components might be associated with neurocognitive and functional impairments in these individuals. The predictive and di...
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Full-text available
Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to structural covariance patterns across brain regions and individuals. We present a mega-analysis of structural covariance with magnetic resonance imaging of 50,699 healthy and diseased individuals (12 studies, 130 sites, and 12 countries)...
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Reelin is an extracellular matrix glycoprotein reduced in brain regions (the prefrontal cortex and the hippocampus) of patients with schizophrenia. There are diverse rodent models of schizophrenia that mimic patient symptoms based on various causal theories; however, likely shared reelin alterations have not yet been systematically assessed in thos...
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Mechanisms underpinning age-related variations in cortical thickness in the human brain remain poorly understood. We investigated whether inter-regional age-related variations in cortical thinning (in a multicohort neuroimaging dataset from the ENIGMA Lifespan Working Group totalling 14,248 individuals, aged 4-89 years) depended on cell-specific ma...
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BACKGROUND Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia (N = 11,095),...
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Background Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/peri-natal period may be reflected in individual variations in cortical surface area. Methods Inter-regional profiles of grou...
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Background Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure...
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This study aimed to characterize the clinical profile of patients with brief psychotic disorders (BPD) triggered by the psychosocial distress derived from the COVID-19 crisis. A multicenter study was conducted from March 14 to May 14, 2020 (the peak weeks of the pandemic in Europe). All consecutive patients presenting non-affective psychotic episod...
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Correction to guideline. This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by a...
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Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schiz...
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Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizoph...
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The prevalence and significance of schizophrenia-related phenotypes at the population-level are debated in the literature. Here we assess whether two recently reported neuroanatomical signatures of schizophrenia, signature 1 with widespread reduction of gray matter volume and signature 2 with increased striatal volume, could be replicated in an ind...
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Full-text available
Previous research suggests an association of loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate a LNL-ISO polygenic score contribution to schizophrenia risk in an independent case-control sample (N = 3,488). We then subset schizophrenia predisposing variation based on its effect on LNL-ISO. We find that genetic varia...
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Introduction: Health-care Workers (HCW) are facing a critical situation caused by Coronavirus Disease 2019 (COVID-19) which could impact on their mental health status. In addition, HCW women have been identified as a group at high-risk of developing psychological distress, although no previous longitudinal studies have explored this issue in a samp...
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The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has...
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Full-text available
This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocard...
Article
Introduction: Cognitive Reserve (CR) has recently been considered a key factor in the onset of a first episode of psychosis (FEP). However, the differences in CR in FEP patients according to sex have not yet been investigated. Material and methods: CR was estimated among 443 FEP patients (246 men and 197 women) and 156 healthy controls (96 men and...
Article
Background : Neurocognition impairments are critical factors in patients with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ), and also in those with somatic diseases such as type 2 diabetes mellitus (T2DM). Intriguingly, these severe mental illnesses are associated with an increased co-occurrence of diabetes (direct...
Article
The main aim of this study is to examine the association between psychosis and immigration, independent of the language barrier, drug consumption, and the social support index. The second aim is to explore the clinical and demographic characteristics of the immigrants in the catchment area, compared with the native Spanish population suffering from...
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Disease heterogeneity is a significant obstacle to understanding pathological processes and delivering precision diagnostics and treatment. Clustering methods have gained popularity for stratifying patients into subpopulations (i.e., subtypes) of brain diseases using imaging data. However, unsupervised clustering approaches are often confounded by...
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Risk of suicidal behaviour (SB) in schizophrenia spectrum disorders (SSD) is a major concern, particularly in early stages of the illness, when suicide accounts for a high number of premature deaths. Although some risk factors for SB in SSD are well understood, the extent to which personality traits may affect this risk remains unclear, which may h...
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Objective Identifying brain differences associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and generating effective approaches to early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites...
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Introduction: Suicidal ideation (SI) represents one of the most prominent predictors of suicidal behavior (SB). Interpersonal Needs Questionnaire (INQ) was developed from Interpersonal Theory of Suicide (ITS) to assess the two core drivers of SI proposed by the theory. Despite the relevance of suicide-related ideations and ITS, there is a lack of p...
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Background Cognitive reserve (CR) has been associated with the development and prognosis of psychosis. Different proxies have been used to estimate CR among individuals. A composite score of these proxies could elucidate the role of CR at illness onset on the variability of clinical and neurocognitive outcomes. Methods Premorbid intelligence quoti...
Article
Background It is unclear what the prevalence of metabolic syndrome (MetS) in drug-naïve first-episode of psychosis (FEP) is, as previous meta-analyses were conducted in minimally exposed or drug-naïve FEP patients with psychotic disorder at any stage of the disease; thus, a meta-analysis examining MetS in naïve FEP compared with the general populat...
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Full-text available
Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape diff...
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The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. W...
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Background: Schizophrenia-spectrum disorders (SSD) and Autism spectrum disorders (ASD) are neurodevelopmental disorders that share clinical, cognitive, and genetic characteristics, as well as particular white matter (WM) abnormalities. In this study, we aimed to investigate the role of a set of oligodendrocyte/myelin-related (OMR) genes and their...
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DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neur...
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In recent years, multiple studies have investigated the role of biomarkers in first-episode psychosis (FEP) to facilitate early diagnosis, disease stratification, therapeutic choice and outcome prediction. Few studies have focused on cerebrospinal fluid (CSF) investigations. In this prospective observational study, 95 FEP inpatients were followed u...
Article
Background This study aimed to compare self-reported changes on lifestyle behaviors during two phases of the COVID-19 pandemic in Spain, and to evaluate clinical and sociodemographic factors associated with lifestyles. Methods Two cross-sectional web surveys were conducted during lockdown (April 15-May 15, 2020) and seven months later (November 16...
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Introduction Brief psychotic disorder (BPD) is a relatively uncommon and underexplored psychotic condition. Even though BPD has been related to a more favorable outcome than other schizophrenia spectrum disorders (SSD), current knowledge of its predictive factors remains scant. This study aimed to examine its prevalence and find early predictors of...
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Few studies have used a multidimensional approach to describe lifestyle changes among undergraduate students during the COVID-19 pandemic or have included controls. This study aimed to evaluate lifestyle behaviors and mental health of undergraduate students and compare them with an age and sex-matched control group. A cross-sectional web survey usi...
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Objective: To evaluate the ten-year stability of schizophrenia diagnosis in a cohort of first-episode psychosis (FEP) patients and the factors associated with it. Methods: Changes in diagnosis of 209 FEP patients were described during ten years of follow-up. Related factors with maintenance or change of schizophrenia diagnosis were evaluated in...
Article
Objective: Neurological correlates of impaired insight in non-affective psychosis remain unclear. This study aimed to review and meta-analyze the studies assessing the grey matter volumetric correlates of impaired insight in non-affective psychosis. Methods: This study consisted of a systematic review of 23 studies, and a meta-analysis with SDM-PSI...
Article
Full-text available
Background: Selecting the most effective treatment represents a critical challenge with the potential of modifying the long-term prognosis of individuals suffering a first break of psychosis. Head-to-head clinical trials comparing effectiveness among antipsychotic drugs in individuals with a first-episode of non-affective psychosis (FEP) are scarc...
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Introduction The SARS-CoV-2 pandemic with psychiatric comorbidities leads to a scenario in which the use of psychotropic drugs may be required. This requires the support of evidence-based medicine to take into account possible interactions between antidepressants, mood stabilizers, benzodiazepines, and coronavirus infection treatments. Methods Thre...
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Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, m...
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Background: Lower levels of education have been associated with the development of psychosis. Investigating educational achievement in the first episode of psychosis (FEP) patients may shed light on the origins of the alterations and on the variability of outcomes in psychotic disorders. Methods: Education achievement was explored in a large sam...