Mara Parellada

Mara Parellada
Hospital General Universitario Gregorio Marañón | HGGM · Department of Psychiatry

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336
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Publications

Publications (336)
Article
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First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15–35 years...
Article
To explore the influence of cardiovascular risk factors (CVRFs) on cognitive symptoms, functional impairment, and systemic inflammatory markers in first-episode psychosis (FEP) patients at baseline and 2-year follow-up. Method: In a sample of 70 FEP patients and 85 age- and sex-matched healthy controls, we assessed nine modifiable CVRFs. All partic...
Article
Dysexecutive syndrome has been consistently reported in children and adolescents with autism spectrum disorders (ASD). Particularly, impairments have been documented in working memory, inhibition, and mental flexibility. However, the relationship between executive impairments and intellectual functioning is far from clear in this population. This s...
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The main objective of the present study was to investigate the association between several epigenetic clocks, covering different aspects of aging, with schizophrenia relapse evaluated over a 3-year follow-up period in a cohort of ninety-one first-episode schizophrenia patients. Genome-wide DNA methylation was profiled and four epigenetic clocks, in...
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Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5x10−8) was crossed for varia...
Article
Schizophrenia is a severely debilitating neurodevelopmental disorder that requires continuous multidisciplinary treatment. Early onset schizophrenia (EOS, onset before 18) is associated with poorer outcomes than the adult-onset type. The transition from adolescent to adult mental healthcare services (AMHS) poses various challenges for maintaining c...
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Relapses are frequent in the first years following a first episode of schizophrenia (FES), being associated with a higher risk of developing a chronic psychotic disorder, and poor clinical and functional outcomes. The identification and intervention over factors associated with relapses in these early phases are timely and relevant. In this study,...
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Introduction: Sex differences in first episode of psychosis (FEP) have been widely studied. However, the existence of controversial results may be attributable to not considering relevant factors such as substance use. Cannabis use is associated with an earlier age of onset of psychosis and rates of cannabis use are consistently higher among men. T...
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Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously bee...
Article
Neurotrophins have been proposed to be involved in biological mechanisms which might underlie different clinical outcomes in schizophrenia. The aims of the present study were to examine the BDNF/NGF plasma levels in a cohort of first-episode schizophrenia (FES) patients in remission as potential biological predictors of relapse; to study the associ...
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Introduction Emotional dysregulation and irritability are common in individuals with autism spectrum disorder (ASD). We conducted the first meta-analysis assessing the efficacy of a broad range of pharmacological interventions for emotional dysregulation and irritability in ASD and predictors of response. Method Following a pre-registered protocol...
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A better understanding of schizophrenia subtypes is necessary to stratify the patients according to clinical attributes. To explore the genomic architecture of schizophrenia symptomatology, we analyzed blood co-expression modules and their association with clinical data from patients in remission after a first episode of schizophrenia. In total, 91...
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Introduction Core dysfunctions proposed for psychotic disorders include prefrontal cortex (PFC) dopaminergic hypoactivity, executive function (EF) deficits and reduced gray matter in the PFC. The Val variant of COMT Val158Met polymorphism is associated with reduced dopaminergic signaling in the PFC. However, it is unclear how COMT Val158Met modulat...
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Background Around 3% of the population suffers a first episode of psychosis (FEP) and a high percentage of these patients subsequently relapse. As the clinical course following a FEP is hard to predict, it is of interest to identify cognitive and biological markers that will help improve the diagnosis, treatment and outcome of such events, and to d...
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Background There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD. Methods We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycIN...
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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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Whether there is a relationship between oxytocin (OXT) use in labor and the risk of autism (ASD), and the nature of such relationship, is unclear. By integrating genetic and clinical data in a sample of 176 ASD participants, we tested the hypothesis that OXT is a marker for abnormal prenatal development which leads to impairments in the process of...
Article
Background . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regi...
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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 t...
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Introduction Advanced parental age (APA) has been associated with an increased risk for autism in the offspring. One explanatory model includes delayed fatherhood in parents with autistic traits. Material and methods We investigated (1) whether autistic traits in parents, evaluated with the Autism-spectrum Quotient (AQ), correlate with APA in 128...
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Resumen Introducción: Algunas de las alteraciones descritas en los trastornos psicóticos incluyen una hipoactividad dopaminérgica en la corteza prefrontal (CPF), déficits en función ejecutiva (FE) y reducción de la material gris en la CPF. La variante Val del polimorfismo COMT Val158Met se asocia con una menor disponibilidad dopaminérgica en la CPF...
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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 th...
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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 gra...
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Background: 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 indic...
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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 Sci...
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Antipsychotics (APs) are associated with weight gain and other metabolic abnormalities such as hyperglycemia, dyslipidemia and metabolic syndrome. This translational study aimed to uncover the underlying molecular mechanisms and identify the key genes involved in AP-induced metabolic effects. An integrative gene expression analysis was performed in...
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There are currently no approved pharmacological treatments to improve social reciprocity and limit repetitive and rigid behaviors in autism spectrum disorder (ASD). We describe the design of two Phase III studies evaluating the efficacy/safety of bumetanide oral liquid formulation in ASD. These are international, multicenter, randomized, double-bli...
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Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, compr...
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The author of the article would like to add a video abstract as a supplementary material for a published article. The supplementary file is published with this correction. The original article has been corrected.
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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...
Article
Up to 80% of first-episode psychosis patients suffer a relapse within five years of the remission. Relapse should be an important focus of prevention given the potential harm to the patient and family. It threatens to disrupt their psychosocial recovery, increases the risk of resistance to treatment and has been associated with greater direct and i...
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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 episod...
Preprint
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Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls. Although these alterations affect multiple and widespread cortical regional asymmetries, the extent to which specific structural networks might be affec...
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Background Healthcare workers are a key occupational group at risk for suicidal thoughts and behaviors (STB). We investigated the prevalence and correlates of STB among hospital workers during the first wave of the Spain COVID‐19 outbreak (March–July 2020). Methods Data come from the baseline assessment of a cohort of Spanish hospital workers (n =...
Article
Among the main social and legislative changes in Spanish family law in recent years, are (i) the increase of judicialised conflicts between parents and (ii) the enactment of the Spanish Law 26/2015, which amended the Spanish Autonomy Law 41/2002, and sought to balance the rights of minors and parents, especially minors who had not reached 16 years...
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Introduction Healthcare workers are vulnerable to adverse mental health impacts of the COVID-19 pandemic. We assessed prevalence of mental disorders and associated factors during the first wave of the pandemic among healthcare professionals in Spain. Methods All workers in 18 healthcare institutions (6 AACC) in Spain were invited to web-based surv...
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Background A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy contr...
Preprint
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Scaling between subcomponents of cortical folding and total brain volume (TBV) in healthy individuals (HI) is allometric, i.e. non-linear. It is unclear whether this is also true in individuals with schizophrenia (SZ) or first-episode psychosis (FEP). The current study first confirmed normative allometric scaling norms in HI using discovery and rep...
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Background Psychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration. Methods We used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case–control study. We...
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Introduction Healthcare workers are vulnerable to adverse mental health impacts of the COVID-19 pandemic. We assessed prevalence of mental disorders and associated factors during the first wave of the pandemic among healthcare professionals in Spain. Methods All workers in 18 healthcare institutions (6 AACC) in Spain were invited to web-based surv...
Article
Background There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation. Methods We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was co...
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Background This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation. Methods Data were derived from the EUGEI project,...
Article
Up to 80% of first-episode psychosis patients suffer a relapse within five years of the remission. Relapse should be an important focus of prevention given the potential harm to the patient and family. It threatens to disrupt their psychosocial recovery, increases the risk of resistance to treatment and has been associated with greater direct and i...
Chapter
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Resumen Entre los principales cambios sociales y legislativos que se han producido en España en los últimos años en materia de familia, se encuentran (i) el aumento progresivo de situaciones de conflicto judicializado entre progenitores y (ii) la aparición de la Ley 26/2015 de Protección a la Infancia, que modificó la Ley 41/2002 de Autonomía del P...
Article
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...
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Background Placebo response in autism spectrum disorder (ASD) might dilute drug-placebo differences and hinder drug development. Therefore, this meta-analysis investigated placebo response in core symptoms. Methods We searched ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (up to July 8, 2018), and PubMed (up to July 4, 2019)...
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Social cognition impairment is a core shared phenotype in both schizophrenia spectrum disorders (SSD) and autism spectrum disorders (ASD). This study compares social cognition performance through four different instruments in a sample of 147 individuals with ASD or SSD and in healthy controls. We found that both clinical groups perform similarly to...
Article
Helsmoortel-Van der Aa syndrome (HVDAS) is a neurodevelopmental condition associated with intellectual disability/developmental delay, autism spectrum disorder, and multiple medical comorbidities. HVDAS is caused by mutations in activity-dependent neuroprotective protein ( ADNP). A recent study identified genome-wide DNA methylation changes in 22 i...
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Abstract There is great phenotypic heterogeneity within autism spectrum disorders (ASD), which has led to question their classification into a single diagnostic category. The study of the common genetic variation in ASD has suggested a greater contribution of other psychiatric conditions in Asperger syndrome (AS) than in the rest of the DSM-IV ASD...
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IntroductionWe 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 peri...
Article
Introduction Schizophrenia spectrum disorders (SSD) share symptoms with autism spectrum disorders (ASD). Autistic phenotypic profiles in SSD may be associated with a poor prognosis. We aimed to assess the evidences for reliability and convergent validity of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Autism Severity Scale (PA...
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Introduction Schizophrenia spectrum disorders (SSD) share symptoms with autism spectrum disorders (ASD). Autistic phenotypic profiles in SSD may be associated with a poor prognosis. We aimed to assess the evidences for reliability and convergent validity of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Autism Severity Scale (PA...
Preprint
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De novo mutations (DNMs), including germinal and postzygotic mutations (PZMs), are a strong source of causality for Autism Spectrum Disorder (ASD). However, the biological processes involved behind them remain unexplored. Our aim was to detect DNMs (germinal and PZMs) in a Spanish ASD cohort (360 trios) and to explore their role across different bi...
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Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods...
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Background In a unique deeply phenotyped longitudinal dataset consisting of first-episode psychosis (FEP) patients with a wide age at FEP onset (15 to 35 years) and healthy controls, we aimed to determine whether cortical abnormalities are already present at FEP, whether they progress further over the first two years of the illness, and, if so, whe...
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Background Family environment plays a key role in the development of psychotic symptoms (Pitschel-Walz et al., 2001; Tienari et al., 2004) and negative family environmental factors are linked to poor prognosis in psychosis (Geller et al., 2000). By contrast, a positive family environment is associated with greater improvements in negative and disor...
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Background Neural correlates of psychotic disorders encompass multiple brain regions in multiple brain circuits, even at early stages. Previous research has characterized structural brain alterations in first-episode psychosis (FEP), but few studies have focused on the relationship between brain alterations and disease trajectories. First psychotic...
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Background Autistic phenotypic profiles in patients with schizophrenia are reportedly associated with poor outcomes, including higher odds of antipsychotic treatment failure. The Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Autism Severity Scale (PAUSS) has been validated as a tool to identify “autistic profiles” in adolescents an...
Preprint
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ADNP syndrome, also known as Helsmoortel-van Der Aa syndrome, is a neurodevelopmental condition associated with intellectual disability/developmental delay, autism spectrum disorder, and multiple medical comorbidities. ADNP syndrome is caused by mutations in the activity-dependent neuroprotective protein (ADNP). A recent study identified genome-wid...
Article
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Background There is consistent evidence that theory of mind (ToM) is impaired in schizophrenia (SZ); however, it remains unclear whether such deficits are trait- or state-dependent. We evaluated ToM in patients with schizophrenia spectrum disorders (SSDs), their healthy first-degree relatives, and controls to test its suitability as an endophenotyp...
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Aims Patients with a first episode of psychosis (FEP) often display different metabolic disturbances even independently of drug therapy. However, antipsychotic (AP) treatment, especially with second-generation APs, is strongly linked to weight gain, which increases patients’ risk of developing obesity and other metabolic diseases. There is an impor...