ORCID Profile
0000-0001-8538-3175
Current Organisations
Swedish Meteorological and Hydrological Institute
,
Department of Child and Adolescent Psychiatry. Institute of Psychiatry and Mental Health. Hospital General Universitario Gregorio Marañón. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM). CIBERSAM. School of Medicine, Universidad Complutense
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Related Links
Publications
Impact of NTRK2, DRD2 and ACE polymorphisms on prolactin levels in antipsychotic-treated patients with first-episode psychosis
Publisher: SAGE Publications
Date: 16-05-2018
Abstract: Hyperprolactinemia is a common side-effect of antipsychotics (APs), which may trigger serious secondary problems and compromise the adherence to treatment which is crucial for prognosis, especially in patients presenting with a first-episode of psychosis (FEP). We evaluated, in some cases for the first time, the effect of polymorphisms in multiple candidate genes on serum prolactin (PRL) levels in an AP-treated FEP cohort recruited in the multicenter PEPs study (Phenotype − genotype and environmental interaction Application of a predictive model in first psychotic episodes). PRL concentration was measured in serum from 222 patients. A total of 167 polymorphisms were selected in 23 genes. Genetic association analysis was performed in the whole s le and also in homogenous subgroups of patients treated with APs with a high (N = 101) or low risk (N = 95) of increasing PRL release, which showed significant differences in their PRL levels. After Bonferroni correction, polymorphisms in NTRK2, DRD2 and ACE genes were associated with PRL concentration. Our results give more support to the impact of DRD2, but also of other genes related to dopamine availability such as ACE. Moreover, this study provides the first evidence for the involvement of NTRK2, which suggests that pathways other than the ones related to dopamine or serotonin may participate in the AP-related PRL levels.
Vegetation-climate feedbacks modulate rainfall patterns in Africa under future climate change
Publisher: Copernicus GmbH
Date: 18-01-2016
DOI: 10.5194/ESD-2015-88
Abstract: Abstract. Africa has been undergoing significant changes in climate patterns and vegetation in recent decades, and continued changes may be expected over this century. Vegetation cover and composition impose important influences on the regional climate in Africa. Climate change-driven changes in regional vegetation patterns may feed back to climate via shifts in surface energy balance, hydrological cycle and resultant effects on surface pressure patterns and larger-scale atmospheric cir culation. We used a regional Earth system model incorporating interactive vegetation-atmosphere coupling to investigate the potential role of vegetation-mediated biophysical feedbacks on climate dynamics in Africa in an RCP8.5-based future climate scenario. The model was applied at high resolution (0.44 x 0.44 degrees) for the CORDEX-Africa domain with boundary conditions from the CanESM2 GCM. We found that changes in vegetation patterns associated with a CO2 and climate-driven increase in net primary productivity, particularly over sub-tropical savannah areas, not only imposed important local effect on the regional climate by altering surface energy fluxes, but also resulted in remote effects over central Africa by modulating the land-ocean temperature contrast, Atlantic Walker circulation and moisture inflow feeding the central African tropical rainforest region with precipitation. The vegetation-mediated feedbacks were in general negative with respect to temperature, d ening the warming trend simulated in the absence of feedbacks, and positive with respect to precipitation, enhancing rainfall reduction over rainforest areas. Our results highlight the importance of vegetation-atmosphere interactions in climate projections for tropical and sub-tropical Africa.
Towards Precision Medicine in Psychosis: Benefits and Challenges of Multimodal Multicenter Studies—PSYSCAN: Translating Neuroimaging Findings From Research into Clinical Practice
Publisher: Oxford University Press (OUP)
Date: 19-08-2019
Abstract: In the last 2 decades, several neuroimaging studies investigated brain abnormalities associated with the early stages of psychosis in the hope that these could aid the prediction of onset and clinical outcome. Despite advancements in the field, neuroimaging has yet to deliver. This is in part explained by the use of univariate analytical techniques, small s les and lack of statistical power, lack of external validation of potential biomarkers, and lack of integration of nonimaging measures (eg, genetic, clinical, cognitive data). PSYSCAN is an international, longitudinal, multicenter study on the early stages of psychosis which uses machine learning techniques to analyze imaging, clinical, cognitive, and biological data with the aim of facilitating the prediction of psychosis onset and outcome. In this article, we provide an overview of the PSYSCAN protocol and we discuss benefits and methodological challenges of large multicenter studies that employ neuroimaging measures.
Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium
Publisher: Springer Science and Business Media LLC
Date: 09-12-2022
DOI: 10.1038/S41380-022-01897-W
Abstract: 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 Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years range 18–72 years 67% male) and 2598 healthy controls (mean age 33.8 years, range 18–73 years, 55% male). Brain-predicted age was in idually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19 I 2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen’s d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.
Vegetation–climate feedbacks modulate rainfall patterns in Africa under future climate change
Publisher: Copernicus GmbH
Date: 26-07-2016
Abstract: Abstract. Africa has been undergoing significant changes in climate and vegetation in recent decades, and continued changes may be expected over this century. Vegetation cover and composition impose important influences on the regional climate in Africa. Climate-driven changes in vegetation structure and the distribution of forests versus savannah and grassland may feed back to climate via shifts in the surface energy balance, hydrological cycle and resultant effects on surface pressure and larger-scale atmospheric circulation. We used a regional Earth system model incorporating interactive vegetation–atmosphere coupling to investigate the potential role of vegetation-mediated biophysical feedbacks on climate dynamics in Africa in an RCP8.5-based future climate scenario. The model was applied at high resolution (0.44 × 0.44°) for the CORDEX-Africa domain with boundary conditions from the CanESM2 general circulation model. We found that increased tree cover and leaf-area index (LAI) associated with a CO2 and climate-driven increase in net primary productivity, particularly over subtropical savannah areas, not only imposed important local effect on the regional climate by altering surface energy fluxes but also resulted in remote effects over central Africa by modulating the land–ocean temperature contrast, Atlantic Walker circulation and moisture inflow feeding the central African tropical rainforest region with precipitation. The vegetation-mediated feedbacks were in general negative with respect to temperature, d ening the warming trend simulated in the absence of feedbacks, and positive with respect to precipitation, enhancing rainfall reduction over the rainforest areas. Our results highlight the importance of accounting for vegetation–atmosphere interactions in climate projections for tropical and subtropical Africa.
Duration of untreated psychosis and neurocognitive functioning in first-episode psychosis: a systematic review and meta-analysis
Publisher: Cambridge University Press (CUP)
Date: 27-11-2017
DOI: 10.1017/S0033291717003002
Abstract: Previous reviews suggest there is minimal evidence for an association between duration of untreated psychosis (DUP) and neurocognition. This is based on tallied findings of studies with small s les and neurocognition viewed as a single construct. We aimed to conduct a systematic review and meta-analysis examining the association between DUP and in idual neurocognitive domains and tests in first-episode psychosis (FEP). MOOSE and PRISMA guidelines were followed. Forty-three studies involving 4647 FEP patients were included. For studies providing correlations between DUP and neurocognition, 12 separate meta-analyses were performed based on neurocognitive domains/indices. The influence of demographic/clinical variables was tested using weighted linear meta-regression analyses. The relationship between DUP and most neurocognitive domains/indices was not significant. Longer DUP was associated with a larger cognitive deterioration index, i.e. current minus premorbid intellectual functioning ( N = 4 mean ES −0.213, 95% confidence interval (CI) (−0.344 to −0.074), p = 0.003). Findings were homogeneous, with no evidence of publication bias or significant influence from moderators. For studies providing mean and standard deviations for neurocognitive measures and DUP, 20 meta-regressions were performed on in idual neurocognitive tests. One significant finding emerged showing that longer DUP was associated with fewer Wisconsin Card Sorting Test-perseverative errors (mean ES −0.031, 95% CI (−0.048 to −0.013), p 0.001). Exploratory meta-regressions in studies with mean DUP days showed longer DUP was significantly associated with poorer performance on Trail Making Test A and B and higher Full-Scale IQ. There may not be a generalised association between DUP and neurocognition, however, specific cognitive functions may be associated with longer DUP or delayed help-seeking.
Genetic variants associated with longitudinal changes in brain structure across the lifespan
Publisher: Springer Science and Business Media LLC
Date: 04-2022
DOI: 10.1038/S41593-022-01042-4
Abstract: Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 in iduals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.
Biogeophysical feedbacks enhance Arctic terrestrial carbon sink in regional Earth system dynamics
Publisher: Copernicus GmbH
Date: 12-05-2014
Abstract: Abstract. Continued warming of the Arctic will likely accelerate terrestrial carbon (C) cycling by increasing both uptake and release of C. There are still large uncertainties in modelling Arctic terrestrial ecosystems as a source or sink of C. Most modelling studies assessing or projecting the future fate of C exchange with the atmosphere are based an either stand-alone process-based models or coupled climate–C cycle general circulation models, in either case disregarding biogeophysical feedbacks of land surface changes to the atmosphere. To understand how biogeophysical feedbacks will impact on both climate and C budget over Arctic terrestrial ecosystems, we apply the regional Earth system model RCA-GUESS over the CORDEX-Arctic domain. The model is forced with lateral boundary conditions from an GCMs CMIP5 climate projection under the RCP 8.5 scenario. We perform two simulations with or without interactive vegetation dynamics respectively to assess the impacts of biogeophysical feedbacks. Both simulations indicate that Arctic terrestrial ecosystems will continue to sequester C with an increased uptake rate until 2060s–2070s, after which the C budget will return to a weak C sink as increased soil respiration and biomass burning outpaces increased net primary productivity. The additional C sinks arising from biogeophysical feedbacks are considerable, around 8.5 Gt C, accounting for 22% of the total C sinks, of which 83.5% are located in areas of Arctic tundra. Two opposing feedback mechanisms, mediated by albedo and evapotranspiration changes respectively, contribute to this response. Albedo feedback dominates over winter and spring season, lifying the near-surface warming by up to 1.35 K in spring, while evapotranspiration feedback dominates over summer exerting the evaporative cooling by up to 0.81 K. Such feedbacks stimulate vegetation growth with an earlier onset of growing-season, leading to compositional changes in woody plants and vegetation redistribution.
The Relationship Between White Matter Microstructure and General Cognitive Ability in Patients With Schizophrenia and Healthy Participants in the ENIGMA Consortium
Publisher: American Psychiatric Association Publishing
Date: 06-2020
Gene-environment interaction as a predictor of early adjustment in first episode psychosis
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.SCHRES.2017.02.021
Abstract: This study aims to explore the gene-environment interaction hypothesis applied to pre-symptomatic neurodevelopmental phenotypes of first episode psychosis (FEP), that is, genetic factors might increase vulnerability to the effects of environmental adverse conditions occurring at later stages of development. We constructed a schematic 'two-hit' model, with Val/Val homozygosity for the catechol-O-methyltransferase (COMT) Val158Met polymorphism as the 'first hit' and history of obstetric complications and parental socioeconomic status as 'second hits'. Early adjustment, measured using the Premorbid Adjustment Scale, was considered the main outcome. The study population comprised 221 adolescents and adults with FEP and 191 sex- and age-matched controls. The interaction between the Val/Val COMT genotype and a positive history of obstetric complications plus low parental socioeconomic status was significantly associated with poorer early adjustment. These results were observed both in FEP in iduals and in controls, and remained significant after controlling for age, sex, and diagnosis. In iduals carrying Val/Val seem to be more sensitive to the synergistic effect of environmental factors acting early in neurodevelopment, which leads to vulnerability phenotypes such as impaired early adjustment.
Services for people at high risk improve outcomes in patients with first episode psychosis
Publisher: Wiley
Date: 11-09-2015
DOI: 10.1111/ACPS.12480
The Association Between Comorbid Autism Spectrum Disorders and Antipsychotic Treatment Failure in Early-Onset Psychosis
Publisher: Physicians Postgraduate Press, Inc
Date: 27-12-2017
DOI: 10.4088/JCP.16M11422
Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group
Publisher: Springer Science and Business Media LLC
Date: 17-10-2017
DOI: 10.1038/MP.2017.170
In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis via the ENIGMA Consortium
Publisher: Cold Spring Harbor Laboratory
Date: 15-02-2022
DOI: 10.1101/2022.02.11.22270818
Abstract: Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP age of onset years). However, as neuroimaging methods vary and s le sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls (CTR) using diffusion tensor imaging (DTI). Our s le included 321 adolescents with EOP (mean age: 16.3 ± 1.4 years, 46.4% females) and 265 adolescent CTR (mean age: 16.0 ± 1.7 years, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to CTR, with the largest effect sizes in the superior longitudinal fasciculus (Cohen’s d = 0.37), posterior corona radiata ( d = 0.32), and superior fronto□occipital fasciculus ( d = 0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI s le to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male patients with early-onset schizophrenia and patients with a shorter duration of illness.
The Interplay of Recent Vegetation and Sea Ice Dynamics—Results From a Regional Earth System Model Over the Arctic
Publisher: American Geophysical Union (AGU)
Date: 16-03-2020
DOI: 10.1029/2019GL085982
Negative Symptoms in Early-Onset Psychosis and Their Association With Antipsychotic Treatment Failure
Publisher: Oxford University Press (OUP)
Date: 24-01-2018
Development of the PSYCHS : Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS
Publisher: Wiley
Date: 28-08-2023
DOI: 10.1111/EIP.13457
Abstract: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR‐P): the Structured Interview for Psychosis‐risk Syndromes (SIPS) and the Comprehensive Assessment of At‐Risk Mental States (CAARMS). The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR‐P through an intensive series of joint videoconferences. Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR‐P criteria. The semi‐structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR‐P criteria and severity scores for both CAARMS and SIPS. Using the PSYCHS for CHR‐P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta‐analyses.
Is cognitive impairment associated with antipsychotic dose and anticholinergic equivalent loads in first-episode psychosis?
Publisher: Cambridge University Press (CUP)
Date: 14-01-2018
DOI: 10.1017/S0033291717003774
Abstract: Cognitive deficits are a core feature of early stages in schizophrenia. However, the extent to which antipsychotic (AP) have a deleterious effect on cognitive performance remains under debate. We aim to investigate whether anticholinergic loadings and dose of AP drugs in first episode of psychosis (FEP) in advanced phase of remission are associated with cognitive impairment and the differences between premorbid intellectual quotient (IQ) subgroups. Two hundred and sixty-six patients participated. The primary outcomes were cognitive dimensions, dopaminergic/anticholinergic load of AP [in chlorpromazine equivalents (Eq-CPZ) and the Anticholinergic Risk Scale (ARS), respectively]. Impairments in processing speed, verbal memory and global cognition were significantly associated with high Eq-CPZ and verbal impairment with high ARS score. Moreover, this effect was higher in the low IQ subgroup. Clinicians should be aware of the potential cognitive impairment associated with AP in advanced remission FEP, particularly in lower premorbid IQ patients.
10Kin1day: A Bottom-Up Neuroimaging Initiative
Publisher: Frontiers Media SA
Date: 09-05-2019
Preventive strategies for mental health
Publisher: Elsevier BV
Date: 07-2018
Evolution of metabolic risk factors over a two-year period in a cohort of first episodes of psychosis
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.SCHRES.2017.06.032
Abstract: Patients with a first episode of psychosis (FEP) display a broad range of metabolic risk factors related to the development of erse medical comorbidities. Initial stages of these disorders are essential in understanding the increased vulnerability of developing cardiometabolic disturbances, associated with a reduced life expectancy. This study aimed to evaluate the metabolic profile of a cohort of patients with a FEP and its evolution during a two year follow-up, as well as the factors that influence the changes in their metabolic status. 16 participating centers from the PEPs Project recruited 335 subjects with a FEP and 253 matched healthy controls, aged 9-35years. We investigated a set of anthropometric measures, vital signs and laboratory data obtained from each participant over two years in a prospective, naturalistic study. From the beginning of the study the FEP group showed differences in the metabolic profile compared to the control group, together with a progressive worsening in the major part of the analyzed variables during the follow-up period, with higher rates of obesity and metabolic syndrome. Certain risk factors were related to determinate clinical variables such as male gender, the presence of affective symptoms or an early onset or to treatment variables such as the use of antipsychotic polypharmacy, antidepressants or mood stabilizers. Our results highlight the extremely high risk of patients at early phases of schizophrenia and other psychotic disorders of developing cardiovascular comorbidity and the fast worsening of the metabolic profile during the first two years.
Biogeophysical feedbacks enhance the Arctic terrestrial carbon sink in regional Earth system dynamics
Publisher: Copernicus GmbH
Date: 08-10-2014
Abstract: Abstract. Continued warming of the Arctic will likely accelerate terrestrial carbon (C) cycling by increasing both uptake and release of C. Yet, there are still large uncertainties in modelling Arctic terrestrial ecosystems as a source or sink of C. Most modelling studies assessing or projecting the future fate of C exchange with the atmosphere are based on either stand-alone process-based models or coupled climate–C cycle general circulation models, and often disregard biogeophysical feedbacks of land-surface changes to the atmosphere. To understand how biogeophysical feedbacks might impact on both climate and the C budget in Arctic terrestrial ecosystems, we apply the regional Earth system model RCA-GUESS over the CORDEX-Arctic domain. The model is forced with lateral boundary conditions from an EC-Earth CMIP5 climate projection under the representative concentration pathway (RCP) 8.5 scenario. We perform two simulations, with or without interactive vegetation dynamics respectively, to assess the impacts of biogeophysical feedbacks. Both simulations indicate that Arctic terrestrial ecosystems will continue to sequester C with an increased uptake rate until the 2060–2070s, after which the C budget will return to a weak C sink as increased soil respiration and biomass burning outpaces increased net primary productivity. The additional C sinks arising from biogeophysical feedbacks are approximately 8.5 Gt C, accounting for 22% of the total C sinks, of which 83.5% are located in areas of extant Arctic tundra. Two opposing feedback mechanisms, mediated by albedo and evapotranspiration changes respectively, contribute to this response. The albedo feedback dominates in the winter and spring seasons, lifying the near-surface warming by up to 1.35 °C in spring, while the evapotranspiration feedback dominates in the summer months, and leads to a cooling of up to 0.81 °C. Such feedbacks stimulate vegetation growth due to an earlier onset of the growing season, leading to compositional changes in woody plants and vegetation redistribution.
Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA
Publisher: Elsevier BV
Date: 09-2020
Cognitive reserve in bipolar disorder: relation to cognition, psychosocial functioning and quality of life
Publisher: Wiley
Date: 30-12-2015
DOI: 10.1111/ACPS.12535
Abstract: Cognitive reserve (CR) is a concept that was postulated as a protective factor for some clinical symptoms after the observation that there is not a direct relationship between the degree of brain damage and its clinical manifestation. This study aimed to explore the association between CR and the main outcomes in bipolar disorder (BD): cognitive functions, psychosocial functioning and perceived quality of life. A s le of 224 euthymic bipolar patients was assessed with a neuropsychological battery, the Functioning Assessment Short Test and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). CR was calculated through three proxies: estimated premorbid Intelligent Quotient, educational level and occupational attainment. Relationships between CR and cognitive functions, psychosocial functioning and quality of life were assessed by multiple linear regression models. Higher CR was associated with better cognitive functioning (P < 0.001 in processing speed, working memory, verbal and visual memory, and executive function P = 0.026 in attention) and better psychosocial functioning (P = 0.008). For quality of life, CR was positively associated with the physical component of the SF-36 (P = 0.016) but negatively associated with the mental component (P = 0.004). The results suggest that CR may play an important role in the course and prognosis of bipolar patients and it should be considered in both clinical and research settings related to BD.
Predicting the Performance of Privacy-Preserving Data Analytics Using Architecture Modelling and Simulation
Publisher: IEEE
Date: 04-2018
Supplementary material to "Biogeophysical feedbacks enhance Arctic terrestrial carbon sink in regional Earth system dynamics"
Publisher: Copernicus GmbH
Date: 12-05-2014
Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations
Publisher: Oxford University Press (OUP)
Date: 24-05-2014
Stratification and prediction of remission in first-episode psychosis patients: the OPTiMiSE cohort study
Publisher: Springer Science and Business Media LLC
Date: 17-01-2019
DOI: 10.1038/S41398-018-0366-5
Abstract: Early response to first-line antipsychotic treatments is strongly associated with positive long-term symptomatic and functional outcome in psychosis. Unfortunately, attempts to identify reliable predictors of treatment response in first-episode psychosis (FEP) patients have not yet been successful. One reason for this could be that FEP patients are highly heterogeneous in terms of symptom expression and underlying disease biological mechanisms, thereby impeding the identification of one-size-fits-all predictors of treatment response. We have used a clustering approach to stratify 325 FEP patients into four clinical subtypes, termed C1A, C1B, C2A and C2B, based on their symptoms assessed using the Positive and Negative Syndrome Scale (PANSS) scale. Compared to C1B, C2A and C2B patients, those from the C1A subtype exhibited the most severe symptoms and were the most at risk of being non-remitters when treated with the second-generation antipsychotic drug amisulpride. Before treatment, C1A patients exhibited higher serum levels of several pro-inflammatory cytokines and inflammation-associated biomarkers therefore validating our stratification approach on external biological measures. Most importantly, in the C1A subtype, but not others, lower serum levels of interleukin (IL)-15, higher serum levels of C-X-C motif chemokine 12 (CXCL12), previous exposure to cytomegalovirus (CMV), use of recreational drugs and being younger were all associated with higher odds of being non-remitters 4 weeks after treatment. The predictive value of this model was good (mean area under the curve (AUC) = 0.73 ± 0.10), and its specificity and sensitivity were 45 ± 0.09% and 83 ± 0.03%, respectively. Further validation and replication of these results in clinical trials would pave the way for the development of a blood-based assisted clinical decision support system in psychosis.
Intracranial and subcortical volumes in adolescents with early‐onset psychosis: A multisite mega‐analysis from the ENIGMA consortium
Publisher: Wiley
Date: 05-10-2020
DOI: 10.1002/HBM.25212
Abstract: Early‐onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early‐onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The s le included 263 patients with early‐onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early‐onset schizophrenia ( n = 183), affective psychosis ( n = 39), or other psychotic disorders ( n = 41). We used linear mixed‐effects models to investigate differences in intracranial and subcortical volumes across the patient s le, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = −0.39) and hippoc al ( d = −0.25) volumes, and higher caudate ( d = 0.25) and pallidum ( d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early‐onset schizophrenia ( d = −0.34) and affective psychosis ( d = −0.42), and early‐onset schizophrenia showed lower hippoc al ( d = −0.24) and higher pallidum ( d = 0.29) volumes. Patients who were currently treated with antipsychotic medication ( n = 193) had significantly lower intracranial volume ( d = −0.42). The findings demonstrate a similar pattern of brain alterations in early‐onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early‐onset psychosis.
Related Organisations
Department Of Child And Adolescent Psychiatry. Institute Of Psychiatry And Mental Health. Hospital General Universitario Gregorio Marañón. Instituto De Investigación Sanitaria Gregorio Marañón (IiSGM). CIBERSAM. School Of Medicine, Universidad Complutense
Location: Spain
Related Funding Activities
No related grants have been discovered for Covadonga Martínez Díaz-Caneja.