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Find video protocols related to scientific articles indexed in Pubmed.
The affective dimension of early-onset psychosis and its relationship with suicide.
J Child Psychol Psychiatry
PUBLISHED: 09-01-2014
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The affective dimension has scarcely been studied in early-onset psychosis. Our aims were to investigate the prevalence and type of affective symptoms in the prodromal and acute phases of early-onset psychosis and to examine their relationship with suicide. We also sought to establish whether the presence of premorbid antecedents or the presence of affective symptoms during the prodromal and acute phase might predict a later diagnosis of bipolar disorder (BP) or schizophrenia (SZ).
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Predictors of schizophrenia spectrum disorders in early-onset first episodes of psychosis: a support vector machine model.
Eur Child Adolesc Psychiatry
PUBLISHED: 08-11-2014
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Identifying early-onset schizophrenia spectrum disorders (SSD) at a very early stage remains challenging. To assess the diagnostic predictive value of multiple types of data at the emergence of early-onset first-episode psychosis (FEP), various support vector machine (SVM) classifiers were developed. The data were from a 2-year, prospective, longitudinal study of 81 patients (age 9-17 years) with early-onset FEP and a stable diagnosis during follow-up and 42 age- and sex-matched healthy controls (HC). The input was different combinations of baseline clinical, neuropsychological, magnetic resonance imaging brain volumetric and biochemical data, and the output was the diagnosis at follow-up (SSD vs. non-SSD, SSD vs. HC, and non-SSD vs. HC). Enhanced recursive feature elimination was performed for the SSD vs. non-SSD classifier to select and rank the input variables with the highest predictive value for a diagnostic outcome of SSD. After validation with a test set and considering all baseline variables together, the SSD vs. non-SSD, SSD vs. HC and non-SSD vs. HC classifiers achieved an accuracy of 0.81, 0.99 and 0.99, respectively. Regarding the SSD vs. non-SSD classifier, a combination of baseline clinical variables (severity of negative, disorganized symptoms and hallucinations or poor insight) and neuropsychological variables (impaired attention, motor coordination, and global cognition) showed the highest predictive value for a diagnostic outcome of SSD. Neuroimaging and biochemical variables at baseline did not add to the predictive value. Thus, comprehensive clinical/cognitive assessment remains the most reliable approach for differential diagnosis during early-onset FEP. SVMs may constitute promising multivariate tools in the search for predictors of diagnostic outcome in FEP.
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Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations.
, Jim van Os, Bart P Rutten, Inez Myin-Germeys, Philippe Delespaul, Wolfgang Viechtbauer, Catherine van Zelst, Richard Bruggeman, Ulrich Reininghaus, Craig Morgan, Robin M Murray, Marta Di Forti, Philip McGuire, Lucia R Valmaggia, Matthew J Kempton, Charlotte Gayer-Anderson, Kathryn Hubbard, Stephanie Beards, Simona A Stilo, Adanna Onyejiaka, François Bourque, Gemma Modinos, Stefania Tognin, Maria Calem, Michael C O'Donovan, Michael J Owen, Peter Holmans, Nigel Williams, Nicholas Craddock, Alexander Richards, Isla Humphreys, Andreas Meyer-Lindenberg, F Markus Leweke, Heike Tost, Ceren Akdeniz, Cathrin Rohleder, J Malte Bumb, Emanuel Schwarz, Koksal Alptekin, Alp Üçok, Meram Can Saka, E Cem Atbaşoğlu, Sinan Guloksuz, Güvem Gümüş-Akay, Burçin Cihan, Hasan Karadag, Haldan Soygür, Eylem Şahin Cankurtaran, Semra Ulusoy, Berna Akdede, Tolga Binbay, Ahmet Ayer, Handan Noyan, Gülşah Karadayı, Elçin Akturan, Halis Ulas, Celso Arango, Mara Parellada, Miguel Bernardo, Julio Sanjuan, Julio Bobes, Manuel Arrojo, Jose Luis Santos, Pedro Cuadrado, José Juan Rodríguez Solano, Angel Carracedo, Enrique García Bernardo, Laura Roldán, Gonzalo Lopez, Bibiana Cabrera, Sabrina Cruz, Eva Ma Díaz Mesa, María Pouso, Estela Jiménez, Teresa Sanchez, Marta Rapado, Emiliano González, Covadonga Martínez, Emilio Sanchez, Ma Soledad Olmeda, Lieuwe de Haan, Eva Velthorst, Mark van der Gaag, Jean-Paul Selten, Daniella van Dam, Elsje van der Ven, Floor van der Meer, Elles Messchaert, Tamar Kraan, Nadine Burger, Marion Leboyer, Andrei Szoke, Franck Schürhoff, Pierre-Michel Llorca, Stéphane Jamain, Andrea Tortelli, Flora Frijda, Jeanne Vilain, Anne-Marie Galliot, Grégoire Baudin, Aziz Ferchiou, Jean-Romain Richard, Ewa Bulzacka, Thomas Charpeaud, Anne-Marie Tronche, Marc De Hert, Ruud van Winkel, Jeroen Decoster, Catherine Derom, Evert Thiery, Nikos C Stefanis, Gabriele Sachs, Harald Aschauer, Iris Lasser, Bernadette Winklbaur, Monika Schlögelhofer, Anita Riecher-Rossler, Stefan Borgwardt, Anna Walter, Fabienne Harrisberger, Renata Smieskova, Charlotte Rapp, Sarah Ittig, Fabienne Soguel-dit-Piquard, Erich Studerus, Joachim Klosterkötter, Stephan Ruhrmann, Julia Paruch, Dominika Julkowski, Desiree Hilboll, Pak C Sham, Stacey S Cherny, Eric Y H Chen, Desmond D Campbell, Miaoxin Li, Carlos María Romeo-Casabona, Aitziber Emaldi Cirión, Asier Urruela Mora, Peter Jones, James Kirkbride, Mary Cannon, Dan Rujescu, Ilaria Tarricone, Domenico Berardi, Elena Bonora, Marco Seri, Thomas Marcacci, Luigi Chiri, Federico Chierzi, Viviana Storbini, Mauro Braca, Maria Gabriella Minenna, Ivonne Donegani, Angelo Fioritti, Daniele La Barbera, Caterina Erika La Cascia, Alice Mulè, Lucia Sideli, Rachele Sartorio, Laura Ferraro, Giada Tripoli, Fabio Seminerio, Anna Maria Marinaro, Patrick McGorry, Barnaby Nelson, G Paul Amminger, Christos Pantelis, Paulo R Menezes, Cristina M Del-Ben, Silvia H Gallo Tenan, Rosana Shuhama, Mirella Ruggeri, Sarah Tosato, Antonio Lasalvia, Chiara Bonetto, Elisa Ira, Merete Nordentoft, Marie-Odile Krebs, Neus Barrantes-Vidal, Paula Cristóbal, Thomas R Kwapil, Elisa Brietzke, Rodrigo A Bressan, Ary Gadelha, Nadja P Maric, Sanja Andric, Marina Mihaljevic, Tijana Mirjanic.
Schizophr Bull
PUBLISHED: 05-24-2014
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Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.
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Synaptic, transcriptional and chromatin genes disrupted in autism.
Silvia De Rubeis, Xin He, Arthur P Goldberg, Christopher S Poultney, Kaitlin Samocha, A Ercument Cicek, Yan Kou, Li Liu, Menachem Fromer, Susan Walker, Tarjinder Singh, Lambertus Klei, Jack Kosmicki, Shih-Chen Fu, Branko Aleksic, Monica Biscaldi, Patrick F Bolton, Jessica M Brownfeld, Jinlu Cai, Nicholas G Campbell, Angel Carracedo, Maria H Chahrour, Andreas G Chiocchetti, Hilary Coon, Emily L Crawford, Lucy Crooks, Sarah R Curran, Geraldine Dawson, Eftichia Duketis, Bridget A Fernandez, Louise Gallagher, Evan Geller, Stephen J Guter, R Sean Hill, Iuliana Ionita-Laza, Patricia Jimenez Gonzalez, Helena Kilpinen, Sabine M Klauck, Alexander Kolevzon, Irene Lee, Jing Lei, Terho Lehtimäki, Chiao-Feng Lin, Avi Ma'ayan, Christian R Marshall, Alison L McInnes, Benjamin Neale, Michael J Owen, Norio Ozaki, Mara Parellada, Jeremy R Parr, Shaun Purcell, Kaija Puura, Deepthi Rajagopalan, Karola Rehnström, Abraham Reichenberg, Aniko Sabo, Michael Sachse, Stephan J Sanders, Chad Schafer, Martin Schulte-Rüther, David Skuse, Christine Stevens, Peter Szatmari, Kristiina Tammimies, Otto Valladares, Annette Voran, Li-San Wang, Lauren A Weiss, A Jeremy Willsey, Timothy W Yu, Ryan K C Yuen, , Edwin H Cook, Christine M Freitag, Michael Gill, Christina M Hultman, Thomas Lehner, Aarno Palotie, Gerard D Schellenberg, Pamela Sklar, Matthew W State, James S Sutcliffe, Christopher A Walsh, Stephen W Scherer, Michael E Zwick, Jeffrey C Barrett, David J Cutler, Kathryn Roeder, Bernie Devlin, Mark J Daly, Joseph D Buxbaum.
Nature
PUBLISHED: 05-18-2014
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The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.
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A longitudinal study on the relationship between duration of untreated psychosis and executive function in early-onset first-episode psychosis.
Schizophr. Res.
PUBLISHED: 02-10-2014
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The relationship between duration of untreated psychosis (DUP) and executive function (EF) in patients with first-episode psychosis (FEP) is controversial. We aim to assess the influence of DUP on changes in EF over a 2-year period in subjects with early-onset FEP (first psychotic symptom before age 18) and less than 6 months of positive symptoms.
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Basal low antioxidant capacity correlates with cognitive deficits in early onset psychosis. A 2-year follow-up study.
Schizophr. Res.
PUBLISHED: 02-07-2014
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The objective of the study is to examine the association of baseline total antioxidant status (TAS) and glutathione (GSH) levels with short- and long-term cognitive functioning in patients with early onset first-episode psychosis, comparing affective and non-affective psychoses. We analysed 105 patients with an early onset-first episode psychosis (age 9-17 years) and 97 healthy controls. Blood samples were taken at admission for measurement of TAS and GSH, and cognitive performance was assessed at baseline and at 2years of follow-up. Regression analysis was used to assess the relationship between TAS/GSH levels at baseline and cognitive performance at both time points, controlling for confounders. Baseline TAS and GSH levels were significantly lower in patients than healthy controls. In patients, baseline TAS was positively associated with the global cognition score at baseline (p=0.048) and two years later (p=0.005), while TAS was not associated with cognitive functioning in healthy controls. Further, baseline TAS in patients was specifically associated with the memory domain at baseline and with the memory and attention domains two years later. Stratifying by affective and non-affective psychoses, significant associations were only found between TAS and cognition in the non-affective psychosis group. Baseline GSH levels were not associated with cognitive functioning at either time point in either group. The antioxidant defence capacity in early onset first-episode psychotic patients is directly correlated with global cognition at baseline and at 2years of follow-up, especially in non-affective psychosis.
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Cortical morphology of adolescents with bipolar disorder and with schizophrenia.
Schizophr. Res.
PUBLISHED: 01-08-2014
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Recent evidence points to overlapping decreases in cortical thickness and gyrification in the frontal lobe of patients with adult-onset schizophrenia and bipolar disorder with psychotic symptoms, but it is not clear if these findings generalize to patients with a disease onset during adolescence and what may be the mechanisms underlying a decrease in gyrification.
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Differential Neurodevelopmental Trajectories in Patients With Early-onset Bipolar and Schizophrenia Disorders.
Schizophr Bull
PUBLISHED: 12-26-2013
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Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders.
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The human cerebral cortex flattens during adolescence.
J. Neurosci.
PUBLISHED: 09-20-2013
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The human cerebral cortex appears to shrink during adolescence. To delineate the dynamic morphological changes involved in this process, 52 healthy male and female adolescents (11-17 years old) were neuroimaged twice using magnetic resonance imaging, approximately 2 years apart. Using a novel morphometric analysis procedure combining the FreeSurfer and BrainVisa image software suites, we quantified global and lobar change in cortical thickness, outer surface area, the gyrification index, the average Euclidean distance between opposing sides of the white matter surface (gyral white matter thickness), the convex ("exposed") part of the outer cortical surface (hull surface area), sulcal length, depth, and width. We found that the cortical surface flattens during adolescence. Flattening was strongest in the frontal and occipital cortices, in which significant sulcal widening and decreased sulcal depth co-occurred. Globally, sulcal widening was associated with cortical thinning and, for the frontal cortex, with loss of surface area. For the other cortical lobes, thinning was related to gyral white matter expansion. The overall flattening of the macrostructural three-dimensional architecture of the human cortex during adolescence thus involves changes in gray matter and effects of the maturation of white matter.
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Duration of untreated psychosis predicts functional and clinical outcome in children and adolescents with first-episode psychosis: A 2-year longitudinal study.
Schizophr. Res.
PUBLISHED: 07-01-2013
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Longer duration of untreated psychosis (DUP) in adult patients with first-episode psychosis (FEP) has been associated with poor clinical and social outcomes. We aimed to estimate the influence of DUP on outcome at 2-year follow-up in subjects with an early-onset (less than 18years of age) FEP of less than 6months duration. A total of 80 subjects (31.3% females, mean age 16.0±1.8years) were enrolled in the study. The influence of DUP on outcome was estimated using multiple regression models (two linear models for influence of DUP on the C-GAF at 2years and C-GAF change through the follow-up period, and a logistic model for influence of DUP on 41 PANSS remission at 2 years in schizophrenia patients (n=47)). Mean DUP was 65.3±54.7days. Median DUP was 49.5days. For the whole sample (n=80), DUP was the only variable significantly related to C-GAF score at 2-year follow-up (Beta=-0.13, p<0.01), while DUP and premorbid adjustment (Beta=-0.01, p<0.01; and Beta=-0.09, p=0.04, respectively) were the only variables significantly related to C-GAF change. In schizophrenia patients, DUP predicted both C-GAF score at 2years and C-GAF change, while in patients with affective psychosis (n=22), DUP was unrelated to outcome. Lower baseline C-GAF score (OR=0.91, p<0.01) and shorter DUP (OR=0.98, p=<0.01) were the only variables that significantly predicted clinical remission in schizophrenia patients. In conclusion, longer DUP was associated with lower C-GAF at 2years, less increase in C-GAF, and lower rates of clinical remission in early-onset FEP. Our findings support the importance of early detection programs, which help shorten DUP.
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Twenty-four months of antipsychotic treatment in children and adolescents with first psychotic episode: discontinuation and tolerability.
J Clin Psychopharmacol
PUBLISHED: 06-18-2013
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The Child and Adolescent First-Episode Psychosis Study is a longitudinal study of early-onset first psychotic episodes. This report describes the naturalistic psychopharmacological treatment administered during a 24-month follow-up period, as well as discontinuation rates, reasons for discontinuation, and adverse effects.
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Peripheral endocannabinoid system dysregulation in first-episode psychosis.
Neuropsychopharmacology
PUBLISHED: 03-28-2013
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Several hypotheses involving alterations of the immune system have been proposed among etiological explanations for psychotic disorders. The endocannabinoid system (ECS) has a homeostatic role as an endogenous neuroprotective and anti-inflammatory system. Alterations of this system have been associated with psychosis. Cannabis use is a robust risk factor for these disorders that could alter the ECS signalling. In this study, 95 patients with a first episode of psychosis (FEP) and 90 healthy controls were recruited. Protein expression of cannabinoid receptor 2 (CB2), the protein levels of the main endocannabinoid synthesizing enzymes N-acyl phosphatidylethanolamine phospholipase (NAPE) and diacylglycerol lipase (DAGL), and of degradation enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) were determined by western blot analysis in peripheral blood mononuclear cells (PBMCs). Patients with a FEP showed a decreased expression of CB2 and of both endocannabinoids synthesizing enzymes (NAPE and DAGL) in comparison to healthy controls. After controlling for age, gender, body mass index, and cannabis use, NAPE and DAGL expression remained significantly decreased, whereas FAAH and MAGL expression were increased. On the other hand, FEP subjects with history of severe cannabis use showed a larger ECS dysregulation compared with healthy controls. These results indicate an ECS dysregulation in PBMC of FEP patients. The alteration of the ECS presented at the initial phases of psychosis could be contributing to the pathophysiology of the disease and constitutes a possible biomarker of psychotic disorders and an interesting pharmacological target to take into account for therapeutic purposes.
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Pro-/Anti-inflammatory Dysregulation in Patients With First Episode of Psychosis: Toward an Integrative Inflammatory Hypothesis of Schizophrenia.
Schizophr Bull
PUBLISHED: 03-13-2013
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Background:Schizophrenia is a chronic syndrome of unknown etiology, predominantly defined by signs of psychosis. The onset of the disorder occurs typically in late adolescence or early adulthood. Efforts to study pathophysiological mechanisms in early stages of the disease are crucial in order to prompt intervention.Methods:Case-control study of first-episode psychotic (FEP) patients and matched controls. We recruited 117 patients during the first year after their FEP according to the DSM-IV criteria and recruited 106 gender-, race-, and age-matched controls between September 2010 and June 2011.Results:Biochemical studies carried out in peripheral mononuclear blood cells (PMBC) and plasma evidence a significant increase in intracellular components of a main proinflammatory pathway, along with a significant decrease in the anti-inflammatory ones. Multivariate logistic regression analyses identified the expression of inducible isoforms of nitric oxide synthase and cyclooxygenase in PMBC and homocysteine plasma levels as the most reliable potential risk factors and the inhibitor of the inflammatory transcription factor NF?B, I?B?, and the anti-inflammatory prostaglandin 15d-PGJ2 as potential protection factors.Discussion:Taken as a whole, the results of this study indicate robust phenotypical differences at the cellular machinery level in PMBC of patients with FEP. Although more scientific evidence is needed, the determination of multiple components of pro- and anti-inflammatory cellular pathways including the activity of nuclear receptors has interesting potential as biological markers and potential risk/protective factors for FEP. Due to its soluble nature, a notable finding in this study is that the anti-inflammatory mediator 15d-PGJ2 might be used as plasmatic biomarker for first episodes of psychosis.
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Psychopathology in children and adolescents with ASD without mental retardation.
J Autism Dev Disord
PUBLISHED: 03-08-2013
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This study analyzes subclinical psychopathology in children and adolescents with autism spectrum disorders (ASD) without mental retardation with no comorbid disorder, assessed by an extensive general psychopathology interview. The K-SADS-PL was administered to a group of 25 patients with ASD (mean age = 12.80 ± 2.86 years) and 25 healthy controls (mean age 12.52 ± 2.86 years). Significant differences were found between patients with ASD and controls for the domains of: depressive disorder, anxiety separation disorder, agoraphobia and specific phobias, obsessive compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). In patients without a comorbid disorder, we found a profile of subclinical disturbances that suggest high risk for comorbid psychiatric conditions derived from the presence of subthreshold symptomatology.
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Borderline intellectual functioning: consensus and good practice guidelines.
Rev Psiquiatr Salud Ment
PUBLISHED: 02-04-2013
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The Borderline Intellectual Functioning (BIF) is conceptualized as the frontier that delimits "normal" intellectual functioning from intellectual disability (IQ 71-85). In spite of its magnitude, its prevalence cannot be quantified and its diagnosis has not yet been defined.
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Risperidone normalizes increased inflammatory parameters and restores anti-inflammatory pathways in a model of neuroinflammation.
Int. J. Neuropsychopharmacol.
PUBLISHED: 12-16-2011
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Inflammation, caused by both external and endogenous factors, has been implicated as a main pathophysiological feature of chronic mental illnesses, including schizophrenia. An increase in pro-inflammatory cytokines has been described both in experimental models and in schizophrenia patients. However, not much is known about the effects that antipsychotic drugs have on intra- and intercellular mechanisms controlling inflammation. The aim of the present study was to investigate the possible anti-inflammatory effect of a standard schizophrenia treatment not only at the level of soluble mediators, but also at intra- and intercellular inflammatory pathways. The present study was conducted in a model of mild neuroinflammation using a lipopolysaccharide (LPS) challenge that was not an endotoxaemic dose (0.5 mg/kg i.p.) in young adult rats. Main results: single doses of risperidone (0.3-3.0 mg/kg i.p.) prevented increased inflammatory parameters induced by LPS in brain cortex [expression of inflammatory cytokines, interleukin (IL)-1? and tumour necrosis factor (TNF)-?, activity of the inducible inflammatory enzymes nitric oxide synthase and cyclooxygenase, p38 mitogen-activated protein kinase (MAPK) and inflammatory nuclear transcription factor ?B] and restored anti-inflammatory pathways decreased by LPS challenge (deoxyprostaglandins and peroxisome proliferator activated receptor ?). This is the first study demonstrating that risperidone elicits a preventive effect on the anti-inflammatory arm of the homeostatic mechanism controlling inflammation in a model of mild encephalitis in rats. Our findings suggest a possible protective effect of risperidone on brain cells.
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Regional specificity of thalamic volume deficits in male adolescents with early-onset psychosis.
Br J Psychiatry
PUBLISHED: 11-24-2011
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Thalamic volume deficits are associated with psychosis but it is unclear whether the volume reduction is uniformly distributed or whether it is more severe in particular thalamic regions.
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Two-year diagnostic stability in early-onset first-episode psychosis.
J Child Psychol Psychiatry
PUBLISHED: 07-20-2011
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Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a 2-year, prospective longitudinal study of early-onset first episodes of psychosis (EO-FEP).
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Placebo effect in child and adolescent psychiatric trials.
Eur Neuropsychopharmacol
PUBLISHED: 06-24-2011
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Much literature has been written in the field of child psychiatry regarding the placebo as a tool to test drug efficacy in clinical trials, but quite little regarding the placebo effect itself or its clinical use in child psychiatry. In this article, we aim to critically review the literature regarding the placebo effect in children and adolescents with mental disorders, focusing especially on factors influencing the placebo effect and how they may influence the interpretation of clinical trials. The placebo effect seems to be more marked in children than adults, and particularly in children and adolescents with depression, although it is pervasive across ages and is present in non-psychiatric conditions as well. The use of a placebo in clinical trials as a comparator with drugs that have moderate efficacy at most makes it difficult to obtain positive results, and much effort is needed to design very high quality clinical trials that may overcome the limitations of using a placebo. In addition, the placebo effect across ages and clinical conditions must be tested directly (compared with no treatment whenever possible), in order to characterise which placebos work for what and to determine their use in clinical settings.
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Influence of resting energy expenditure on weight gain in adolescents taking second-generation antipsychotics.
Clin Nutr
PUBLISHED: 03-11-2011
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Weight gain is an undesirable side effect of second-generation antipsychotics (SGAs). We performed this study to examine the influence of SGAs on resting energy expenditure (REE) and the relationship of REE to weight gain in adolescent patients.
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Reduced antioxidant defense in early onset first-episode psychosis: a case-control study.
BMC Psychiatry
PUBLISHED: 02-14-2011
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Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group.
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Dysbindin-1 gene contributes differentially to early- and adult-onset forms of functional psychosis.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 02-08-2011
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Dysbindin-1 is a relatively ubiquitous protein in the brain which is involved in the modulation of synaptic homeostasis. The dysbindin-1 gene (DTNBP1) has been associated with schizophrenia and bipolar disorder diagnoses. However, its contribution to the severity of the clinical and neurocognitive expression of these disorders remains controversial. We aimed to explore the association between DTNBP1 and the phenotypes which are more directly linked with the underlying biology, such as age at onset and neurocognitive impairment. The present family sample comprised 894 Caucasian individuals: 268 patients affected by functional psychosis [58% with illness onset before 18 years, mean age at onset (SD): 14.71 (2.10)], 483 parents and 143 siblings. Ten DTNBP1 single nucleotide polymorphisms were genotyped in all individuals and their transmission disequilibrium was tested in relation to: (i) the risk for psychosis; (ii) patients age at onset; and (iii) familial neurocognitive performance (including IQ estimation and executive functioning). In early-onset families a 5-marker haplotype encompassing exons 2-4 and the surrounding introns was significantly over-transmitted to cases, while in adult-onset families two haplotypes corresponding to the region between introns 4 and 7 were over-transmitted to cases. Estimated IQ was associated with the rs760666 marker in the whole sample, whereas a significant association between executive functioning and the rs2619522 marker appeared in early-onset families. Our findings confirm the role of the dysbindin-1 gene in the risk for functional psychosis and show a differential haplotypic risk pattern in families with early as opposed to adult onset in the affected offspring.
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Neurological soft signs in juvenile patients with Asperger syndrome, early-onset psychosis, and healthy controls.
Early Interv Psychiatry
PUBLISHED: 10-28-2010
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The study of neurological soft signs (NSS) in patients with Asperger syndrome may help us to elucidate the neurological basis of this disorder and to clarify its relationship with other neurodevelopmental disorders. The goal of this study was to compare the prevalence of NSS in a sample of patients with Asperger syndrome, early-onset psychosis and healthy controls.
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Multicenter study of brain volume abnormalities in children and adolescent-onset psychosis.
Schizophr Bull
PUBLISHED: 05-16-2010
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The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of "schizophrenia" or "other psychosis" showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents.
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Efficacy and safety of second-generation antipsychotics in children and adolescents with psychotic and bipolar spectrum disorders: comprehensive review of prospective head-to-head and placebo-controlled comparisons.
Eur Neuropsychopharmacol
PUBLISHED: 05-13-2010
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To review data on efficacy and safety of second-generation antipsychotics (SGAs) in children and adolescents with psychotic and bipolar spectrum disorders.
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Can positive family factors be protective against the development of psychosis?
Psychiatry Res
PUBLISHED: 04-26-2010
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Genetic and environmental factors are both involved in the aetiology of psychotic disorders. The aim of this study was to assess if positive and negative environmental factors, together with psychotic family antecedents, are associated with the recent development of psychosis. We also investigated the interactions between family history of psychosis and positive and negative family environment. The sample comprised 110 children and adolescents, who had suffered a first psychotic episode and 98 healthy controls. All subjects were interviewed about their socioeconomic status, family history of psychosis and family environment (Family Environment Scale, FES). Early onset psychosis was significantly associated with a family history of psychosis. Family environment was perceived as more negative and less positive among patients than among controls. A negative family environment increased the risk of psychosis independently of the family history of psychosis. However, there was a significant protective effect of a positive family environment for persons with a family history of psychosis. This effect was not seen in subjects without a family history of psychosis. Therefore, our results support the importance of considering both family history of psychosis and family environment in the early stages of psychosis.
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Metabolic effects of second-generation antipsychotics in bipolar youth: comparison with other psychotic and nonpsychotic diagnoses.
Bipolar Disord
PUBLISHED: 04-21-2010
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Despite known metabolic effects of second-generation antipsychotics (SGAs) on children and adolescents, comparative effects in youth with different diagnoses remain underreported. We compared differences in metabolic changes three months after starting treatment with SGAs in youth with bipolar disorder and with other psychotic and nonpsychotic disorders.
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Predominance of symptoms over time in early-onset psychosis: a principal component factor analysis of the Positive and Negative Syndrome Scale.
J Clin Psychiatry
PUBLISHED: 03-25-2010
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Early-onset psychosis is a symptomatically nonspecific and heterogeneous entity composed of several diagnoses. This study examined the dimensional structure of symptoms and the temporal stability of this structure during a 6-month follow-up.
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[Quetiapine treatment in adolescents: A 6-month naturalistic study].
Rev Psiquiatr Salud Ment
PUBLISHED: 03-17-2010
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The aim of this study was to evaluate discontinuation of quetiapine treatment in adolescents (12-18 years) in a 6-month naturalistic follow-up study and to assess the influence of distinct demographic and clinical factors on quetiapine discontinuation.
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Brain morphology and neurological soft signs in adolescents with first-episode psychosis.
Br J Psychiatry
PUBLISHED: 09-02-2009
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Adolescents with first-episode psychosis have increased severity of neurological soft signs when compared with controls, but it is unclear whether increased severity of neurological soft signs is an expression of specific structural brain deficits.
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Cognitive efficacy of quetiapine and olanzapine in early-onset first-episode psychosis.
Schizophr Bull
PUBLISHED: 08-25-2009
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The primary purpose of this study was to compare changes in cognition in early-onset psychosis after 6-months treatment with quetiapine or olanzapine. This is a randomized, single-blind, 6-month study in 50 adolescents with a diagnosis of early-onset psychosis. Patients were randomized to quetiapine (n = 24) or olanzapine (n =26). A thorough neuropsychological battery was administered at baseline and after 6-month treatment. Out of the total sample included in the study, 32 patients completed at least 6-months treatment with the assigned medication (quetiapine, n =16; olanzapine, n = 16). No changes were observed in cognitive performance after 6-month treatment with quetiapine or olanzapine. Although some trends toward cognitive improvement were observed for the olanzapine group after 6-month treatment, neither group showed statistically significant gains. Furthermore, there was no evidence of any differential efficacy of olanzapine or quetiapine on cognitive improvement in this sample of adolescents with psychosis.
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Cannabis use in children and adolescents with first episode psychosis: influence on psychopathology and short-term outcome (CAFEPS study).
Schizophr. Res.
PUBLISHED: 04-04-2009
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To know the prevalence of substance use and its relationship with psychopathology at onset and after six months in children and adolescents with first episode psychosis (FEP).
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Gyral and sulcal cortical thinning in adolescents with first episode early-onset psychosis.
Biol. Psychiatry
PUBLISHED: 03-31-2009
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Psychosis is associated with volumetric decreases of cortical structures. Whether these volumetric decreases imply abnormalities in cortical thickness, surface, or cortical folding is not clear. Due to differences in cytoarchitecture, cortical gyri and sulci might be differentially affected by psychosis. Therefore, we examined differences in gyral and sulcal cortical thickness, surface, folding, and volume between a minimally treated male adolescent population with early-onset first-episode psychosis (EOP) and a healthy control group, with surface-based morphometry.
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Progression of brain volume changes in adolescent-onset psychosis.
Schizophr Bull
PUBLISHED: 03-31-2009
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Little is known about the changes that take place in the adolescent brain over the first few years following the onset of psychosis. The present longitudinal study builds on an earlier cross-sectional report demonstrating brain abnormalities in adolescent-onset psychosis patients with a recent-onset first episode of psychosis. Magnetic resonance imaging studies were obtained at baseline and 2 years later from 21 adolescents with psychosis and 34 healthy controls matched for age, gender, and years of education. Whole-brain volumes and gray matter (GM) and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured at baseline and at 2-year follow-up. In the frontal lobe, the rate of GM volume loss was significantly higher in male patients (2.9% and 2.0%, respectively, for left and right) than in controls (1.2% and 0.7%, respectively, for left and right). In the left frontal lobe, male patients showed a significantly higher rate of CSF volume increase than controls (8.6% vs 6.4%). These differences in rates of volume change were observed in male and female patients, although only males showed significant time x diagnosis interactions. This negative finding in females should be interpreted with caution as the study was underpowered to detect change in women due to limited sample size. An exploratory analysis revealed that schizophrenia and nonschizophrenia psychotic disorders showed similar volume change patterns relative to controls. Change in clinical status was not correlated with longitudinal brain changes. Our results support progression of frontal lobe changes in males with adolescent-onset psychosis.
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Olanzapine compared to quetiapine in adolescents with a first psychotic episode.
Eur Child Adolesc Psychiatry
PUBLISHED: 02-05-2009
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To compare the efficacy, safety, and tolerability of olanzapine and quetiapine in adolescents with first episode psychosis.
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Obstetric complications as a risk factor for first psychotic episodes in childhood and adolescence.
Eur Child Adolesc Psychiatry
PUBLISHED: 01-28-2009
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There are reports of significant association between obstetric complications (OC) and childhood psychosis. Authors conducted a case-control study of 102 children and adolescents with a first episode psychosis (FEP) and 94 healthy controls (HC), using the obstetric complications scale (OCS) and their medical records, to examine the risk of FPE. Patients were recruited from child and adolescent psychiatry units at six university hospitals and controls from publicly-funded schools of similar characteristics and from the same geographic areas. A logistic regression was performed to quantify the risk of psychosis in childhood and adolescence, based on OC, adjusting for potential confounding factors like socio economic status (SES) and family psychiatric history (FPH). OC appeared more frequently in the records of patients. Significant differences between patients and controls were found in Prenatal OC (15.7% vs. 5.3%, P < 0.05) and among them, bleeding in pregnancy showed the greatest difference between groups (12.7% vs. 2.1%, P < 0.01). In the logistic regression, bleeding in pregnancy showed a crude odds ratio (OR) of 6.7 (95%CI = 1.4-30.6) and 5.1 (CI 95% = 1.0-24.9) adjusted for SES and FPH. Therefore, bleeding in pregnancy is a likely risk factor for early-onset psychosis.
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Antipsychotics in children and adolescents: increasing use, evidence for efficacy and safety concerns.
Eur Neuropsychopharmacol
PUBLISHED: 01-08-2009
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Second-generation antipsychotics (SGA) are increasingly used to treat children and adolescents. The European College of Neuro-psychopharmacology convened an expert panel to review relevant efficacy and safety data, and identify needs for further research. Controlled studies support the short-term efficacy of several SGA for treating psychosis, mania, and aggression within certain diagnostic categories. Except for clozapine, no clinically significant superiority in efficacy has been demonstrated for any specific antipsychotic, including both first- and second-generation agents, in children and adolescents. Major differences exist, however, with respect to type and severity of adverse effects; therefore the choice of treatment is primarily guided by tolerability and safety considerations. Children appear to be at higher risk than adults for a number of adverse effects, such as extrapyramidal symptoms and metabolic and endocrine abnormalities. While the safety profile during acute and intermediate treatment has been evaluated, the distal benefit/risk ratio during long-term treatment remains to be determined. Research is also needed to understand the mechanisms underlying antipsychotic-induced toxicities in order to develop effective preventive and treatment strategies.
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Predictors of suicide attempt in early-onset, first-episode psychoses: a longitudinal 24-month follow-up study.
J Clin Psychiatry
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To study the prevalence of suicide attempts and factors associated with risk for suicide during the first episode of psychosis, and to identify early predictors of suicide attempts over a 24-month follow-up period in an early-onset, first-episode psychosis cohort.
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Assessing clinical and functional outcomes in a gene-environment interaction study in first episode of psychosis (PEPs).
Rev Psiquiatr Salud Ment
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The PEPs study is a multicenter, naturalistic, prospective, longitudinal study designed to evaluate clinical, neuropsychological, neuroimaging, biochemical, environmental and pharmacogenetic variables in a sample of nearly 350 first episode of psychosis patients and 250 healthy controls. The PEPs project was conducted in Spain from January 2009 to December 2011. This article describes the rationale for the measurement approach adopted, providing an overview of the selected clinical and functional measures. The main objectives are: a) the thorough clinical and neurocognitive characterization of a sample of first episodes of psychosis, and b) the study of the interactions between the genetic and environmental variables selected to predict clinical and brain structural outcomes, and to determine the relationship of genetic polymorphisms involved in the pharmacokinetics and pharmacodynamics, and the responses and adverse effects of treatment.
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Polypharmacy with antidepressants in children and adolescents.
Int. J. Neuropsychopharmacol.
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The aim of this study was to review current epidemiological data on the use of antidepressants in co-prescription with other psychotropic drugs in children and adolescents, as well as available efficacy and safety information. A Medline search from inception until February 2012 was performed to identify epidemiological and clinical studies, reviews and reports containing potentially relevant information on polypharmacy with antidepressants in young people. There has been an increase in polypharmacy in children and adolescents involving antidepressants in recent years. Antidepressants have become one of the drug classes most frequently prescribed in combination and are commonly co-prescribed with stimulants and antipsychotics. Most information regarding efficacy and safety of polypharmacy patterns was provided by case series and open-label studies. Efficacy studies gave some support for the use of a combination of antidepressants and antipsychotics in the management of refractory obsessive-compulsive disorder and some residual symptoms in major depressive disorder. Even less empirical support was found for a combination of stimulants and antidepressants in co-morbid attention deficit hyperactivity disorder and mood or anxiety disorders. Adverse events were similar to those found with individual medication groups, with severe adverse events mostly reported by individual case reports. The use of polypharmacy with antidepressants has become a regular practice in clinical settings. Although there is still little efficacy and safety information, preliminary evidence points to the potential clinical usefulness of some polypharmacy patterns. Further research on patients with co-morbidities or more severe conditions is needed, in order to improve knowledge of this issue.
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Cognitive reserve as a predictor of two year neuropsychological performance in early onset first-episode schizophrenia.
Schizophr. Res.
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The concept of cognitive reserve (CR) has been defined as individual differences in the efficient utilization of brain networks which allow some people to cope better than others with brain pathology. CR has been developed mainly in the field of aging and dementia after it was observed that there appears to be no direct relationship between the degree of brain pathology and the severity of clinical manifestations of this damage. The present study applies the concept of CR to a sample of children and adolescents with a first episode of schizophrenia, aiming to assess the possible influence of CR on neuropsychological performance after two year follow-up, controlling for the influence of clinical psychopathology.
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The state of psychiatry in Spain.
Int Rev Psychiatry
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The 1986 General Health Act and the so-called psychiatric reform were key issues in the development of the mental healthcare system (MHCS) in Spain. The World Health Organization Declaration and Action Plan on Mental Health in 2005 gave it a revitalizing impetus and resulted in the first National Health System (NHS) Mental Health Strategy in 2006. A literature search was performed using MEDLINE, Spanish journals, reference lists, national databases, and European and Spanish official documents to describe the current state of the MHCS in Spain. The main results were: (1) existence of great variability among the autonomous communities with respect to mental health resources and provision of care; (2) lack of national epidemiological information on mental disorders with the exception of substance use disorders and suicide, which comprise powerful longitudinal national data, (3) training in psychiatry is well established, although there is no specialism of child and adolescent psychiatry, and (4) a dramatic increase in scientific productivity in the last decade among research groups, in part due to the creation of the Spanish Mental Health Network, the Centro de Investigación Biomédica en Red en el Área de Salud Mental (CIBERSAM). Quantifiable and reliable indicators are needed to provide efficient monitoring and analysis of epidemiological events and subsequently to understand the status of the Spanish MHCS.
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Decreased glutathione levels predict loss of brain volume in children and adolescents with first-episode psychosis in a two-year longitudinal study.
Schizophr. Res.
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Progressive loss of cortical gray matter (GM), as measured by magnetic resonance imaging, has been described early in the course of first-episode psychosis. This study aims to assess the relationship between oxidative balance and progression of cortical GM changes in a multicenter sample of first-episode early-onset psychosis (EOP) patients from baseline to two-year follow-up. A total of 48 patients (13 females, mean age 15.9±1.5 years) and 56 age- and gender-matched healthy controls (19 females, 15.3±1.5 years) were assessed. Magnetic resonance imaging (MRI) scans performed both at the time of the first psychotic episode and 2 years later were used for volumetric measurements of left and right gray matter regions (frontal, parietal, and temporal lobes) and total sulcal cerebrospinal fluid (CSF). Total glutathione (GSH) blood levels were determined at baseline. In patients, after controlling for possible confounding variables, lower baseline GSH levels were significantly associated with greater volume decrease in left frontal (B=0.034, 95% confidence interval (CI): 0.011 to 0.056, r=0.620, p=0.006), parietal (B=0.039, 95% CI: 0.020 to 0.059, r=0.739, p=0.001), temporal (B=0.026, 95% CI: 0.016 to 0.036, r=0.779, p<0.001), and total (B=0.022, 95% CI: 0.014 to 0.031, r=0.803, p<0.001) gray matter, and with greater increase in total CSF (B=-0.560, 95% CI: -0.270 to -0.850, r=-0.722, p=0.001). Controls did not show significant associations between brain volume changes and GSH levels. GSH deficit during the first psychotic episode was related to greater loss of cortical GM two years later in patients with first-episode EOP, suggesting that oxidative damage may contribute to the progressive loss of cortical GM found in patients with first-episode psychosis.
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Plasma antioxidant capacity is reduced in Asperger syndrome.
J Psychiatr Res
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Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8-12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness.
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