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Resumen Introduccion El implante valve in valve mitral es una nueva herramienta terapeutica que ha surgido recientemente en el campo del intervencionismo estructural en cardiologia para pacientes con disfuncion bioprotesica por insuficiencia mitral severa y alto riesgo quirurgico. El objetivo es elaborar un plan de cuidados enfermero individualizado destinado a una paciente que se somete a este procedimiento, siendo el primer caso en nuestro centro. Descripcion del caso Mujer de 75 anos, independiente para las actividades de la vida diaria, con antecedentes de insuficiencia renal cronica y recambio valvular mitral biologico por valvulopatia reumatica. Ingresada en la unidad de cuidados cardiologicos agudos por insuficiencia mitral severa sintomatica secundaria a disfuncion de la bioprotesis mitral. Descartada para cirugia cardiaca por comorbilidades y alto riesgo quirurgico, se procedio al valve in valve mitral percutaneo, siendo exitoso su implante. Valoracion La valoracion enfermera se realizo siguiendo el modelo conceptual de Marjory Gordon, donde se identificaron los siguientes patrones alterados: patron 2: edemas maleolares bilaterales sin fovea; patron 3: sondaje vesical y uso de diuretico intravenoso; patron 4: disnea a moderados esfuerzos, tos seca nocturna, ortopnea y alteraciones respiratorias e intolerancia a la actividad; patron 5: necesidad de ayuda farmacologica para el buen descanso nocturno. Diagnosticos Mediante la taxonomia NANDA se establecieron los diagnosticos enfermeros: Exceso de volumen de liquidos; Patron respiratorio ineficaz; Intolerancia a la actividad y el problema de colaboracion: Hipotension y anemizacion secundaria al hematoma profundo en muslo. Planificacion Basandonos en la taxonomia NOC se determinaron los objetivos: Equilibrio hidrico; Estado respiratorio: ventilacion; Estado cardiopulmonar, y las siguientes intervenciones NIC: Manejo de la hipervolemia; Monitorizacion respiratoria y Oxigenoterapia; Monitorizacion de los signos vitales, y Cuidados cardiacos. Discusion Intervenciones enfermeras dirigidas hacia la monitorizacion del estado hemodinamico, la restriccion de liquidos, juntamente con la eficacia del tratamiento diuretico, consiguieron un balance hidrico negativo que contribuyo a la deplecion, mejorando los sintomas respiratorios y permitiendo llegar al implante en mejores condiciones. Conclusiones El progreso tecnologico en las ciencias de la salud, y concretamente en el ambito de la cardiologia aguda, conlleva directamente la necesidad de capacitacion, revision y actualizacion de los cuidados criticos enfermeros. Ante este proceso dinamico y en continua evolucion, la figura de la enfermera especialista en intensivos, asi como la inclusion de la enfermera experta en cuidados cardiovasculares en equipos multidisciplinares como el Heart team y la expansion de la consulta enfermera en hemodinamica, se hacen imperiosamente necesarias para garantizar unos cuidados enfermeros optimos, de seguridad y de calidad asistencial.

Background: Schizophrenia-spectrum disorders (SSD) and Autism spectrum disorders (ASD) are neurodevelopmental disorders that share clinical, cognitive, and genetic characteristics, as well as particular white matter (WM) abnormalities. In this study, we aimed to investigate the role of a set of oligodendrocyte/myelin-related (OMR) genes and their epistatic effect on the risk for SSD and ASD. Methods: We examined 108 SNPs in a set of 22 OMR genes in 1749 subjects divided into three independent samples (187 SSD trios, 915 SSD cases/control, and 91 ASD trios). Genetic association and gene-gene interaction analyses were conducted with PLINK and MB-MDR, and permutation procedures were implemented in both. Results: Some OMR genes showed an association trend with SSD, while after correction, the ones that remained significantly associated were MBP, ERBB3, and AKT1. Significant gene-gene interactions were found between (i) NRG1 MBP (perm p-value¼0.002) in the SSD trios sample, (ii) ERBB3 AKT1 (perm p-value¼0.001) in the SSD case-control sample, and (iii) ERBB3 QKI (perm p-value¼0.0006) in the ASD trios sample. Discussion: Our results suggest the implication of OMR genes in the risk for both SSD and ASD and highlight the role of NRG1 and ERBB genes. These findings are in line with the previous evidence and may suggest pathophysiological mechanisms related to NRG1/ERBBs signalling in these disorders.

Contains fulltext : 235396.pdf (Publisher’s version ) (Open Access) In the last decade there has been a revolution in terms of genetic findings in neurodevelopmental disorders (NDDs), with many discoveries critical for understanding their aetiology and pathophysiology. Clinical trials in single-gene disorders such as fragile X syndrome highlight the challenges of investigating new drug targets in NDDs. Incorporating a developmental perspective into the process of drug development for NDDs could help to overcome some of the current difficulties in identifying and testing new treatments. This paper provides a summary of the proceedings of the 'New Frontiers Meeting' on neurodevelopmental disorders organised by the European College of Neuropsychopharmacology in conjunction with the Innovative Medicines Initiative-sponsored AIMS-2-TRIALS consortium. It brought together experts in developmental genetics, autism, NDDs, and clinical trials from academia and industry, regulators, patient and family associations, and other stakeholders. The meeting sought to provide a platform for focused communication on scientific insights, challenges, and methodologies that might be applicable to the development of CNS treatments from a neurodevelopmental perspective. Multidisciplinary translational consortia to develop basic and clinical research in parallel could be pivotal to advance knowledge in the field. Although implementation of clinical trials for NDDs in paediatric populations is widely acknowledged as essential, safety concerns should guide each aspect of their design. Industry and academia should join forces to improve knowledge of the biology of brain development, identify the optimal timing of interventions, and translate these findings into new drugs, allowing for the needs of users and families, with support from regulatory agencies.

We 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. Protein-protein interaction (PPI) networks previously created from three pharmacogenomic models (in vitro, animal, and peripheral blood inhumans) were used to, by means of several bioinformatic tools; identify key transcription factors (TFs) that regulate each network. Once the TFs wereidentified, SNPs disrupting the binding sites (TFBS) of these TFs in the genes of each network were selected for genotyping. Finally, SNP-basedassociations with EPS were analyzed in a sample of 356 psychiatric patients receiving AP. Our analysis identified 33 TFs expressed in the striatum, and 125 SNPs disrupting TFBS in 50 genes of our initial networks. Two SNPs (rs938112,rs2987902) in two genes (LSMAP and ABL1) were significantly associated with AP induced EPS (p

Healthcare workers (HCW) are at high risk for suicide, yet little is known about the onset of suicidal thoughts and behaviors (STB) in this important segment of the population in conjunction with the COVID-19 pandemic. We conducted a multicenter, prospective cohort study of Spanish HCW active during the COVID-9 pandemic. A total of n = 4809 HCW participated at baseline (May-September 2020; i.e., just after the first wave of the pandemic) and at a four-month follow-up assessment (October-December 2020) using web-based surveys. Logistic regression assessed the individual- and population-level associations of separate proximal (pandemic) risk factors with four-month STB incidence (i.e., 30-day STB among HCW negative for 30-day STB at baseline), each time adjusting for distal (pre-pandemic) factors. STB incidence was estimated at 4.2% (SE = 0.5; n = 1 suicide attempt). Adjusted for distal factors, proximal risk factors most strongly associated with STB incidence were various sources of interpersonal stress (scaled 0-4; odds ratio [OR] range = 1.23-1.57) followed by personal health-related stress and stress related to the health of loved ones (scaled 0-4; OR range 1.30-1.32), and the perceived lack of healthcare center preparedness (scaled 0-4; OR = 1.34). Population-attributable risk proportions for these proximal risk factors were in the range 45.3-57.6%. Other significant risk factors were financial stressors (OR range 1.26-1.81), isolation/quarantine due to COVID-19 (OR = 1.53) and having changed to a specific COVID-19 related work location (OR = 1.72). Among other interventions, our findings call for healthcare systems to implement adequate conflict communication and resolution strategies and to improve family-work balance embedded in organizational justice strategies. This work was supported by grants from the Instituto de Salud Carlos III (ISCIII)/Ministerio de Ciencia e Innovación/FEDER, Spain (Jordi Alonso, grant number COV20/00711); ISCIII-FEDER, Spain (Jordi Alonso, grant number PI17/00521); ISCIII-FSE, Spain: Sara Borrell and Miguel Servet grants (Philippe Mortier, grant number CD18/00049 and CP21/00078); Generalitat de Catalunya, Spain (2017SGR452); and PERIS, Departament de Salut, Spain (Itxaso Alayo; SLT017/20/000009). Additional partial funding was received from the Gerencia Regional de Salud de Castilla y León (SACYL), Spain (José María Pelayo Terán, grant number GRS COVID 32/A/20). Sí

Funding Acknowledgements Type of funding sources: None. Background Venous to arterial CO2 gap (CO2gap) is calculated by subtracting partial pressure of arterial CO2 to central venous partial pressure of CO2 (ScvCO2). This marker has been studied in septic shock and indicates hypoperfusion when exceeds 6mmHg. Its kinetics and applicability in cardiogenic shock (CS) are unclear, being mixed/central venous saturation and lactate more commonly used. Purpose The objective of the study is to describe CO2gap kinetics in patients with CS. Secondary objective is to analyze if CO2gap is as marker of prognosis in CS. Methods Prospective observational study that included patients admitted for CS in the Acute Cardiovascular Care Unit of a tertiary hospital. Gasometric samples were obtained at admission, 6, 12, 24 and 48 hours from the onset of shock. In-hospital mortality was registered. Results We included 40 patients with CS during 1 year. Most patients were male (80%), average age was 68 years. There was a high incidence of cardiac arrest (58%), most frequent cause of CS was STEMI (45%), in-hospital mortality was 45%, most cases from non-cardiovascular causes (61%). Refractory shock was frequent (28%). Average lactate peak was 6.02 mmol / L. CO2gap kinetics consisted in a peak at admission (8.8mmHg), a valley 6h (7.7mmHg), new peak at 12h (8.5mmHg) and progressive decrease at at 24 (6.8mmHg) and 48h (5.7 mmHg). Significantly, higher CO2gap values at admission (10.97mmHg vs 8.16mmHg, p = 0.007) was predictor of cardiovascular mortality. Lactate values at 6, 12 and 48 hours were also predictors of cardiovascular mortality, as well as ScvO2 at admission. Conclusions Patients with CS present with high CO2gap values during first hours of admission. The kinetics of this marker consists in two peaks at admission and 12 hours from CS onset, a valley at 6 hours and a progressive decrease at 24 and 48 hours. Its determination at admission is associated with cardiovascular mortality. We suggest the potential benefit of combining this marker, along with lactate and ScvO2 values, to guide management of patients with CS. Abstract Figure. CO2 gap and cardiovascular mortality

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 replication samples. Cross-sectional and longitudinal diagnostic differences in folding subcomponents were then assessed using an allometric analytic framework.Structural imaging from a longitudinal (sample 1: HI and SZ, nHI Baseline= 298, nSZ Baseline= 169, nHI Follow-up= 293, nSZ Follow-up= 168, a total of 1087 images, all individuals ≥ 2 images, age 16-69 years) and a cross-sectional sample (sample 2: nHI= 61 and nFEP= 89, age 10-30 years) is leveraged to calculate global folding and its nested subcomponents: sulcation index (SI, total sulcal/cortical hull area) and determinants of sulcal area; sulcal length and sulcal depth.Scaling of the SI, sulcal area, and sulcal length with TBV in SZ and FEP was allometric and did not differ from HI. Longitudinal age trajectories demonstrated steeper loss of SI and sulcal area through adulthood in SZ. Longitudinal allometric analysis revealed that both annual change in SI and sulcal area was significantly stronger related to change in TBV in SZ compared to HI.Our results detail the first evidence of the disproportionate contribution of changes in SI and sulcal area to TBV changes in SZ. Longitudinal allometric analysis of sulcal morphology provides deeper insight into lifespan trajectories of cortical folding in SZ.

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 biological hierarchies (gene, biological pathway, cell and brain areas) using bioinformatic approaches. For the majority of the analysis, a combined ASD cohort (N = 2171 trios) was created using previously published data by the Autism Sequencing Consortium (ASC). New plausible candidate genes for ASD such as FMR1 and NFIA were found. In addition, genes harboring PZMs were significantly enriched for miR-137 targets in comparison with germinal DNMs that were enriched in GO terms related to synaptic transmission. The expression pattern of genes with PZMs was restricted to early mid-fetal cortex. In contrast, the analysis of genes with germinal DNMs revealed a spatio-temporal window from early to mid-fetal development stages, with expression in the amygdala, cerebellum, cortex and striatum. These results provide evidence of the pathogenic role of PZMs and suggest the existence of distinct mechanisms between PZMs and germinal DNMs that are influencing ASD risk AA-G was supported by Fundación María José Jove. CR-F was supported by a contract from the FEDER. Instituto de Salud Carlos III/PI1900809/Cofinanciado FEDER supported this study SI

The EUGEI project was supported by the European Community’s Seventh Framework Program under grant agreement no. HEALTH-F2-2009-241909 (Project EU-GEI). Dr O’Donovan is supported by MRC programme grant (G08005009) and an MRC Centre grant (MR/ L010305/1). Dr Rutten was funded by a VIDI award number 91718336 from the Netherlands Scientific Organisation. Drs Guloksuz and van Os are supported by the Ophelia research project, ZonMw grant number: 636340001. Dr Arango was supported by the Spanish Ministry of Science and Innovation; Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024); CIBERSAM; Madrid Regional Government (B2017/BMD-3740, AGES-CM-2); Fundación Familia Alonso and Fundación Alicia Koplowitz., Pries, L.-K., Dal Ferro, G.A., Van Os, J., Delespaul, P., Kenis, G., Lin, B.D., Luykx, J.J., Richards, A.L., Akdede, B., Binbay, T., Altlnyazar, V., Yallnçetin, B., Gümüş-Akay, G., Cihan, B., Soygür, H., Ulaş, H., Åžahin Cankurtaran, E., Ulusoy Kaymak, S., Mihaljevic, M.M., Andric Petrovic, S., Mirjanic, T., Bernardo, M., Mezquida, G., Amoretti, S., Bobes, J., Saiz, P.A., Garciá-Portilla, M.P., Sanjuan, J., Aguilar, E.J., Santos, J.L., Jiménez-López, E., Arrojo, M., Carracedo, A., López, G., González-Penãs, J., Parellada, M., Maric, N.P., AtbaşoÄalu, C., Ucok, A., Alptekin, K., Can Saka, M., Arango, C., O'Donovan, M., Tosato, S., Rutten, B.P.F., Guloksuz, S., and Genetic Risk and Outcome of Psychosis (GROUP) investigators

BackgroundAutism Spectrum Disorders (ASD) and psychosis share deficits in social cognition. The insular region has been associated with awareness of self and reality, which may be basic for proper social interactions.MethodsTotal and regional insular volume and thickness measurements were obtained from a sample of 30 children and adolescents with ASD, 29 with early onset first-episode psychosis (FEP), and 26 healthy controls (HC). Total, regional, and voxel-level volume and thickness measurements were compared between groups (with correction for multiple comparisons), and the relationship between these measurements and symptom severity was explored.ResultsCompared with HC, a shared volume deficit was observed for the right (but not the left) anterior insula (ASD: p = 0.007, FEP: p = 0.032), and for the bilateral posterior insula: (left, ASD: p = 0.011, FEP: p = 0.033; right, ASD: p = 0.004, FEP: p = 0.028). A voxel-based morphometry (VBM) conjunction analysis showed that ASD and FEP patients shared a gray matter volume and thickness deficit in the left posterior insula. Within patients, right anterior (r = −0.28, p = 0.041) and left posterior (r = −0.29, p = 0.030) insular volumes negatively correlated with the severity of insight deficits, and left posterior insular volume negatively correlated with the severity of ‘autistic-like’ symptoms (r = −0.30, p = 0.028).ConclusionsThe shared reduced volume and thickness in the anterior and posterior regions of the insula in ASD and FEP provides the first tentative evidence that these conditions share structural pathology that may be linked to shared symptomatology.

In previous work we developed a pharmacogenetic predictor of antipsychotic (AP) induced extrapyramidal symptoms (EPS) based on four genes involved in mTOR regulation. The main objective is to improve this predictor by increasing its biological plausibility and replication. We re-sequence the four genes using next-generation sequencing. We predict functionality "in silico" of all identified SNPs and test it using gene reporter assays. Using functional SNPs, we develop a new predictor utilizing machine learning algorithms (Discovery Cohort, N = 131) and replicate it in two independent cohorts (Replication Cohort 1, N = 113; Replication Cohort 2, N = 113). After prioritization, four SNPs were used to develop the pharmacogenetic predictor of AP-induced EPS. The model constructed using the Naive Bayes algorithm achieved a 66% of accuracy in the Discovery Cohort, and similar performances in the replication cohorts. The result is an improved pharmacogenetic predictor of AP-induced EPS, which is more robust and generalizable than the original.

Brain plasticity has demonstrated to play a role in the pathophysiology of schizophrenia. Cognitive deterioration in these patients can be prevented by ensuring the adequate functioning of signaling pathways associated with brain plasticity. As BDNF exerts its action through receptors, in this study, we hypothesized that levels of some BDNF receptors during a first episode of psychosis (FEP) would correlate with the cognitive and global functioning of patients in the long term. We also hypothesized that the improvement of the ratio of full-length (TrKB-FL) and truncated (TrKB-T) TrKB receptors, and the predominance of the full-length isoform would be associated with better cognition and functioning. Peripheral levels of full-length (TrKB-FL) and truncated (TrKB-T) TrKB receptors were assessed in a sample of 97 FEP patients and 97 matched healthy controls. TrKB-FL/TrKB-T ratio(hereinafter, FL/T) was calculated for each patient. Cognitive and global functioning was measured at inclusion and at two years. A high baseline FL/T ratio was found to be related to a better cognitive function (global cognition, verbal memory, working memory and premorbid IQ). Cognitive performance at disease onset and at two years improved when the levels of the ratio were higher than one, with functional BDNF receptor (TrKB-FL) exceeding the value of the truncated isoform (TrKB-T). In addition the increase in the FL/T ratio during the two years of follow-up had positive effects on global functioning. This may be due either to a reduction in TrKB-T or to an increase in TrKB-FL, or both. In conclusion FL / T ratio was related to general functioning and cognition in the long-term.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission. © 2019, The Author(s).

Background: We aimed to investigate the state of cardiovascular risk/protection factors in early psychosis patients. Methods: A total 119 subjects were recruited during the first year after their first episode of psychosis. Eighty-five of these subjects were followed during the next 6 months. Cardiovascular risk/protection factors were measured in plasma and co-variated by sociodemographic/clinical characteristics. Multiple linear regression models detected the change of each biological marker from baseline to follow-up in relation to clinical scales, antipsychotic medication, and pro-/antiinflammatory mediators. Results: Glycosylated hemoglobin is a state biomarker in first episode of psychosis follow-up patients and inversely correlated to the Global Assessment of Functioning scale. We found opposite alterations in the levels of VCAM-1 and E-selectin in first episode of psychosis baseline conditions compared with control that were absent in the first episode of psychosis follow-up group. Adiponectin levels decreased in a continuum in both pathological time points studied. E-Selectin plasma levels were inversely related to total antipsychotic equivalents and adiponectin levels inversely co-related to the Global Assessment of Functioning scale. Finally, adiponectin levels were directly related to antiinflammatory nuclear receptor PPARy expression in first episode of psychosis baseline conditions and to proinflammatory nuclear factor nuclear factor kB activity in follow-up conditions, respectively. Conclusions: Our results support the need for integrating cardiovascular healthcare very early after the first episode of psychosis.

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 2 years 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 2 years of follow-up, especially in non-affective psychosis.

Data is progressively and robustly accumulating regarding the biological basis of autism. Autism spectrum disorders (ASD) are currently considered a group of neurodevelopmental disorders with onset very early in life and a complex, heterogeneous, multifactorial aetiology. A comprehensive search of the last five years of the Medline database was conducted in order to summarize recent evidence on the neurobiological bases of autism. The main findings on genetic influence, neuropathology, neurostructure and brain networks are summarized. In addition, findings from peripheral samples of subjects with autism and animal models, which show immune, oxidative, mitochondrial dysregulations, are reported. Then, other biomarkers from very different systems associated with autism are reported. Finally, an attempt is made to try and integrate the available evidence, which points to a oligogenetic, multifactorial aetiology that converges in an aberrant micro-organization of the cortex, with abnormal functioning of the synapses and abnormalities in very general physiological pathways (such as inflammatory, immune and redox systems).

BackgroundThe interest in studying gene–gene interactions is increasing for psychiatric diseases such as schizophrenia-spectrum disorders (SSD), where multiple genes are involved. Dysbindin-1 (DTNBP1) and Neuritin-1 (NRN1) genes have been previously associated with SSD and both are involved in synaptic plasticity. We aimed to study whether these genes show an epistatic effect on the risk for SSD.MethodsThe sample comprised 388 SSD patients and 397 healthy subjects. Interaction was tested between: (i) three DTNBP1 SNPs (rs2619537, rs2743864, rs1047631) related to changes in gene expression; and (ii) an haplotype in NRN1 previously associated with the risk for SSD (rs645649-rs582262: HAP-risk C-C).ResultsAn interaction between DTNBP1 rs2743864 and NRN1 HAP-risk was detected by using the model based multifactor dimensionality reduction (MB-MDR) approach (P = 0.0049, after permutation procedure), meaning that the risk for SSD is significantly higher in those subjects carrying both the A allele of rs2743864 and the HAP-risk C-C. This interaction was confirmed by using a logistic regression model (P = 0.033, OR (95%CI) = 2.699 (1.08–6.71), R2 = 0.162).DiscussionOur results suggest that DTNBP1 and NRN1 genes show a joint effect on the risk for SSD. Although the precise mechanism underlying this effect is unclear, the fact that these genes have been involved in synaptic maturation, connectivity and glutamate signalling suggests that our findings could be of value as a link to the schizophrenia aetiology.

BackgroundCognitive deficits are present from the onset of psychosis and are considered a core feature of the disorder. Increasing evidence suggests that cognitive function is associated with inflammatory processes. This study evaluated the association between cognition and inflammatory biomarkers in first-episode psychosis (FEP), in order to identify cognitive phenotypes from inflammatory expression profiles.MethodA case-control study of 92 FEP patients and 80 matched controls was used. Neurocognitive assessment, including verbal ability, sustained attention, verbal memory, working memory and executive function, was performed. The expression of pro- and anti-inflammatory mediators of the main intracellular inflammatory pathway was measured in peripheral blood mononuclear cells and plasma.ResultsFEP patients performed worse in all cognitive domains compared to controls and had higher expression of pro-inflammatory mediators and lower expression of anti-inflammatory mediators. In the FEP group, cognition and psychopathology were associated with inflammation. Hierarchical regression analysis showed that association between the anti-inflammatory prostaglandin 15d-PGJ2 and sustained attention on one hand, and COX-2 expression and executive function on the other, were statistically significant.ConclusionsOur study provides evidence for an association between anti-inflammatory biomarkers and cognition in FEP. The identification of a subgroup of patients based on these measures could be useful to guide treatment programmes by providing tools to select a personalized treatment approach, but longitudinal studies are needed before. In the future, establishment of biomarkers linked to cognition would be useful to monitor the course of cognitive impairment, but substantially more data will be required. Determination of IκBα, the inhibitory protein of the pro-inflammatory transcription factor NFκB, could be useful in early phases to assess clinical severity.

BackgroundThe longitudinal neuropsychological study of first-episode early-onset psychosis (EOP) patients, whose brain maturation is still in progress at the time of illness onset, provides a unique opportunity to compare their cognitive development with that of healthy subjects, in search of specific patterns resulting from the interaction between neurodevelopmental processes and the presence of psychotic disorders.MethodSeventy-five first-episode EOP patients (schizophrenia n = 35; bipolar disorder n = 17; other forms of psychosis n = 23) with a mean age of 15.53 years were assessed with a neuropsychological battery that included measures of attention, working memory, memory and executive functions within 6 months following the onset of the first psychotic symptom (baseline) and 2 years later. Psychotic symptoms were assessed at both times with the Positive and Negative Symptom Scale (PANSS). Seventy-nine healthy subjects matched for age and education served as controls.ResultsEOP patients showed significant cognitive impairment at both baseline and the 2-year follow-up, with no significant differences between diagnostic groups at either time. Both healthy controls and EOP patients improved in all cognitive measures, except for patient working memory. Improvement in patient attention lost significance after controlling for psychotic symptom reduction. No significant time/diagnosis interaction was found among patients (p > 0.405).ConclusionsCognitive impairment in EOP is already present at the first episode, and cognitive development seems to be arrested early in EOP patients compared to their healthy peers, at least for some cognitive functions. These and previous similar results support the neurodevelopmental hypothesis of psychosis.