Using gene expression and systems biology to interrogate auditory hallucinations in schizophrenic patients

Schizophrenia is a severe mental disorder affecting around 1% of the opulation. This disease presents a complex aetiology that has not been completely unveiled yet. Auditory hallucinations are a very significant and disruptive symptom of schizophrenia affecting between 60% and 80% of schizophrenic patients. In this paper we have used a network-based transcriptomic analysis aiming to identify differences in gene expression between schizophrenic patients with and without auditory hallucinations. Gene expression data from blood samples drained from 30 schizophrenia patients were generated using Affymetrix Human Gene 2.0 ST Genechips. Affymetrix Expression console was used for normalization and quality control purposes. The RMA normalization method was applied for gene summarization and then a filter applied to keep only the most variably expressed probesets (4,508). These dataset was analysed using the weighted gene co-expression network analysis (WGCNA) package in R. The gene co-expression network analyses allowed us to identify eleven different gene modules based on their topological overlap. These modules were related to the relevant phenotypic information and allowing us to identify modules related with different phenotypic traits of interest. Gene co-expression network analysis is a useful tool for the analysis of gene expression analysis. Its application in the analysis of schizophrenia gene expression provides an insight on the molecular mechanisms related with this disease and the differences at the molecular level between patients presenting auditory hallucinations and those that do not. In our analysis we have been able to identify different gene modules containing genes expression profiles that can be related with clinically relevant phenotypes. These gene modules could be functionally annotated and related with different pathways and gene ontology terms that are relevant in the context of this analysis

First-Episode Psychotic Patients Showed Longitudinal Brain Changes Using fMRI With an Emotional Auditory Paradigm

Most previous longitudinal studies of functional magnetic resonance imaging (fMRI) in first-episode psychosis (FEP) using cognitive paradigm task found an increased activation after antipsychotic medications. We designed an emotional auditory paradigm to explore brain activation during emotional and nonemotional word processing. This study aimed to analyze if longitudinal changes in brain fMRI BOLD activation is present in patients vs. healthy controls. A group of FEP patients (n = 34) received clinical assessment and had a fMRI scan at baseline and follow-up (average, 25-month interval). During the fMRI scan, both emotional and nonemotional words were presented as a block design. Results were compared with a pair of healthy control group (n = 13). Patients showed a decreased activation at follow-up fMRI in amygdala (F = 4.69; p = 0.04) and hippocampus (F = 5.03; p = 0.03) compared with controls. Middle frontal gyrus was the only area that showed a substantial increased activation in patients (F = 4.53; p = 0.04). A great heterogeneity in individual activation patterns was also found. These results support the relevance of the type of paradigm in neuroimaging for psychosis. This is, as far as we know, the first longitudinal study with an emotional auditory paradigm in FEP. Our results suggested that the amygdala and hippocampus play a key role in psychotic disease. More studies are needed to understand the heterogeneity of response at individual level

Alterations of perineuronal nets in the dorsolateral prefrontal cortex of neuropsychiatric patients

Background: Alterations in the structure and physiology of interneurons in the prefrontal cortex (PFC) are important factors in the etiopathology of different psychiatric disorders. Among the interneuronal subpopulations, parvalbumin (PV) expressing cells appear to be specially affected. Interestingly, during development and adulthood the connectivity of these interneurons is regulated by the presence of perineuronal nets (PNNs), specialized regions of the extracellular matrix, which are frequently surrounding PV expressing neurons. Previous reports have found anomalies in the density of PNNs in the PFC of schizophrenic patients. However, although some studies have described alterations in PNNs in some extracortical regions of bipolar disorder patients, there are no studies focusing on the prefrontocortical PNNs of bipolar or major depression patients. For this reason, we have analyzed the density of PNNs in post-mortem sections of the dorsolateral PFC (DLPFC) from the Stanley Neuropathology Consortium, which includes controls, schizophrenia, bipolar and major depression patients. Results: We have not observed differences in the distribution of PV+ cells or PNNs, or in the percentage of PV+ interneurons surrounded by PNNs. The density of PV+ interneurons was similar in all the experimental groups, but there was a significantly lower density of PNNs in the DLPFC of bipolar disorder patients and a tendency towards a decrease in schizophrenic patients. No differences were found when evaluating the density of PV+ cells surrounded by PNNs. Interestingly, when assessing the influence of demographic data, we found an inverse correlation between the density of PNNs and the presence of psychosis. Conclusions: The present results point to prefrontocortical PNNs and their role in the regulation of neuronal plasticity as putative players in the etiopathology of bipolar disorder and schizophrenia. Our findings also suggest a link between these specialized regions of the extracellular matrix and the presence of psychosis

FOXP2 expression and gray matter density in the male brains of patients with schizophrenia

Common genetic variants of FOXP2 may contribute to schizophrenia vulnerability, but controversial results have been reported for this proposal. Here we evaluated the potential impact of the common FOXP2 rs2396753 polymorphism in schizophrenia. It was previously reported to be part of a risk haplotype for this disease and to have significant effects on gray matter concentration in the patients. We undertook the first examination into whether rs2396753 affects the brain expression of FOXP2 and a replication study of earlier neuroimaging findings of the influence of this genetic variant on brain structure. FOXP2 expression levels were measured in postmortem prefrontal cortex samples of 84 male subjects (48 patients and 36 controls) from the CIBERSAM Brain and the Stanley Foundation Array Collections. High-resolution anatomical magnetic resonance imaging was performed on 79 male subjects (61 patients, 18 controls) using optimized voxel-based morphometry. We found differences in FOXP2 expression and brain morphometry depending on the rs2396753, relating low FOXP2 mRNA levels with reduction of gray matter density. We detected an interaction between rs2396753 and the clinical groups, showing that heterozygous patients for this polymorphism have gray matter density decrease and low FOXP2 expression comparing with the heterozygous controls.This study shows the importance of independent replication of neuroimaging genetic studies of FOXP2 as a candidate gene in schizophrenia. Furthermore, our results suggest that the FOXP2 rs2396753 affects mRNA levels, thus providing new knowledge about its significance as a potential susceptibility polymorphism in schizophrenia

La medicina y el ciclo vital del ser humano: Aspectos Psicológicos

Una de las diferencias más relevantes que distinguen al ser humano del resto de los animales es el largo periodo de desarrollo por el que pasa el niño hasta alcanzar su madurez (Brines 2009). Este largo periodo de desarrollo le confiere a nuestra especie indudables ventajas: aumenta el periodo de aprendizaje y nuestro cerebro tiene más oportunidades de almacenar múltiples estrategias para responder de forma más adecuada a nuestro entorno. Sin embargo, esto también conlleva riesgos. Los bebes humanos precisan de una atención y cuidados más prolongados que los de otras especies y durante todo ese largo periodo están más expuestos a peligros. Aunque el desarrollo psicológico del niño es unitario se puede dividir, a efectos tanto de investigación como didácticos, en dos grandes apartados el desarrollo emocional y el desarrollo cognitivo. Esta exposición solo pretende subrayar algunos de puntos relevantes de dichos desarrollo

Psicothema

Resumen tomado de la publicaciónEs fundamental un mayor conocimiento del temperamento infantil puesto que puede predecir el desarrollo de psicopatología posterior. Los cuestionarios adaptados a población infantil española cubren un rango de edad limitado. La escala más utilizada para estudios de genética del temperamento infantil es la Emotionality Activity and Sociability Temperament Survey (EAS). El principal objetivo de este estudio es realizar la versión española del EAS y comprobar sus propiedades psicométricas. Se administró la versión española del cuestionario a una muestra de 229 madres y sus hijos a los 18 y 42 meses. Se ha encontrado una fiabilidad comparable a la obtenida en población de la misma edad. Los resultados sugieren una medida del temperamento basada en tres factores.AsturiasColegio Oficial de Psicólogos de Asturias; Calle Ildefonso Sánchez del Río, 4-1 B; 33001 Oviedo; Tel. +34985285778; Fax +34985281374;Universidad de Oviedo. Facultad de Psicología; Plaza Feijoo, s. n.; 33003 Oviedo; Tel. +34985104146; Fax +34985104126;ES

Individualized diagnosis of psychosis based on machine learning from functional magnetic resonance data using an emotional auditory paradigm

Sanjuán Arias, J.; Castro-Bleda, MJ.; España Boquera, S.; Garcia-Marti, G.; Carot Sierra, JM.; Corripio, I.; Soldevila-Matias, P.... (2019). Individualized diagnosis of psychosis based on machine learning from functional magnetic resonance data using an emotional auditory paradigm. Schizophrenia Bulletin. 45(Supplement 2):333-334. https://doi.org/10.1093/schbul/sbz020.615S33333445Supplement

Challenges for Food and Nutrition Security in the Americas: Costa Rica and its commitment to sustainability

As a small nation with high biodiversity and an extensive system of protected areas, Costa Rica will face particular challenges regarding food security over the next few years. Thus, whatever development model the country chooses, it must achieve a compromise between conservation and production (agricultural, energy and so on). Although the country’s malnutrition levels are below 5%, socioeconomic asymmetries - which have been increasing in recent years - put a growing proportion of the population at risk. Costa Rica also has a high disaster risk (due to volcanism, seismicity and climatic events), which is likely to be increased by climate change. Moreover, the country’s population is aging and growing very little in absolute numbers, which is also reflected in the predominance of farmers growing older. It is important to mention that the country relies heavily on food imports, mainly of basic grains, to cover the needs of its population. Food production uses a large amount of imported seed and propagating material, which are often not suited to local conditions, as well as very intensive use of agrochemicals, with negative consequences for health and the environment. Over the next few years, it will be crucial to maintain solid public higher-education and research structures in the agricultural field. Although there is no shortage of water in the country in general, water is unevenly distributed at certain times and between regions. Another important challenge is that overweight and obesity show an increasing and alarming upward trend. A comprehensive approach considering many actors and positions is required to ensure food and nutrition in Costa Rica over the next fifty years. To this end and to be consistent with a long tradition that has earned the country recognition, the government should continue with its policies to conserve protected areas and biodiversity. At the same time, it should increase productivity and yields in land with a clear agricultural vocation. This is important for reducing dependence on imported food in order to meet the basic needs of the country’s inhabitants. In order to achieve broad access to sufficient nutritious food, it is essential to reduce the gaps in the population’s socioeconomic conditions. Production systems should be more environmentally friendly by reducing the use of agrochemicals, and making more and better use of soil, and integrated pest, water resources, waste and residue-management practices. It will also be important to encourage, where possible, the use of local species or those adapted to local conditions, some of which are little known and underutilized, which are important for the diet beyond caloric intake (as a source of micronutrients, vitamins and functional compounds). This requires considering the enormous biodiversity present in the country and encouraging genetic improvement in order to reduce dependence on imported seed and propagation materials, since these were often developed for other climatic and edaphic conditions, as well as different productive systems. It is essential to achieve greater differentiation of products that follow certain quality standards in terms of production, marketing and nutritional value over the next few years, and for this to provide some form of competitive advantage. Prevention and mitigation measures must be taken against disasters that can be caused by specific events (hurricanes, volcanoes, earthquakes, etc.) or climate change. It will be important to continue the construction and maintenance of water collection, storage and supply works to reduce water shortages in particular areas and at specific times. Agricultural activity must be made attractive so that young people choose to remain in the countryside rather than migrating to cities. State funding for research on priority issues for the country must be increased, and incentives created so that the private sector also becomes interested in supporting research. It is also necessary to continue promoting high-level human resource training, preferably at top universities abroad, to promote agricultural research. Likewise, technical and vocational education must be promoted with the participation of various institutions (such as the Instituto Nacional de Aprendizaje, technical and vocational colleges and dual education). The country must consider a wide range of options for agricultural production with a view toward ensuring food and nutrition for its inhabitants. This framework must consider all the (bio)technological options, provided they do not conflict with the environment and health. It is also essential to continue and intensify programs that seek to promote healthy eating habits and encourage physical activity among the population.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Centro para Investigaciones en Granos y Semillas (CIGRAS)UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Instituto de Investigaciones Agrícolas (IIA