The Effects of Video Games on Cognition and Brain Structure: Potential Implications for Neuropsychiatric Disorders.

Video games are now a ubiquitous form of entertainment that has occasionally attracted negative attention. Video games have also been used to test cognitive function, as therapeutic interventions for neuropsychiatric disorders, and to explore mechanisms of experience-dependent structural brain changes. Here, we review current research on video games published from January 2011 to April 2014 with a focus on studies relating to mental health, cognition, and brain imaging. Overall, there is evidence that specific types of video games can alter brain structure or improve certain aspects of cognitive functioning. Video games can also be useful as neuropsychological assessment tools. While research in this area is still at a very early stage, there are interesting results that encourage further work in this field, and hold promise for utilizing this technology as a powerful therapeutic and experimental tool.

Antipsychotic induced weight gain: genetics, epigenetics, and biomarkers reviewed.

Antipsychotic-induced weight gain (AIWG) is a prevalent side effect of antipsychotic treatment, particularly with second generation antipsychotics, such as clozapine and olanzapine. At this point, there is virtually nothing that can be done to predict who will be affected by AIWG. However, hope for the future of prediction lies with genetic risk factors. Many genes have been studied for their association with AIWG with a variety of promising findings. This review will focus on genetic findings in the last year and will discuss the first epigenetic and biomarker findings as well. Although there are significant findings in many other genes, the most consistently replicated findings are in the melanocortin 4 receptor (MC4R), the serotonin 2C receptor (HTR2C), the leptin, the neuropeptide Y (NPY) and the cannabinoid receptor 1 (CNR1) genes. The study of genetic risk variants poses great promise in creating predictive tools for side effects such as AIWG.

Pharmacogenetics and outcome with antipsychotic drugs.

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

Los antípsicóticos son los medícamentos utilizados como gold standard para el tratamiento de la esquizofrenía y además se emplean con frecuencia para otros trastornos mentales. Sin embargo, los perfiles de eficacia y efectos secundarios de estos fármacos son heterogéneos y con gran varíabílidad ínterindividual. A raíz de esto, la selección del tratamiento sígue siendo un largo proceso de ensayo-error, con muchas fallas terapéuticas que se deben soportar antes de encontrar un balance aceptable entre el manejo sintomático y los efectos secundarios. Mucha de la varíabílidad ínterindividual en la respuesta y los efectos secundarios se debe a factores genéticos (heredabilidad, h2~ 0.60 - 0.80). La farmacogenética es un área emergente que posee el potencial de facílitar la selección de la mejor medicación para un paciente en particular, en base a su información genética. En esta revisión se discuten los marcadores genéticos más promisorios en los resultados del tratamiento antipsicótico, y se presentan los esfuerzos actuales de la investigación translacional que tienen como objetivo llevar estos hallazgos farmacogenéticos a la clínica en un futuro cercano.

Les médicaments antipsychotiques, traitement de référence pour la schizophrénie, sont souvent prescrits pour d'autres maladies mentales. Néanmoins, leur efficacité et leurs effets indésirables sont hétérogenes, avec une grande variabilité selon les individus. En conséquence, le choix du traitement procède en grande partie par tâtonnements, beaucoup de schémas thérapeutiques échouant avant que soit trouvé un rapport correct entre les effets sur les symptômes et les effets indésirables. Des facteurs génétiques sont responsables de la majeure partie de la variabilité interindividuelle dans les réponses au traitement et les effets indésirables (héritabilité, h2~ 0,60-0,80). La pharmacogénétique est un domaine en plein essor qui permet d'aider au choix du meilleur traitement pour un patient donné, d'après ses informations génétiques. Nous analysons dans cet article les marqueurs génétiques les plus prometteurs dans le traitement antipsychotique et nous présentons les travaux actuels de recherche translationnelle dont le but est d'appliquer ces résultats de pharmacogénétique à la clinique dans un futur proche.

The carboxyl terminus of Rtt109 functions in chaperone control of histone acetylation.

Rtt109 is a fungal histone acetyltransferase (HAT) that catalyzes histone H3 acetylation functionally associated with chromatin assembly. Rtt109-mediated H3 acetylation involves two histone chaperones, Asf1 and Vps75. In vivo, Rtt109 requires both chaperones for histone H3 lysine 9 acetylation (H3K9ac) but only Asf1 for full H3K56ac. In vitro, Rtt109-Vps75 catalyzes both H3K9ac and H3K56ac, whereas Rtt109-Asf1 catalyzes only H3K56ac. In this study, we extend the in vitro chaperone-associated substrate specificity of Rtt109 by showing that it acetylates vertebrate linker histone in the presence of Vps75 but not Asf1. In addition, we demonstrate that in Saccharomyces cerevisiae a short basic sequence at the carboxyl terminus of Rtt109 (Rtt109C) is required for H3K9ac in vivo. Furthermore, through in vitro and in vivo studies, we demonstrate that Rtt109C is required for optimal H3K56ac by the HAT in the presence of full-length Asf1. When Rtt109C is absent, Vps75 becomes important for H3K56ac by Rtt109 in vivo. In addition, we show that lysine 290 (K290) in Rtt109 is required in vivo for Vps75 to enhance the activity of the HAT. This is the first in vivo evidence for a role for Vps75 in H3K56ac. Taken together, our results contribute to a better understanding of chaperone control of Rtt109-mediated H3 acetylation.