Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Interaction between COMT rs5993883 and second generation antipsychotics is linked to decreases in verbal cognition and cognitive control in bipolar disorder

Abstract Background Second generation antipsychotics (SGAs) are increasingly utilized in Bipolar Disorder (BD) but are potentially associated with cognitive side effects. Also linked to cognitive deficits associated with SGA-treatment are catechol-O-methyltransferase (COMT) gene variants. In this study, we examine the relationship between cognition in SGA use and COMT rs5993883 in cohort sample of subjects with BD. Methods Interactions between SGA-treatment and COMT rs5993883 genotype on cognition was tested using a battery of neuropsychological tests performed in cross-sectional study of 246 bipolar subjects. Results The mean age of our sample was 40.15 years and was comprised of 70 % female subjects. Significant demographic differences included gender, hospitalizations, benzodiazepine/antidepressant use and BD-type diagnosis. Linear regressions showed that the COMT rs5993883 GG genotype predicted lower verbal learning (p = 0.0006) and memory (p = 0.0026) scores, and lower scores on a cognitive control task (p = 0.004) in SGA-treated subjects. Interestingly, COMT GT- or TT-variants showed no intergroup cognitive differences. Further analysis revealed an interaction between SGA-COMT GG-genotype for verbal learning (p = 0.028), verbal memory (p = 0.026) and cognitive control (p = 0.0005). Conclusions This investigation contributes to previous work demonstrating links between cognition, SGA-treatment and COMT rs5993883 in BD subjects. Our analysis shows significant associations between cognitive domains such as verbal-cognition and cognitive control in SGA-treated subjects carrying the COMT rs5993883 GG-genotype. Prospective studies are needed to evaluate the clinical significance of these findings.http://deepblue.lib.umich.edu/bitstream/2027.42/134550/1/40359_2016_Article_118.pd

Sapienza monastica. Saggi di storia, spiritualit\ue0 e problemi monastici. Saggi di Benedetto Calati

Il volume \ue8 la pubblicazione degli scritti di Benedetto Calati (1914-2000), edita in occasione del suo 80\ub0 compleanno. Calati, gi\ue0 priore generale dei monaci camaldolesi, docente di spiritualit\ue0 monastica medievale presso la Facolt\ue0 teologica di S. Anselmo in Roma, fu attivo propugnatore del rinnovamento conciliare, anche in materia di ermeneutica del testo sacro. Questo volume, accolto dalla casa editrice Studia Anselmiana come summa del lavoro di B. Calati, presenta un'ampia antologia ragionata di testi editi e inediti, considerata fondamentale per la ricostruzione dell\u2019opera di Calati, attenta al rinnovamento conciliare, alla ripresa degli studi patristici e alla teologia mistica. La prima sezione del libro raccoglie saggi e articoli che presentano i nuclei propositivi del discorso di Calati; la seconda e la terza sezione comprendono studi di carattere storico, accordando attenzione particolare ai temi privilegiati dalla ricerca di Calati: la figura di Gregorio Magno e l'evento del Concilio Vaticano II. Gli studi consacrati ai Padri e gli scritti dedicati alla tradizione benedettina mettono in luce le feconde tensioni che hanno segnato lo sviluppo del monachesimo occidentale. Il volume comprende anche la redazione della bibliografia completa degli scritti di B. Calati