Rationale Identification of biomarkers that establish diagnosis or treatment response is critical to the advancement of research and management of patients with depression. Objective Our goal was to identify biomarkers that can potentially assess fluoxetine response and risk to poor treatment outcome. Methods We measured behavior, gene expression, and the levels of 36 neurobiochemical analytes across a panel of genetically diverse mouse inbred lines after chronic treatment with water or fluoxetine. Results Glyoxylase 1 (GLO1) and guanine nucleotide-binding protein 1 (GNB1) mostly account for baseline anxiety-like and depressive-like behavior, indicating a common biological link between depression and anxiety. Fluoxetine-induced biochemical alterations discriminated positive responders, while baseline neurobiochemical differences differentiated negative responders (p < 0.006). Results show that glial fibrillary acidic protein, S100 beta protein, GLO1, and histone deacetylase 5 contributed most to fluoxetine response. These proteins are linked within a cellular growth/proliferation pathway, suggesting the involvement of cellular genesis in fluoxetine response. Furthermore, a candidate genetic locus that associates with baseline depressive-like behavior contains a gene that encodes for cellular proliferation/adhesion molecule (Cadm1), supporting a genetic basis for the role of neuro/gliogenesis in depression. Conclusion We provided a comprehensive analysis of behavioral, neurobiochemical, and transcriptome data across 30 mouse inbred strains that has not been accomplished before. We identified biomarkers that influence fluoxetine response, which, altogether, implicate the importance of cellular genesis in fluoxetine treatment. More broadly, this approach can be used to assess a wide range of drug response phenotypes that are challenging to address in human samples.

Pharmacogenomics provides a personalized approach to pharmacotherapy by using genetic information to guide drug dosing and selection. However, partly due to lack of education, pharmacogenomic testing has not been fully implemented in clinical practice. With pharmacotherapy training and patient accessibility, pharmacists are ideally suited to apply pharmacogenomics to patient care. Student pharmacists (n = 222) participated in an educational intervention that included voluntary personal genotyping using 23andMe. Of these, 31% of students completed both pre- and post-educational interventions to evaluate their attitudes and confidence towards the use of pharmacogenomics data in clinical decision making, and 55% of this paired subset obtained personal genotyping. McNemar’s test and the Wilcoxon signed-rank test were used to analyze responses. Following the educational intervention, students regardless of genotyping were more likely to recommend personal genotyping (36% post-educational intervention versus 19% pre-educational intervention, p = 0.0032), more confident in using pharmacogenomics in the management of drug therapy (51% post-educational intervention versus 29% pre-educational intervention, p = 0.0045), and more likely to believe that personalized genomics would have an important role in their future pharmacy career (90% post-educational intervention versus 51% pre-educational intervention, p = 0.0072) compared to before receiving the educational intervention. This educational intervention positively influenced students’ attitudes and confidence regarding pharmacogenomics in the clinical setting. Future studies will examine the use of next-generation sequencing assays that selectively examine pharmacogenes in the education of student pharmacists.

Tacrolimus exhibits high inter-patient pharmacokinetics (PK) variability, as well as a narrow therapeutic index, and therefore requires therapeutic drug monitoring. Germline mutations in cytochrome P450 isoforms 4 and 5 genes (CYP3A4/5) and the ATP-binding cassette B1 gene (ABCB1) may contribute to interindividual tacrolimus PK variability, which may impact clinical outcomes among allogeneic hematopoietic stem cell transplantation (HSCT) patients. In this study, 252 adult patients who received tacrolimus for acute graft versus host disease (aGVHD) prophylaxis after allogeneic HSCT were genotyped to evaluate if germline genetic variants associated with tacrolimus PK and pharmacodynamic (PD) variability. Significant associations were detected between germline variants in CYP3A4/5 and ABCB1 and PK endpoints (e.g., median steady-state tacrolimus concentrations and time to goal tacrolimus concentration). However, significant associations were not observed between CYP3A4/5 or ABCB1 germline variants and PD endpoints (e.g., aGVHD and treatment-emergent nephrotoxicity). Decreased age and CYP3A5*1/*1 genotype were independently associated with subtherapeutic tacrolimus trough concentrations while CYP3A5*1*3 or CYP3A5*3/*3 genotypes, myeloablative allogeneic HSCT conditioning regimen (MAC) and increased weight were independently associated with supratherapeutic tacrolimus trough concentrations. Future lines of prospective research inquiry are warranted to use both germline genetic and clinical data to develop precision dosing tools that will optimize both tacrolimus dosing and clinical outcomes among adult HSCT patients.

Aim: To determine the projected impact of a multigene pharmacogenetic (PGx) test on medication prescribing. Materials & methods: A retrospective analysis was conducted with 122 cardiac catheterizat...

Aim: This study assesses the technical performance and cost of a targeted next-generation sequencing (NGS) multigene pharmacogenetic (PGx) test. Materials & methods: A genetic test was developed fo...