Project description:It remains unclear why many patients with depression do not respond to antidepressant treatment. In three cohorts of individuals with depression and treated with serotonin-norepinephrine reuptake inhibitor (N=424) we show that responders, but not non-responders, display an increase of GPR56 mRNA in the blood. In a small group of subjects we also show that GPR56 is also downregulated in the PFC of individuals with depression that died by suicide. In mice, we show that chronic stress induced Gpr56 downregulation in the blood and prefrontal cortex (PFC), which is accompanied by depression-like behaviour, and can be reversed by antidepressant treatment. Gpr56 knockdown in mouse PFC was is associated with depressive-like behaviors, executive dysfunction and poor response to antidepressant treatment. GPR56 peptide agonists had antidepressant-like effects and up-regulated AKT/GSK3/EIF4 pathways. Our findings uncover a potential role of GPR56 in antidepressant response.
Project description:This SuperSeries is composed of the following subset Series: GSE34906: Genetic and epigenetic determinants of neurogenesis and myogenesis [ChIP-seq] GSE34907: Genetic and epigenetic determinants of neurogenesis and myogenesis [expression profiling] Refer to individual Series
Project description:Successful antidepressant treatments are still difficult to achieve. Recently, bright light stimulation (BLS) was shown effective in non-seasonal depression but its mode of action remains elusive. We demonstrate, using a new mouse model of depression resistant to antidepressants including ketamine, that both chemogenetic activation of lateral habenula (LHb) astroglia and serotonin (5-HT) depletion prevented the potentiating effect of BLS on the antidepressant response. These results show that improved behavioral outcome produced by BLS requires habenular astroglia and 5-HT tone as crucial buffer systems.
Project description:Pharmacogenetic Optimization of Anticoagulant Response (POAT) and Genetic and Environmental Determinants of Warfarin Response (GEDWR)