Altered Kinase Networks in Major Depressive Disorder
University of Toledo
Major depressive disorder (MDD) is a chronic debilitating psychiatric disorder with an unknown etiology. MDD is associated with the altered expression and activity of protein kinases, which regulates signaling in complex biological networks. Abnormalities in kinase-mediated signaling are involved in the pathophysiology of MDD. To identify the kinases and kinase networks (“the kinome”) that are perturbed in MDD, we assayed the activity of the serine/threonine subfamily of protein kinases in human postmortem tissue from dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), human induced pluripotent stem cells (hiPSCs), and from a loss-phenotype animal model using an array-based platform (Pamgene12, Pamgene Int). We observed relative changes in kinase activity in MDD subjects, MDD subjects who died by suicide and non-psychiatrically ill controls, in male and female cohorts. Integrating kinome data from human postmortem, hiPSCs, and animal model of environmental loss, we identified previously reported kinases in MDD and MDD suicide subjects, novel kinases that have not been previously studied, common kinases between male and female cohorts that could represent disease hits, and unique kinases that could be related to sex differences.
Major depressive disorder, Human postmortem tissue, Kinase, Dorsolateral prefrontal cortex, Anterior cingulate cortex, Loss-phenotype animal model, human induced pluripotent stem cells