About this Research Topic
Depression is a devastating and chronic illness impacting more than 100 million people worldwide. While generally considered effective, currently available pharmacological antidepressant treatments have severe limitations in terms of the speed of efficacy onset, and the rate of response failures in clinical patient populations. Perhaps the most significant recent advance in MDD treatment has been the observation that the dissociative anesthetic ketamine has a fast antidepressant effect in treatment resistant MDD patients that is extended in time past the drug’s elimination from the body. Given that ketamine is thought to primarily act on glutamatergic neurotransmission, where it behaves directly as an antagonist at glutamatergic N-methyl-D-aspartate (NMDA) receptors, and may indirectly enhance postsynaptic signaling mediated via glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, glutamate neurotransmission is increasingly thought to play a central role in the treatment and neuropathology of MDD.
Glutamate has numerous roles in the central nervous system in addition to its role as the primary excitatory neurotransmitter, and for this reason it is regulated in a complex manner via multiple modulatory mechanisms. These modulatory systems include several with long-recognized roles in MDD, including glucocorticoid signaling and serotonergic neurotransmission, as well as systems with a more recently emerging recognition for a glutamate modulatory role, such as glia. From this perspective, if aberrations in glutamate neurotransmission lie at the heart of the neuropathology of MDD, then it may be possible to see dysregulation in several of these modulatory systems in depressed patients or biological models thereof, or to leverage these modulatory systems to normalize MDD-related aberrations in glutamate biology.
Thus, the overall goal of this Research Topic is to bring together a substantial body of original experimental papers and review articles which summarize and expand our current state of knowledge in the field of glutamate-modulatory systems and their role in MDD, whether from a pathological or a therapeutic perspective. We will welcome noted scientists to explore the effects on glutamate neurotransmission of chronically overactive glucocorticoid receptor stimulation or glial pathology, both of which are currently associated with MDD, and further to explore how aberrations in these modulatory systems may lead to MDD-like phenotypic aberrations. Furthermore, we will examine the role of glutamate neurotransmission in MDD-focused pharmacotherapies, including agents that directly target aspects of glutamate neurotransmission such as rapastinel, traxoprodil and ketamine, as well as those that have indirect, but documented effects on glutamate neurotransmission, such as the multimodal antidepressant vortioxetine.
To our knowledge, a volume of work focused on this topic would be highly novel, and we expect that original experimental papers and review articles which summarize the relationships between the modulatory systems described above and glutamate neurotransmission would be of broad interest to the readership of Frontiers in Neuropharmacology.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.