Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders
TLDR
There is growing evidence that the glutamatergic system is central to the neurobiology and treatment of mood disorders and exciting new prospects for the development of improved therapeutics for these devastating disorders are discussed.Abstract:
Mood disorders are common, chronic, recurrent mental illnesses that affect the lives of millions of individuals worldwide. To date, the monoaminergic systems (serotonergic, noradrenergic and dopaminergic) in the brain have received the greatest attention in neurobiological studies of mood disorders, and most therapeutics target these systems. However, there is growing evidence that the glutamatergic system is central to the neurobiology and treatment of these disorders. Here, we review data supporting the involvement of the glutamatergic system in mood-disorder pathophysiology as well as the efficacy of glutamatergic agents in mood disorders. We also discuss exciting new prospects for the development of improved therapeutics for these devastating disorders.read more
Citations
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Journal ArticleDOI
Major depressive disorder
Christian Otte,Stefan M. Gold,Stefan M. Gold,Brenda W.J.H. Penninx,Carmine M. Pariante,Amit Etkin,Maurizio Fava,David C. Mohr,Alan F. Schatzberg +8 more
TL;DR: An overview of the current evidence of major depressive disorder, including its epidemiology, aetiology, pathophysiology, diagnosis and treatment, is provided.
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The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission
TL;DR: Understanding of the mechanisms by which stress and glucocorticoids affect glutamate transmission provides insights into normal brain functioning, as well as the pathophysiology and potential new treatments of stress-related neuropsychiatric disorders.
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Synaptic Dysfunction in Depression: Potential Therapeutic Targets
TL;DR: Findings highlight the central importance of homeostatic control of mood circuit connections and form the basis of a synaptogenic hypothesis of depression and treatment response.
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Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
TL;DR: Treatment with new agents results in an improvement in mood ratings within hours of dosing patients who are resistant to typical antidepressants, and these new agents have also been shown to reverse the synaptic deficits caused by stress.
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Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial
James W. Murrough,Dan V. Iosifescu,Lee C. Chang,Rayan K. Al Jurdi,Charles Green,Andrew M. Perez,Syed Z Iqbal,Sarah Pillemer,Alexandra Foulkes,Asim A Shah,Dennis S. Charney,Sanjay J. Mathew +11 more
TL;DR: Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression.
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