Depression and Anxiety
March 10, 2014
Ronald S. Duman
213 citations
Stress and depression are associated with atrophy and loss of neurons in limbic and cortical brain regions that could contribute to the symptoms of depression. Typical monoamine reuptake inhibitor antidepressants have only modest efficacy and require long-term treatment, and are only weakly effective in blocking or reversing these structural changes caused by stress. Recent findings demonstrate...
Journal of Molecular Psychiatry
September 17, 2013
Jason M. Dwyer, Ashley E. Lepack, Ronald S. Duman
81 citations
BACKGROUND: Depression is a prevalent neuropsychiatric disorder that affects an estimated 350 million people worldwide. Currently available treatments for depression are lacking in both speed of onset and efficacy. Recent pharmacological efforts have targeted the glutamatergic neurotransmitter system using the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine to produce rapid and robust...
Science
October 4, 2012
Ronald S. Duman, George K. Aghajanian
1,613 citations
Basic and clinical studies demonstrate that depression is associated with reduced size of brain regions that regulate mood and cognition, including the prefrontal cortex and the hippocampus, and decreased neuronal synapses in these areas. Antidepressants can block or reverse these neuronal deficits, although typical antidepressants have limited efficacy and delayed response times of weeks to...
Philosophical Transactions of the Royal Society B Biological Sciences
July 23, 2012
Ronald S. Duman, Nanxin Li
361 citations
Molecular and cellular studies have demonstrated opposing actions of stress and antidepressant treatment on the expression of neurotrophic factors, particularly brain-derived neurotrophic factor, in limbic structures of the brain. These changes in neurotrophic factor expression and function result in structural alterations, including regulation of neurogenesis, dendrite length and spine density...
Neuropharmacology
January 2012
Ronald S Duman, Nanxin Li, Rong-Jian Liu et al.
Currently available medications have significant limitations, most notably low response rate and time lag for treatment response. Recent clinical studies have demonstrated that ketamine, an NMDA receptor antagonist produces a rapid antidepressant response (within hours) and is effective in treatment resistant depressed patients. Molecular and cellular studies in rodent models demonstrate that...
The International Journal of Neuropsychopharmacology
November 24, 2011
Jason M. Dwyer, Ashley E. Lepack, Ronald S. Duman
169 citations
Recent studies demonstrate that ketamine, a fast-acting antidepressant, rapidly activates the mammalian target of rapamycin (mTOR) and increases synaptogenesis in the prefrontal cortex. Because of the side-effect and abuse potential of ketamine we are investigating alternative agents that produce similar effects. Here, we demonstrate that a single dose of LY 341495, an mGluR₂/₃ antagonist,...
Biological Psychiatry
February 3, 2011
Nanxin Li, Rong-Jian Liu, J. Dwyer et al.
Background Despite widely reported clinical and preclinical studies of rapid antidepressant actions of glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonists, there has been very little work examining the effects of these drugs in stress models of depression that require chronic administration of antidepressants, or the molecular mechanisms that could account for the rapid responses....
Science
August 19, 2010
Nanxin Li, Boyoung Lee, Rongjian Liu et al.
2,875 citations
The rapid antidepressant response after ketamine administration in treatment-resistant depressed patients suggests a possible new approach for treating mood disorders compared to the weeks or months required for standard medications. However, the mechanisms underlying this action of ketamine [a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist] have not been identified. We observed...
Journal of Neuroscience
April 15, 1997
Vidita A Vaidya, Gerard J. Marek, George K. Aghajanian et al.
482 citations
The influence of 5-HT receptor agonists on the expression of BDNF in brain was determined. Administration of a hallucinogenic 5-HT2A /2C receptor agonist, but not a 5-HT1A receptor agonist, resulted in a significant but differential regulation of BDNF mRNA levels in hippocampus and neocortex. In the hippocampus, the 5-HT2A /2C receptor agonist significantly decreased BDNF mRNA expression in the...