Synaptic Dysfunction in Depression: Potential Therapeutic Targets

By R. Duman, G. Aghajanian. Science, 2012

1,531 citations recorded by the source corpus.

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 months. A notable recent discovery shows that ketamine, a N-methyl-d-aspartate receptor antagonist, produces rapid (within hours) antidepressant responses in patients who are resistant to typical antidepressants. Basic studies show that ketamine rapidly induces synaptogenesis and reverses the synaptic deficits caused by chronic stress. These 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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Pharmacology

View Paper: https://www.semanticscholar.org/paper/0424ba9f21c388af3a81e3c53dbc3193d3aa2cc8

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In Cellular and Molecular Neuroscience

In Cognitive Neuroscience

In Pharmacology

Citations in the corpus

Psychedelics Promote Structural and Functional Neural Plasticity (2018, background): “Psychedelics Promote Spinogenesis and Synaptogenesis In addition to dendritic atrophy, loss of dendritic spines is a hallmark of depression and other neuropsychiatric disorders (Christoffel et al., 2011; Duman and Aghajanian, 2012), so we next assessed the effects of psychedelics on spinogenesis.”
From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression (2014, background): “Another instance may be under conditions of acute stress that indicate increased social threat or the possibility of physical danger (Duman & Aghajanian, 2012).”
New design strategies for antidepressant drugs (2013, background): “Ketamine and other NMDA glutamate receptor antagonists elicit an antidepressant response within hours, as opposed to the weeks required of monoamine-based drugs [69].”
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial (2013, positive): “Ketamine appears to rapidly reverse both behavioral and neuronal changes associated with chronic stress, in part through activation of the mammalian target of the rapamycin signaling pathway and stimulation of brain-derived neurotrophic factor signaling (35).”