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Archive for the ‘AMPA receptor’ Category

By Richard Wheeler (Zephyris) 2006.Image via Wikipedia From time to time, it just seems hopeless to adhere to a reductionist strategy in the area of psychiatry and psychology. How, indeed, can our infinitely complex mind be understood in terms of tiny chemical bits ? Just when you’re ready to give up and bid adieu to Descartes and his mechanisms, along comes a reinvigorating paper like Professor Morgan Sheng’s, “Synaptic Accumulation of PSD-95 and Synaptic Function Regulated by Phosphorylation of Serine-295 of PSD-95” (DOI). This paper demonstrates that the the addition and removal of a single – that’s right, a single – phosphate group to Serine 295 of the PSD-95 protein is sufficient to activate or inhibit the recruitment of synaptic proteins such as AMPA receptors and potentiate excitatory post-synaptic current. Given that many complex mental illnesses are associated with synaptic deterioration, there seems to be great therapeutic significance to this finding. [Neuron, Vol 56, 488-502, 08 November 2007]

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Oil on canvasImage via Wikipedia The recent paper, “Genetic Markers of Suicidal Ideation Emerging During Citalopram Treatment of Major Depression” finds that among 68 candidate genes, markers for 2 AMPA-type glutamate receptors (rs4825476, rs2518224: GRIA3 and GRIK2) show significant association in 120 individuals who experienced suicidal ideation in a large medication trial for major depressive disorder. Many families with loved ones suffering from depression remain wary and confused about a possible causal relationship between selective serotonin reuptake inhibitor (SSRI) antidepressants and suicide. A current FDA-mandated black box warning advises youths on the potential risks. This recent genetic study seems to provide a meaningful step forward in better understanding the mechanism of shifts in mood and cognition that occur in some individuals. But like many brain research studies though, shining a tiny ray of light on a puzzle suddenly illuminates massive complexities, previously unseen. A great deal of research shows that SSRI exposure leads to long lasting changes in AMPA receptor expression, localization and function, – but it’s unclear where a specific link between this and changes in mood and cognition will be drawn.

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