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]
Archive for the ‘AMPA receptor’ Category
Image 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.