The Known World: Words of the Reach and Words of the Crownlands

The present Lord of Highgarden, Mace Tyrell, fought loyally for House Targaryen during Robert’s Rebellion, defeating Robert Baratheon himself at the Battle of Ashford and later besieging his brother Stannis in Storm’s End for the better part of a year. With the death of the Mad King Aerys II and his son Prince Rhaegar, however, Lord Mace laid down his sword, and is today once again Warden of the South and a leal servant of the Iron Throne.

                                             - [The World of Ice and Fire] The Reach: House Tyrell

Why do antidepressants take so long to work?

An episode of major depression can be crippling, impairing the ability to sleep, work, or eat. In severe cases, the mood disorder can lead to suicide. But the drugs available to treat depression, which can affect one in six Americans in their lifetime, can take weeks or even months to start working.

Researchers at the University of Illinois at Chicago have discovered one reason the drugs take so long to work, and their finding could help scientists develop faster-acting drugs in the future. The research was published in the Journal of Biological Chemistry.

Rasenick long suspected that the delayed drug response involved certain signaling molecules in nerve-cell membranes called G proteins.

Previous research by him and colleagues showed that in people with depression, G proteins tended to congregate in lipid rafts, areas of the membrane rich in cholesterol. Stranded on the rafts, the G proteins lacked access to a molecule called cyclic AMP, which they need in order to function. The dampened signaling could be why people with depression are “numb” to their environment, Rasenick reasoned.

Samuel J. Erb, Jeffrey M. Schappi, Mark M. Rasenick. Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G protein, Gαs. Journal of Biological Chemistry, 2016; jbc.M116.727263 DOI: 10.1074/jbc.M116.727263