Most commonly used antidepressant drugs increase the synaptic content of serotonin and/or norepinephrine. It is commonly believed that this results from the ability of these drugs to prevent their breakdown or reuptake. This theory is contra-indicated by the fact that most antidepressants require 6-8 weeks before any clinical improvement is noted. Thus, antidepressants are likely to have more than one site of action.
Dr. Rasenick and colleagues sought to determine identify those additional sites. What they discovered is that the antidepressants accumulate in the lipid rafts of the cell membrane, but do not cause improvement unless and until the Gsα protein is activated to move out of the lipid rafts so that it can bind with the enzyme adenylyl cyclase to begin a chemical cascade that supports improved neurotransmitter activity.
Gsα resides in cell membranes and is responsible for conveying information from neurotransmitters as serotonin or norepinephrine to the cell interior. One effect of depression is to diminish this action of Gsα, by shuttling Gsα to a cholesterol-rich region of the cell membrane, known as a lipid raft.
Antidepressants have the opposite effect, moving Gsα from lipid rafts and increasing responsiveness to certain neurotransmitters. Thus, the association of Gsα with lipid rafts serves as a biomarker to indicate both depression and the extent of response to antidepressant drugs. Most importantly, this is evident after just a few days of antidepressant treatment–weeks before any therapeutic effect is evident.
MoodMarkDx measures and compares the amount of Gsα in rafts vs. the amount of Gsα not in rafts, providing a new biomarker for depression and antidepressant action.