Most of the time when we teach about the biological basis of major
depression, we make use of the monoamine hypothesis that asserts
that clinical depression is due to an imbalance in the monoamine
neurotransmitters serotonin, norepinephrine and dopamine -- this
view is supported by the results of treatment of depression with
drugs that prevent the reuptake of these neurotransmitters. For
more on this point and additional support, see the Wikipedia entry:
http://en.wikipedia.org/wiki/Serotonin%E2%80%93norepinephrine%E2%80%93dopamine_reuptake_inhibitor#Monoamine_Hypothesis
However, there is a major problem with this hypothesis: it is well
known that the changes in synaptic function related to the inhibition
of monoamine reuptake usually take place in about 72 hours but
changes in mood and behavior, if there are any, usually do not
appear until 4-6 week of treatment. This has led some theorists
to argue that the effect of monoamine reuptake inhibition is
indirect, affecting some other process involving some other
neurochemicals. But which neurochemicals? Various ones have
been suggested and there is new research that provides
support for the neurochemical RAC1.
Medscape has a popular media account of the ("Potential Cause
of Depression Identified" by Megan Brooks, Feb 19, 2013) but
I believe one may have to have a Medscape account to access it.
Registration is free but some may not want to bother with it.
At this point in time (Friday night, 2/22) there are no other popular
media account but I assume that it is a matter of time before
there are. In the meantime, the research was published in the
journal "Nature Medicine" and the abstract can be read here:
http://www.nature.com/nm/journal/vaop/ncurrent/abs/nm.3090.html
The article is not available for free but may be available through
your institution. The reference for the article is:
Golden, Sam A., Christoffel, Daniel J., Heshmati, Mitra, Hodes,
Georgia E., Magida, Jane, Davis, Keithara, . . . Russo, Scott J.
(2013). Epigenetic regulation of RAC1 induces synaptic remodeling
in stress disorders and depression. Nat Med, advance online publication.
doi:
http://www.nature.com/nm/journal/vaop/ncurrent/abs/nm.3090.html#supplementary-information
For more on the biochemical class of agents that RAC1 belongs
to, see the Wikipedia entry on "Rho famile of GTPases":
http://en.wikipedia.org/wiki/Rho_family_of_GTPases
and
http://en.wikipedia.org/wiki/Rac1
If Scott Russo, the researcher who directed the researcher, is correct,
we may have to leave a lot more neurochemistry.
-Mike Palij
New York University
[email protected]
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