Well, here’s what happens:
The decrease in receptor number on the outside of the cell, is associated with an increase inside the cell of “cyclic AMP” (cAMP). That’s just the first in a string of these “second messengers”. Just what each one is or does is not as important as seeing what happens when they all work together to reach the nucleus of the cell — that yellow oval up there. Here they are:
Finally we have arrived at the new “discovery” of the last several years of research: brain derived neurotrophic factor” (BDNF). Although there are probably other important molecules in the story of depression, this molecule appears to be a probably “final common pathway” — a way that they all work eventually, even when they start very differently — for several different antidepressant approaches. These include antidepressants like Prozac, but also other effective antidepressants like lithiumRicken, ECTDuman, exerciseOliff, and transcranial magnetic stimulation (TMS)Muller. All of these treatments increase BDNF ( at least in rats, and likely in humans, as supported by multiple threads of evidence, e.g. direct measures of BDNF in the bloodstreamShimuzu and indirect measures through the immune systemChen). What is this molecule and what does it do?
As it sounds, this is a molecule that “trophs” neurons. What do “trophs” do? This term comes from the Greek word trophe, which means nourishment. A trophic factor is a molecule that causes neurons to grow, and to flourish. Without such factors neurons decrease in activity and decrease their connections to other cells. Both lithium and valproate, mood stabilizers used in bipolar disorder, increase another neurotrophic factor called bcl-2. Estrogen is another neurotrophic factor! (Unfortunately, we don’t know exactly what to do with that fact, but as we learn, I’ll keep you posted on the Hormones and Mood page).
So, we just learned that the end effect of taking an antidepressant — or regular exercise, or ECT, or rTMS — is to increase BDNF; and that when the cell nucleus makes more BDNF, it helps nourish the neuron. The neuron becomes more active and makes more connections to other cells.
Here’s an irony for you: one study in rats showed that eating a diet high in fat and sugar lowered BDNF levelsMolteni — a result which if shown again in humans has some really stunning implications, don’t you think?
Does psychotherapy, which also definitely works in depression, increase BDNF too? That hasn’t been tested yet. There are several recent powerful studies of brain changes from effective psychotherapy, though, at which you might want to look.
If you want to see some nifty pictures of BDNF itself, and see Prozac maintaining BDNF levels under stress, read more on BDNF.
Otherwise, you can go on to Chapter 10.