Chapter 4: The Biologic Basis of Depression

(updated 12/2014) — this is a short one…

In contrast to mania, depression is now quite well understood at a molecular and cellular level. Even some of the genes which are associated with susceptibility to depression have been connected into this molecular-cellular story. A general mechanism by which many antidepressant treatments work, even exercise, has been mapped out.

In brief, this turns out to be a story about cell growth and cell death. The brain is highly “plastic”, a jargon term meaning that the brain is very changeable in response to the demands placed upon it. Brand-new cells can grow in certain regions of the brain. (I know, that’s not what you learned once upon a time, it is a recent discovery). The bad news is that a sustained depression appears to be associated with a decrease in the number of brain cells, and in the number of connections each brain cell makes with others.

The good news is that treatment appears to be able to halt and even reverse this decrease in neuron number and connections. Indeed, this seems to be the fundamental way that effective treatments work.

We have come a long way from understanding depression to be a problem with neurotransmitters like serotonin and norepinephrine. The story is vastly more complicated, and yet a good portion of that complexity is now understood. This is an amazing success story of modern research, and one of my favorite stories to demonstrate that psychiatry can do science too!

I hope that this brief summary will make you want to know more, and see more details about all this. You’ll find them presented step-by-step in a series of mini-chapters that are part of my essay about the brain chemistry of depression (each chapter is only about one long page). The story above begins in Chapter 6 of that series. Alternatively, you might want to start with the introduction to the entire 12- chapter series, then choose to jump to Chapter 6 if you wish.

Link to Chapter 5 (in this series on bipolar mechanism): The Big Picture