This is an excellent question and one that we have thought about and begun to investigate. In fact, the Brain Bank of the Pritzker Consortium under the directorship of William Bunney, M.D. (at UC Irvine and also a member of the Foundation’s Scientific Council) collects careful data on medication history. And the answer is: Yes, treatment reverses some of the damage caused by the illness, but not all the way back to normal. It is important to note that the brains we are studying are those of people who have died while carrying a diagnosis of depression. So, by definition, the antidepressants were not fully effective in helping them clinically, and we can see that they were not effective in reversing the biological impact of the illness on the brain. If we had access to brains of individuals who had a history of depression that was well-controlled by antidepressants, we might see either a more complete reversal of the damage induced by depression, or some compensation where other genes and brain circuits are induced to counteract the consequences of the illness. From animal studies, we actually believe that this would be the case. But this process takes time, which is why even when people feel better after receiving some fast-acting treatments, repeated treatment is needed for sustained recovery—brain remodeling is not instantaneous.

Ideally, as we understand more and more about the causes of various types of depression, we can target treatments more strategically to reverse or, better yet, prevent the changes we see in chronic depression. In fact, preventing or rapidly reversing these brain changes should greatly accelerate clinical recovery and prevent recurrence.