In a recent article in the journal Science, researchers working in Italy announced that giving laboratory rats fluoxetine (AKA: Prozac)had the effect of turning on the development of brain cells in the visual area of the animals’ brains. You may be asking yourself “What does that have to do with making depression better!?” If so, you are probably still thinking about mood disorders as “chemical imbalances.” Well, that idea is so-o-o 20th Century! There is now a lot of evidence that new brain cells (neurons) are constantly being born in certain areas of the the brain (the most important is the hippocampus) and that the growth and development of these new cells is needed for normal mood control. One way to think about this process is that this area of the brain must constantly reprogram itself by bringing new neurons on line and making and re-making the connections between these new and the older neurons. The ability to do this remodeling is called neuroplasticity (remember that the original definition of “plastic” is “capable of being molded, or of receiving form.”

These researchers took advantage of a well-known fact regarding the development of the brain’s visual system, namely that this brain area needs visual stimulation just after birth to develop properly. If the visual cortex does not receive this stimulation, this area of the brain doesn’t organize its connections properly and individuals cannot see properly. You may have heard of “lazy eye” (amblyopia) being treated in children by covering their “good” eye with a patch, essentially over-stimulating the “lazy” eye so it can catch up. It’s important to know that the “catching up” happens in the brain, not the eyeball. Also, as individuals mature, this ability to catch up is lost. This brain area loses its plasticity. It used to be thought that the ability of the visual area of the brain to organize in response to this stimulation (its plasticity) completely and irretrievably disappeared in adulthood.

These researchers artificially created a “lazy eye” problem (really, for the reasons stated above, it should be called “lazy brain” or better yet: “lazy visual cortex”) in young rats by covering one of their eyes. As the rats approached adulthood, they gave some of them fluoxetine for several weeks, and they switched the eye patch to the other eye in all the rats. In the rats that did not receive the antidepressant, the artificially created “lazy visual cortex” never recovered when the eye was uncovered. The brain had lost its plasticity, and could no longer respond to the signals from the now opened eye. The rats that had received the antidepressant for two weeks, on the other hand, recovered their vision completely! The fluoxetine had turned on the brain’s ability to adapt. Brain plasticity was restored.

It’s been hypothesized for some years that antidepressants increased plasticity in the hippocampus, but it’s been hard to measure this increase. This study is different, because the researchers looked at an area of the brain (the visual cortex) that completely loses its plasticity in adulthood. Proving that antidepressant treatment restored plasticity to this brain area in adult brains is further evidence that this process is crucial to how antidepressants work.

Two articles in the February issue of Archives of General Psychiatry explore the connction between trauma in childhood and depression in adulthood–on a molecular level. In one study (Bradley et al) researchers examined a gene for a hormone (CRH) in almost 500 persons. CRH acts in the body to set off a whole cascade of stress responses, most importantly: cortisol, the “stress hormone” par excellence. They found that individuals with particular variations in this gene who had been abused were more likely to have depression problems. In other words, particular variations of this gene make if more likely that a person will develop depression if they are a victim of abuse. This is supportive evidence for several theories about causes of depression: 1) An interaction between genetics and environment is responsible for depression, and 2) The stress hormone cortisol is an important factor in the development of depression.

In the other study, ( Ouellet-Morin et al ) 346 pairs of twins were evaluated at 19 months of age. The children were exposed to a mildly stressful situation (having the child and his mother sit in a room into which a women dressed as a clown enters and talks to the child) and the change in the childs’s cortisol level before and after the incident was measured by testing a sample of saliva. The researchers found that a more exaggerated change in cortisol level occurred in the children in which there was some evidence of stress at home (e.g., low income family, single parent household.) It’s interesting to note that in the “stressed” twins, there was no difference between the monozygotic (identicle) and dyzogotic (fraternal) twins. This is interesting because one would expect that there would be a difference in the different kinds of twins if genetics (rather than the stressful environment alone) were the cause of the exaggerated stress response.

Thus, we have a bit of a contradiction between the two findings: the first study found genetic differences in a cortisol-related gene put people at risk for depression, the second found that environment was the more important factor in determining who would develop the exaggerated stress response that is thought to lead to depression. One possible explanation is that there were not enough identical twins in the study to be able to pick up the difference between twin types (the issue of the power of the study.)

The take-home message: Childhood adversity is very likely to be an important risk factor to depression