Depression, Brain Shrinkage and Antidepressants

Medical Reviewer

These days a variety of brain scanning techniques enable us to examine the working brain. The upshot is we have a far better understanding of the areas of the brain affected by depression, as well as the way functions like memory recall and the laying down of new memories is affected. We know, for example, that a part of the brain called the hippocampus can be up to 13 percent smaller in people with depression. Furthermore, the more depression that is suffered the greater the shrinkage. So what’s going on?

In my last post on depression and the brain, I mentioned I'd follow up a comment about depression and associated brain shrinkage. The hippocampus is part of something called the limbic system. This is an area of the brain concerned with basic emotions and drives. The hippocampus has a big role to play in memory but it also has strong connections to another part of the brain concerned with fear and anxiety – the amygdala. Scans tell us that the amygdala becomes much more active when a person is depressed and it remains more active even after recovery from depression.

A recent report in the medical journal Molecular Psychiatry claims to settle the chicken-and-egg question over which comes first: shrinkage of the hippocampus leading to depression, or depression resulting in shrinkage and it appears it’s the depression that triggers brain damage.

As much as there is evidence for shrinkage of the hippocampus there is also evidence the process can be reversed. Co-director of the University of Sydney’s brain and mind research institute, Professor Ian Hickie, is quoted in the Guardian newspaper as stating, ‘the hippocampus is one of the unique areas of the brain that rapidly generates new connections between, and what are lost here are connections between cells rather than the cells themselves.’

It leads us to a question that has puzzled clinicians for some time. Antidepressant medication generally takes several weeks before any clinical improvements are seen (if at all). If depression were simply due to an imbalance in neurotransmitters the effect of antidepressants should be almost immediate. The answer may be that the real antidepressant effect comes from something called neurogenesis, which refers to the generation of new neurons. New neurons strengthen existing nerve cell connections and improve connectivity more broadly. The action of antidepressant medication seems to help spur on the process of neurogenesis. As Professor Hickie points out, there is some evidence that the hippocampus is larger in people taking antidepressants, which suggests they have a protective effect.

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