.DrewRamseyMD and J. John Mann, MD, discuss the serotonin hypothesis of depression. PsychTwitter
Hello, everyone. Welcome back to Medscape Psychiatry. I'm Dr Drew Ramsey. I'm an assistant clinical professor of psychiatry and part of the Medscape Psychiatry editorial board.
Is it true that the chemical imbalance hypothesis is just wrong, and we shouldn't think about that or explain depression like that to patients anymore?First, we need to remember that there is a significant genetic component to both MDD and bipolar disorder. That means that there is a biology out there that's at least partly genetic. Then we also know that adverse childhood experiences significantly increase the risk for the development of a mood disorder in adulthood.
You've been interested in these other systems, the GABAergic and glutamatergic systems, since I was a resident 20 years ago. In addition, there's a whole new interest in inflammation and neuroplasticity. Serotonin plays an important role in early brain development, but it also plays a fundamental role in ongoing brain health throughout life. We can see now that. For example, if you look at the brain of individuals who died and who suffered from, say, MDD, the dentate gyrus, which is part of the hippocampus where neurogenesis occurs in adulthood, is half the size in depressed patients.
The longer they stay in this state of depression untreated, the worse the condition gets. The sooner they start treatment and the more consistently they stick with a treatment, the sooner they're going to get on the path toward normality. Meanwhile, inflammation is tied in with this. Some of the inflammation is protective, and some of the inflammation is damaging, like in many medical conditions.
Could you help us understand a little bit about the long-term safety of SSRIs? It sounds like one way we should think about explaining them to patients is around the neurogenesis effect and the anti-inflammatory effects. These aren't serotonin medicines making serotonin go up. You haven't thought about them that way for a long time.SSRIs have been prescribed to huge numbers of people for a very long time. They don't have a long-term, cumulative, toxic, bad effect.
What's the downside of long-term use? Some people don't like the side effects, and maybe most people don't like side effects. Of course, that's completely standard. You're trading side effects vs benefit. That's true of any medication.
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