Modulation of Dopamine Neurons and Depression

Both the Tye et al and Chaudury et al articles really got me thinking about the bigger picture of how we have developed treatments for depression and what we might do in the future to be more effective and individualized about treatment plans. The Tye article highlighted the idea that there are several interconnected mechanisms at play that cause the varying symptoms of depression. This means that it will be complicated to tease out one or two circuits with a group of experiments, and that we then have to determine how these mechanisms interact with or against each other in different individuals. The complexity of these systems explains why the same antidepressants can have such varying affects on different people and how different depression symptoms can look in different people.

I have also wondered about the difference between acute anxiety and stress and how this can be observed in animal models. Also, behaviorally, humans differ greatly in their outward expression of depression and I believe can suffer from chronic depression without suffering from acute anxiety. The Chaudhury article alludes to this when they mention research that has been done that shows that chronic mild stress and more severe stressors have opposite effects on the activity of VTA dopamine neurons and produce “different changes in levels of extracellular levels of several neurotransmitters in a number of brain areas”.

The Chaudhury article also talks about the differences between susceptible and resilient mice and what stimulation can cause an instant switch between the two phenotypes. This makes me wonder about what future capabilities we might have with humans to test for susceptibility, and in conjunction with the type of research done in the Tyre article with complex and varying mechanisms, what ability we might someday have to test individuals for specific mechanisms and produce individualized and much more effective treatment.