https://www.theguardian.com/society/2022/oct/22/it-is-a-flaw-in-our-cell...

I was reading the above Article by Dr Siddartha Mukherjee, who is an Oncologist at Columbia University Medical Centre. He has been remarkably open about his health issues and the problem of long term depression that does not seen to lift, His friend , Dr Paul Greengard, a Nobel Laureate, was able to think with him about how medication can revive serotonin levels in the short term giving some relief. However networks of brain cells need time to recover. How do we understand this slower process of recovery as well as the gradual emergence of depression in the first place? How does Serotonin affect the function of the neurone in detail and how dose this differ from one person to another? If the nerve ending and synapses are flooded with serotonin there may be a reduction in the number of serotonin receptors in the nerve ending. How do the different Serotonin receptor subtypes differ from each other in relation to their effects on the cell?  Antidepressants may exert stronger effects in neural chemistry in the raphe nuclei and the thalamus and other midbrain areas in order to diminish the impact of recurrent thinking and anxiety.

In the second part of the article Siddartha is considering Dr Helen Mayberg;s work on Deep Brain Stimulation which has an postive effect on a few patients. The way I am looking at it these days is that everyone;s brain us uniquely designed. Layers of complexity in development may arise from:

1. The migration of nerve cells in development

2. The growth of nerve cells

3. The communication between nerve cells

4. The impact of neural pruning and the dying back of nerve cells, in reduciing connection between nerve cells

5. We experience uniquely different lives that shape our brain and cause unqiue folding of the brain and a unique combination of neural connections. These complex processed are linked to our interaction with the environment and capacity to learn in order to survive.

6. The impact of stress, anxiety and developmental trauma on hypermethylation of certain parts of DNA, thereby reducing the expression of genes that would be protective to cells in the hippocampus.

There will be other stages in the development of the brain , but we can see how a simple model of depression and the revival with serotonin is only going to be part of the story. There are at least 100 neurotransmitters in the brain and it would be good to know what is going on with these in the course of a depressive illness. 

I will return to these themes in future blog posts but hopefully I have given some ideas that can inform our discussions on depression.

Why don't we have more antidepressants targetted at some of the other 1000 neurotransmitters and neuromodulators in the brain?

Is there a future of a tailor made understanding for each individual's experience of depression in terms of neuroscience that is specific to the individual?