I just finish a chapter (chapter 7, if one of y'all have the book) in Lights Out that discussed serotonin levels and has left me a bit bemused. The author discusses how high levels of serotonin lead to depression, rather than the more common assertion that low levels are the root cause. It delved into how SSRI's lead to such high levels of serotonin that one experiences a 'resistance' and is comparable to having low levels - and that is why depression is lowered ...
I think I should re-read the chapter to make sure I fully understood, but my question is:
Do high levels or low levels lead to depression? How does this work (e.g. neurobiology behind it)? Any good links? (I have bought my quota of books for a while ... so links are preferred ... but if you have a good book suggestion that would good ...)
Its gonna be long but detailed. Serotonin is made from dietary breakdown of carbohydrates especially in foods high in phenylalanine, Leucine and tryptophan. These are found in fruits that grow in long light conditions. Serotonin balance in the brain is just that.....a balancing act. It is a question of balance from hormonal control and our biochemistry. Once the carbs are absorbed most of the AA that form serotonin are collected in the enterochromaffin cells of the gut. There is also serotonin in the brains serotonergic nerve tracts. Serotonin is closely regulated in the gut and brain. Excess serotonin is converted to melatonin by the brains' pineal gland when darkness is present for at least 3-4 hrs. This assumes that your pineal gland is not calcified and is working well. Don't assume this because I have not seen a non calcified pineal in 20 years of being a neurosurgeon. If there excess is greater it remain tied up in the gut but will eventually have to be dealt with.
Sleep diurnal rhythms are tied to light cycles of our sun. Carbohydrates tend to be more plentiful when the light is out for longer periods of time. That is why fruit is plentiful in summer. Therefore, sleep tends to control your appetite for carbs. And we know scientifically that serotonin balance is tied to ghrelin and leptin. Nature matches biology in balance. Of course that assumes you still have control and that loss of insulin regulation or signaling is not present, or there is no sources of artificial things like light or "fake foods" (HFCS) to fool your biochemistry. Approximately 80 percent of the human body's total serotonin is located in the enterochromaffin cells in the gut, where it is used to regulate intestinal movements. So excess is stored here. The brain serotoninergic nerves have the rest. The plasma level is the variable part of the equation based upon the organisms surroundings and hormone status and their light levels.
So when there is no control in this system one gets even more serotonin from carbohydrate use. You have zero balance. TO ANSWER YOUR QUESTION HERE, BOTH LOW AND HIGH LEVELS OF SEROTONIN CAN CAUSE DEPRESSION! And if your eating more carb substrate the problem is even worse. And when you don't sleep well you don't convert serotonin to melatonin so it builds up even more. The brain has to do alternative things with the serotonin. High levels of serotonin then are allowed to persist and it begins to fry your neurochemistry in many parts of your brain. The sympathetic nervous system is one of those systems among others. But that system requires nerve growth factor, and brain derived neurotropic factor. Both of these chemical replenish old worn out cells from our stem cell population. If those systems no longer work then high serotonin constantly makes cells stressed and drives cells into apoptosis (suicide) and there is less chemicals around that allow our stem cells to replace them. When cells are not replaced at appropriate times the synapse ages and the amount of serotonin in the nerve terminals seriously degrades. That means intracellular serotonin plummets!!!! So the serotnergic system in the brain has LOW LEVELS of serotonin in it but the PLASMA LEVELS ARE HIGH and the serotonin can not be utilized in the cells of the brain. The constant high levels of plasma serotonin exacerbate the condition further. Simultaneously, High levels of serotonin also increase ROS generation from our mitochondria because as cells age and they can be replaced because there are no more stem cells, older cells have to stick around and face the constant bombardment of oxidative phosphoryaltion. This is a chemical process necessary for life but incredibly abrasive to biologic systems. That is why the mitochondria is walled off from the cell and why it has an inner and outer membrane too.
Low levels of newly generated NGF also completely depletes our ability to lay down new memories because we can not make new nerve cells from stem cells. So we become more forgetful too and depressed because our old worn out cells are stuck. Loss of sleep also leads to higher levels of cortisol......you know this is not going to end well don't you now. This is like throwing gasoline on a burning house. It does not get better. Cortisol chronically raised, decreases your immune system function. Specifically, natural killers and T cells. We also know from Dr Dean Cruess work at UPenn that people who lack sleep are more likely to choose foods upon waking that put on extra pounds. Refined Carbs to replenish the perceived CNS losses! The factory worker dont realize there is no more boxes to stroe all the serotonin they have got!!! They want to replace the old serotonergic synapses that cant be recycled because of the stem cell issue. Subsequently, you're less motivated to make better decisions when your tired. You're also less motivated to exercise for the same reason.
You become a dog chasing its tail. Its a feedback loop that goes awry. Same as it does in insulin resistance, leptin resistance and any other hormonal feedback loop you want to study.
Read http://raypeat.com/articles/articles/serotonin.shtml and search through the articles in Dr.Peat's website.
Link fixed in edit.
Sorry, but, I think that you both are crazy, Dr Kruse article was very informative and spelled out exactly the answer to her question about Depression, to bad, maybe you just didn't have the will to read the article in the first place.