What is the Neurochemical Basis of Mania?
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Q:  What is the Neurochemical Basis of Mania?

Dear Dr. Phelps,

I am interested in the neuro-physio processes of bipolar disorder.  I also suffer from chronic pain resulting from a back injury, so one particular area of interest to me is the correlation between manic symptoms and decreased sensitivity to pain, and what triggers this action.  I realize that there may be an increase in endorphins during the course of my manic episode, and the increased adrenalin most likely contributes to the increased energy and decreased need for sleep, which creates some hazards for me.  But, what else is going on and why are these chemicals/hormones being released or suppressed on one occasion, but not on another?  The synapses seem to function normally, then suddenly malfunction.  Sometimes my manic symptions are brought on by a major stressor but other times the onset appears to come out of nowhere (or I have not yet recognized the antecedent(s)). 

Have there been any studies that have measured the (known) chemical processes before, during, and after a manic episode?  I have a somewhat related question as well: When percocet did not relieve my pain, I found that cocaine did, but became horribly addicted to the substance.  My manic episodes are quite similar to that of being high on cocaine.  I was diagnosed with bipolar when I stopped using the drug when I was about 26yrs old.  Did my cocaine addiction cause or contribute to my bipolar diagnosis, or was it something I have always had and the diagnosis was simply age related-- the approximate time that symptoms of bipolar begin to appear?  I've asked you for quite a bit of information and I appreciate your time and expertise.  Many thanks for any information or  resources you may be able to provide.


Dear Ms. K' -- 
Taking your two (at least) interesting questions here: 

1. what else is going on and why are these chemicals/hormones being released or suppressed on one occasion, but not on another?  
What is the neurochemical basis of mania? Ah, that's simple. Just kidding. I hope a Nobel prize will be awarded someday to Dr. Husseini Manji, whose research group has led the hunt for the answer to this question. You'd be amazed at how far they've come, but the answer is turning out to be tremendously complex. Indeed it seems to tie in directly to our huge human capacity for learning, a phenomenon called "neuroplasticity". You can learn about this concept as applied to depression on my education website by taking this link to the
Brain Chemistry of Depression pages; look particularly at Part Two: Stress Mechanisms, From Molecules to Brains.

But that doesn't get into the mechanisms of mania (and, presumably, hypomania) because these are as yet still much fuzzier -- though what Dr. Manji and others have learned so far points at the same mechanisms, this "neuroplasticity" business, as likely the basis of mania as well. Another 10 years or so (although that's what I was saying 10 years ago; but the pace of understanding is accelerating dramatically, so this time I hope I'm right). 

2. Did my cocaine addiction cause or contribute to my bipolar diagnosis, or was it something I have always had and the diagnosis was simply age related? 
You can imagine that this question comes up all the time. Even if you hadn't used cocaine, there might have been something else going on around age 26 that we could now wonder -- "did that cause it?" And plenty of people seem to have symptom onset with no clear cause -- so you're certainly right to wonder if it could have happened anyway. 

On the other hand, some new research has recently suggested that for schizophrenia, smoking marijuana really is a potential "cause". For that illness also, people always wonder if the substance use was part of the cause, or not. I've always answered in this "maybe yes, maybe no" fashion (as above) -- until this new research came along (in the carriers of a particular variation of a dopamine-related gene, marijuana users had a higher of developing schizophrenia; whereas in those with another common gene variation, there was no association between marijuana use and the illness: Caspi). 

If we had these kinds of data for bipolar disorder and cocaine, we could give you a much better answer. Since cocaine is if anything a more potent stimulus for some of the same kinds of experiences (like mania, as you point out) that are part of bipolar disorder; and since there is some concern that each episode of mania may in some people, not all, increase the likelihood of subsequent episodes, it does rather seem as simple as adding two plus two to arrive at the conclusion that cocaine could have played a role in landing where you are. And yet this conclusion is really the result of adding together a series of guesses (albeit educated guesses); and guesses based on guesses are not worth much in the world of science. Politics, perhaps. Sounds like you've already had enough experience with cocaine to know you should avoid it in the future, though: that's probably more than an educated guess! 

Good luck from here. 

Dr. Phelps

Published July, 2006


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