Help: Neurochemistry question

post by Will_Newsome · 2011-01-06T15:55:58.866Z · LW · GW · Legacy · 12 comments

I was looking at a hypothesis that bipolar disorder is probably due to problems with neocortical sodium-potassium pump activity cyclically decreasing and thus allowing increased resistance, which increases neuronal excitability by the square of the resistance. According to what I've read on Wikipedia it seems that agonizing Gi proteins would inhibit cAMP production and therefore downregulate sodium pump activity (this was the most tenuous part, and the reference was unintelligible) and increase neuronal excitability. But 5-HT1A (a type of Gi protein) agonists have been shown to be useful for improving symptoms of schizophrenia, which is typically thought of as resulting from increased neuronal excitability. Sign error? What's up? I don't have any model of the underlying mechanisms, and only vaguely know what words like 'downregulate' mean.

ETA: But apparently , a 5-HT2A agonist, also supposedly mitigates symptoms of schizophrenia, which is weird because it increases neuronal excitation. It seems that the flawed assumption is that schizophrenia has something to do with 5-HT-caused neuronal excitability.

Thus it seems like maybe you can reduce bipolar tendencies by taking 5-HT1A antagonists, and schizophrenia is its own separate problem that is perhaps solved by taking a D2 antagonist. 5-HT2A agonists increase neuronal excitation which may interact somehow with the the 5-HT1A antagonists. I'm still confused.

There's this other problem where if the main reason D2 and 5-HT1A work is by decreasing neuronal excitability that might just be because sedate people are more similar to each other than manic people, but the kind of neuronal excitability that makes people manic and the kind that makes people schizoid are qualitatively different, and hence the difference in receptors being important. It could be that 5-HT2A agonists and 5-HT1A antagonists increase and decrease neuronal excitability respectively, but in different ways such that they're not countervailing.


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comment by Will_Newsome · 2011-01-06T16:19:58.504Z · LW(p) · GW(p)

Motivation: I'm trying to figure out how my brain works. I definitely have bipolar tendencies (and genetic reasons to suspect so) and schizoid personality disorder, along with scoring rather highly on autism/Asperger's quizzes. I have a tendency to take more ideas more seriously than most, which I suspect for completely unrelated reasons has to do with increased neuronal excitability. I also seem to have rather high neural plasticity (I learn quickly in varied domains, update ontologies quickly, update beliefs quickly, et cetera) though it's possible that such plasticity is not abnormal among those of roughly my age and fluid intelligence. These factors led me to find the dysfunctional sodium pump hypothesis to be reasonably likely, at least in my case, but it saddens me that I don't seem to be able to easily construct a model out of the hints that Wikipedia is giving me.

Ultimately I think my intellectual productivity (and quality of life, happiness level, interestingness, et cetera) is better when I'm manic and I'd like to take advantage of that, but I feel obligated to see how Algernon's principle applies and if trying to be always-manic-schizo would significantly increase my risk of actual schizophrenia or something else bad like increased neurotoxins due to purposefully messed up sodium pump activity patterns or something unanticipated.

comment by drc500free · 2011-01-06T21:30:24.097Z · LW(p) · GW(p)

I may be reading between the lines too much, but I get the sense that you're not diagnosed by a psychiatrist, or undergoing treatment. If that's the case, this might not be the exact area to try to outdo the professionals.

comment by jimrandomh · 2011-01-06T22:36:59.066Z · LW(p) · GW(p)

Professionals aren't allowed to optimize for their patient's intelligence and productivity, they're only allowed to prescribe medicines to treat the conditions listed in the DSM, which, sadly, does not recognize the lack of superhuman productivity as a disease.

comment by Douglas_Knight · 2011-01-07T06:17:31.257Z · LW(p) · GW(p)

I don't think that's an accurate description of the legal restrictions on doctors. But the legal restrictions are not relevant, only the actual behavior, which has some resemblance to what you say.

comment by playtherapist · 2011-01-08T19:44:42.747Z · LW(p) · GW(p)

As a clinical social worker and a therapist, I can attest to the fact that if you want to bill an insurance company for therapy you have to label the patient/client with a DSM diagnosis. If one is paying a doctor themselves for medication, there probably is a bit more leeway.

comment by drc500free · 2011-01-07T14:30:57.185Z · LW(p) · GW(p)

Believe me, I know that high intelligence can skew a professional's diagnosis. But the underlying disorder is still the same and still treatable with essentially the same methods. You have to shop around a bit anyway to find someone you can work with, and even more so if you are high functioning and cope well.

There's no reason you can't do things traditionally as a baseline, and then decide how to proceed; mania is a terrible place to make a decision from.

comment by David_Gerard · 2011-01-07T17:54:16.145Z · LW(p) · GW(p)

This does not fit my anecdotal knowledge of treatment of friends with these disorders who are smart and insightful.

What are you basing your statement on?

comment by CronoDAS · 2011-01-06T18:13:52.878Z · LW(p) · GW(p)

Ultimately I think my intellectual productivity (and quality of life, happiness level, interestingness, et cetera) is better when I'm manic and I'd like to take advantage of that, but I feel obligated to see how Algernon's principle applies

People who are experiencing mania or hypomania often exhibit overconfidence, impulsiveness, and irritability, and often make poor decisions.

comment by Will_Newsome · 2011-01-06T18:25:46.805Z · LW(p) · GW(p)

Hmuh, in the evolutionary environment where there's not much intellectual work to do these would be enough to somewhat punish mania, but in modern society I think that the increased cognitive performance of manic states is probably a stronger factor... in which case Algernon's law need not be feared. But maybe there are other detriments related to personal health?

comment by Nornagest · 2011-01-06T18:40:33.673Z · LW(p) · GW(p)

I think I'd be more worried about what's causing the tendency toward poor decisions, and whether that generalizes to your own case.

comment by Mitchell_Porter · 2011-01-10T04:18:49.961Z · LW(p) · GW(p)

I know a neuroscientist who explains bipolar disorder using a "sticky switch" theory of hemispheric oscillation. It's related to Ramachandran's theory of hemispheric function. Pettigrew adds to this the idea that there is a natural alternation of hemispheric dominance, on a timescale of seconds, and that in bipolar disorder, the switch rate is much slower, so that a person will spend hours or days with one hemisphere dominant. These long periods are mania and depression. He had some intriguing circumstantial evidence to do with binocular rivalry - the alternation between images was slower in people with bipolar disorder, as if this was driven by the same process.

comment by playtherapist · 2011-01-08T20:05:02.337Z · LW(p) · GW(p)

I'm a clinical social worker/therapist and know a bit about bi-polar disorder and schizophrenia. My clients are all children and few have been given either diagnosis yet, although more will probably when they are older. I don't think that we really know yet whether avoiding medication increases ones chances of actual schizophrenia. One article I recently read actually suggested that taking anti-psychotics long term might prevent one from making a full recovery after a psychotic episode.

I do know that you should avoid certain psychoactive substances, most of which are illegal (LSD, uppers, etc.) and heavy alcohol use. It is also best to try to avoid super stressful situations as much as you can.

It is my understanding that many people with bi-polar disorder (and schizophrenia) don't like their medications because it makes them feel flat.

If you can get objective feedback from family or friends about your behavior in manic states it would be helpful for you to assess whether you should get treatment. You could ask them whether you are doing risky things? Are you so irritable/manic that you are antagonizing others?

My 2nd cousin once removed, Lizzie Simon has bi-polar disorder. She wrote a book, "Detour : My Bipolar Road Trip in 4-D " in which she writes about her own experiences and interviews with other individuals with bi-polar disorder. She was looking for individuals who were functioning well. Lizzie goes around the country lecturing about bi-polar disorder. You might want to check out the book or/and her website.