Which interleukin is the culprit!?

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Okay, for those of you who don't know, I'm referring to the association between abnormalities of the immuno-defensive system and the expression of autism. Apparently, many autists have either abnormally sturdy or dangerously unstable immune systems. I'm not entirely sure which is more common because I've only recently been exposed to the idea, but it's quite curious what led me to this reasoning. A friend of mine who seems to suffer from albinism, adult ADD, depersonalization, and schizotypal personality disorder, all at once, got me curious when he mentioned that his albinism is supposed to be linked with a tyrosinase deficit. Now, tyrosinase is a highly important enzyme in the human body; it's necessary for translating tyrosine into pigment. Well, since I've got a constant obsession with the opioid system's interactions with various workings of the human body, I eventually managed to mine out from the depths of various scientific studies that tyrosinase also performs the action of converting certain opioids into what are called "opiomelanins," pigment-like molecules. Now, don't make fun of me: I supposed at first that the opioids not being put through this conversion could be performing the action of lowering his norepinephrine levels and raising his dopamine levels. The guy's a bit of a mathematical savant, so this actually made a bit of sense.

However, I then got curious as to how dopamine is translated into norepinephrine and discovered from extensive reading that the enzyme that does this work is called dopamine beta-hydroxylase (DBH). Well, naturally, I eventually discovered something about a rare disorder in which the body cannot make this enzyme, and I also discovered that it's possible for there to be a weakness in this gene as well without it being completely absent. A weakness in performing this activity is associated with stillbirths, which I did consider possibly linked with the stillbirth of my father's younger brother. What really turned me on was several of the symptoms, though: during my childhood and, to a lesser degree, today, I have always expressed many of the symptoms of the disorder. However, I couldn't quite go with that because I have never CONSISTENTLY expressed these symptoms, and none of the Parkers (My mother's maternal grand-family), who also SEEM to express symptoms of the disorder, have ever had to be hospitalized for any symptoms related to it. No heart failure, no nothing. They just went their whole lives suffering from chronic nasal stuffiness, and they try EVERY SINGLE TRICK IN THE BOOK to get rid of it. Nothing works, apparently, so I'm stuck with it if I inherited the trait from them.

I realize I'm rambling, but stick with me. You see, all of this seems to have a lot to do with the immuno-defensive system, so I began excitedly exploring any possible relationships between the immuno-defensive system and my little network of enzymes and neurotransmitters. AHAH! HAHA! I actually discovered some parts of the immune system that have the effect of both suppressing the expression of pigment and interfering in the activity of DBH. Actually, I'm not sure whether there's any that do both, but, anyway, they're called "hypopigmenting cytokines." They also affect the opioid system, so you can be sure I was feeling just groovy, see? Part of my inspiration for this line of thinking was that my friend mentioned that many of the better mathematical theorists of the early 20th Century said they couldn't function without constantly being on low-dose amphetamines (which suggests certain types of ADD), AND my friend happens to be a mathematical savant. Well, I'm not sure which amphetamines they were using, but an l-amphetamine would have the effect of correcting a norepinephrine-dopamine instability, which suggests either trouble converting dopamine into adrenal hormones or excessive activity in certain opioid systems. He's otherwise only comfortably superior as far as I can tell. Math is his savant skill. Oh, and another thing of note is that he has two stillbirths in his immediate family, which suggests a POSSIBILITY of a connection with his issues. I'm not sure how much of this is potentially factual and how much of it is just naive speculation, but it's very interesting. Sorry for my thinking seeming so incomplete, but it's hard to express two days of intensive research in just a few minutes here; besides, I wouldn't be here asking questions if I was entirely sure how this all tied together, I'd just publish it in a scientific journal and get rich. I would be too busy spending my money to post here, lol.

Now, from there, I learned about how various interleukins are involved in the expression of schizophrenia and various other issues. Interleukins are a species of cytokine, you see. Now, from here, we're going on the theory that these interleukins are the main culprits in the expression of autism. I know you all have your own hypotheses and favorite theories, and I respect that. Now, looking at the information you have on this subject matter, which interleukins seem to be most responsible for the expression of autism? If we're assuming them to be the culprits, anyway.

And does anyone have any alternative ideas that may be related? How many of you are actually following this? I appreciate any criticism, ideas, or just chatter. If I don't seem to be as versed in this subject matter as I should be, realize I've only been reading about it for a little less than two days.

Oh, and the crazy math guy has recently gotten me addicted to Dorris Day.

Hehe, Doris Day... my mom and you would get along great; she's been a fan since the 40s!

Anyways, on to your actual subject of the thread. I've been reading up on ASC immunology (actually doing an independent study on it atm with the bio department at my uni). As of now, they don't know all the intricacies of the immune system-- not to mention its interactions with the endocrine system, the CNS, etc.-- to proffer anything other than guesses.

Despite that the studies have tended to be small so far, a variety of immune abnormalities have turned up in ASCs and their families, ranging from autoimmune disorders on down to cytokine abnormalities. At present, it seems like there are MANY things which may be different in the immune systems of auties, and they're having difficulties finding any underlying themes other than just "different". On average though, the cytokine profile tends to suggest an activity in the inflammatory branch of the immune system; however, even though abnormalities have been found in the brain tissue, such as various antibodies to self, glial activation, etc., it still doesn't present with a classic inflammatory response within the CNS, such as that seen with encephalitis or meningitis. So they're not sure what is "inflammatory" about it other than there is definite activity in particular inflammatory markers (e.g, cytokines, phagocytes, etc.).

On the other hand, immune differences could not only be a trigger of some of ASC but also a symptom, in that it is not the end-all of causes. Some have suggested, what with the feedback loops between the immune system and the methylation pathway, that perhaps oxidative stress is the key factor, and abnormalities in oxidation may then affect the immune system.

Also, the endocrine system may play a role, since Baron-Cohen's extreme male brain theory and hormonal differences in ASC does seem to carry some weight. The immune system and endocrine system are also involved in a feedback loop with each other. And with the CNS.

In the end, even the slightest change in the feedback interactions between CNS, immune, endocrine, and methylation could drastically alter presentation in any one of the other systems, making behavioral traits still the most common underlying factor (i.e., autism).

Right now, sadly, science seems still in its infancy in understanding complex feedback loops such as these. And can only guess at how one system affects another affects another, etc. Also, science is poorly studied on foetal development when it comes to some of these systems, so without knowing how it all began to develop, it's even more of a guessing game.

I can understand your excitation, your feeling of eureka, and I hope it continues. I, however, found that once I began to acquaint myself with the literature available, it seems like a whole big mess of random pieces at the moment, with no two people being exactly alike-- and not enough scientific knowledge available on these systems in general, let alone related to autism, to begin to make sense of it.

I don't get "eureka moments." I live in one. My dopamine levels never go down, unfortunately. I need to get myself on naltrexone or something of that nature, though I'd prefer low-dose amphetamine or some norepinephrine reuptake antagonist. I don't mind the high dopamine levels, but I have trouble with mental alertness due to it being so disproportionate to my adrenal levels. Anyway, I'm just interested in the possible role of the immuno-defensive system in autism. The only one that I know much about so far is IL-6. I have no idea whether the hypopigmenting cytokines would play the role I THINK they do in human neurology, but I'll work out the connections, if any, in due time. Do you know whether they play any role in the immune system?

The thing is, I think that different things are going to cause different kinds of autism. You'll have my albino friend, for example (schizotypal personality disorder is his diagnosis, but it's related enough to autism), and you'll have sufferers of Addison's Disease which causes excessive tanning of the skin. Autists are going to be just as diverse as any other group of people. The problem with tracking down a definite cause for autism is that we're still limited to diagnosing these disorders by their symptoms. It's like the old form of taxonomy that grouped animals together by habitat and appearance, such as grouping bats together with birds. Once we've sorted out the root causes, many things will be simplified. For example, it's possible that my friend's albinism is a result of abnormal cytokine activity rather than being tyrosinase-negative, and, if so, he'd be held seperate from true albinos, you see? I don't KNOW this is the case for him, but the distinction would be EXTREMELY important.

I think that the "extreme male brain" idea is interesting, but it may be an oversimplification. Also, it doesn't take into account the possibility that autists who completely fit into this theory might be extremely rare. I think it's more productive to examine what is actually happening.

I didn't say his research was bad. I think the research is good. I've actually been torn up quite a few times for voicing my support for the general principles of the theory, and my highly educated opinion remains the same: although I get the impression that he's on to something, my own reading indicates that autism and schizotypy are too diverse to receive such a simplistic label. A variety of conditions could lead to convergent symptoms.