tag:blogger.com,1999:blog-8353442983052145851.post4241957594764032916..comments2024-03-14T18:26:18.208-07:00Comments on autism's gadfly: The Locus Coeruleus and autismjonathanhttp://www.blogger.com/profile/14972394536850151087noreply@blogger.comBlogger12125tag:blogger.com,1999:blog-8353442983052145851.post-58080347594643322392009-04-07T19:01:00.000-07:002009-04-07T19:01:00.000-07:00Wow, I was just going to blog on this article, but...Wow, I was just going to blog on this article, but seems you and your commenters have all my major points covered ;-)<BR/><BR/>-ParisSavedAspiehttps://www.blogger.com/profile/08711812514826013534noreply@blogger.comtag:blogger.com,1999:blog-8353442983052145851.post-28866196663166114942009-04-06T23:42:00.000-07:002009-04-06T23:42:00.000-07:00I was forwarded an article about this topic the ot...I was forwarded an article about this topic the other day, only the source I received came from an online science blog.<BR/><BR/>Oh, I'd love it if there was a way the neurons stuck together in a bundle in the Locus Coeruleus could be seperated and migrated to the proper brain regions so me and the other 'sheltered' autistics (ND folks especially seem to enjoy being sheltered and likely don't get outside their houses much) could be free of this curse!<BR/><BR/>When I was little, I actually did feel a bit hyperactive whenever I'd get a fever at times (really stimming and wanting to play video games- really the same one(s) I had playing for a while...whatever game(s) I was focused on and enjoyed playing at the time of my fever). My mom would wonder if I should have gone to school whenever the middle to the end of the first day or second, or usually third day coming off a fever if I should have attended school instead of deciding to stay home. <BR/><BR/>I never enjoyed taking a nap until I got older and depressed and insecure due to having repressed some things due to no one understanding my co-morbid problems that come along with my autism and from sensing I knew all along I've been living with brain dysfunction glitches that turn out they have needed 're-wiring' for years, only no one else or myself really ever thought it was because I needed to see a speech-language pathologist who specializes in dealing with those on the autistic spectrum and other disabilities who've gained speech and language regardless of having had speech therapy as a child. No one could ever understand where I was coming from (or could they have in reality?) despite dealing with some of the smartest people online.<BR/>Half of them thought I was annoying after a while even though they were the ignorant ones. <BR/><BR/>Oh well! It's the Internet!Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-8353442983052145851.post-52442626041409779852009-04-06T15:22:00.000-07:002009-04-06T15:22:00.000-07:00An interesting article that explains epigenetic, i...An interesting article that explains epigenetic, it should be apparent as to why this is very relevant to autism. <BR/><BR/>http://pubs.acs.org/cen/science/87/8714sci1.html<BR/><BR/>In my opinion autism is a condition with altered integration between systems, between brain regions, between the brain and the periphery and the CNS and there are many way to impede that integration. (This is a view shared by others like Martha Herbert). That could explain why there is no consensus about specific brain regions implicated, specific genes, or specific trigger. I have seen people without a diagnosis of autism behaving in very autistic ways because some of their senses are affected for example deftness, also, there are co morbidity of autism with several genetic conditions- which are totally unrelated in term of etiology, same is true of some infectious disease contracted at critical time of development . Finally, I think anyone can behave in an autistic way under certain circumstances, being an illness, being an intense emotional trauma, being a sensory overload.SM69https://www.blogger.com/profile/16239400845268784984noreply@blogger.comtag:blogger.com,1999:blog-8353442983052145851.post-14598672017899625662009-04-06T00:09:00.000-07:002009-04-06T00:09:00.000-07:00Hi JakeThanks for flagging this study- I measure t...Hi Jake<BR/><BR/><BR/>Thanks for flagging this study- I measure the same markers in the urine and have the same findings (collecting data as we speak to look at ASD population level), isoprostane, but also 2 others markers that results form oxidative damage to DNA and RNA. The results are very interesting as these markers correlate with others, neopterine, a merker of cell-mediated immunity (meaning immune system is activated), and also often, but not always elevated porphyrins, particularly pre-coproporhyrin (mercury related porphyrin). The profile is very tight, that’s possibly the most interesting tools we have at the moment as initial screen to sub-categorize the kids, all in the urine and pretty inexpensive to run. Oxydative stress/ inflammation is very very common in autism.SM69https://www.blogger.com/profile/16239400845268784984noreply@blogger.comtag:blogger.com,1999:blog-8353442983052145851.post-75928055756220050272009-04-05T22:52:00.000-07:002009-04-05T22:52:00.000-07:00"Well Jon, problems with the locus coerulus would ..."Well Jon, problems with the locus coerulus would definitely explain our problems with executive functioning"<BR/><BR/>Jake, the inability to properly footnote is not necessarily an executive functioning issue and based on your statements that you don't require any accommodations, I don't believe you have executive functioning issues.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-8353442983052145851.post-78985373044578139792009-04-05T15:49:00.000-07:002009-04-05T15:49:00.000-07:00Well Jon, problems with the locus coerulus would d...Well Jon, problems with the locus coerulus would definitely explain our problems with executive functioning, however it would not explain our problems pertaining to communication, but those of the frontal and pariental lobes would which is probably explained by cerebral vasoconstriction.Jake Crosbyhttp://www.ageofautism.com/jake-crosbynoreply@blogger.comtag:blogger.com,1999:blog-8353442983052145851.post-5698396198631265552009-04-05T11:50:00.000-07:002009-04-05T11:50:00.000-07:00Well, from personal experience Tom has just come d...Well, from personal experience Tom has just come down with chicken pox. He is itching, feverish and downright miserable. There is absolutely no mitigation of his autism.bulletnoreply@blogger.comtag:blogger.com,1999:blog-8353442983052145851.post-15253635516721215232009-04-05T09:58:00.000-07:002009-04-05T09:58:00.000-07:00well that is an interesting study, don't really ha...well that is an interesting study, don't really have a comment on it, other than I am more interested in specifically what brain areas are affected in autism. I was interested in posting about the locus coeruleus because i had that theory for a long time. <BR/><BR/>Of course, now it seems the most widely replicated findings are in mirror neuron dysfunctions in the frontal and parietal lobes. I may blog about that in the near future.jonathanhttps://www.blogger.com/profile/14972394536850151087noreply@blogger.comtag:blogger.com,1999:blog-8353442983052145851.post-82636996131589070972009-04-05T09:34:00.000-07:002009-04-05T09:34:00.000-07:00Sorry about that, here's the text, if your search ...Sorry about that, here's the text, if your search "autism" "penn" and "vasoconstriction" you should be able to find the original page...<BR/><BR/><BR/>NEWS RELEASE <BR/>--------------------------------------------------------------------------------<BR/>AUGUST 15, 2006 <BR/> Penn Researchers Find Link Between Autism and Abnormal Blood-Vessel Function and Oxidative Stress <BR/> New Findings Could Help Explain Pathology of Autistic Syndrome <BR/> (Philadelphia, PA) - Researchers at the University of Pennsylvania School of Medicine discovered that children with autism showed signs of abnormal blood-vessel function and damaging levels of oxidative stress compared to healthy children. The children with autism possessed levels of biochemicals that indicate the presence of constricted blood vessels via the endothelium (the cells that line vessels) with a higher tendency to form clots (through cells called platelets). <BR/><BR/>By exploring the relationship between oxidative stress and blood-vessel function in autistic patients, investigators hope to find new therapeutic options for this syndrome. The researchers, led by Domenico Pratico, MD, Associate Professor of Pharmacology, published their findings in the August issue of the Archives of Neurology.<BR/><BR/>According to the Autism Society of America, the reported number of autism cases is increasing 10 to 17 percent per year in the United States. Autism, an early onset neurological disorder, is characterized by impaired social interactions, limited verbal and nonverbal communication, and repetitive and restricted behavioral patterns. Patients with autism can differ in the severity and scope of their symptoms, suggesting that multiple factors contribute to explaining the disorder’s symptoms. Previous studies at other institutions have shown that autistic patients have reduced cerebral blood flow, presumably due to constricted blood vessels in the brain, versus healthy controls.<BR/><BR/>Urinary samples of autistic children who were similar in age and healthy controls were provided by the Pfeiffer Treatment Center, where patients were diagnosed with autism disorder and evaluated. Patients were excluded from analysis if they had ever received anti-oxidant treatments or medicine with any known anti-oxidant effect; if they suffered from chronic illnesses, such as depression, psychosis, or inflammatory disorders; and/or if they were sick at the time of the sample collection. These strict criteria resulted in the small sample size in this preliminary study: 26 children with autism and 12 healthy controls.<BR/><BR/>Pratico’s team measured isoprostane, a biomarker for oxidative stress; thromboxane, an index of platelet activation; and prostacyclin, a measure of blood vessel activation in the samples. “This study represents the first observation that the rates of thromboxane and prostacyclin synthesis are both not only significantly increased in autism, but are closely correlated with the rate of oxidative stress,” says Pratico. Compared with controls, children with autism had significantly higher urinary levels of isoprostane, thromboxone, and prostacyclin. <BR/>Oxidative stress is the result of an excessive formation of chemically unstable byproducts, called free radicals, within the cell. Under normal conditions, the cell is able to destroy the free radicals. However, when excessive free radicals accumulate, these molecules mount an attack against the cell in search of chemical stability. <BR/><BR/>“During oxidative stress, it is as if the free radicals have only one leg,” explains Pratico. “They are searching for the second leg in order to keep from falling. Unfortunately, the ability of the excessive free radicals to reestablish their chemical equilibrium comes always with a price for the organ -- irreversible cellular and organ damage.” Free radicals can damage cell membranes, proteins, and genes by oxidation -- the same chemical reaction that causes iron to rust.<BR/><BR/>Pratico and colleagues measured levels of isoprostane, the chemical byproduct of free radicals attacking fat cells and found that patients with autism possess nearly double the level of oxidative stress than that measured in healthy controls. <BR/><BR/>The samples from autistic patients also revealed a biochemical imbalance in the patients’ blood vessels, resulting in high levels of thromboxane - an indicator of platelet activity - and prostacyclin, an indicator of constricting endothelial cells. During normal function, thromboxane and prostacyclin work together to maintain the integrity of vessels. In response to different kinds of stress, platelets release thromboxane, which causes vessels to contract. The endothelium responds to elevated levels of thromboxane by releasing prostacyclin. This event counterbalances the effect on vessels, inducing dilation of the vessel and, in turn, more blood flow. <BR/><BR/>Autism is a complex neurological disorder and oxidative imbalance is one feature of the autistic syndrome. Several lines of evidence support the hypothesis that oxidative imbalance may also play a role in this disease: autism is characterized by an impaired anti-oxidant defense system, higher free-radical production, and improvement of behavioral symptoms after taking anti-oxidants.<BR/><BR/>“In general, it is known that abnormalities in blood vessels can be clinically reflected by an abnormal blood flow,” says Pratico. “In this regard, it is interesting that earlier neuroimaging studies of autistic children have demonstrated a reduced amount of blood reaching the brain. Shedding more light on the relationship of oxidative stress and blood-vessel health to the pathology of autism could lead to improvements in therapy.”<BR/><BR/>Study co-authors are Yuemang Yao from Penn; William J. Walsh, Pfeiffer Treatment Center (Warrenville, IL); and Woody R. McGinnis, Oxidative Stress in Autism Initiative (Ashland,OR). The research was supported in part by the Pfeiffer Treatment Center.Jake Crosbyhttp://www.ageofautism.com/jake-crosbynoreply@blogger.comtag:blogger.com,1999:blog-8353442983052145851.post-81326546997095747382009-04-05T09:05:00.000-07:002009-04-05T09:05:00.000-07:00hi jake, i checked out that link, but the server w...hi jake, i checked out that link, but the server won't let me read that file.jonathanhttps://www.blogger.com/profile/14972394536850151087noreply@blogger.comtag:blogger.com,1999:blog-8353442983052145851.post-46692325705919862622009-04-04T23:05:00.000-07:002009-04-04T23:05:00.000-07:00Hi Jon, what do you think of this study by Penn re...Hi Jon, what do you think of this study by Penn researchers linking autism to vasoconstriction and subsequent oxidative stress on the brain?<BR/>http://www.uphs.upenn.edu/news/News_Releases/aug06/autbldvsl.htmJake Crosbyhttp://www.ageofautism.com/jake-crosbynoreply@blogger.comtag:blogger.com,1999:blog-8353442983052145851.post-3353770999728999222009-04-03T20:05:00.000-07:002009-04-03T20:05:00.000-07:00Yeap, I saw this report earlier this week but have...Yeap, I saw this report earlier this week but have not yet read the study- one thing came to my mind right away when this was mentioned, that is of course, that although yes some kids with autism improve with fever, it is by no mean all of them (this has been reported maybe in 20 of 300 kids I have seen, at most, I do not know for sure on the top of my head). And unlike what was stated in the news report, no one could ever claim that these improvements equal to recovery, who would test autism rigorously in a child who has fever anyway? That’s just unethical. Also, generally speaking these kids also present with clear indication of latent infection and a better explanation relate to the improvement of their immune system with fever (which is we should remember a natural healthy good response to infection- many of our kids do not develop fever when they have an infection). I think this is much more of a theory than any of the other issues you have discussed in your post, but one should always consider ideas as a matter of principle. Regarding the imaging brain studies you brought in your psot, you need to keep in mind the incredible disparities in both structural and functional imaging findings obtained so far- the only consensus is that they don’t agree and virtually nearly every part of the brain has been implicated one way or another in autism, prefrontal, temporal, parietal, cortex yes the limbic system, the cerebellum, and even the brain stem. Also, many studies have found little brain abnormalities that could be detected with the techniques used. There are a few post-mortem studies in children dying accidentally, the most impressive one in my opinion is from Vargas 2005, it shows some abnormalities in the cortex and in the cerebellum with loss of Purkinje cells, but most of all the most dramatic differences found were in the levels of inflammatory cytokines with 200 fold increase for IFN-gamma (interferon gamma) for example and activation of microglia (also relating to inflammation). A whole bunch of immune markers and growth factors were tested in that study. It is very elegant. There are also studies coming up that suggest that in cases of regression, there is acute demyelination (seen by MRI scan and also with the presence of antibodies against Myelin basic protein) and that these abnormalities resolve after the acute phase of deterioration of function. It is possible that even within individuals, there are temporal longitudinal variations. <BR/><BR/>Well that post contrasts with the poem I sent earlier on! I can share references /papers for the very keens.SM69https://www.blogger.com/profile/16239400845268784984noreply@blogger.com