Dr. Wakefield Sues Brian Deer and BMJ's Fiona Godlee
That’s My Boy!

The Inflammation Highway: aka Autism

  Tummy-ache-abdominal-pain-t13513By Lisa Goes

"The one thing about my husband and I...we laugh...A lot. We find a way. We really do. Poop filled sleepless nights, injuries, missed appointments, clutter everywhere, missing paperwork...sometimes all you can do is laugh. But today, looking at the dark circles we've seen so many times under our children's eyes, seeing the suffering, the real genuine human suffering that we have worked for three years to alleviate...to see it reach these depths...there is no laughing today. There is sadness. Even the fight is gone. I should be sleeping, but I have to read up on one of our new remedies. Maybe this will be the one that touches his immune damage and regulates him? Maybe. Maybe, it will work for him like it has for THOUSANDS of other children. Maybe. I can't sleep when this could be it and I could be calling the next doctor tomorrow and we could have one less day of this. Plus, I already have an appointment to see a doctor tomorrow and I will need him to know that I know what I'm talking about. If there is one thing you learn as an autism parent it is that YOU MUST KNOW WHAT YOU ARE TALKING ABOUT WITH DOCTORS. You must learn to speak their language. If you don't you will get dismissed. Must read, now.

But, before I go, just need to let everyone know the women who work for us are angels from God. They were hurt today. Two of them. In their sweetest voices they kept repeating, "nice hands." And "time to get down monkey" when he climbed on the counter for the 27th time on their shift. He is 50 lbs now. Very fast and very strong. They get him. They see the real Noah in there, fighting like hell. He is mad. In fact, that's what he said in therapy today, "I'm MAD!" His therapists were thrilled. They were so excited to see him emote appropriately. I agree with them, it's encouraging. It's just that, he's mad he's sick. He's mad his head hurts all the time. He's mad his three year old brother can use the toliet and he cannot. He's mad that his body is rebelling against him and everything hurts. He's mad that in addition to not getting to go where everyone else goes and doing all the fun things other 5 year olds do, he also cannot EAT anything they do. It seems cruel doesn't it? It is.

Autism is the cruelest most malicious, devious, conniving, heinous disease. If you fear the chicken pox or diarrhea more you are in big, big trouble. Because I guarantee with the new schedule autism will come a knocking at your door. And it will get in. It finds a way. Sometimes it looks like OCD, sometimes it looks like ADHD, even arthritis. "That's nuts!", you say. Not really. It should all just be called autism. Because any time pharma causes inflammation they don't want you to find out about, they just make up a word for it. Autism. Asthma. ADD. Just made up words for inflammation. Off to read ABOUT AUTISM . It's a good one, you might want to check it out yourself... Much hope for all our beautiful children. xo lj "

Lisa Goes is Contributing Editor to Age of Autism.



There is more delved into than just depression in the article. Here is a snippet.

Could Depression Be Caused By An Infection?

"Dr. Roger McIntyre, a professor of psychiatry and pharmacology at the University of Toronto, tells Shots that he believes an upset in the "immune-inflammatory system" is at the core of mental illness and that psychiatric disorders might be an unfortunate cost of our powerful immune defenses. "Throughout evolution our enemy up until vaccines and antibiotics were developed was infection," he says. "Our immune system evolved to fight infections so we could survive and pass our genes to the next generation. However, our immune-inflammatory system doesn't distinguish between what's provoking it." McIntyre explains how stressors of any kind — physical or sexual abuse, sleep deprivation, grief — can activate our immune alarms. "For reasons other than fighting infection, our immune-inflammatory response can stay activated for weeks, months or years and result in collateral damage," he says."


Stress sounds the alarmin: The role of the danger-associated molecular pattern HMGB1 in stress-induced neuroinflammatory priming.




As inositol is made in the body it is often thought that you need not supplement it. I don't think it is in most multi vitamins, but as you know, it can be purchased. Benedetta may have more thoughts on it as she said she used it for one of her children and seemed to think lithium actually facilitated it's availability though I have found literature still stating that lithium interferes with its metabolism. There are those who say it helps with mood, ocd, and anxiety, but I have found little about how much it might be of use in Autism. While we never used it in additional amounts wo what was in the Vitamin complex we used it seems reasonable that in some cases it would be helpful with some symptoms.








Very interesting about thiamin, and leptin, too. Info on leptin and grehlin is very interesting to me right now, in regard to their effect on mood.

I'm interested, too, in the mention of inositol 1,4,5 in relation to relevant neurological pathways, though I don't see mention of tics on the chart, though anxiety and OCD are there and I think of tics being in that same behavior class.
Would supplementing with inositol alone be worthwhile? Isn't it a b vitamin? I'm not sure it's included in regular B vitamin complexes or not, though. It's necessary for the growth of yeast, I read, so I could see how one might think twice about using it, yet other b vitamins are critical, it appears, so why not b8?


Some of the inflammatory mediators have been connected to Autism others have not, though they seem to all be involved in my wife's case. {NLRP3 = NALP3}

The redox state of the alarmin HMGB1 is a pivotal factor in neuroinflammatory and microglial priming: a role for the NLRP3 inflammasome.


"The alarmin high mobility group box-1 (HMGB1) has been implicated as a key factor mediating neuroinflammatory processes. Recent findings suggest that the redox state of HMGB1 is a critical molecular feature of HMGB1 such that the reduced form (fr-HMGB1) is chemotactic, while the disulfide form (ds-HMGB1) is pro-inflammatory. The present study examined the neuroinflammatory effects of these molecular forms as well as the ability of these forms to prime the neuroinflammatory and microglial response to an immune challenge. To examine the neuroinflammatory effects of these molecular forms in vivo, animals were administered intra-cisterna magna (ICM) a single dose of fr-HMGB1 (10 μg), ds-HMGB1 (10 μg) or vehicle and basal pro-inflammatory effects were measured 2 and 24h post-injection in hippocampus. Results of this initial experiment demonstrated that ds-HMGB1 increased hippocampal pro-inflammatory mediators at 2h (NF-κBIα mRNA, NLRP3 mRNA and IL-1β protein) and 24h (NF-κBIα mRNA, TNFα mRNA, and NLRP3 protein) after injection. fr-HMGB1 had no effect on these mediators. These neuroinflammatory effects of ds-HMGB1 suggested that ds-HMGB1 may function to prime the neuroinflammatory response to a subsequent immune challenge. To assess the neuroinflammatory priming effects of these molecular forms, animals were administered ICM a single dose of fr-HMGB1 (10 μg), ds-HMGB1 (10 μg) or vehicle and 24h after injection, animals were challenged with LPS (10 μg/kg IP) or vehicle. Neuroinflammatory mediators and the sickness response (3, 8 and 24h after injection) were measured 2h after immune challenge. We found that ds-HMGB1 potentiated the neuroinflammatory (NF-κBIα mRNA, TNFα mRNA, IL-1β mRNA, IL-6 mRNA, NLRP3 mRNA and IL-1β protein) and sickness response (reduced social exploration) to LPS challenge. fr-HMGB1 failed to potentiate the neuroinflammatory response to LPS. To examine whether these molecular forms of HMGB1 directly induce neuroinflammatory effects in isolated microglia, whole brain microglia were isolated and treated with fr-HMGB1 (0, 1, 10, 100, or 1000 ng/ml) or ds-HMGB1 (0, 1, 10, 100, or 1000 ng/ml) for 4h and pro-inflammatory mediators measured. To assess the effects of these molecular forms on microglia priming, whole brain microglia were pre-exposed to these forms of HMGB1 (0, 1, 10, 100, or 1000 ng/ml) and subsequently challenged with LPS (10 ng/ml). We found that ds-HMGB1 increased expression of NF-κBIα mRNA and NLRP3 mRNA in isolated microglia, and potentiated the microglial pro-inflammatory response (TNFα mRNA, IL-1β mRNA and IL-1β protein) to LPS. fr-HMGB1 failed to potentiate the microglial pro-inflammatory response to LPS. Consistent with prior reports, the present findings demonstrate that the disulfide form of HMGB1 not only potentiates the neuroinflammatory response to a subsequent immune challenge in vivo, but also potentiates the sickness response to that challenge. Moreover, the present findings demonstrate for the first time that ds-HMGB1 directly potentiates the microglia pro-inflammatory response to an immune challenge, a finding that parallels the effects of ds-HMGB1 in vivo. In addition, ds-HMGB1 induced expression of NLRP3 and NF-κBIα in vivo and in vitro suggesting that the NLRP3 inflammasome may play role in the priming effects of ds-HMGB1. Taken together, the present results suggest that the redox state of HMGB1 is a critical determinant of the priming properties of HMGB1 such that the disulfide form of HMGB1 induces a primed immunophenotype in the CNS, which may result in an exacerbated neuroinflammatory response upon exposure to a subsequent pro-inflammatory stimulus."


Innate Immunity and Neuroinflammation



The relation between things like Fibro and Chronic Fatigue show a relation to microglia as has been known. They are related to Autism and lately to Schizophrenia it appears. While not quoted below the article mentions Naltrexone and Curcumin related to calming neuroinflammation. This article ties Leptin to CFS as seems true and addressed in the following.

Solving the mysteries of fibromyalgia could help patients break free

"Younger, an associate professor recruited to the UAB College of Arts and Sciences Department of Psychology in 2014, became interested in fibromyalgia and chronic fatigue syndrome as a postdoctoral fellow at Stanford University's medical school. He had been studying pain more broadly when he realized how poorly understood these disorders were.

"Patients are wholly affected," Younger says. "Some used to be athletes, some used to be business owners, and then their lives are taken over." Often, he points out, patients visit doctor after doctor, only to be told repeatedly that they're healthy—and that the pain or fatigue is all in their heads.

Younger, along with many other researchers and clinicians, believed otherwise. "I made it my mission to figure out what is wrong with these patients and how to treat them," he says.

As a Stanford postdoctoral fellow and faculty member, Younger spearheaded studies that surveyed immune molecules in the blood. He homed in on one particular protein called leptin, released by fat tissue, which appears in greater amounts in the blood of chronic fatigue patients. In fact, Younger could even gauge the day-to-day severity of a patient's symptoms just by tracking his or her leptin levels. These initial findings spurred him to continue investigating inflammatory immune molecules—and to start looking at the brain's role in the diseases.

Leptin has the ability to cross the blood-brain barrier and affect neural cells, causing pain and fatigue. But exactly how that happens remains a mystery. Younger thinks it has something to do with microglia, a type of immune cell found in the brain that normally helps to protect neurons.

"Microglia defend our brain against everything," Younger explains. "When we get the flu, for instance, microglia are activated. These cells make us want to crawl into bed and do nothing—so our body can devote its resources to fighting off the flu."

In both fibromyalgia and chronic fatigue patients, Younger hypothesizes, the microglia are turned on when they're not supposed to be, causing fatigue or pain, a depressed mood, and cognitive dysfunction. At UAB, he is planning follow-up studies to help find evidence supporting this idea. He faces a crucial challenge, however: Currently, no methods are available to look directly at the activation or inflammation of microglia in living humans. But Younger and his colleagues are working on solutions, including specialized brain scans that measure the temperature of the brain or the presence of certain chemicals.

"It's only very recently that people are starting to explore what sensitizes microglia," Younger says. "The cells can be in a quiet, helpful state, or an active, warlike state." His findings, he hopes, will help reveal the difference."


The next report emphasizes maternal infection and immune response as effecting neurodevelopment, but the immune response is goes beyond what may happen in the womb for most and may happen in the individual post utero in most imo. Both pre and post utero or a combination of effect may be the case from person to person.

Infections and Brain Development.


"Several different bodies of evidence support a link between infection and altered brain development. Maternal infections, such as influenza and human immunodeficiency virus, have been linked to the development of autism spectrum disorders, differences in cognitive test scores, and bipolar disorder; an association that has been shown in both epidemiologic and retrospective studies. Several viral, bacterial, and parasitic illnesses are associated with alterations in fetal brain structural anomalies including brain calcifications and hydrocephalus. The process of infection can activate inflammatory pathways causing the release of various proinflammatory biomarkers and histological changes consistent with an infectious intrauterine environment (chorioamnionitis) or umbilical cord (funisitis). Elevations in inflammatory cytokines are correlated with cerebral palsy, schizophrenias, and autism. Animal studies indicate that the balance of proinflammatory and anti-inflammatory cytokines is critical to the effect prenatal inflammation plays in neurodevelopment. Finally, chorioamnionitis is associated with cerebral palsy and other abnormal neurodevelopmental outcomes. In conclusion, a plethora of evidence supports, albeit with various degrees of certainty, the theory that maternal infection and inflammation that occur during critical periods of fetal development could theoretically alter brain structure and function in a time-sensitive manner."



Just a note.

I read and post all studies and articles posted with the notion others will follow the overall understanding of the complete picture by comprehending the information in it's full by reading and seeing the full picture and by following up by researching elements contained within. For Benedetta I add this link.

Activation of ligand-responsive sigma-1 receptor by agonists is likely to have beneficial effects in the cells.

Activation of sigma-1 receptor chaperone in the treatment of neuropsychiatric diseases and its clinical implication
Accumulating evidence suggests that sigma-1 receptor regulates a variety of cellular functions, such as inositol 1,4,5-triphosphate (IP3) receptor-mediated Ca2+ signaling, ion channel firing, protein kinase location/activation, cellular redox, neurotransmitter release, inflammation, cellular differentiation, neuronal survival and synaptogenesis (3), (4) and (5). Furthermore, sigma-1 receptor plays an important role in neuronal plasticity, a process implicated in the pathophysiology of neuropsychiatric diseases (5), (6), (7), (8) and (9).



I have stalled and taken a good break on the recent area of study in the last several posts and hope to re-engage the subjects, but the theme of microglia, Angiotensin, and inflammatory aspects are something I like to note. The gut immune relation, and the bacterial toxins figure as agents priming the inflammation as many like ,myself hold. Gene expression is theorized to be effected in this scenario of dysfunction.

Chronic Brain Inflammation: The Neurochemical Basis for Drugs to Reduce Inflammation.


"It is now recognized that the brain and the peripheral immune system have bidirectional communication in both health and neuronal diseases. Brain inflammation results after both acute injury and also with the appearance of mutated proteins or endogenous neurotoxic metabolites associated with slow neurodegenerative diseases such as Alzheimer's and Parkinson's diseases and some psychiatric disorders. Microglia play a key role in brain inflammation by the release of pro-inflammatory cytokines and with ageing, microglia exhibit 'priming' leading to increased basal release of the pro-inflammatory cytokines. Neurochemical targets to reduce or slow chronic brain inflammation include cyclooxygenase enzymes, Nrf2 transcription factor, angiotensin AT1 receptors and sigma-1 receptors. Development of more selective drugs to act at these targets is occurring but large scale clinical trials to validate the drugs will take significant time."



This is a quote I meant to place from this report:

Rats fed a thiamin-deficient diet had higher concentra-
tions of P450, cytochrome b5, and NADPH:cytochrome c
reductase activity in liver microsomes than those fed a diet
sufficient in thiamin. The deficient rats also had increased
rates in the metabolism of acetaminophen, NDMA, amino-
pyrine, ethylmorphine, zoxazolamine, heptachlor, aniline,
N-methylaniline, acetanilide, and BP, but not in the metabo-
lism of hexobarbital (8). Recent studies from our laboratory
indicated that thiamin deficiency increased the hepatic micro-somal P450 2E1 level (two- to fivefold) but not the P450 2Cll level (44). This observation provides an enzymatic basis for the enhanced rate of in vivo metabolism of aniline, NDMA, and acetaminophen, all of which are substrates for P450 2El. Thiamin deficiency was shown to increase cytosolic glutathi-one S-transferase activity moderately but not steroid isomer-ase activity (44). The mechanisms of these effects on drug-metabolizing enzymes remain to be elucidated.



edit last post..I meant:

"How this relates to pregnancy issues like morning sickness and p450 function"


Thiamine relation to autism is not obscure as many have reported on, and discussed the matter as it pertains to autism and possible PON 1 function and other areas. This report discusses a lot of factors that those of us finding diet and yeast being involved in ASD. It discusses thiamine deficiency and totally syncs with many accounts I have read of others dealing with such factors. It also briefly mentions vaccination. How this relates to pregnancy issues like morning sickness and p400 function is what I am looking at related to some heavy metals and toxins like glyphosate. The their is apparently something going on in pregnancy that is perturbed in these areas and morning sickness and some areas of detoxification in the mother may be because of nutrient metabolism or deficiency or even some levels of nutrient levels like thiamine may be lowered in early pregnancy to balance certain detox function. Still studying. The whole report is very good and I suggest you read it. I am just posting a small snippet.

Dysautonomia in Autism Spectrum Disorder: Case Reports of a Family with Review of the Literature

"Pregnancy toxemia has been linked to thiamine deficiency..."


Not much of a credential with this, but I thought I would post it for thought.


"As all these hormonal changes are occurring there are also some symptoms the mother experiences, such as morning sickness. Pregnancy sickness is an adaptation or solution to the problem of teratogen ingestion during fetal organogenesis. Teratogens are drugs and other agents that can cause fetal malformation. During pregnancy sickness the mother experiences nausea, with or without vomiting, during the first trimester. It has been shown that women that experience morning sickness are less likely to miscarry during the first trimester than are asymptomatic women.


Effects of thiamine deficiency on hepatic cytochromes P450 and drug-metabolizing enzyme activities.


Dietary effects on cytochromes P450, xenobiotic metabolism, and toxicity.


"The levels and activities of cytochrome P450 enzymes are influenced by a variety of factors, including the diet. In this article, the effects of selected non-nutritive dietary chemicals, macronutrients, micronutrients, and ethanol on cytochromes P450 and xenobiotic metabolism are reviewed in the light of our current understanding of the multiplicity and substrate specificity of cytochrome P450 enzymes. Although the mechanisms of action of several dietary chemicals on specific cytochrome P450 isozymes have been established, those for macro- and micronutrients are largely unknown. It is known, however, that specific nutrients may have varied effects on different cytochrome P450 forms and thus may affect the metabolism of various drugs differently. Nutritional deficiencies generally cause lowered rates of xenobiotic metabolism. In certain cases, such as thiamin deficiency and mild riboflavin deficiency, however, enhanced rates of metabolism of xenobiotics were observed. The effects of dietary modulation of xenobiotic metabolism on chemical toxicity and carcinogenicity are discussed...."

"During fasting, microsomal aminopyrine N-demethylase
and hexobarbital hydroxylase activities were decreased, but
aniline p-hydroxylase and p-nitroanisole O-demethylase ac-
tivities were increased in male rats (32). The induction of
P450 2E1 by fasting (17) can account for the increased ani-
line hydroxylase and NDMA demethylase activities. Fasting
for 2 or 3 days caused a 50% decrease in the level of the
male-specific P450 2C11 (33), and this may account for the
previously observed decrease in aminopyrine demethylase
activity. During fasting, the mRNA for P450 2E1 was sig-
nificantly elevated, a situation similar to diabetes (34), but such elevation was not observed during the induction of
P450 2E1 by acetone pretreatment (19). The results Suggest
that there are differences in the mechanisms of P450 2E1 in-
duction under these conditions."


Sex steroid hormones regulate constitutive expression of Cyp2e1 in female mouse liver.


"CYP2E1 is of paramount toxicological significance because it metabolically activates a large number of low-molecular-weight toxicants and carcinogens. In this context, factors that interfere with Cyp2e1 regulation may critically affect xenobiotic toxicity and carcinogenicity. The aim of this study was to investigate the role of female steroid hormones in the regulation of CYP2E1, as estrogens and progesterone are the bases of contraceptives and hormonal replacement therapy in menopausal women. Interestingly, a fluctuation in the hepatic expression pattern of Cyp2e1 was revealed in the different phases of the estrous cycle of female mice, with higher Cyp2e1 expression at estrus (E) and lower at methestrus (ME), highly correlated with that in plasma gonadal hormone levels. Depletion of sex steroids by ovariectomy repressed Cyp2e1 expression to levels similar to those detected in males and cyclic females at ME. Hormonal supplementation brought Cyp2e1 expression back to levels detected at E. The role of progesterone appeared to be more prominent than that of 17β-estradiol. Progesterone-induced Cyp2e1 upregulation could be attributed to inactivation of the insulin/PI3K/Akt/FOXO1 signaling pathway. Tamoxifen, an anti-estrogen, repressed Cyp2e1 expression potentially via activation of the PI3K/Akt/FOXO1 and GH/STAT5b-linked pathways. The sex steroid hormone-related changes in hepatic Cyp2e1 expression were highly correlated with those observed in Hnf-1α, β-catenin, and Srebp-1c. In conclusion, female steroid hormones are clearly involved in the regulation of CYP2E1, thus affecting the metabolism of a plethora of toxicants and carcinogenic agents, conditions that may trigger several pathologies or exacerbate the outcomes of various pathophysiological states."


Hypoxia-inducible factor 1 transactivates the human leptin gene promoter.


"Increased placental leptin has been demonstrated in preeclampsia, a pregnancy disorder associated with placental hypoxia. This suggests that leptin gene expression is enhanced in response to oxygen deficiency in this organ. In support of this hypothesis, we have previously shown that hypoxia activates the leptin promoter in trophoblast-derived BeWo cells. Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric HIF-1alpha/HIF-1beta complex that regulates the transcription of hypoxia-responsive genes. To test whether this factor is involved in hypoxia-induced leptin promoter activation, BeWo cells were transiently transfected with a HIF-1alpha expression vector. Exogenous HIF-1alpha markedly increased luciferase reporter activity driven by the leptin promoter when HIF-1beta was co-expressed in the same cells. This effect was similar to that elicited by CoCl2, an agent known to stabilize endogenous HIF-1alpha. These data suggest that HIF-1alpha/HIF-1beta dimers are involved in the effect of CoCl2 to activate the leptin promoter. To confirm the implication of HIF-1, the cells were transfected with a dominant negative form of HIF-1alpha producing transcriptionally inactive HIF-1beta/HIF-1alpha dimers. This mutant HIF-1alpha protein abolished CoCl2 activation of the leptin promoter, providing direct evidence that the effect of CoCl2 is mediated by endogenous HIF-1alpha. Deletion analysis and site-specific mutagenesis demonstrated that a HIF-1 consensus binding site (HRE) spanning -120 to -116 bp relative to the start site was required for CoCl2 and exogenous HIF-1alpha induction of leptin promoter activity. Electrophoretic mobility shift assays performed with in vitro-translated HIF-1alpha and HIF-1beta proteins demonstrated binding to this HRE and not to mutated sequences only when both subunits were used together. These data demonstrate that leptin is a new hypoxia-inducible gene, which is stimulated in a placental cell line through HIF-1 interaction with a consensus HRE site located at -116 in the proximal promoter."


Hypoxia-ischemia and thiamine deficiency.


"In order to test the hypothesis that Wernicke's encephalopathy is of topographic rather than of pathogenetic specificity we examined the brains of 49 patients without any evidence of chronic alcoholism. They had died at least four days after an event of severe hypoxia-ischemia. They all showed extensive lesions in the cortex, in the thalamus and in other regions. In 19 of them there was additional necrosis in the mamillary bodies which apparently was of the same age as the associated cortical and thalamic lesions and which could not be distinguished from Wernicke's encephalopathy. In three of the 19 cases there was a total necrosis within the mamillary bodies. By re-examining the mamillary bodies of 12 known alcoholics without any evidence for an ischemic impact we could affirm that total necrosis may fit into the spectrum of Wernicke's encephalopathy. Our findings demonstrate that the morphological changes in the mamillary bodies due to thiamine deficiency and those due to hypoxia-ischemia may be identical."


One more with added overview ideas.

The Role of Thiamin in High Calorie Malnutrition



The fact fat is a toxin repository is also of note. Some this relates a good bit with a lot Dr. Seneff mentions in one of her reports. The proposed effect of Glyphoste effecting gut bacterial composition and subsequent sulfate and phenol levels and function do ties together a great deal of the things That I had believed and documented.

Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern




The tremendous amount of system interaction in physiology does make this whole process so daunting that attempting to find key areas that point to the etiology of ASD's a vast challenge. How each person's system handles toxicity from chemicals, and in relation metals, along with degrees and type of exposure along with how the fetus's genetics may respond to the mother's status at least raises the question about how morning sickness and things like leptin and ghrelin levels may be involved. Adipose tissue, esp. visceral fat, relates to neuroendocrine and lymphoid function and bear on energy production and metabolism and involve the hypothalmus. Fatty acid metabolism and peroxisomal function and disorders and perturbed function in these systems would certainly present as areas related to the hormonal, immune and energy production and nutrition all intricately related to the changes in, and processes in pregnancy. How morning sickness severity or lack thereof relates to possible abilities of dealing with toxins or a sensitivity to them and how this bears on the development of the fetus is compelling in my view. It may be that severe morning sickness in some cases helps in fetal development in ways or in some may be a sign of a pathology or even some of both. Yet, there appears to be a relationship. The fact the brain uses so much energy and is mainly fat also buttress the ides of studying the finding of altered leptin and ghrelin levels in autism and their changes in pregnancy. How this relates to fatty acid metabolism, an area that many of us already believe to be a factor, is also somewhat researched and seems to tie into all of this.

Solving the Autism Puzzle – The Fatty Acid Question and “Big, Fat Neurons”!


When you consider detoxifying enzymes, esp. the cytochrome P450 enzymes as Stephanie Seneff has reported on related to Glyphoste the problems with toxicity in pregnancy you also wonder how morning sickness relates to these matters.

Adipose Tissue Immune Response: Novel Triggers and Consequences for Chronic Inflammatory Conditions

Aryl Hydrocarbon Receptor Agonists

"The rapid increase in the number of people with obesity and obesity-induced chronic inflammatory diseases is now attributed to intricate cross talk between genetic makeup and so termed environmental “obesogens” [96]. Among these, more than 20 chemicals have been shown to cause long-term weight gain based on exposures during critical periods of development. Smoking and nicotine, persistent organophosphate pesticides, flame retardants, plasticizers and plastics, and fungicides, for example, have all been linked to obesity in animals. These highly lipophilic toxicants have very long half-lives that allow them to accumulate in the food chain. Western style diet, based on high consumption of animal fat, increases human exposure to these ubiquitous toxicants. The dioxin and dioxin-like pollutants are among the most dangerous. Due to their long half-life and lipophilicity, they accumulate in adipocytes and participate in the pathophysiology of obesity and obesity-associated chronic inflammatory diseases [97, 98] through activation of the aryl hydrocarbon receptor (AhR) [99, 100]. AhR is a ligand-activated transcription factor with important roles not only in the xenobiotic metabolism but in developmental and normal physiology as well. This particular receptor is ubiquitously present in adipocytes and, most importantly, in all the cells that participate in the immune system responses [101, 102]. Moreover, the preadipocytes that differentiate into mature adipocytes in the presence of even low levels of these toxic AhR ligands produce significantly more inflammatory cytokines such as TNF-α, IL-6, and chemokine MCP-1 [103]. Long-term exposure of mice to dioxin-like AhR agonists led to increased visceral adipose tissue mass, ectopic fat deposition in the liver (hepatic steatosis) and peritoneal cavity, and abnormal serum lipid profile similar with the metabolic syndrome [98]. Importantly, under the same treatment, AhR KO mice appear resistant to obesity and its metabolic consequences. Consistent with these observations, ApoE−/−mice that received dioxin-like PCBs (AhR agonists) developed atherosclerosis, as early event in the pathogenesis of abdominal aortic aneurysms (AAAs) [98]."


The things I have mentioned are only the broadest associations and often I just post these broad matters as to allow others to simply see the concept. If I post something too intricate or lengthy I doubt any would delve into reading these posts. I have looked at the systems in depth and there is a lot of reasonableness to connect toxins, enzyme function and attendant metabolic and immune effects in gestation and even morning sickness to these functions.


I appreciate it, too, Visitor. I'm just not as fast at absorbing and processing it all as you are. I'm still intrigued about the intersection of some stuff you've found and the information both Teresa Conrick and Eileen Nicole Simon post, combined with vitamin (prehormone D3) and their combined roles, and the new lymph findings take it all to another level.

Re: lymph around the head/brain area, brings to mind discussions I've read on sites about cranialsacral therapy and people that find it helpful. Obviously oxygen is critical in the body for certain chemical reactions to occur properly so any challenges to that need to be remedied, and then there has to be an ONGOING way to remove the toxic byproducts of that. I read periodic stuff about advance glycation endpoints, etc, and see interesting info in the Anti-Aging medicine movement/organizations and their work on telomeres. I haven't checked to see if there have been any studies done on autistic children on what their telomeres look like comparatively. And I also want to look into the Heritage Study about VO2max non-responders, which have found that going beyond a certain level of exercise actually causes health problems, ie, their stuff may have clues as to the existance of a subgroup of people epigenetically at a loss to properly process oxygen based reactions in the body and/or manage its byproducts, which to me would be them at a higher risk for ANY other environmental challenges, including vaccine adverse reactions(thrombocytopenia, for example)that might normally cause only minimal or transient damage in people that are NOT VO2max non-responders.

I think the morning sickness leptin/ghrelin stuff is intriguing but haven't read through the science - my primary question there is do any of those studies look at the diets of the women who do or do not have morning sickness. It goes against my intuition to think that those with morning sickness miscarry less than those without. Personally, I interpret most and maybe all physical discomforts as symptoms of reaction against an existing problem/imbalance not some mysterious preventive mechanism. For instance, if HCG is present in higher levels early on in a pregnancy and morning sickness got its name from brief mild nausea in the am, HCG may be cyclical not just from a trimester standpoint, but from a daily cyclical standpoint, just like cortisone in the body and melatonin, for example (both known to be affected by diet, and of course various stressors). What would cause HCG & leptin & ghrelin to NOT to maintain their natural cycles? Is there some molecular mimicry going on there or something? What effect does a healthy/unhealthy microbiome have on hormone cycles? We know the gut microbiome creates seratonin - what does it do for these other hormones?

There are many questions and not enough time in the day - and all of it needs to be conveyed somehow to the public and politicians, but at $35 per article in general, the big corporations have it shut down tight.


I appreciate that Donna K. Glad to know someone is maybe getting something from this.

Donna K

Always interested in seeing what new info or insights you have come across to contribute. Thank you.


This quote is related the 2nd post back on leptin and related matters. I have been looking at ghrelin for a long time and had missed this report until recently. Then whole report is well worth reading.

Altered ghrelin levels in boys with autism: a novel finding associated with hormonal dysregulation

"Numerous hormone studies have been undertaken in children with autism; however, to our knowledge, this study is the first in which ghrelin was measured. Plasma levels of both AG and DG were significantly reduced in the autism group compared with healthy controls. This result can be attributed to local factors affecting ghrelin-secreting cells and to hormonal influences. Gastrointestinal (GIT) problems are frequent in autism, including dysbiosis, chronic GIT inflammation and chronic fungal, viral and bacterial infections19. These disorders could affect the gastric mucosa and interfere with the normal function of ghrelin-secreting cells. Furthermore, ghrelin deficiency by itself can affect the gastric mucosa, as ghrelin is known for its role in maintaining mucosal health and integrity20. Thus, a loss of mucosal health and integrity could result in a further decrease in plasma ghrelin levels.

Alterations in plasma ghrelin levels may also be part of the extensive, well-studied hormonal dysregulation that characterizes autism, particularly the dysregulation of TT, FT, leptin and GH. In agreement with the findings of the current study, previous studies have shown that androgen levels are significantly higher in autism patients11. At the same time, it is well established that ghrelin plasma levels are negatively correlated with high plasma testosterone levels12. The current study confirms the negative correlation between FT and DG. This correlation may indicate that the reduced plasma level of ghrelin in autistic children is in part a consequence of suppression by elevated androgens.

Another hormone that has been studied in autism is leptin. Its relevance to ghrelin function comes from the observation that elevated plasma leptin levels are associated with reduced plasma ghrelin levels14, 15. This finding is in agreement with the results of the current study, which revealed a significant elevation of leptin and a reduction of ghrelin levels in the autism group. In support of this notion, Komori et al. provided a novel molecular link between leptin and ghrelin signaling, namely, the leptin-induced negative regulatory element-binding protein (NREBP), which suppresses ghrelin signalling21. The high serum leptin levels in the current study is consistent with other studies that reported a significant elevation of leptin levels in autistic children14, 22. The elevation of leptin levels can be explained in part by the observed significant elevation of androgen levels in autistic children. Both animal and human studies have shown that adipocytes have androgen receptors (ARs), and androgens are known to modulate the plasma leptin level23, 24. Consistent with these reports, the current study revealed a significant positive correlation between leptin and FT. The significant elevation of leptin levels in autism may also be a consequence of the significant decrease in GH levels in autistic children, as will be discussed later.

Alterations in the levels of both ghrelin and leptin are known to be associated with adiposity25, 26. As can be noted from the anthropometric data in the current study, the only significant difference between the autism and control groups was in body weight, which was significantly higher in the autism group. To exclude the effect of weight on the levels of these hormones, we excluded four children with high body weight from the autism group to create a group that was age-, sex- and weight-matched with the controls, as shown in Table 3. As presented in Table 3, there were significant reductions in both AG and DG plasma levels, with a significant increase in the plasma leptin level in the autism group compared with weight-matched controls."



They are showing the pieces, but haven't much of a clue about the triggers or causes. A very good overview though.

The Many Roads To Mitochondrial Dysfunction In Neroimmune And Neuropsychiatric Disorders



This addresses autism with a specific idea about metals/toxicity and enzyme function. Since my wife had such severe morning sickness{hyperemesis gravidarum} I am also proposing a relationship in the chemistry and functions believed to be involved with it and a relationship with autism that may exist in her as well as possibly mothers of children who have autism.

1,25-Dihydroxyvitamin D regulates expression of the tryptophan hydroxylase 2 and leptin genes: implication for behavioral influences of vitamin D.


"To investigate vitamin D-related control of brain-expressed genes, candidate vitamin D responsive elements (VDREs) at -7/-10 kb in human tryptophan hydroxylase (TPH)2 were probed. Both VDREs bound the vitamin D receptor (VDR)-retinoid X receptor (RXR) complex and drove reporter gene transcription in response to 1,25-dihydroxyvitamin D3 (1,25D). Brain TPH2 mRNA, encoding the rate-limiting enzyme in serotonin synthesis, was induced 2.2-fold by 10 nM 1,25D in human U87 glioblastoma cells and 47.8-fold in rat serotonergic RN46A-B14 cells. 1,25D regulation of leptin (Lep), encoding a serotoninlike satiety factor, was also examined. In mouse adipocytes, 1,25D repressed leptin mRNA levels by at least 84%, whereas 1,25D induced leptin mRNA 15.1-fold in human glioblastoma cells. Chromatin immunoprecipitation sequencing analysis of the mouse Lep gene in response to 1,25D revealed a cluster of regulatory sites (cis-regulatory module; CRM) at -28 kb that 1,25D-dependently docked VDR, RXR, C/EBPβ, and RUNX2. This CRM harbored 3 VDREs and single C/EBPβ and RUNX2 sites. Therefore, the expression of human TPH2 and mouse Lep are governed by 1,25D, potentially via respective VDREs located at -7/-10 kb and -28 kb. These results imply that vitamin D affects brain serotonin concentrations, which may be relevant to psychiatric disorders, such as autism, and may control leptin levels and affect eating behavior."


Leptin and leptin receptor levels in pregnant women with hyperemesis gravidarum


"Objective:  To investigate the association between the leptin, leptin receptor and hormone levels and hyperemesis gravidarum, and to determine whether these two parameters may be early markers for hyperemesis gravidarum.

Methods:  The study group consisted of 18 pregnant women with hyperemesis gravidarum and the control group consisted of 18 healthy pregnant women. Demographic characteristics were recorded and body mass index (BMI) values were calculated for all the pregnant women. Serum leptin, leptin receptor, insulin, cortisol, thyroid hormone and human chorionic gonadotrophin (hCG) levels were measured.

Results:  When the two groups were compared with respect to leptin levels, the group with hyperemesis gravidarum was found to have significantly higher leptin levels (P = 0.037). No intergroup differences were observed in serum cortisol, insulin, hCG, thyroid hormone levels or BMI values. In the group with hyperemesis gravidarum, an inverse correlation was detected between cortisol and leptin (r = –0.762, P < 0.01), and hCG and thyroid-stimulating hormone (r = –0.503, P < 0.05), whereas a significant correlation was detected between insulin and leptin (r = 0.538, P < 0.05), leptin and BMI (r = 0.711, P < 0.01), and between TT3 and hCG (r = 0.605, P < 0.01).

Conclusion:  It was concluded that leptin could play a role in, and be defined as, a marker of hyperemesis gravidarum."


Hyperemesis gravidarum - Wiki

"Intravenous fluids[edit]

IV hydration often includes supplementation of electrolytes as persistent vomiting frequently leads to a deficiency. Likewise, supplementation for lost thiamine (Vitamin B1) must be considered to reduce the risk of Wernicke's encephalopathy.[20] A and B vitamins are depleted within two weeks, so extended malnutrition indicates a need for evaluation and supplementation. In addition, electrolyte levels should be monitored and supplemented; of particular concern are sodium and potassium."

"Signs and symptoms[edit]

When hyperemesis gravidarum is severe or inadequately treated, it may result in the following:[1]
##Loss of 5% or more of pre-pregnancy body weight
##Dehydration, causing ketosis,[3] and constipation
##Nutritional disorders such as vitamin B1 (thiamine) deficiency, vitamin B6 deficiency or vitamin B12 deficiency
##Metabolic imbalances such as metabolic ketoacidosis[1] or thyrotoxicosis[4]"...


There are numerous theories regarding the cause of HG, but the cause remains controversial. It is thought that HG is due to a combination of factors which may vary between women and include: genetics,[1] body chemistry, and overall health.[8]

One factor is an adverse reaction to the hormonal changes of pregnancy, in particular, elevated levels of beta human chorionic gonadotropin (hCG).[9][10] This theory would also explain why hyperemesis gravidarum is most frequently encountered in the first trimester (often around 8–12 weeks of gestation), as hCG levels are highest at that time and decline afterward. Another postulated cause of HG is an increase in maternal levels of estrogens (decreasing intestinal motility and gastric emptying leading to nausea/vomiting).[1]

Morning sickness
Although the pathophysiology of HG is poorly understood, the most commonly accepted theory suggests that levels of hCG are associated with it.[11] Leptin may also play a role."


Wernicke–Korsakoff syndrome

"One as-yet-unreplicated study has associated susceptibility to this syndrome with a hereditary deficiency of transketolase, an enzyme that requires thiamine as a coenzyme.[17]"


Wernicke's encephalopathy _ Wiki


Thiamine deficiency and errors of thiamine metabolism are believed to be the primary cause of Wernicke encephalopathy. Thiamine, also called B1, helps to break down glucose. Specifically, it acts as an essential coenzyme to the TCA cycle and the pentose phosphate shunt. Thiamine is first metabolised to its more active form, thiamine diphosphate (TDP), before it is used. The body only has 2–3 weeks of thiamine reserves, which are readily exhausted without intake, or if depletion occurs rapidly, such as in chronic inflammatory states or in diabetes.[6][34] Thiamine is involved in:[34][42]
1.Metabolism of carbohydrates, creating energy.
2.Production of neurotransmitters including glutamic acid and GABA.
3.Lipid metabolism, necessary for myelin production.
4.Amino acid modification. Probably linked to the production of taurine, of great cardiac importance.[43][44]


The primary neurological-related injury caused by thiamine deficiency in WE is three-fold: oxidative damage, mitochondrial injury leading to apoptosis, and directly stimulating a pro-apoptotic pathway.[45] Thiamine deficiency affects both neurons and astrocytes, glial cells of the brain. Thiamine deficiency alters the glutamate uptake of astrocytes, through changes in the expression of astrocytic glutamate transporters EAAT1 and EAAT2, leading to excitotoxicity. Other changes include those to the GABA transporter subtype GAT-3, GFAP, glutamine synthetase, and the Aquaporin 4 channel.[46"...

"Other nutritional abnormalities should also be looked for, as they may be exacerbating the disease.[28][58] In particular, magnesium, a cofactor of transketolase which may induce or aggravate the disease.[34]

Other supplements may also be needed, including: cobalamin, ascorbic acid, folic acid, nicotinamide, zinc,[59][60] phosphorus (dicalcium phosphate)[61] and in some cases taurine, especially suitable when there cardiocirculatory impairment.[62][63] Patient-guided nutrition is suggested. In patients with Wernicke-Korsakoff syndrome, even higher doses of parenteral thiamine are recommended."


Morning sickness - Wiki

Morning sickness as a defense mechanism[edit]

"Morning sickness is understood as an evolved trait that protects the fetus against toxins ingested by the mother.[6] [7] Many plants contain chemical toxins that serve as a deterrent to being eaten. Adult humans, like other animals, have defenses against plant toxins, including extensive arrays of detoxification enzymes manufactured by the liver and the surface tissues of various other organs. In the fetus, these defenses are not yet fully developed, and even small doses of plant toxins that have negligible effects on the adult can be harmful or lethal to the embryo.[8] Pregnancy sickness causes women to experience nausea when exposed to the smell or taste of foods that are likely to contain toxins injurious to the fetus, even though they may be harmless to her.

There is considerable evidence in support of this theory, including:[9][10]
##Morning sickness is very common among pregnant women, which argues in favor of its being a functional adaptation and against the idea that it is a pathology.
##Fetal vulnerability to toxins peaks at around 3 months, which is also the time of peak susceptibility to morning sickness.
##There is a good correlation between toxin concentrations in foods, and the tastes and odors that cause revulsion.

Women who have no morning sickness are more likely to miscarry.[11] This may be because such women are more likely to ingest substances that are harmful to the fetus.[12]"


The role of trace elements, thiamin (e) and transketolase in autism and autistic spectrum disorder.


"Although there has been much research into autism or autistic spectrum disorder (ASD), there is room for considerable conjecture regarding the etiology of these developmental brain disorders. ASD is marked by a complex interaction between environmental factors and genetic predisposition, including epistasis. This manuscript argues that changes in oxidative metabolism, thiamine homeostasis, heavy metal deposition and cellular immunity have a role in the etiopathogenesis of autism and ASD. Recent findings from our group and others provide evidence for abnormal thiol metabolism, marked by significant alteration in the deposition of several trace heavy metal species. Together with these, we find differences in thiamine homeostasis in ASD patients, which can be corrected by supplementation. We hypothesize that altered thiol metabolism from heavy metal toxicity, one of the key mechanisms for oxidative stress production, may be responsible for the biochemical alterations in transketolase, dysautonomia and abnormal thiamine homeostasis. Although it is unknown why these particular metals accumulate, we suspect that children with ASD and forms of autism may have particular trouble excreting thiol-toxic heavy metal species, many of which exist as divalent cations. We maintain mercury accumulation is evidence of altered clearance. Together with concomitant oxidative stress, these findings may offer an intriguing component or possible mechanism for oxidative stress-mediated neurodegeneration in ASD patients. Regardless of the exact cause, these factors may be more important to the etiology of this symptomatically diverse disease spectrum. Here, we offer insight into new avenues of exploration as well as the development of novel treatment approaches for these growing and devastating diseases."


Altered Heavy Metals and Transketolase Found in Autistic
Spectrum Disorder



Well, on a simpler note -- maybe by parental instinct there are so many trampolines in back yards.

Of all the toys to have, I have often wondered how those became so popular.

I will be the first to admit that my parental instincts really stink as I kept allowing vaccinations after tons of reactions.

But an up note; They did have a bouncing horse or two.


I am also wondering whether heavy metals, mercury and aluminum of course being of interest, would be present in lymph fluid longer than in blood, possibly leading to a new lab test that could indicate heavy metal overload, different from or supporting provoked urine tests. Could be a better indicator of how efficiently or not a body rids itself of toxins, and therefore offer insight about whether a person could be severely damaged by vaccines or not.



Have you been up on some of the ideas on oxygen that you mentioned or were you just surmising that it was a logical idea. On one sight I linked in another article the author indeed mentions the idea of oxygen related to lymphatic circulation. I am aware that some have called these quack ideas, but they also did not know about these new lymph vessels. Some quacks are looking better all the time. Even though the author here also did not know of these new found vessels the association was not excluded as apparently other evidence indicated the importance.

Activating Lymphatics Improves Detoxification In The Brain

"The brain depends on proper circulation to detox acidic cellular waste from its tissues. Even though the brain has no lymph vessels the membranes that surround the spinal cord and brain has lymph vessels. By manually activating the lymphatics in the neck and face you dramatically improve circulation and reabsorption of cerebrospinal fluid and cellular waste into the lymphatic system. This improved circulation delivers oxygen and nutrition to the cells while improving cellular detoxification throughout the body."

"My point, if you have a young child with autism like behavior, you need to see that acid is a contributing factor in their cognitive problems, digestive issues, skin irritations, aggression, hyperactivity or lethargy. The first step should be to balance their pH and activate the lymphatic system. Start with Epsom salt and baking soda baths, alkalizing supplements, systemic enzymes, probiotics, and some type of lymph drainage therapy to open the lymph-brain connection."




The mechanical assistance that could move the lymphatic system along is reasonable as a therapeutic idea. The fact that the immune system and brain function have been so compelling in study and observation to some has had some element of problem due to how this is/was occurring. The blood brain barrier has seemed a possible route, and still may be, for some of the interplay, but this news of these lymphatic vessels gives a new route to consider strongly. There is still some element of uncertainty about the extent these vessels could impact the brain as there is little known about them at this point. Yet, the plausible effects are hard not to be very interested about. I don't know about oxygen availability, but I will be looking more into this. As for now this seems to be interesting to a good number who are also of the mind that the immune system is related to Autism. That is good to me. This is also an area that has already be in view by some studying Autism, though the vessels found is a new thing. Please share what you find here as I will do the same.

Discovery of brain-immune link could advance understanding of autism


Activating the Lymphatic System Can Help Autism Spectrum Disorders


Helping autism spectrum disorders by opening the lymph/brain connection


Lymphatic Therapy



Visitor re: lymph propulsion cessation: I had started pondering last year that in certain cancer therapies, trampolining or vibration is deemed important - to force the lymph fluid to move when it otherwise might. I thought that the movement would be very similar to children with autism responding well to horse riding therapy and could explain the nature of those benefits. If so, once again, the solution points to the problem. I also wonder if / what lymph propulsion cessation might do re: oxygen availability in the body, if anything.


N-iminoethyl-L-lysine mentioned in the abstract in the last post is in view here. This is focusing on Alzheimer, but may relate to inflammation in other neurological conditions like Autism.

N-iminoethyl-L-lysine improves memory and reduces amyloid pathology in a transgenic mouse model of amyloid deposition.


"A large body of evidence suggests the importance of inflammation and oxidative or nitrosative stress in Alzheimer's disease (AD) pathogenesis. Inflammatory stimuli upregulate transcription of inducible nitric oxide synthase (iNOS), which can lead to the production of nitric oxide and other reactive nitrogen species. We previously found that genetic deletion of iNOS in mice overexpressing the amyloid precursor protein (APP) and presenilin-1 (PS1) reduced mortality, nitrosative stress, amyloid plaque burden, microgliosis, astrocytosis, and peri-plaque tau phosphorylation. We therefore examined the effects of N6-(1-iminoethyl)-L-lysine (L-NIL), a pharmacological iNOS inhibitor, or d-NIL, its enantiomeric control, in a transgenic mouse model of amyloid deposition. Tg19959 mice carry human APP with two mutations and develop amyloid plaques and memory impairment starting at 3-4 months of age. Mice were given L-NIL or D-NIL in the drinking water from 1 month of age and assessed behaviorally and histopathologically at 8 months of age. We found that L-NIL administration reduced disinhibition in the elevated plus maze, improved spatial memory performance in the Morris water maze, and decreased cortical amyloid deposition as well as microglial activation in 8-month-old Tg19959 mice. These findings are consistent with previous reports demonstrating that iNOS inhibition ameliorates AD pathogenesis."


The following may be of relevance here.

Nitric Oxide Can Regulate Gene Expression



Ridiculous to speculate I guess, but concerning the last post here is an early Idea.

Cytokines are systemic effectors of lymphatic function in acute inflammation.


"The response of the lymphatic system to inflammatory insult and infection is not completely understood. Using a near-infrared fluorescence (NIRF) imaging system to noninvasively document propulsive function, we noted the short-term cessation of murine lymphatic propulsion as early as 4h following LPS injection. Notably, the effects were systemic, displaying bilateral lymphatic pumping cessation after a unilateral insult. Furthermore, IL-1β, TNF-α, and IL-6, cytokines that were found to be elevated in serum during lymphatic pumping cessation, were shown separately to acutely and systemically decrease lymphatic pulsing frequency and velocity following intradermal administration. Surprisingly, marked lymphatic vessel dilation and leakiness were noted in limbs contralateral to IL-1β intradermal administration, but not in ipsilateral limbs. The effects of IL-1β on lymphatic pumping were abated by pre-treatment with an inhibitor of inducible nitric oxide synthase, L-NIL (N-iminoethyl-L-lysine). The results suggest that lymphatic propulsion is systemically impaired within 4h of acute inflammatory insult, and that some cytokines are major effectors of lymphatic pumping cessation through nitric oxide-mediated mechanisms. These findings may help in understanding the actions of cytokines as mediators of lymphatic function in inflammatory and infectious states."



Curious as to what this may eventually show, but it is interesting.

Missing link found between brain, immune system



New hope for autism: Canadian researcher reports to Sweden's Nobel Forum

"Autism rates have skyrocketed from 1 in 10,000 a half a century ago to 1 in 68 persons today. Expert opinion and funding to date has mostly focused on genetic causes and have attempted to explain the increase as better reporting of autism cases. MacFabe's research points strongly in another direction: changes in our gut bacteria.

Dr. MacFabe and his colleagues have shown that compounds, known as short chain fatty acids, which are produced by bacteria found in our intestines affect brain function and behaviour. Collaborating with Dr. Richard Frye of the University of Arkansas, their research has shown that these compounds affect the efficiency of mitochondria, the energy storehouse of cells.

Work with Dr. Bistra Nankova of New York Medical College has revealed that these fatty acid products can also act as epigenetic modulators, in effect acting as "switches" for many autism associated genes known to affect neural development and transmission, but also those involved in inflammation and energy metabolism, also reported in autism.

MacFabe, whose work has been featured on CBC Television's The Nature of Things, says these associated autism genes need not only be irreversibly damaged but can actually be switched on and off by compounds produced by autism associated intestinal bacteria. This provides an important link between the gut and the brain in autism. It also lends credibility to reports from parents who often see a connection between digestive upsets and autism symptoms in their children, he says. Such symptoms include impaired language, repetitive behaviours, restricted interests, social impairment and self-injurious behaviour, but often of a variable course or severity.

Dr. Suzanne Lewis, Director of the Autism Spectrum Interdisciplinary Research (ASPIRE) Program, Department of Medical Genetics, University of British Columbia has worked collaboratively with Dr. MacFabe for the past six years. Dr. Lewis states: "Genetic changes alone cannot explain the rising rate of autism within one generation. We need to look at environmental factors that can impact autism behaviours, for which a growing evidence points to changes involving the gut microbiome."



Biochemical, Histopathological and Morphological Profiling of a Rat Model of Early Immune Stimulation: Relation to Psychopathology.


"Perinatal immune challenge leads to neurodevelopmental dysfunction, permanent immune dysregulation and abnormal behaviour, which have been shown to have translational validity to findings in human neuropsychiatric disorders (e.g. schizophrenia, mood and anxiety disorders, autism, Parkinson's disease and Alzheimer's disease). The aim of this animal study was to elucidate the influence of early immune stimulation triggered by systemic postnatal lipopolysaccharide administration on biochemical, histopathological and morphological measures, which may be relevant to the neurobiology of human psychopathology. In the present study of adult male Wistar rats we examined the brain and plasma levels of monoamines (dopamine, serotonin), their metabolites, the levels of the main excitatory and inhibitory neurotransmitters glutamate and γ-aminobutyric acid and the levels of tryptophan and its metabolites from the kynurenine catabolic pathway. Further, we focused on histopathological and morphological markers related to pathogenesis of brain diseases - glial cell activation, neurodegeneration, hippocampal volume reduction and dopaminergic synthesis in the substantia nigra. Our results show that early immune stimulation in adult animals alters the levels of neurotransmitters and their metabolites, activates the kynurenine pathway of tryptophan metabolism and leads to astrogliosis, hippocampal volume reduction and a decrease of tyrosine hydroxylase immunoreactivity in the substantia nigra. These findings support the crucial pathophysiological role of early immune stimulation in the above mentioned neuropsychiatric disorders."


I wonder if vaccines fit in their idea of "perinatal immune challenges"?


Treating the brain and the immune system in tandem

"For years, studies have shown that patients with a wide range of mental illnesses tend to have signs of inflammation, the body’s natural response against infection and injury. But lately, scientists have been zeroing in on an explanation. They’re accumulating evidence to suggest that infection, autoimmune diseases and environmental factors such as stress or diet can trigger the immune system to go awry, causing it to damage the brain instead of attacking foreign pathogens. The result: an array of psychiatric conditions, including schizophrenia, autism spectrum disorder, Alzheimer’s disease, depression and anorexia nervosa."

"This hypothesis does not suggest immune responses are at the root of all psychiatric cases. Rather, it points to the idea that common mental illnesses have multiple causes, a haywire immune system being just one. The immune hypothesis is nevertheless a paradigm shift that not only offers a tangible, biological basis for subsets of many previously inexplicable psychiatric conditions, it raises the possibility of successfully diagnosing, treating and perhaps even preventing them by homing in on the immune system and managing inflammation. Although the research is still in its early days, there’s a growing sense of excitement over the prospect that certain individuals may regain mental health with antibiotics, intravenous immunoglobulin (IVIG) treatments (infusions of antibodies) and possibly dietary changes, instead of traditional psychiatric drugs and brain stimulation treatments."

“I think we’re on the cusp of something that’s really huge and truly revolutionary in the way in which we ... both diagnose people, as well as to make them better,” says Mady Hornig, associate professor of epidemiology at the Columbia University Medical Center, whose research focuses on the role of microbes and immune factors in neuropsychiatric illness."

"Scientists are now recognizing that a host of external stimuli can disrupt the normal crosstalk between the brain and the immune system. Those stimuli can include stress, changes in the microbiome (the universe of microbes that live in our bodies), and certain viruses and bacteria."

"It’s believed this disruption can affect the brain, and thereby behaviour. In PANDAS, it is suggested that streptococcal bacteria may mimic brain proteins, prompting the body to produce antibodies that mistakenly target the brain."

"So why doesn’t everyone infected with strep throat come down with the same neurological and psychiatric symptoms that O’Donnell’s daughter experienced? The answer may lie in genetics. Hornig explains that some individuals may be more genetically susceptible to producing a faulty immune response."

"What is so remarkable and so exciting to researchers is that if certain neuropsychiatric disorders are triggered by external stimuli, it means they can be controlled, Hornig says. However, she adds, since genetics likely play a role, susceptible individuals could be vulnerable to falling ill again whenever they encounter such triggers."

"A month after her symptoms disappeared, O’Donnell’s daughter experienced a relapse of Tourette and OCD-like behaviour, and again tested positive for strep. Though she fully recovered a second time, O’Donnell notes that her child has since shown other signs of potential immune-related sensitivities. For example, she experienced a bout of anxiety after an unidentified viral infection. Meanwhile, recent dietary changes aimed at reducing inflammation, specifically eliminating gluten, seemed to alleviate her anxiety."

“Anything that your immune system sees as an invader, whether it’s gluten or a bee sting or whatever, or a virus or a bacteria, you now have to be careful and watching for almost a mental health symptom,” O’Donnell says."...

“It probably brings us closer to hammering in the idea that mental illness is a disease,” she says. “It’s a disease we don’t fully understand.”

"Each new finding, however, is tempered with caution.

"Using nationwide data from Denmark, Benros found a strong link between infection and autoimmune diseases and mood disorders. People who had visited the hospital for an infection at any time had a 62-per-cent higher risk of later being diagnosed with depression or bipolar disorder. Those who were hospitalized for autoimmune diseases had a 45-per-cent risk of subsequent depression or bipolar disorder."...

"This suggests the need for immunopsychiatry, a new approach that recognizes the immune system and the brain are inexorably linked and should be treated in tandem, he adds."

“I am one of the believers who thinks that the body is one big entity that shouldn’t be split into different disciplines,” Sakic says. “The problem is it’s way more complex than we like to think.”



Considering the role of the immune system and increasing evidence of microbiome effect in autism this may shed more light on heritability and environment in the demographics of autism.

Environment, not genes, plays starring role in human immune variation, study finds

The power of environment

"Examining differences in the levels and activity states of these components within pairs of monozygotic and dizygotic twins, the Stanford scientists found that in three-quarters of the measurements, nonheritable influences — such as previous microbial or toxic exposures, vaccinations, diet and dental hygiene — trumped heritable ones when it came to accounting for differences within a pair of twins. This environmental dominance was more pronounced in older identical twins (age 60 and up) than in younger twins (under age 20)"...

“Nonheritable influences, particularly microbes, seem to play a huge role in driving immune variation,” said Davis. “At least for the first 20 or so years of your life, when your immune system is maturing, this amazing system appears able to adapt to wildly different environmental conditions. A healthy human immune system continually adapts to its encounters with hostile pathogens, friendly gut microbes, nutritional components and more, overshadowing the influences of most heritable factors.”



A number of those with autism display psychotic traits according to studies. A lot of of effected brain areas are the same in both conditions.Some of the cause for both conditions may overlap. When and how much "damage" is occurring could be the difference with autism and psychotic disorders.

Gray matter loss and inflamed brain associated with development of psychosis

"Thirty-five individuals ultimately converted to psychosis and they showed a steeper rate of thinning in prefrontal cortex compared with those who did not convert and the healthy control group. Importantly, this tissue loss was not explained by exposure to antipsychotic drugs."

"Because this differential rate of tissue loss was observed among subjects who had never been exposed to psychiatric drugs, we can conclude that the brain changes are part of the natural course of the disorder rather than being a consequence of treatment," explained Cannon."

"Interestingly, the tissue loss observed in the converters was correlated with levels of proinflammatory cytokines in plasma, suggesting the presence of systemic neuroinflammation."

"The findings are also important in showing that markers of proinflammatory cytokines at the baseline assessment predicted the rate of gray matter loss among the individuals who converted to psychosis, suggesting that activation of microglia was involved in the tissue loss," he added. "This could mean that psychosis is associated with an abnormal acceleration in the processes underlying normal synaptic pruning during late adolescence/early adulthood, or that some kind of immune-related process is involved in psychosis onset, or both."

"Inflammation is increasingly recognized as a contributing factor to the emergence of progression of disease in every organ in the body," said Dr. John Krystal, Editor of Biological Psychiatry. "This report suggests that neuroinflammation may be a process that in some cases 'tips people over' from the at-risk state into psychosis."


Psychosis and autism: magnetic resonance imaging study of brain anatomy

Overlapping developmental brain abnormalities

"People with autism-spectrum disorder already have significant developmental abnormalities in brain regions typically affected in psychosis (e.g temporal and frontal lobes), therefore it may be more difficult to detect subtle additional differences associated with further neuropsychiatric disorder."


Toddlers' Autistic Behaviors Linked to Preteen Psychosis

"Autistic-like behaviors in toddlers might predict psychotic events in adolescence, a retrospective study has determined."

"Speech problems and ritualistic behaviors in 3- and 7-year-olds showed a particularly strong influence, increasing the risk of psychosis in preteens by up to 300%, Rhys Bevan Jones, Ph.D., and colleagues wrote in the March issue of Schizophrenia Research (Schizophr Res. 2012;135:164-9)."

"In the study, nearly 20% of children with these characteristics at age 7 went on to develop psychotic episodes by age 12."

"The findings of this study suggest that clinicians should ask about psychotic experiences in those with autistic traits," wrote Dr. Jones of Cardiff (Wales) University. "Clinicians should also assess for traits of autism in those who develop psychotic experiences (23% of those with psychotic experiences in adolescence had at least one autistic trait at the age of 3, and 10% had at least one psychotic trait at the age of 7). Clinical care is likely to be enhanced by careful consideration of premorbid and comorbid autistic traits that might be impacting on patient function."

"It is also possible that [autism spectrum disorders] and psychotic disorders represent part of the same disorder that is manifest differently at different stages of development."



Mounting Research Shows Gut-Brain Connection

"The work of these three researchers (some of the studies on mice) raises the possibility that brain disorders, including anxiety, depression, and autism, may be treated through the gut, which is a much easier target for drug delivery than the brain."

"The human body contains trillions of microbes, collectively called the microbiome. In just one person’s body, they are estimated to weigh two to six pounds — up to twice the weight of the average human brain."

"Most reside in the gut and intestines, where they can help us to digest food, synthesize vitamins, and fight off infection. But their influence seems to reach the brain in a powerful way."

“The big question right now is how the microbiome exerts its effects on the brain,” said Christopher Lowry, Associate Professor of Integrative Physiology at the University of Colorado, Boulder..."

"Dr. Sarkis Mazmanian, a Louis & Nelly Soux Professor of Microbiology at the California Institute of Technology, is investigating the connection between gut bacteria, gastrointestinal disease and autism, a neurodevelopmental disorder."

"He has found that the gut microbiome communicates with the brain through molecules that are produced by gut bacteria and then enter the bloodstream. These molecules are strong enough to change the behavior of mice."

“We’ve shown, for example, that a metabolite produced by gut bacteria is sufficient to cause behavioral abnormalities associated with autism and with anxiety when it is injected into otherwise healthy mice,” said Mazmanian."

"There is still much more work to be done to understand the gut-microbiome-brain connection, the researchers said. Mazmanian’s lab is also exploring whether the microbiome plays a role in neurodegenerative diseases such as Alzheimer’s and Parkinson’s."

“There are flash bulbs going off in the dark, suggesting that very complex neurodegenerative disorders may be linked to the microbiome. But once again this is very speculative. These seminal findings, the flash bulbs, are only just beginning to illuminate our vision of the gut-microbiome-brain connection,” said Mazmanian."



We are less crazy as the days go by. My wife was diagnosed with RA, but with diet mod and immune modulation we have reversed it to a very large degree. That was a few years ago. The effects in some autism will be more clear soon it seems.

Joint Pain, From the Gut

“It’s become more and more clear that these microbes can affect the immune system, even in diseases that are not in the gut,” says Veena Taneja, an immunologist at the Mayo Clinic in Rochester, Minnesota, who has found clear differences in the bacterial populations of mice bred to be genetically prone to rheumatoid arthritis. In those more susceptible to the disease, a species of bacteria from the Clostridium family dominates. In mice without arthritis, other strains flourish, and the Clostridium strains are scarce...."

“This is frontier stuff,” says Scher, the director of the NYU’s Microbiome Center for Rheumatology and Autoimmunity. “This is a shift in paradigm. By including the microbiome, we’ve added a new player to the game.”

"In fact, these bacteria have a powerful vested interest in controlling how our bodies respond to interlopers. Blaser and others say that it appears that many of the bugs that live inside us have thrived by modulating the immune system to avoid being recognized—and attacked—as invaders; in essence, these organisms train immune cells not to be trigger-happy. A microbiome with the wrong sorts of bugs, or the wrong ratio of bugs—a situation known as dysbiosis—may unbalance this immune system, causing immune cells to assault not only bacteria, but also the body itself."

"Microbes are especially influential in the gut, which houses two-thirds of the body’s immune cells. As the pathway for digestion, the gastrointestinal tract must deal with a constant stream of food-related foreign microbes, which must be monitored and, if they are harmful, destroyed. To do this, our intestines have developed an extensive immune system, whose effects reach far beyond the gut. Immune cells in the gut seem to be able to activate inflammatory cells throughout the body, including in joints."



Peripheral Blood Monocytes and innate immune dysregulation in ASD-IS or ASD-Inflammatory Subtype. So, peripheral blood cytokines and non IgE food allergy are proposed as possible bio markers that appear to effect behavior according to this study. This has to be effecting the brain too and suggests dealing with these elements in the periphery can be beneficial in this sub type. I am guessing this is a fairly large group in the ASD world.

Cytokine profiles by peripheral blood monocytes are associated with changes in behavioral symptoms following immune insults in a subset of ASD subjects: an inflammatory subtype?


"In summary, studies of purified PB Mo from ASD-IS children indicate that they have dysregulated innate immune responses. Specifically, these relate to the production of IL-1ß and IL-10, revealing significant changes in ‘flare’ versus ‘non-flare’ states. These responses, for the most part, were not observed in ASD/non-ASD controls. These results indicate that further analysis of the regulatory mechanisms of PB Mo in ASD-IS subjects may lead to the identification of biomarkers and even treatment options for ASD-IS subjects who typically do not respond well to the first-line therapeutic measures."



Understanding why some of the immune genes are constantly turned on will be key it appears, but they did say that mutations are not the reason as I suspected they were not. This is a good read and seems on track. Again, etiology is a ways off in their pursuit it seems.

Postmortem brains point to molecular signature of autism

"The new study suggests that autism-linked mutations tend to strike genes involved in neurons’ functions. By contrast, the activation of microglia-related genes appears to be unrelated to mutations."



Have read this in the past, but it should be pinned somewhere.

The Danger of Excessive Vaccination During Brain Development



This article may be controversial, but in my wife's case it is confirming information of her condition. It deals with autism and perception of self.

Autism markers found in CMU study of brain activity

"For example, thinking about the word “hug” evoked activity in the posterior midline region of the brain in “neurotypical” individuals — where activation is associated with the “self factor,” or thoughts of oneself. The study investigated this verb and other similar verbs because in autism social interactions are believed to be experienced in an altered way. The new results now identify what the alteration is: People with autism think about social interactions without including thoughts of themselves."

"The machine learning program was able to accurately classify people as having autism or not by assessing whether or not the self factor was activated during functional magnetic resonance imaging of their brains as they thought about the social-interaction verbs."


Years ago when first documenting my wife's condition I wrote this in a list of her physical and mental markers:

"11. Lack of self, only reacting to others in a patterned way, she had no motives or feelings of her own and was often just operating at the prompting of others."

"14. Avoidance of eye contact especially during serious conversation {this trait was something I noticed from the time we were married and probably not noticed by others in that it occurred in relation to my trying to get her to make decisions or give opinions concerning matters that revolved around self; i.e. why do you like or dislike this, that, or someone and why did you do this or that."

"Over time, with hundreds of hours of counseling and my constantly teaching her about social interaction and logical thinking, she has developed a self. But this counseling /therapy would have been useless without dealing with the maze of biological problems she had and changing her diet."

Many things were part of her recovery, but this self aspect is exactly in sync with what she was like.


There are other foods and a few drugs mentioned in literature that ameliorate microglial inflammation, but apparently some drugs are untested or produce bad long term effects. Apparently there are systemic ways of tempering microglial activation as many have seen their children recover without any of these substances being used, only diet and other supplements.


Dr. Datis Kharraaian; said that once the T Cells of the body get the immune cells of the brain going there is no shutting these brain immune cells -- glial cells off. Three was No known drug. He said though that certian types of foods would;

Reveratorol, turmeric and luteolin

I went to a concert a couple of years in a role when my kids were teenagers to see Michael Smith. He is wonderful.


My sister sent me this song and I would like to share.



Yes, I do remember the studies done about the stuff they got out of broccoli.

Thanks for reminding me. That is a big push in nutrition right now .


Another report on the "Inflammation" study:

Researchers: ‘Inflammation Is A Marker For Autism — Could Treating Inflammation Eliminate Symptoms?’

"The idea that treating inflammation will mitigate the symptoms of autism is in no way novel. Vast numbers of parents of children with autism have claimed diets that treat inflammation have helped their children, though the idea has been ridiculed over the years. Now researchers are finally able to explain some of the complexities of autism-related inflammation, and are setting their sights on advanced scientific research into the possibility of treating autism symptoms by treating inflammation itself."


"vast numbers of parents" --- uh huh.

ROS and Brain Diseases: The Good, the Bad, and the Ugly

"The key trigger to this neuroprotective cascade is the binding of Nrf2 to the antioxidant response elements (AREs) [140–142]. Therefore, exogenous Nrf2/ARE activators may represent powerful drugs to activate the antioxidant and defensive acting genes. The Nrf2/ARE pathway can be pharmacologically activated both by natural products such as sulforaphane [143, 144], polyphenols, epigallocatechin 3-gallate (EGCG), and curcumin [145] and synthetic drugs including triterpenoids and N-(4-(2-pyridyl)(1,3-thiazol-2-yl))-2-(2,4,6-trimethylphenoxy) acetamide, known as CPN-9 [146]."


This is likely known among readers here, but

Sulforaphane Improves Autism Symptoms

"What the authors concluded was that the activity of sulforaphane in terms of activating the Nrf2 pathway was likely the reason for its success. The Nrf2 gene pathway, when activated, dramatically reduces inflammation in the brain while increasing antioxidant protection. Sulforaphane is a powerful activator of Nrf2 and this is the reason we have included it in Nrf2 Advantage. Nrf2 Advantage has become one of my top nutritional supplements that we use in our clinic."


The immune system and the brain seem to have a feedback relationship. If Olmesartan does not directly activate NRF2{their is some evidence it does} than the control of other mediators{cytokines} may be ameliorate the inflammation in some.



The report does not mention what drug depleted the microglia or if it would be safe use in humans. You may have gathered that I believe Olmesartan does something to curb the brain inflammation, but I don't know. I only know what I have seen and that is not enough to translate it to others though I would love to see this drug tried for a few months as it is generally safe.


Thanks Visitor for bringing this research to our attention.
Wonder what kind of drug it was?

I wonder if it is some kind of psych drug that we are using already.

Long term use shrinks the brains.

There is a lot of talk about anti - inflammatory food right now. They said there was no drug known to stop inflammation of the brain - just certain types of foods. Maybe no safe drugs???


The actual study is does not say what the reports on it say exactly. It only says it is possible the downstream mechanisms may be altered. I guess that means it does not actually say the inflammation is definitely caused by these common upstream genes or mutations.

Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism

"Despite the extreme genetic heterogeneity observed in autism, it is possible that common downstream mechanisms may be altered10. Thus, there has been an effort to use transcriptomics to identify and dissect molecular pathways that may be altered in autism spectrum disorder (ASD)."



Posted this ealier,but this relates to the latest on microglia and behavior.{mice}
The next hot topic in autism research? Immune cells

"To test more directly whether microglia are involved in social behavior, Kipnis’ team looked at a different kind of mice — an inbred model called BTBR that is known to be asocial. After four weeks of consuming a drug that depletes microglia, the animals’ social behaviors improved. As soon as they stopped taking the drug, the microglia repopulated and the social deficits returned. This suggests that microglia are somehow involved in the animals’ social deficits, although exactly how is as yet unclear."



I another report on the new "brain inflammation" report it says:
"There are many different ways of getting autism, but we found that they all have the same downstream effect," says Prof. Dan Arking regarding his research team's finding that brains affected by autism share a pattern of inflammation as a result of increased immune responses."


All these ways of getting autism lead to this "pattern of inflammation as a result of increased immune responses"? Also, this is supposedly caused by an "upstream mutation related to all these ways of "getting autism"? Something doesn't fit. Maybe a more common trigger is causing this constant gene expression and immune response.


Concerning the last post quote I doubt this part{quote below} is true, at least a mutation causing this without environmental factors.

""This is a downstream consequence of upstream gene mutation."


Yes, that is the one I listened to. Thanks for finding the study Nick.
Hope you had a good Thanksgiving.



I watched this by Dr Datis Kharrazian:


It was quite interesting and makes sense. Some ideas, like gluten and molecular mimicry, I have long known about.
I saw the part about the 3 "foods" that can shut down glial cells. It could that they are the only things that will work for now, and luteolin is what Dr. Theoharides has suggested as a substance to use in some autism cases.
Have been studying the effect of ARB's on glial cell activation. They might be able to arrest some aspects of activation.

Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications.

"Direct blockade of AT1 receptors in target cells within the brain parenchyma also play a major role. Neuronal AT1 receptors are selectively localized in many brain areas located inside the blood-brain barrier (Jöhren and Saavedra, 1996; Mendelsohn et al., 1984). AT1 receptors have been clearly identified, within the brain and spinal cord parenchyma, not only in neurons but also in astrocytes and resident microglia (Pavel et al., 2008; Imboden et al., 2009; Tang et al., 2009; Lanz et al., 2010; Wosik et al., 2007). Enhanced AT1 expression in brain neurons has been described, both in vivo and in vitro, in rodent models of genetic hypertension (Saavedra et al., 1986; Yang and Raizada, 1998). More recently, enhanced AT1 receptor expression has been reported in brain lesions of patients suffering from multiple sclerosis (Platten et al., 2009). A complete RAS has been described in cultured microglia, and ARBs reduce LPS-induced inflammation in these cells (Miyoshi et al., 2008). Since ARBs have been shown to cross the blood-brain barrier and to inhibit neuronal AT1 receptors not accessible to circulating Angiotensin II (Nishimura et al., 2000a), it is likely that inhibition of AT1 receptors located in neurons, microglia and astrocytes play a significant role in the anti-inflammatory effects of ARBs."...

"Brain Angiotensin II, through AT1 receptor stimulation, is a master regulator of the cerebral circulation and of the central response to stress and inflammation. Excessive AT1 receptor stimulation contributes to determine the extent of allostatic load. Inhibition of brain AT1 receptor activity may be achieved with the use of orally administered ARBs, of tested efficacy in the treatment of cardiovascular disease and a good margin of safety. ARB treatment is neuroprotective: reduces brain ischemia, stress-related disorders and brain inflammation, and increases the lifespan. Preclinical data in rodent models has translational value, as indicated by increasing evidence of beneficial effects of ARBs in brain disorders, such as recent reports of significant decrease in stroke, protection of cognition, and amelioration of Alzheimer's disease, depression and stress. The anti-ischemic, anti-stress and anti-inflammatory effects of ARBs indicate that these compounds may be considered as contributors to the therapy of a wide range of conditions, including mood disorders and neurodegenerative diseases of the brain. It is hoped that in the near future ARBs will be tested, in controlled and carefully designed clinical trials, for the therapy of neurological and psychiatric disorders."


There are multiple ways to activate glial cells and what works in attenuating them is complex and I am still trying to understand this system.


It appears that Pardo himself was involved in trialing minocycline for 6 months in some with Autism. The outcome does not really address whether neuroinflammation is a problem, but rather the failure of minocycline to reduce the markers of neuroinflammation. Some neurotrophic growth factors were modulated. As a far as cytokines and chemokines the snippet below illuminates the lack of effect.
I guess they thought minocycline was safe, how about trying something else? that actually effects the immune mediators?

A pilot open-label trial of minocycline in patients with autism and regressive features

Cytokines and Chemokine profiles

'There were no significant changes in the quantitative assessment of cytokines and chemokines in both serum and CSF as measured by multiplexed microbead array technology (Luminex™). Expression of chemokines, such as CCL2 (MCP-1) or cytokines such as TNF-α, CD40L, IL-6, IFN-γ and IL-1β, well recognized immune mediators implicated in inflammatory mechanisms, were not affected in serum or CSF when pre- and post-treatment levels of these proteins were compared (Table 3). Only the chemokine CXCL8 (IL-8) in serum was significantly reduced after treatment (P = 0.047) (Figure 1A); seven of ten patients had reduction in the serum level of CXCL8 (IL-8)"...

"The trial revealed no significant effects of minocycline on the profile of immune mediators implicated in inflammatory mechanisms in either the serum or CSF of treated children with the exception of a reduction in the levels of CXCL8 (IL-8), a chemokine that appears to have neuroprotective effects [41] and regulates the release of MMPs [42]."




If you happen to read this, what is trans-indolylacrylglycine. Is is a bacterial{closridial} metabolite of tryptophan?




The BBB and gut barrier function are still poorly studied it seems. The cytokines Il-6 and Il-1b can cross the BBB in any event. These cytokines and other immune components are correlated in enough studies to merit a lot of attention. I may get around to listening to those "digestive sessions" too. Thanks for the thoughts.

p.s. Neuroinflammation still lingers as a central player. Pardo with John Hopkins history has tempered focus on microglia in his latest release on the subject, but I think that is simply to dissuade any experimental "treatments" targeting them. I tend to think that is wise at this point of understanding.


I spent a few days listening to the digestive session u tubes hosted by Sean from Underground Wellness. Sean has a lot of things on health and calls in all kinds of experts to interview them. .

One expert he interviewed was Dr. Datis Kharrazian.
He was saying something like you the study that you just last posted.

Zonnulin opens up the gut and it also opens up the blood brain barrier too.

He says if the outside world turns on the zonnulin and opens up the gut it opens up the blood brain barrier too. TO close the gut is to close the BBB.

As far back as 30 years ago they were saying if a baby had colic that, that baby had a good chance of having a bad reaction to a vaccine. Ones that Mother's noticed.

I bet this is the study that he got his information from.

They also talk about the Vegus nerver a lot, and how messages are sent from the stomach to the brain.

That is no surprise to me though since in 2000, my son and I traveled one cold snowy night 2 hours away to hear about vegus nerve stimulation. They implant an instrument close to the nerve and when an epileptic feels a seizure coming on they push a button some where and it gives the vegaus nerve a little shock.

He said that once the brain's immune system it turned on -it is not turned off easily. There are foods that will do this resveratrol, turmeric and luteolin.

Of course Dr. Wakefeild has had to live through terrible frustration of all of them smirking low lifes saying the gut is not attached to the brain -- and Dr. Wakefleld pointing out that beer that goes to the gut effects the brain.


This is in mice...but interesting. If the BBB is not as strong in those that might be affected then environmental triggers, gut microbiome metabolites, and immune/allergic responses may interact in brain function and development.

{selective qutoes from}
Mother’s Microbes Protect Baby’s Brain

"It’s also known, he said, “that [gut] microbes could modulate brain function and development.” Pettersson and his colleagues therefore wondered whether the effect of gut microbes on the brain might be manifested in part by control of the BBB."

This increased barrier permeability was associated with low expression and disorganization of tight junction proteins and was shown by additional methods to persist into adult life. That is, pups that were born to germ-free mothers and that remained germ-free throughout life had leakier BBBs as adults.

“The interesting thing here is that it is [controlled by] the mother’s microbiome,” said John Cryan, chair of anatomy and neuroscience at University College Cork in Ireland. “We largely think of the influence of the microbiome as having a postnatal effect, but here they show clearly that even before the animals get exposed to microbes, the fact that their mothers are germ-free is already impacting on their development,” he said.

"In the adult mice, transplantation of fecal matter from animals with normal microbiomes into the germ-free animals, not only corrected the expression of BBB tight junction proteins but reduced barrier permeability, the team showed. A similar effect was obtained by giving the germ-free mice bacteria-derived short chain fatty acids, suggesting that the production of metabolites may be part of the mechanism by which the bacteria control barrier integrity."

Although the precise mechanisms remain to be determined, said Cryan, “we know that the microbiota is critical for the developing brain and now we know it is also critical for the blood-brain barrier.”

“Therefore,” he added, “anything that threatens the microbiota homeostasis could potentially threaten the integrity of the blood-brain barrier.”

"Indeed, “anything that happens to the mother during pregnancy that can have a negative effect on her intestinal bacteria could adversely affect the development of the fetal brain,” speculated Stephen Collins, director of the Farncombe Family Digestive Health Research Institute at McMaster University in Ontario. “For example, antibiotic usage during pregnancy theoretically—if these results can be extrapolated to humans—could actually have some impact on brain development.”



If the 80% detection rate is accurate and the bio-markers mentioned are actually involved{they are in my view in many cases} then this is in part a verification of biomedical approaches.{diet, gluten, carnitine}

Company hopes test will revolutionize autism diagnosis, treatment

“If we can understand which biomarkers signal a child who's not able to process those things well, then we might be able to suggest that may be the first line of defense,” Donley said.

Defenses that are similar to doctors discovering high blood sugar in someone with diabetes and changing their diet or adding insulin. This autism blood test is looking for problems like a carnitine deficiency, which helps break down fat, or negative gluten reactions.

“And if we can change diet we should see an improvement both in those antibodies and the behavior that's associated with autism,” Donley said."


Jerry says he is not on the spectrum...surprise.


Cesarean birth alters immune system, social behavior in mice

"Babies born vaginally are thought to receive two crucial exposures in the birth canal: microbes and extreme stress. Researchers suspect that this journey helps prime the infants’ immune systems and stress responses for the rest of their lives..."

"They found that compared with this control group, the C-section mice show several symptoms reminiscent of autism, including repetitive behavior, anxiety and mild social deficits..."

"Cells from the spleen of these mice produce excess levels of pro-inflammatory cytokines — signaling molecules of the immune system — such interleukin 1 beta, TNF-alpha and IL-6. Cytokines, including IL-6 in particular, have been linked to autism-like features in mouse models of autism and in people with the disorder..."

"The researchers don’t know why or how C-sections lead to changes in behavior. One hypothesis, the so-called ‘leaky gut’ theory, suggests that because of an altered immune system, microbes and other molecules in the gut somehow seep into the peripheral circulation and eventually reach the brain, altering behavior..."

"As with many studies linking the gut, immune system and brain, many parts of the story are not yet worked out. All three systems feed back on one another across development, making it difficult to tease out cause and effect. “They don’t have the mechanism — that’s what’s missing,” Foster says."


Clearly this is not about c-sections causing Autism, but microbes and altered immune systems being clues to developmental issues.


Interesting, it is intuitive to think about the effects of adjuvants long term on the immune system too. Microglia are discussed..worth a read.

"The next hot topic in autism research? Immune cells"

"The link between the brain and the immune system is in fact somewhat intuitive: “When you get sick, you don’t feel well,” says Anthony Filiano, a postdoctoral fellow in Kipnis’ lab who presented the new findings. “But the fact that the immune system can contribute to normal brain function is fairly new. And it’s really neat because the immune system is a lot easier to treat than synapses in the brain.”



You are welcome Donna and Jenny.


Thank you Visitor for the information. I am very interested in tryptophan metabolism in ASD since one of the initial urine labs performed for my child revealed a high result for tIAG trans-indolylacrylglycine. The lab was also looking for any opioid peptide metabolites, which in my child's case was negligible. Another urinalysis at the time identified high microbial metabolites from clostridia. My child suffered a significant regression with significant GI issues as a toddler and I am always interested in any new research that investigates this particular aspect.


Metabolomics as a Tool for Discovery of Biomarkers of Autism Spectrum Disorder in the Blood Plasma of Children

"Previous metabolic studies of ASD have used biological matrices such as cells, organelles, urine and blood, and have implicated a wide range of metabolites including fatty acids, sterols, intermediary metabolites, phospholipids, and molecules associated with oxidative stress [12]–[16]. Two recent reports highlight the potential use of metabolomic analysis of urine to identify signatures of ASD. One study used 1H-NMR methods and showed changes in metabolites associated with the tryptophan/nicotinic acid metabolic pathway, sulphur and amino acid pathways, as well as microbial metabolites implicating the involvement of microbial metabolism in the etiology of ASD [16]. Ming et al. used a combination of liquid- and gas-chromatography based mass spectrometry methods to identify changes in a number of amino acids and antioxidants such as carnosine, as well as confirming the changes associated with altered gut microbiomes.

"This potential connection between the gut microbiome and ASD is also receiving considerable attention [55]. Metabolomic studies of urine from individuals with ASD have identified molecules associated with the microbiome such as dimethylamine, hippuric acid and phenylacetylglutamine [16], [17]. We observed decreased plasma levels of p-hydroxyphenyllactate, a metabolite associated with bifidobacteria and lactobacilli that is known to serve as an antioxidant both in the circulation and tissues [56]. We have yet to identify other microbiome related metabolites."

"Metabolomics determines changes in small molecule metabolites that are reactants and products of endogenous biochemical processes as well as small molecules derived from diet, the gut microbiome and contact with the environment. Perturbations in their abundance can result not only from genomic and proteomic influences, but from environmental and epigenetic influences as well."



Interesting - thanks for posting, visitor


Neuroprotective Effects of Angiotensin Receptor Blockers.



Century-old drug reverses signs of autism in mice


The article has a link to the researcher's {Robert K. Naviaux} original theory, one I linked to in this thread last year. I am waiting for conclusive proof that living pathogens are causing, contributing to, or perpetuating a number of conditions, or part of these conditions per Marshall, but this theory fits the picture and the cell danger scenario with inflammation. Here is the link from within the article.

p.s. Yes, they are mice, not people.

Metabolic features of the cell danger response



That study I linked was from a population in Finland with higher CRP. It was Finland that was having increasing rates of Type 1 Diabetes. The idea this was a true increase was something Dr. Noel Rose mentioned in his talk on autoimmune conditions linked in this thread elsewhere. In the gut bug thread I mentioned that vaccines could be opening the door for organisms to become pathogenic for the host due to the deregulation of the immune system. Finland is one population and CRP increases may be widespread, but many of the organisms are not easily cultured or known. Time will tell, but the microbiome shift as immune systems are altered alters the whole person in many cases{disease in many cases}.



Age of Autism put an article up on this website of a rsearch paper -- were the researchers said they found that when a woman had the flu while pregnant that she had a better chance of having a baby with autism. What they found -- it was not a virus or bacteria -- or any certian pathogen but rather the Mother's own immune system reaction that was causing her baby to be more prone to autism.

In the last meeting at the IACC at the very end -- Lyn Redwood brought up this research paper -and told them that if it was an immune reaction rather than the pathogen itself perhaps flu shots for pregnant women was not a good ides- but their eyes became shifty and they just set there like knots on the log.


Since I had taken a break the following article and study have likely been seen here at AoA and I am not aware of it, but inflammation is in view here and it points out a study relating C-reactive protein and possible linkage to Autism. That was discussed a good bit at the very first part of this thread.

Inflammation and the Origin of Autism


Elevated maternal C-reactive protein and autism in a national birth cohort

A S Brown, A Sourander, S Hinkka-Yli-Salomäki, I W McKeague, J Sundvall and H-M Surcel


"Autism is a complex neuropsychiatric syndrome with a largely unknown etiology. Inflammation during pregnancy may represent a common pathway by which infections and other insults increase risk for the disorder. Hence, we investigated the association between early gestational C-reactive protein (CRP), an established inflammatory biomarker, prospectively assayed in maternal sera, and childhood autism in a large national birth cohort with an extensive serum biobank. Other strengths of the cohort included nearly complete ascertainment of pregnancies in Finland (N=1.2 million) over the study period and national psychiatric registries consisting of virtually all treated autism cases in the population. Increasing maternal CRP levels, classified as a continuous variable, were significantly associated with autism in offspring. For maternal CRP levels in the highest quintile, compared with the lowest quintile, there was a significant, 43% elevated risk. This finding suggests that maternal inflammation may have a significant role in autism, with possible implications for identifying preventive strategies and pathogenic mechanisms in autism and other neurodevelopmental disorders."



Edit last post:

Compare that with the inflammation/disease ideas in the Discovery Journal paper, like this quote:
{actual quote from that paper not correct in last post}
"Since the immune system strives to target the persistent microbes but never fully succeeds, a stalemate results, a low grade inflammation accumulates."

{pardon me}


Inflammation may help explain depression, diabetes link

"Death rates are up to twice as high among people with depression and diabetes as those with diabetes alone, Ismail said.

“The conventional wisdom is that this is a consequence of the psychological burden of having diabetes,” she said. “If that’s the case, if you treat the depression, the diabetes control should improve.”

But it does not, Ismail said. So she began to wonder if inflammation, often seen in people with diabetes, could help explain both conditions and the worse outcomes.

“It’s a bit like an engine,” Ismail said. “You’re running a bit higher. So there’s this constant low-grade inflammation and that’s causing damage to your brain, your pancreas and to your vascular system.”"


Compare that with the inflammation/disease ideas in the Discovery Journal paper, like this quote:

"So there’s this constant low-grade inflammation and that’s causing damage to your brain, your pancreas and to your vascular system.”


The last link on Inflammation and the microbiome has a interesting background. Dr. Noel Rose of John Hopkins apparently invited this papers submission.
Here is what Trevor Marshall said:

A couple of months ago we received an invitation from Noel Rose (head of Autoimmunology at Johns Hopkins) to write a paper for Discovery Medicine, a journal affiliated with Johns Hopkins. We did, and it has just been published:





Since this is in view on the main page it may be of interest to some.

Inflammatory Disease and the Human Microbiome



Good sleuthing Nick.
but the way it is going - chromosome 16 after being pushed by gluten and soemthing else - probably sends a signal to Chromosome 21

Then maybe not. Still thanks for putting yourself out there to look it up.


Zonulin is related to chromosome 16 while MIR155HG is tied to 21 I think.


"You know those two other things that Dr. Fassino was talking about."

I hadn't thought about it, but would like to know what you find in a follow up if you do so. If I find anything of interest I will post on this, but have no idea at the moment.


MIR155HG do you suppose is on the zonulin chromosome but won't turn on unless there are the other two things that interact with that chromosome turning it one. You know those two other things that Dr. Fassino was talking about.


No metaphor from me, but you made it lighthearted. That has it's plusses.


Okay first of all I like Sting singing Fields of Gold better -- and besides there is a metaphor in there some where with a name like ing singing a song about a field of gluten with a bunch of celiacs listening.

Let me be silly -- I am most of the time anyway:

You'll remember me when the westwind moves among the fields of barley.

You can tell the sun in his jealous sky when we walk the fields of gold

In his arms she fell in an epileptic seizure down among the field of gold.

Will you stay with me, will you be my love among the fields of barley.

No, I can not stay because I had a reaction and now I have to walk the inflamation highway instead.


Ha, Ha Visitor;
It took me a while to figure out why you had linked us to the song "Fields of Gold"

Barley - gulten and we were talking about it's role in inflamation


Meant to add this:










Thanks Visitor for the link. I see that Alessio Fasano is still at it and has finally published his finding in the NIH files.

I also noticed that Fasano did not mention how he came about finding this thing that causes a leaking gut - hmmmm used the words genetically susceptible a lot.

I just skimmmed tonight - no time for any really deep reading.

I notice that Dr. Blaylock says that carbohydrates drive the Microgli the immune system macrophages of the spinal chord and brian.

Just something to think about. Is there more carbohydrates getting into the brain that normally there would be causing not only mental problems but diabetes and obsesity too.


It is a bit amusing to reflect on some things. A few years ago when I started a brief dialogue with a forum group that dealt with dealing with pathogens that effect the immune system. While the problems these pathogens cause are real by my lights I noticed that the leader of the group had to dismiss DAN doctors and many if not most biomed treatments and also pretty much dismissed gut bacteria and nutrition as being relevant. He and some of them are countenancing these elements now. . Since then some of these folks now see the wheat issue and Zonulin problem which many of us in biomed have known about and reasoned it may be involved.. One article linked in a forum thee discusses how antigens that get through the intestinal barrier may trigger autoimmune issues among others.
Here is the report they linked.


and here is earlier autism news saying much of the same.



GABA and Glutamate Receptors of the Autistic Brain



Dr. Blaylock's is not taking a great many things into account in the lecture imo and maybe he is being selective, but glutamate has been on the radar for a long time. In the 90's may were talking about even MSG being an excitatory even though the mechanism were not clear then. Why science blurbs like the this next piece lead with the notion that this is news or is maybe foremost about stress or mood disorders is beyond me. It is misleading to the subject overall as well. They do manage to include I that it may be involved in other disorders too.

Glutamatergic Agents Show Promise for Mood, Anxiety Disorders



Will check further, but the suppressor effect of Olmesartan to glutamate is probably more ubiquitous than the area cited in this report.

Chronic administration of olmesartan attenuates the exaggerated pressor response to glutamate in the rostral ventrolateral medulla of SHR.



Many probably have seen this:

The Central Mechanism By Which Vaccines Induce Autism - Dr. Russell Blaylock Lecture




As to not be labeled I believe man has gone to the moon, I have been before myself. Think our captain's name was Morgan.

Some Einstein in the comments has to say; "What? People at an anti-vaccination conference believe that vaccines cause autism? Imagine that."

Where would he expect them to gather, at a cotton candy convention?


At least this isn't one sided, but no one said there were none with autism over 40. Even if you stipulate the early 1940's for a main point of more general diagnosis and existence you have people over 70 with autism. But, as is noted within if their were a lot of severe autism it would have been seen. I can't buy that they, at least the severe, existed in large numbers and were hidden away and not at least a major source of professional journal marked curiosity or known to many circles of families that kept it relatively quiet, which is not evident by inquiry. I have noted the increase of immune related disorders rising for a while and noted Dr. Rose acknowledging the fact, and he says it is not just better diagnosing alone in that regard.

Debate continues: Is autism really growing?

"David Amaral leans the other way. Noting that the rates of other immune disorders like asthma, multiple sclerosis and rheumatoid arthritis also are going up in America, he postulates that something in the environment may be triggering immune reactions that could play a part in autism.

"I believe there are environmental factors [that play a role], and I think we have to stay open to whatever influences there might be and be willing to explore them."


David Amaral and I concur, and wow am in agreement with Dr. Insel too.


Thanks for the links Visitor -- they are very insightful!


Some central ideas have gained support it seems. This was a year ago.

Brain Inflammation, Oxidative Damage & Autism



...and one more on chronic fatigue by the same people as the other two.

Increased nuclear factor-κB and loss of p53 are key mechanisms in Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS).



This is an odd take that mentions autophagy which does seem to be involved. The vagueness still contains some perspectives that are refreshing. Even though it mentions genes in the title it's reliance on genes as explanatory is limited and tenuous.

Deleted genes 'offer autism clues'

"UK experts said genetic factors were one promising area of research into the causes of autism.

About 1% of the population has an ASD. They can run in families - but scientists have not identified a cause.

Gene deletions or additions happen in everyone - it is why people are different....

The researchers found many of the most common deletions in the autistic group were linked to autophagy - kind of waste-disposal and renewal process for cells,

Prof Buxbaum said: "There is a good reason to believe that autophagy is really important for brain development because the brain produces many more synapses [connections through which brain cells communicate] than it needs, and the excess needs to be pruned back."

He added: "Too many, or too few, synapses have the same effect of not making communication work very well. It could mean that some synaptic connections come in too late and may not solidify properly."...

Many experts believe that the pattern of behaviour from which autism is diagnosed may not result from a single cause.

"There is strong evidence to suggest that autism can be caused by a variety of physical factors, all of which affect brain development.

"Genetic factors may be responsible for some forms of autism, but it is likely to have multiple genes responsible rather than a single gene."


Also, here is an earlier piece than the one a couple of posts back on autoimmunity and chronic fatigue by the same people.

A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome.



Recently came across a good video by Dr. Shaw.

"Interpretation of the Organic Acids Test" by Dr. William Shaw"



Additionally there is more to metabolic issues in some autism than the abstract on "Unraveling the Mechanisms Responsible for the Comorbidity between Metabolic Syndrome and Mental Health Disorders" is addressing. Metabolic dysfunction that is not noted simply by the presence of hypertension or elevated triglyceride levels and may actually not be out of range and varies from the typical due to varied effects in mitochondrial function and changes in systemic function. Yet, those expressions with these obvious symptoms show the relationship in some as well.


Also interesting how chronic fatigue debut in the early/mid 80's was in sync was right before the increase in autism rates and autoimmune diseases, wonder aids timing too. {no lying Scotsman either}

The Emerging Role of Autoimmunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/cfs).



This is a small very incomplete sketch, but a good start.

Unraveling the Mechanisms Responsible for the Comorbidity between Metabolic Syndrome and Mental Health Disorders.


The increased prevalence and high comorbidity of metabolic syndrome and mental health disorders have prompted investigation into the potential contributing mechanisms. There is a bidirectional association between metabolic syndrome and mental health disorders including schizophrenia, bipolar disorder, depression, anxiety, attention deficit/hyperactivity disorder, and autism spectrum disorders. Medication side effects and social repercussions are contributing environmental factors, but there are a number of shared underlying neurological and physiological mechanisms that explain the high comorbidity between these two disorders. Inflammation is a state shared by both disorders, and it contributes to disruptions of neuroregulatory systems, including the serotonergic, dopaminergic, and neuropeptide Y systems, as well as dysregulation of the hypothalamic-pituitary-adrenal axis. Metabolic syndrome in pregnant women also exposes the developing fetal brain to inflammatory factors that predispose the offspring to metabolic syndrome and mental health disorders. Due to the shared nature of these conditions, treatment should address aspects of both mental health and metabolic disorders. Additionally, interventions need to be developed that can interrupt the transfer of increased risk of the disorders to the next generation. © 2013 S. Karger AG, Basel.



I usually refrain form negative remarks, but the more I read by Emily the more I think of the adage that "even a broken clock is right twice a day".

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