The Unexpected Connection Between Estrogen and Autism

Science has been studying autism spectrum disorder for better part of a century, and yet there’s one thing they can’t seem to figure out: why the brain of people with autism develop differently. But because it’s more common in boys, some researchers have long suspected that testosterone levels in the womb are the key.

The only problem is, their evidence has become up short. Turns out they might have been looking at the wrong hormones. Just this week, a team of scientist at the University of Cambridge and the State Serum Institute in Denmark announced that they’ve identified a link between autism and a different sex hormone: estrogen.

While it might sound like the complete opposite of what you’d expect for something more prevalent in boys, it actually lines up with our understanding of autism better than you’d think.

Autism spectrum disorder affects about every on of 59 children, but even after correcting for underdiagnosis and misdiagnosis, it’s roughly three times more likely in boys than in girls. Girls with autism also generally have fewer autism traits than boys. And all that may imply that there’s some kind of connection between autism and the physiological difference that generally come with Y chromosome.

Some even suggested that autism is basically what happens when you take typically male neurological traits and dial them up to 11. This is what’s known as the “extreme male brain theory” of autism. Now, it’s important to note that this doesn’t mean that the autistic people are super masculine overall–it just mean that they have more of the traits that you see more frequently on average, in the brains of men. And the difference is very small.

Studies consistently show that men and women are more psychologically similar that they are different. But there are some traits that, again, on average more common or more pronounced in the brains of people with Y chromosome or who identify as me. And it does seem like the traits are amplified in people with autism. To give one example, the brains of men tend to have weaker connectivity in the brains default mode network.

There’s a group of brain region that’s most active when you’re not focused on the outside world. And it turns out that both men and women with autism have even lower connectivity on this region than the average neurotypical man. Because there does seem to be some merit to this extreme male brain idea, researchers have suggested that the biological pathways involved in the development of typically masculine traits might be at the root of autism. And all traces back to fetal sex differentation:

The biological cues that lead to the development of typically masculine or feminine traits So in recent years, researchers begin to look for clues to autism in fetal development and conditions fetuses experience in-utero. And at first, many thought androgens- the hormones involved in typically male traits- might be to blaim, which makes intuitive sense.

The thing is, studies on prenatal testosterone levels alone- which is arguably the most important androgen–have found no relationship between it and autistic features. Then in the study published in 2015, Cambridge and Danish researchers found elevated levels of several sex hormones in the amniotic fluid of male fetuses that went on to develop autism. And while that did include testosterone and another androgen, it also included progesterone: which got the researchers thinking maybe they needed to widen their scope. Which brings us to estrogen.

Estrogen actually refers to the group of hormones which includes estriol, estradiol, estrone, and estetrol–none of which tested in the 2015 study. And these so called “female” hormones are very important for fetal development regardless of sex. Estradiol, in particular, contributes a lot development. It helps to form and prune neurons and synapses, and it regulates the activity of neurotransmitter GABA. In the brains of people with autism, synapses and neuron formation and GABA regulation are all typical.

So it might make sense that estrogen levels in the womb could play a role in the development of autism, too. To find out, those same researchers returned to the amiotic fluid samples they used in their 2015 study. These initially came from the Danish Historic Birth Cohort: a set of biological samples are more than a hundred thousand pregnant people collected between 1980 and 2004 who were followed up with the monitor the children’s health overtime, including whether they were diagnosed with autism. The researchers ended up with amniotic fluid samples from 98 males with autism and 177 neurotypical males. They then analyzed the samples for various forms of estrogen.

They found that elevated levels of estradiol and estriol, and estrone were all associated with an autism diagnosis. Estradiol has the biggest effect: a rise in this hormone from the 25th to the 75th percentile came with an almost 50% increase in the likelihood of autism. What this study suggests is that high level of estrogen, at least at about 15 weeks gestation, it might lead to differences in the brain development. As for why estrogen levels are higher at that time, the researchers suggested the placenta may have something to do with it. It acts as a hormone regulator between mom and fetus, and it’s fetus’ main source of estrogen.

And all that said, the researchers didn’t find that amniotic fluid hormones perfectly predict autism.

Parasites, stress, and auto-immune hormone connection

Every week, I have foot massage, walk on the beach, eat salads and whole foods and tried to get adequate sleep. I want to avoid chronic inflammation from parasites, effects of high stress hormones and to prevent cancer and other auto-immune disease.  Low stress can mean we work 4 days a week but high stress is working 2 jobs, more than 60 hours a week in our 50s.

It is not so late even in my 50s. I wish to save and do preventive actions now regarding my health than spend all my savings in health care. Health care costs can be avoided if we spend time and money on preventive measures.  Libraries will soon receive the free ebook that I am completing about health and conversations about cancer, parasites, self care and home care.

Connie Dello Buono

Chronic Stress, Cortisol Dysfunction, and Pain: A … – NCBI – NIH

 

 

Cortisol is also a potent anti-inflammatory hormone; it prevents the widespread tissue and nerve damage associated with inflammation. In addition to its paramount role in normal daily function, cortisol is a key player in the stress response.

Missing: parasites ‎| Must include: parasites

Stress & the gut-brain axis: Regulation by the microbiome – NCBI

 

 

The linkage between gut functions on the one hand and emotional and … yeasts, helminth parasites, viruses, and protozoa (Lankelma et al., 2015, Eckburg et al., …. salivary cortisol awakening response in healthy people (Schmidt et al., 2015). ….. Peripheral administration of pro-inflammatory cytokines in rodents induces a …

How stress influences disease: Study reveals inflammation as the …

 

 

Missing: parasites ‎| Must include: parasites

Why Cortisol Is Good for You – Healthy Gut Company

 

https://healthygut.com › Healthy Gut Company › Why Cortisol Is Good for You

 

 

Adrenal Fatigue, Blastocystis hominis, and Cortisol – Dirty Good Co.

 

 

RHR: High Cortisol and Brain Fog | Kresser Institute

 

https://kresserinstitute.com › Kresser Institute › RHR: High Cortisol and Brain Fog

 

Is Stress Damaging Your Gut? – Amy Myers MD

 

 

The Autoimmune Hormone Connection – Dr. Jolene Brighten

 

https://drbrighten.com › Blog › Autoimmune

 

5 Ways to Reduce Inflammation | The Chopra Center

 

 

Check your bile acid production and stress level for fat metabolism

Bile acids are synthesized from cholesterol

Bile begins its life in the liver and spends a significant amount of time somewhere between the liver, gallbladder, and gastrointestinal tract, specifically the intestines. Liver cells manufacture bile before it undergoes modification in the bile duct epithelium, and then it is transported to the gallbladder for storage and, ultimately, use. Bile acids are synthesized from cholesterol with the aid of several different enzymes.

Soup of Sulfur rich bile acids will help balance bile production:

Mix these root crops to pinch of organic chicken broth powder: rutabaga, kale, carrot, parsnip, onion, garlic and a tsp of apple cider vinegar or lemon juice added in the last boiling.

bile

Short-chain fatty acids :  The gut microbiota can ferment complex dietary residues that are resistant to digestion by enteric enzymes.

This process provides energy for the microbiota but culminates in the release of short-chain fatty acids including butyrate, which are utilized for the metabolic needs of the colon and the body.

Butyrate has a remarkable array of colonic health-promoting and antineoplastic properties:

  • It is the preferred energy source for colonocytes,
  • It maintains mucosal integrity and it suppresses inflammation and carcinogenesis through effects on immunity, gene expression and epigenetic modulation.

Note:  Protein residues and fat-stimulated bile acids are also metabolized by the microbiota to inflammatory and/or carcinogenic metabolites, which increase the risk of neoplastic progression.

The makeup of bile is largely water, at about 95%. The remaining five percent is made up of bile acids, bilirubin, amino acids, enzymes, steroid hormones including estrogen, glutathione, cholesterol, vitamins (especially vitamin D and some of the B vitamins), porphyrins, insulin, and other items, including toxins such as heavy metals, xenobiotics, medications and drugs, and environmental toxins targeted for excretion. There are also electrolytes, including sodium, potassium, chloride, calcium, magnesium, phosphate, sulfate, and bicarbonate. As you excrete more bile acid, bile flow is stimulated. There is also a circadian rhythm to the synthesis and circulation of bile acids.

In total, there are more than 50 species of bile acids in humans, but the main ones include cholic acid and chenodeoxycholic acid (CDCA). Although bile salts and bile acids are frequently used interchangeably, technically bile acids become bile salts upon conjugation with glycine or taurine. The gut bacteria metabolize bile acids to create secondary bile acids, of which there are more than 400 species. After the gut bacteria metabolize them, cholic acid becomes deoxycholic acid and CDCA becomes lithocholic acid. The amount of bile acids making their way into the colon affects the microbiome makeup. Bile acids are reabsorbed in the small intestine and colon to then come back into circulation as part of the enterohepatic circulation, which is a bidirectional pathway.

Bile acids, a key component of bile, are the main emulsifiers of fat. As such, bile ultimately finds its way into the small intestine for this function. When fat enters your small intestine, you secrete CCK (cholecystokinin), which signals your gallbladder to send bile into the small intestine to aid in digestion and absorption.

Functions of bile acid

Although this may be the function of bile most commonly known, there are actually many, many more. Some of the key functions of bile include:

  • Aids the immune system through excreting certain immune system signals, such as IgA and inflammatory cytokines
  • Elimination of certain hormones and pheromones
  • Endogenous ligand (binder to stimulate a signal) for several receptors, including nuclear receptor farnesoid X receptor (FXR), vitamin D receptor, and G protein-coupled receptor TGR5
  • Excretion of fat-soluble toxins and other waste, including endogenous substrates
  • Modulation of metabolic pathways, including lipid metabolism, glucose metabolism, and insulin sensitivity
  • Regulation of tight junction permeability
  • Removal of cholesterol
  • Signaling molecule and hormone

With so many different functions, it should come as no surprise that problems in the flow, metabolism, or synthesis of bile and/or bile acids could contribute to a variety of diseases.

Diseases such as colon and liver cancer

Problems with bile may stem from dysfunction in the synthesis of bile, an impairment in the secretion, or problems with the flow of bile. The metabolism of bile may become disturbed through problems stemming from the synthesis or conjugation with cholesterol, problems with the membrane transport, issues with the transport between the organs, or problems with the bacterial degradation of bile during the enterohepatic cycling. There may also be malabsorption of the bile acid, leading to higher concentrations in the colon, which may then negatively impact the function of the mucosal cells in the colon. Furthermore, when the concentration of bile acids is too high, it can be toxic and cause problems. Alterations to bile acids are also associated with disease.

The level of bile acids that reach the colon may contribute to functional bowel diseases. Elevated concentrations may contribute to diarrhea, while lower levels may play a role in constipation. In one study on children with functional constipation, the fecal bile acid profile was normal, but there were some who had the 3-sulfate version of CDCA as the dominant fecal bile acid, which could demonstrate a link for some cases.

Stress and Bile acids

Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage-specific reverse cholesterol transport, m-RCT) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid-treated animals, we investigated if chronic intermittent restraint stress would modify m-RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium-dependent bile acid transporter (ASBT), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m-RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage-derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m-RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m-RCT induction could have antiatherogenic potential under conditions of chronic stress.

Vinegar helps increase bile production

Polyphenols such as chlorogenic acid which is present in high levels in apple cider vinegar could inhibit oxidation of LDLs and improve health by preventing cardiovascular diseases (Laranjinha and others 1994).

Epileptics Living in High Crime Areas Have Three Times As Many Seizures

Epileptics Living in High Crime Areas Have Three Times As Many Seizures

Summary: According to a new study, those with epilepsy who live in high crime neighborhoods have three times as many seizures as those living in lower crime areas.

Source: University of Illinois.

People with epilepsy living in high crime neighborhoods in Chicago had three times as many seizures as those living in neighborhoods with lower crime rates according to new research from the University of Illinois at Chicago presented at the American Epilepsy Society 2018 conference in New Orleans.

Epilepsy is a chronic neurological disorder characterized by abnormal brain activity and seizures that affects more than 65 million people worldwide. About one-third have difficulty controlling their seizures even with medication. Seizures can interfere with work, relationships, and the ability to live independently. Previous research has shown that living in neighborhoods with high rates of crime have significantly higher levels of the stress hormone, cortisol. Stress is also a factor that is commonly reported to trigger seizures in people with epilepsy.

The UIC study included 63 adults with epilepsy living within the city limits of Chicago who were participating in a larger study testing the efficacy of a tablet-based educational tool that provides tailored information about epilepsy. That study, called PAUSE, involves patients at the University of Illinois Hospital’s epilepsy clinic and in the Chicagoland community and is facilitated by the Epilepsy Foundation of Greater Chicago.

The researchers determined the levels of crime in neighborhoods of the 63 participants by mapping their zip codes to specific neighborhoods and then cross-referencing those neighborhoods with local crime rates available through the City of Chicago Police data portal. Participants self-reported the number of seizures they had in the past month and in the past three months.

brain

“We found that people living with epilepsy who live in high-crime neighborhoods experienced significantly more seizures,” said Jessica Levy, a research coordinator in the UIC department of neurology and rehabilitation who presented the findings. “On average, people in high-crime neighborhoods had three seizures versus one for people living in low-crime neighborhoods when we looked back over the last 30 days. Over the course of 90 days, people in high-crime neighborhoods had seven seizures on average compared to three for those living in low-crime neighborhoods, so the link between crime and seizure activity is significant.”

The researchers found no overall association between neighborhood crime status and the duration of epilepsy or between crime status and poverty.

Having more seizures can significantly lower quality of life. Seizures that result in falls can cause bruising or even broken bones. There can also be a stigma associated with having a seizure in public.

“Understanding the impact of violence and crime as potential triggers for seizures underscores the need for further research that might allow clinicians to make better-informed recommendations for self-management education and stress management skills,” said Dr. Dilip Pandey, associate professor of neurology and rehabilitation at UIC and an investigator on the study.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Katharine Ozenberger is a co-investigator on the study.

The PAUSE study is conducted through the UIC department of neurology and rehabilitation by Dr. Dilip Pandey and Dr. Jeffery Loeb.

Funding: PAUSE is supported by the University of Illinois Prevention Research Center and the Centers for Disease Control and Prevention (CDC) Managing Epilepsy Well (MEW) Network under CDC cooperative agreement no. U48-DP005010.

Source: Sharon Parmet – University of Illinois
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: The study will be presented at the American Epilepsy Society Meeting.

Chronic stress predisposes brain to mental illness

Link to placental marker of prenatal stress to bran mitochondrial dysfunction