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.

Step 1 to cancer free: Limit stress that leads to high blood glucose and lipids

Adrenals and liver come to the rescue as blood sugar levels drop.  The endocrine pancreas, liver and adrenal glands work to normalize blood sugar and triglycerides.

Take care of your stress so it will be easier for you to prevent obesity, depression, sugar cravings and nerve pain which may start to happen at around 55 years of age. When we take care of our stress level, we take care of our metabolism , brain , whole body and we then prevent chronic diseases that lead to cancer.

Activities to make you happy

Beach stroll, dancing, watching comedians , laughing , sleeping at nigh, massage , happy and loving friends and relationships , spending time with family and friends , playing with your pets, gardening , singing , praying , deep breathing exercise, meditation

Side effects of chronically elevated cortisol can include:

Anxiety , Autoimmune diseases , Cancer,  Chronic fatigue syndrome , Common Colds , Hormone imbalance , Irritable bowel disease , Thyroid conditions , Weight loss resistance

Needed nutrients

Digestive enzymes, vitamin C (citrus, kiwi, berries, tamarind), vitamin B, L-carnitine, chromium, anti-oxidants, fiber-rich foods (squash, yams, sulfur family of garlic and onions, greens, okra, radish), spearmint, ginger, beets, carrots, all root crops, sprouts, pineapple, papaya , taurine rich foods (breastmilk, sea algae, fish)

Adaptogenic herbs

  1. Eleuthero ginseng
  2. Holy basil
  3. Rodiola rosea
  4. ashwagandha
  5. Astralagus
  6. Sour date
  7. Mimosa pudica
    Extracts of Mimosa pudica are successful in wiping out harmful bacteria and can be useful in antibacterial products
  8. Medicinal mushrooms
    Mushrooms are rich in B vitamins such as riboflavin (B2), folate (B9), thiamine (B1), pantothenic acid (B5), and niacin (B3).
  9. Licorice root
  10. Valerian

 

Why Cannabis Affects Women Differently

Source: Frontiers.

Cannabis use is riding high on a decade-long wave of decriminalization, legalization and unregulated synthetic substitutes. As society examines the impact, an interesting disparity has become apparent: the risks are different in females than in males.

A new review of animal studies says that sex differences in response to cannabis are not just socio-cultural, but biological too. Published in Frontiers in Behavioral Neuroscience, it examines the influence of sex hormones like testosterone, estradiol (estrogen) and progesterone on the endocannabinoid system: networks of brain cells which communicate using the same family of chemicals found in cannabis, called ‘cannabinoids’.

Animal studies

“It has been pretty hard to get laboratory animals to self-administer cannabinoids like human cannabis users,” says study co-author Dr Liana Fattore, Senior Researcher at the National Research Council of Italy and President of the Mediterranean Society of Neuroscience. “However, animal studies on the effects of sex hormones and anabolic steroids on cannabinoid self-administration behavior have contributed a lot to our current understanding of sex differences in response to cannabis.”

So how does cannabis affect men and women differently? Besides genetic background and hormonal fluctuations, the paper highlights a number of important sex differences.

Men are up to four times more likely to try cannabis – and use higher doses, more frequently.

“Male sex steroids increase risk-taking behavior and suppress the brain’s reward system, which could explain why males are more likely to try drugs, including cannabis” explains Fattore. “This is true for both natural male sex steroids like testosterone and synthetic steroids like nandrolone.”

But despite lower average cannabis use, women go from first hit to habit faster than men. In fact, men and women differ not only in the prevalence and frequency of cannabis use, pattern and reasons of use, but also in the vulnerability to develop cannabis use disorder.

“Females seem to be more vulnerable, at a neurochemical level, in developing addiction to cannabis,” explains Fattore.

“Studies in rats show that the female hormone estradiol affects control of movement, social behavior and filtering of sensory input to the brain – all targets of drug taking – via modulation of the endocannabinoid system, whose feedback in turn influences estradiol production.

“Specifically, female rats have different levels of endocannabinoids and more sensitive receptors than males in key brain areas related to these functions, with significant changes along the menstrual cycle.

cannabis leaves

“As a result, the interactions between the endocannabinoid system and the brain level of dopamine – the neurotransmitter of “pleasure” and “reward” – are sex-dependent.”

Human impact

The inconsistency of conditions in these studies greatly complicates interpretation of an already complex role of sex hormones in the endocannabinoid system and cannabinoid sensitivity.

“The effects varied according the specific cannabinoid studied, as well as the strain of animals tested and duration of hormone exposure,” admits Fattore. However, the human data so far are consistent with the idea that estradiol regulates the female response to cannabinoids. As in animals, human males and females are diverse in their genetic and hormonally driven behaviour and they process information differently, perceive emotions in different ways and are differently vulnerable to develop drug addiction.

“Blood levels of enzymes which break down cannabinoids fluctuate across the human menstrual cycle, and imaging studies show that brain levels of cannabinoid receptors increase with aging in females – mirroring in each case changes in estradiol levels.”

Fattore believes that deepening our understanding of the interactions between cannabinoids and sex steroids is crucial in assessing the impact of increasing cannabis use, and tackling the fallout.

“Gender-tailored detoxification treatments and relapse prevention strategies for patients with cannabis addiction are increasingly requested. Optimizing personalized evidence-based prevention and treatment protocols demands further research on the source of sex disparities in cannabis response.”

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Source: Matt Prior – Frontiers
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Open access research for “The Modulating Role of Sex and Anabolic-Androgenic Steroid Hormones in Cannabinoid Sensitivity” by Dicky Struik, Fabrizio Sanna and Liana Fattore in Frontiers in Behavioral Neuroscience. Published October 26 2018.
doi:10.3389/fnbeh.2018.00249

CITE THIS NEUROSCIENCENEWS.COM ARTICLE
Frontiers”Why Cannabis Affects Women Differently.” NeuroscienceNews. NeuroscienceNews, 26 October 2018.
<http://neurosciencenews.com/women-cannabis-10093/&gt;.

Abstract

The Modulating Role of Sex and Anabolic-Androgenic Steroid Hormones in Cannabinoid Sensitivity

Cannabis is the most commonly used illicit drug worldwide. Although its use is associated with multiple adverse health effects, including the risk of developing addiction, recreational and medical cannabis use is being increasing legalized. In addition, use of synthetic cannabinoid drugs is gaining considerable popularity and is associated with mass poisonings and occasional deaths. Delineating factors involved in cannabis use and addiction therefore becomes increasingly important. Similarly to other drugs of abuse, the prevalence of cannabis use and addiction differs remarkably between males and females, suggesting that sex plays a role in regulating cannabinoid sensitivity. Although it remains unclear how sex may affect the initiation and maintenance of cannabis use in humans, animal studies strongly suggest that endogenous sex hormones modulate cannabinoid sensitivity. In addition, synthetic anabolic-androgenic steroids alter substance use and further support the importance of sex steroids in controlling drug sensitivity. The recent discovery that pregnenolone, the precursor of all steroid hormones, controls cannabinoid receptor activation corroborates the link between steroid hormones and the endocannabinoid system. This article reviews the literature regarding the influence of endogenous and synthetic steroid hormones on the endocannabinoid system and cannabinoid action.

Happy genes love to eat

 Special people with special genes are always happy and love to eat. We are also influence by our environment but our genes is our master control until we harmed our genes from forces in the environment, prenatal nutrition , stress and other factors.

Connie

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How the Brain Responds to Injustice

How the Brain Responds to Injustice

Summary: A new study implicates oxytocin in corrective punishment that helps maintain fairness.

Source: SfN.

Punishing a wrongdoer may be more rewarding to the brain than supporting a victim. That is one suggestion of new research published in JNeurosci, which measured the brain activity of young men while they played a “justice game.”

Study participants played a game in which two players — a “Taker” and a “Partner” — each start out with 200 chips. The Taker can steal up to 100 of the Partner’s chips, and then the Partner can retaliate by spending up to 100 chips to reduce the Taker’s stash by up to 300 chips. Participants played as either a Partner or an Observer, who could either punish the Taker or help the Partner by spending chips to increase the Partner’s stash.

Mirre Stallen and colleagues found that participants were more willing to punish the Taker when they experienced injustice directly as a Partner as opposed to a third-party Observer.

The decision to punish was associated with activity in the ventral striatum, a brain region involved in reward processing, and distinguishable from the severity of the punishment.

Image shows the game.

Before beginning the experiment, all participants were given a nasal spray, with some randomly assigned to receive the hormone oxytocin, which has been suggested to have a role in punishing.

Participants in the oxytocin group chose to give more frequent, but less intense, punishments.

This finding implicates oxytocin in corrective punishments akin to a “slap on the wrist” to maintain fairness.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Funding: Funding provided by European Research Council, Erasmus Research Institute of Management.

Source: David Barnstone – SfN
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to Stallen et al., JNeurosci (2018).
Original Research: Abstract in Journal of Neuroscience.
DOI:10.1523/JNEUROSCI.1242-17.2018

CITE THIS NEUROSCIENCENEWS.COM ARTICLE
SfN “How the Brain Responds to Injustice.” NeuroscienceNews. NeuroscienceNews, 19 February 2018.
< http://neurosciencenews.com/brain-injustice-8522/&gt;.

Abstract

Neurobiological Mechanisms of Responding to Injustice

People are particularly sensitive to injustice. Accordingly, deeper knowledge regarding the processes that underlie the perception of injustice, and the subsequent decisions to either punish transgressors or compensate victims, is of important social value. By combining a novel decision-making paradigm with functional neuroimaging, we identified specific brain networks that are involved with both the perception of, and response to, social injustice, with reward-related regions preferentially involved in punishment compared to compensation. Developing a computational model of punishment allowed for disentangling the neural mechanisms and psychological motives underlying decisions of whether to punish and, subsequently, of how severely to punish. Results show that the neural mechanisms underlying punishment differ depending on whether one is directly affected by the injustice, or whether one is a third-party observer of a violation occurring to another. Specifically, the anterior insula was involved in decisions to punish following harm, while, in third-party scenarios, we found amygdala activity associated with punishment severity. Additionally, we employed a pharmacological intervention using oxytocin, and found that oxytocin influenced participants’ fairness expectations, and in particular enhanced the frequency of low punishments. Together, these results not only provide more insight into the fundamental brain mechanisms underlying punishment and compensation, but also illustrate the importance of taking an explorative, multi-method approach when unraveling the complex components of everyday decision-making.

SIGNIFICANCE STATEMENT

The perception of injustice is a fundamental precursor to many disagreements, from small struggles at the dinner table to wasteful conflict between cultures and countries. Despite its clear importance, relatively little is known about how the brain processes these violations. Taking an interdisciplinary approach, we combine methods from neuroscience, psychology, and economics to explore the neurobiological mechanisms involved in both the perception of injustice as well as the punishment and compensation decisions that follow. Using a novel behavioral paradigm, we identified specific brain networks, developed a computational model of punishment and found that administrating the neuropeptide oxytocin increases the administration of low punishments of norm violations in particular. Results provide valuable insights into the fundamental neurobiological mechanisms underlying social injustice.

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