Estrogen and autism

A study shows that the number of estrogen receptors a person has may be linked to autism.

Significantly lower levels of a key estrogen receptor may play a role in autism spectrum disorders, according to a new study.

This link between autism and sex hormones could help explain why the condition is about four times more common among men than women, the researchers noted.

"Our study is the first indicator that estrogen receptors in the brain of autism spectrum disorder patients may be different to controls," study author Anilkumar Pillai, from Georgia Regents University, said in a news release. "Though this suggests a possible reason for the gender bias, we still need to determine what causes the reduced production of estrogen-related proteins."

Autism spectrum disorders refer to a group of disorders that affect brain development. Signs and symptoms of autism include impaired social interaction and communication skills as well as restricted and repetitive behavior.

For the study, published Sept. 9 in the journal Molecular Autism, the researchers compared the brains of 13 people with autism to 13 people who didn't have the condition. The difference they found was in the brain's estrogen signaling.

Specifically, the researchers measured levels of an estrogen receptor molecule known as ERβ in the participants' brains. They also measured levels of aromatase, an enzyme that converts testosterone to estradiol, the most potent estrogen.

The study revealed the brain tissue of those who had autism had 35 percent less ERβ mRNA and 38 percent less aromatase mRNA. This could affect the conversion of testosterone to estradiol, increasing testosterone levels.

The researchers noted their study was small, and said more research is needed to explore how changes in estrogen signaling are related to autism.

"It is worth looking at whether drugs which modulate estrogen reception, but do not cause feminization, could allow for the long-term treatment of male patients with autism spectrum disorders," said Pillai. "Current treatment involves the use of antipsychotics, which has long been a major concern as these patients are typically still in a stage of life where brain development is very rapid. However, additional studies are needed to test the estrogen mechanism."

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Why Women Need More Sleep Than Men

This article discusses the differences that occur between men and women who get inadequate sleep.

Ever noticed how after a late night out with your man, you have a harder time the next day than he does? It's not all in your head. Thanks to different hormonal makeups, we suffer more emotionally and physically when we're short on zzzs.

"Poor sleep certainly had a more profound effect on women than on men," says Edward Suarez, Ph.D., an associate professor at Duke University School of Medicine and lead researcher of a studythat looked at the relationship between poor sleep and poor health. He found that for women, reduced sleep was associated with a significant increase in risk of heart disease and diabetes, as well as more stress, depression, anxiety, and anger. However, these associations were weaker or nonexistent for men.

What gives? Testosterone. Levels of this hormone rise after poor sleep in men, and "because it decreases insulin and increases muscle mass, testosterone has an anti-inflammatory effect, which kept men's stress hormones lower," he explains.

Unfortunately for us, women's hormones, especially progesterone, do not have that same stress-dampening effect. Estrogen is known to have an anti-inflammatory effect, so the decline in the hormone as we get older could contribute both to worse sleep and to feeling even crappier after a night spent tossing and turning.

And while you may have seen recent headlines proclaiming that women need more sleep than men, the truth is a lot more complicated, says Aric Prather, Ph.D., an assistant psychiatry professor at the University of California, San Francisco and author of a larger 2013 study that confirmed Suarez's findings. "I don’t think there is any good evidence yet that women needmore sleep than men," Prather says. "The present data is more in support of the fact that women may be more susceptible to the negative effects of poor sleep quality."

In both studies, physiological stress was measured by looking at blood levels of C-reactive protein (CRP), which rises in response to inflammation and is considered a better marker of stress than looking at cortisol levels alone. The volunteers were also asked to rate their sleep quality. 

In addition to overall snooze time, Suarez's study looked at four different aspects of "disturbed" sleep: how long it took subjects to fall asleep, how many times they woke in the night, how long it took them to fall asleep again, and if they awoke too early in the morning. Surprisingly, it wasn't just the total number of hours in the sack that made the difference. According to Suarez, the No. 1 factor correlated with an increase in CRP for women was taking more than 30 minutes to fall asleep when they first hit the sheets. This is a double-whammy for women, he says, who not only are we 20 percent more likely to suffer from insomnia than men but also suffer more ill effects from it.

Large epidemiological studies have found that women tend to rate their quality of sleep as worse than men even when their sleep is shown through objective measures to be better. "This raises the question of whether women may be more sensitive to sleep problems, which may have biological consequences, including elevations in inflammation," Suarez says.

Kelly Glazer Baron, Ph.D., clinical psychologist and director of the Behavioral Sleep Program at Northwestern University Feinberg School of Medicine, adds that bad sleep can become a vicious cycle: Shoddy shut-eye boosts stress, which in turn causes insomnia for many people, leading to even more stress on top of what you experience every day.

But there are things women can do to mitigate these effects. "We can improve how we prevent disease over lifetime simply by making small improvements in our sleep," Suarez says. This is why it's important to promptly treat sleep problems, especially insomnia. Baron says that if your insomnia reaches the point where it is making it hard to function during the day, talk to your doctor about lifestyle modifications and other options. 

She also recommends establishing a regular fitness routine. "It’s been known for a long time that exercisers sleep better," she says, citing her recent studies showing that 16 weeks of aerobic exercise at moderate intensity four days a week helped women get at least seven hours of sleep a night and also improved their perception of the quality of their rest.

Finally, don't forget the recommendations from the National Sleep Foundation, Prather says (which you likely can recite in your sleep—or as you stare at the ceiling): Go to bed at the same time every day of the week, avoid heavy meals before bed, establish a relaxing bedtime routine, don't nap, and exercise daily.

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Pediatric migraines may be caused by environment

Different environmental factors, such as sleep deprivation, diet, and school, could play a role in pediatric migraines.

Environmental stressors play a large role in triggering migraines in children, according to Dr. Eric Pearlman.

"Migraine is definitely a pediatric disorder. It peaks in young adulthood, but it definitely occurs in kids," Dr. Pearlman, chair of the department of pediatrics at Mercer University in Savannah, Ga., said at the annual meeting of the American Academy of Pediatrics.

Epidemiologic data suggest that migraine occurs in 10.5% of 10- to 15-year-old children and 3% of 7-year-olds, and that headaches – possibly including migraines – occur in 4% of 3-year-olds. By about 13 years of age, the prevalence of migraines starts reaching adult levels of about 6% in males, and 18% in females.

Environmental factors such as sleep deprivation, dehydration, dietary factors, school stressors, hidden stressors (like peers), and hormonal fluctuations represent triggers that can be particularly pronounced in children, he noted.

With International Classification of Headache Disorders, third edition (ICHD-III) criteria, migraines can be differentiated from acute, acute recurrent, and chronic progressive or chronic nonprogressive headaches if a child has experienced at least five attacks lasting up to 72 hours (whether untreated or unsuccessfully treated), if nausea and/or vomiting or photophobia and phonophobia are present, and if the child has at least two of four characteristics, including unilateral location, pulsating quality, moderate to severe intensity, and a tendency to be aggravated by – or avoid – routine physical activity.

In children, photophobia and phonophobia can be inferred (if they report having to lie down in a dark, quiet room, for example), as many have difficulty describing or understanding these symptoms

Unilateral headaches are rare in children, Dr. Pearlman noted.

If a diagnosis of migraine is established, it is important to make the diagnosis known to the child, and to educate the child about the condition and treatments.

Consider providing handouts and referring to websites (such as theAmerican Headache Society or the National Headache Foundationsites), to help educate patients and to manage their expectations, as they need to understand you cannot cure their migraine, he advised.

Involving both the patient and their parents in decision making can improve compliance with treatment recommendations, he said.

Pharmacologic interventions can include nonspecific short-term therapies, migraine-specific therapies, and preventive treatment.

Nonspecific short-term therapies may include acetaminophen, nonsteroidal anti-inflammatory drugs, or combination drugs. Migraine-specific therapies include ergotamine and dihydroergotamine, and the "triptans."

Seven triptans are available, including two that are approved for use in children; rizitriptan (Maxalt) is approved for children older than age 6 years, and almitriptan (Axert) is approved for those aged 12-17 years.

Maxalt comes in both an oral and orally disintegrating form, and is available as a generic drug. Generic sumitriptan (Imitrex) also is available.

"There are good data for most of the triptans for adolescents aged 12 and older," Dr. Pearlman said.

Rescue medications for those who have an inadequate response to short-term therapy can include a combination of an analgesic like a nonsteroidal and an antiemetic, or an opiate and an antiemetic if the patient used a nonsteroidal initially. Rescue medications may be needed "because nothing is going to work 100% of the time," he said.

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Common migraine triggers to avoid

This article discusses seven common migraine triggers that those prone to migraines should avoid.

It’s estimated that 28 million americans suffer from migraines. Migraines are intense headaches that are often accompanied by nausea, vomiting and sensitivity to light. They don’t simply come and go; each migraine can last between four hours and three days. Most migraine sufferers know to avoid certain things like dairy, alcohol and food with excessive additives, but there are other external factors that could trigger a migraine. Here are some to watch out for.

1. Change in Routine

For some migraine sufferers, routine is key to keeping the headaches at bay.  Change in sleep patterns, work hours or even holidays can create stress and lead to migraines.

2. Stress

As mentioned above, migraines and stress are strongly linked. Some people report migraines start when stress reduces, sometimes leading to “weekend headaches” after a stressful work week.

3. The Environment 

High altitude, weather changes and humidity can all trigger migraines.

4. Computer Screens

Both the posture you take when sitting in front of a computer and the glare from the screen can lead to migraine pain. Be sure to sit comfortably to avoid muscle tension and use an anti-glare screen.

5. Lack of Food

Insufficient food is one of the main dietary triggers of migraines. Avoid missing meals or snacking on treats high in sugar. Eating small, nutritious snacks throughout the day can help control migraine attacks.

6. Hormonal Change (In Women)

Fluctuation in estrogen may cause headaches in women who suffer from migraines. These women often report an increase in migraines immediately before or during their menstrual cycle, when there is a major drop in estrogen levels.

7. Sensory Overstimulation

Bright lights, loud noises and unusual smells, including perfume and secondhand smoke can trigger migraines. 

Migraine triggers are unique to every individual, and can happen as early as 6 to 8 hours prior to a migraine attack.

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Ways to get children to sleep more

This article discusses why children may not be sleeping much and how to get them to sleep more.

Asking sleep experts for advice on how to put children to bed often feels like an exercise in futility. The standard tips are banal and predictable: avoid caffeine; remove the TV from their bedroom; don’t sleep on a full stomach; put up dark blinds. You have the feeling the experts are holding out on us—there has to be something more. And there is. Here’s the stuff they’d love to tell you, if they weren’t afraid of overwhelming you with science.

• Ever wonder why most people sleep better when their bedrooms are cool? It’s because the circadian rhythm system that helps regulate sleep cycles is not just light sensitive, it’s temperature sensitive. Anything above a neutral air temperature both slows the body’s initiation of sleep and changes sleep patterns—a hotter room means an increase in non-REM sleep.

• 77 percent of children use television as part of their pre-bedtime routine. Sitting still and vegging out for half an hour should, theoretically, help a child unwind, as long as they’re not watching a show that excites them too much. However, the brightness of the screen undermines the theory. The light from a television or computer can delay both the necessary drop in core body temperature and melatonin production—and thus delaying sleep onset—by two hours.

• We’re all familiar with the agony of being super exhausted, yet not being able to fall asleep for hours. What gives? It’s because after just a few days of shortened sleep, the brain starts making extra stress hormone cortisol. It takes six times as long for this stress hormone to drop to a low-enough level that sleep is possible.

• In one study of 170 children, those in white-collar families tended to be in bed later and get up earlier than those in working-class families. Yet they actually got more actual sleep. How is that possible? It’s because their bedtimes and wake-times were more consistent; they stuck to their routine. This made their sleep more efficient—they rolled around in bed far less.

• Inconsistent bedtimes are, for all practical purposes, homemade jet lag—the desynchronization of the two systems that regulate sleep, the circadian rhythm and the homeostatic pressure system. Staying up three hours later on weekends is equivalent to flying across three time zones every weekend.

• With children averaging three hours of television per day, it’s hard to make the case children are universally overscheduled. But the most driven children are the most overscheduled—and the most sleep deprived. In some ways, these busy overachievers are those who concern the experts the most. According to University of Minnesota’s Dr. Kyla Wahlstrom, a motivated student can sacrifice sleep to maintain high GPAs, but she may pay for that success with higher levels of depression and stress. Teen boys who have a high number of extracurriculars are significantly more likely to be involved in a fall-asleep car crash. And those with part-time jobs both sleep less and have lower grades.

• For the majority of kids, rather than thinking it’s a choice between sleep and activities, the opposite is true: Students who sleep more are involved in more afterschool activities—with no detriment to their grades. They have the energy to be involved. Schools that have delayed start times have seen their students sleep more and increase their participation in sports and extracurriculars.

• Naps are not quite the salve we imagine. They appease the homeostatic pressure system, but not the circadian. You wake up feeling better—a two-hour nap is equivalent to 150 mg of caffeine—but naps do nothing to repair diminished cognitive functioning. The intellect is just as dulled after the nap as before. Kindergartners who take long naps, for instance, do worse on puzzle-solving.

• 16 percent of kids snore a few times a week. As recently as 2002, the American Academy of Pediatrics opined that children’s snoring was a benign condition not warranting treatment. Just five years later, researchers now caution that kids’ snoring is not like adult snoring at all—even a little snoring is a major cause for concern, because their developing brains can be deprived of oxygen.

• Common sleep disorders such as nightmares, restless leg syndrome, and frequent night waking can have a startlingly negative impact on children’s development—from using drugs at 14 to having clinical-level anxiety as adults. Research by University of Michigan’s Dr. Ronald Chervin indicates as many as 25 percent of kids diagnosed with ADHD have an underlying sleep disorder causing their symptoms. If treated for their sleep disorder, the ADHD would magically disappear. Despite the risks posed by sleep disturbance, the number of children treated for them is “vanishingly small.” Parents should consult a qualified sleep specialist—few pediatricians have expertise with sleep problems. Waiting to see if a child grows out of a sleep problem isn’t the answer.

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Study: Mother's thyroid can influence autism in children

A study claims that a pregnant mother's under active thyroid and less thyroid hormone gives a greater chance at a child having autism.

Pregnant women who don't make nearly enough thyroid hormone are nearly 4 times likelier to produce autistic children than healthy women, report scientists from the Houston Methodist Neurological Institute and Erasmus Medical Centre in an upcoming Annals of Neurology.

The association emerged from a study of more than 4,000 Dutch mothers and their children, and it supports a growing view that autism spectrum disorders can be caused by a lack of maternal thyroid hormone, which past studies have shown is crucial to the migration of fetal brain cells during embryo development.

"It is increasingly apparent to us that autism is caused by environmental factors in most cases, not by genetics," said lead author Gustavo Román, M.D., a neurologist and neuroepidemiologist who directs the Nantz National Alzheimer Center. "That gives me hope that prevention is possible."

The researchers also found that autistic children had more pronounced symptoms if their mothers were severely deficient for T4, also called thyroxine. Mild T4 deficiencies in mothers produced an insignificant increase in autistic children's symptoms.

The most common cause of thyroid hormone deficiency is a lack of dietary iodine -- because both the thyroid hormones, T3 and T4, contain that element.

Iodine deficiency is common throughout the world, including developed countries. The World Health Organization estimates nearly 1 in 3 people are affected globally. A 2005 CDC-University of Kansas study estimated that in the U.S., where iodine deficiency had been practically eradicated thanks to iodized salt, 1 in 7 Americans is believed deficient.

The present work was based on the Generation R Study, conducted by Erasmus Medical Centre (Rotterdam, Netherlands) doctors and social scientists, in which thousands of pregnant women were voluntarily enrolled between 2002 and 2006.

Blood was withdrawn from the mothers at or around 13 weeks into their pregnancies to measure levels of T4 and two proteins that could indicate the cause of thyroid deficiency. Six years later, mothers were asked to describe the behavioral and emotional characteristics of their children using a standardized psychology checklist.

Researchers identified 80 "probable autistic children" from a population of 4,039 -- a number consistent with the Dutch rate of autism spectrum disorders. 159 mothers were identified as being severely T4 deficient (defined as having 5 percent or less of normal T4, but producing a normal amount of thyroid stimulating hormone), and 136 were identified as mildly T4 deficient. The researchers found a weak association between mild T4 deficiency and the likelihood of producing an autistic child, but a strong association between severe T4 deficiency and autism (3.89 more likely, as compared with mothers with normal thyroid hormone).

Román, who is a physician, says he has advice for women who are now pregnant, or who are considering having children. "If you are planning to become pregnant, have your doctor measure urine iodine and thyroid function beforehand. If you have just become pregnant, have your doctor measure urine iodine, thyroid function, and begin using prenatal vitamins, making sure iodine is present."

A lack of dietary iodine interferes with normal thyroid function, leading to pregnancy complications, as well as deafness and developmental delay in the baby and loss of control of fat and sugar metabolism and heat generation in the mother.

It is well established that expecting mothers' poor thyroid function (whether caused by poor diet, disease, or genetics) can lead to serious problems with fetal brain development, but only in the last 10 years or so has hypothyroidism been implicated as a possible cause of autism spectrum disorders.

Previous work by Román and others has shown that a deficiency of T4 during a crucial period of embryonic development causes mild to severe brain development errors, such as the lackluster migration of specialized brain cells from the cortex to the outer areas of the cerebrum -- a characteristic of autistic brains. In a 2007 review Román published in theJournal of the Neurological Sciences, he presented a wide swath of evidence that the near-epidemic rise in autism diagnoses -- which Román says cannot be accounted for by heightened awareness alone -- could be at least partly the result of an iodine-starved diet and/or exposure to toxins that interfere with normal thyroid function.

The Annals of Neurology study presents a troubling correlation, but it does not prove that the thyroid function of expecting mothers causes autism in their children.

"The next steps are interventional studies," Román said. "We must look at a large nationwide population of women in early pregnancy, to measure urine iodine and thyroid function. We must then correct thyroid deficiencies, if present, and provide prenatal vitamins with supplementary iodine. If autism cases fall precipitously compared with recent historical numbers, I think we will be able to conclude that thyroid function is critical."

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