Motor control problems may be core issue for people with autism

Photograph by Michael Phillips
Photograph by Michael Phillips

If you’ve ever had an MRI scan, you know that it can be hard to lie still in the noisy, claustrophobic scanner. People often move involuntarily, requiring scientists to correct or eliminate the imaging data during movement.

Recently, a collaboration of Rutgers University and Columbia University researchers used this seemingly unhelpful data to further their understanding of a neurodevelopmental disease.

“We asked ourselves, ‘What could these involuntary movements, which researchers usually consider a nuisance, tell us about autism?’” Elizabeth Torres, PhD, an associate professor of cognitive psychology at Rutgers University, said in a news release.

The neuroscientists analyzed functional magnetic resonance imaging (fMRI) data for 1048 participants, aged 6 to 50 years old, including individuals with autism spectrum disorders and healthy controls. The data was publicly available primarily through the Autism Brain Imaging Data Exchange databases.

The researchers determined that people with autism had more problems controlling their head movements than healthy controls. They also found that motor control problems were exacerbated with the presence of secondary neuropsychiatric diagnoses, lower verbal and performance intelligence and autism severity, as reported in a recent paper in Scientific Reports.

“For the first time, we can demonstrate unambiguously that motor issues are core issues that need to be included in the diagnosis criteria for autism,” Torres said in the release.

In addition, they found that psychotropic medications, commonly used to treat people on the autism spectrum, were associated with lower levels of motor control. These medications include anti-convulsants and anti-depressants. Autistic people who were taking more than one psychotropic medication moved the most during the fMRIs, and their movement worsened over the scanning session.

The researchers conclude in their paper, “Nevertheless, it remains to be demonstrated if changes in head micro-movements directly capture targeted changes in symptomology brought about by a specific medication.” Their findings are also complicated by the simultaneous presence of autism and other diseases, such as attention deficit hyperactivity disorder. So more research is needed.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Oxytocin May Help Rejuvenate Old Muscles


muscle cells of old and young mice
The left image shows healthy muscle tissue from a young mouse. The middle image demonstrates that the efficiency of muscle repair mechanisms decreases with age, resulting in a lower density of muscle fibers and increased scar tissue in an old mouse. Injecting oxytocin rapidly rejuvenates the old tissue, as shown on the right image. (Wendy Cousin and Christian Elabd)

From birth until about the age of 30, your muscles continue to grow larger and stronger. But at some point in your 30s, you begin to lose muscle mass and strength which in turn affects your coordination. As part of the natural aging process, this disease, sarcopenia, is most commonly seen in inactive people but it also affects those who remain physically active throughout their lives.

Now UC Berkeley researchers have discovered that oxytocin – the “trust hormone” associated with maternal nurturing, social attachments, childbirth and sex – may combat this age-related muscle wasting. Their new study was recently published in Nature Communications.

Role in Muscle Regeneration

Led by associate professor of bioengineering Irina Conboy, the researchers found in mice that oxytocin is required to maintain healthy muscles, but the level of oxytocin in the blood and the number of oxytocin receptors in muscle stem cells naturally reduce with age. For instance, old (18 to 24 months) mice were found to have 3 times lower circulating levels of oxytocin than young (2 to 4 months) mice.

The research team performed a series of experiments using young and old mice to better understand oxytocin’s role in muscle repair. They injected the mice daily with oxytocin (or a control solution) under the skin for nine consecutive days, while causing a muscle injury midway on day 4. The researchers found that the old mice that received the oxytocin were able to repair their muscle injury at a level comparable to the young mice – far better than the old control group that didn’t get oxytocin. Systemic administration of oxytocin appears to rapidly improve muscle regeneration by enhancing aged muscle stem cell proliferation.

In contrast, the young mice already had sufficient levels of oxytocin and efficient muscle regeneration, so the oxytocin injections had no significant effect. This is important since most molecules that boost tissue repair are also associated with an increased risk of cancer.

“This is good because it demonstrates that extra oxytocin boosts aged tissue stem cells without making muscle stem cells divide uncontrollably,” explained Wendy Cousin, a senior scientist in Conboy’s lab, in a press release.

The researchers also performed similar experiments using mice with an inactivated gene for oxytocin and control mice. At the young age of 3 months, the two groups of mice appeared to have comparable muscle mass and repair efficiency after a muscle injury. However, muscle atrophy and a significant decline in muscle regeneration were observed for the 1-year old adult mice with the disabled oxytocin gene, signifying premature aging due to a lack of oxytocin.

It is unclear how long it will take the researcher to move beyond mice studies to human use. However, oxytocin is already approved by the FDA for clinical use in humans for other applications. For instance, oxytocin is commonly used to help increase contractions and control bleeding during childbirth. So getting approval for human studies should be straightforward once the researchers are ready.

Conboy’s research team is ultimately interested in applications beyond just maintaining healthy muscles. For instance, they are also investigating whether oxytocin could become a viable alternative to hormone replacement therapy to impede the symptoms of male and female aging. They also believe that aging is the underlying cause of a number of chronic diseases, including Parkinson’s and Type 2 diabetes.

Oxytocin Hype

In fact, researchers around the world are studying the use of oxytocin for seemingly every condition imaginable, including using oxytocin nasal spray to alleviate symptoms associated with mental disorders such as autism, schizophrenia and dementia. However, this research currently demonstrates mixed and inconsistent results, particularly regarding oxytocin’s influence on social skills.

The current excitement about oxytocin, particularly as a remedy for autism, could lead to a dangerous situation given the widespread availability of oxytocin supplements – as an accelerator spray, sublingual liquid that is absorbed under the tongue, pills and mouth lozenges. It is important to consult with your doctor before taking oxytocin.

This is a repost of my KQED Science blog.

Infections During Pregnancy May Increase Autism Risk

B&W photograph of pregnant woman sitting on couch
Photograph courtesy of Stuart Handy via a Creative Commons license.

Every day our brains help us make sense of the world around us, interpreting the things we see, hear, taste, touch, smell and experience. But if someone’s brain has trouble processing this incoming information, it can be hard to communicate, understand or learn.

Autism spectrum disorders (ASD) are characterized by difficulties in social interaction, verbal and nonverbal communication, and repetitive behaviors. These disorders include autism, Asperger syndrome and Pervasive Developmental Disorder-Not Otherwise Specified.

About 1 in 88 children have been identified with an autism spectrum disorder and over 2 million people are affected in the United States, according to the Centers for Disease Control and Prevention. Government statistics also suggest that the proportion of people with autism spectrum disorders have increased 10 to 17 percent annually in recent years. This is in part due to wider awareness and better screening, but the continued increase is not fully understood.

The cause of ASD is also not fully known, but current research indicates that it is likely due to a complex combination of genetic predisposition and environmental risk factors that influence early brain development. Significant environmental risk factors include the advance age of either parent at the time of conception, maternal illness during pregnancy, extreme prematurity, and very low birth weight.

Over 40 years ago, epidemiological studies determined that the risk of having a child with ASD is increased when the mother has an infection early in the pregnancy. Since a wide range of bacterial and viral infections can increase the risk, studies suggest that activation of the mother’s general immune system is responsible. However, scientists do not completely understand how the activated immune system can disrupt normal brain development to cause ASD.

Research at the University of California Davis Center for Neuroscience provides new insight. Recently published in the Journal of Neuroscience, their studies identify a new biological mechanism that links maternal immune activation to neurodevelopmental disorders.

Kimberley McAllister, a senior author of the study, explained in a press release, “This is the first evidence that neurons in the developing brain of newborn offspring are altered by maternal immune activation. Until now, very little has been known about how maternal immune activation leads to autism spectrum disorder and schizophrenia-like pathophysiology and behaviors in the offspring.”

The researchers studied pregnant mice with immune systems that were activated halfway through gestation compared to pregnant control mice without activated immune systems. They found that the mice exposed to a viral infection had offspring with dramatically elevated levels of immune molecules called major histocompatibility complex 1 (MHC1) on their brain surface.

In the affected newborn mice, these high levels of MCH1 disrupted the development of neural cells in the brain. Specifically, the increase in MCH1 interfered with the neurons’ ability to form the synapses that allow neurons to pass electrical or chemical signals to other cells; consequently these offspring had less than half as many synapses than the control offspring. When MCH1 were returned to normal levels in the neurons of maternal immune-activated offspring, the synapses density returned to normal.

However, MCH1 doesn’t work alone. In a series of additional experiments, the researchers identified the new biological signaling pathway that regulates synapses development caused by maternal immune activation. This signaling pathway requires calcineurin, myocyte enhancer factor-2 and MCH1 to limit synapses density.

A better understanding of the underlying biological mechanisms will hopefully lead to the development of improved prenatal health screening, diagnostic tests and eventually therapies for neurodevelopmental disorders.

Of course, not every child of a bacterially or virally infected mother develops a neurodevelopmental disorder like autism. The effect of maternal immune activation depends on a complex interaction involving the strength of the infection and genetic predisposition.

This is a repost of my KQED Science blog.

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