A new study of prairie voles shows that they can not only tell when a member of their family has been hurt, they also show empathy.

Prairie voles mate for life and live in family groups (although they may have sex outside of the pair bond).

Larry Young (one of the original researchers who discovered oxytocin's role in animal bonding) and James Burkett of Emory University gave shocks to some voles in the family and then returned them. The other voles tried to soothe the ones that had been shocked by licking them.

I think it's pretty cool that this study showed that animals share some of humans' "higher emotions."

And, of course, research has identified the oxytocin system as a possible cause of or influence on autism for several years. Maybe this is a way scientists could study autism? The article quotes Larry Young:

"Many complex human traits have their roots in fundamental brain processes that are shared among many other species," Young said, according to the publication. "We now have the opportunity to explore in detail the neural mechanisms underlying empathetic responses in a laboratory rodent with clear implications for humans."

What a study about empathy in animals may be able to tell us about autism in humans

Admission: I was a hippie (well, a semi-hippie). In the early 1970s I lived in my van, hitchhiked around and asked people on the street, "Do you have a place we can crash?"

I still clearly remember a time I was hitchhiking with a boyfriend. A guy picked us up and we smoked a joint. As we were riding along, this guy said, "Isn't this cool? We're sitting here together like we've been friends for years."

It was true. There was no feeling of nervousness, anxiety or constraint with this stranger.

I've often thought that marijuana, at its best, activated the oxytocin system. Here's research showing  that that is the case. A study by Daniele Piomelli, a neuroscientist at the University of California, Irvine, found that -- in mice -- " it is social interaction between mice plus oxytocin—the hormone involved in social bonding—that drive cannabinoid activity in the animals’ brains."

According to the article,

The finding may also point to a possible treatment for autism spectrum disorders, which can involve social-interaction difficulties. (The team initially homed in on the interaction of oxytocin and anandamide (an endocannabinoid) while studying autism mouse model of autism.)

I'm not sure this would necessarily work for people on the spectrum, nor for those who experience social anxiety. Although my experience in that car was very positive, marijuana more often than not makes me feel paranoid and more anxious around other people. There might be something different in my brain that inhibits the pleasant social effect.

Read the article in The Scientist here.

Here is a very alarming study from Rebecca Larke, a researcher in Karen Bales' lab at UC Davis: Female prairie voles that were given fluoxetine (generic Prozac) during pregnancy gave birth to babies that had significant abnormalities in their oxytocin and reward systems -- and this led to anxious behavior later in life.

According to Spectrum News, the offspring of the mothers that had been given the antidepressant preferred to spend time alone and were less likely to want to interact with unfamiliar voles, as well as being more anxious.

The adult voles that had been exposed to fluoxetine during gestation had symptoms similar to those of autism:

• fewer oxytocin and vasopressin receptors in the amygdala (fear center)
• fewer oxytocin receptors in the reward center (oxytocin receptors here make social interaction rewarding)

According to the article,

“Changes to the oxytocin system could underlie changes in social behavior,” says Larke.

Researchers have noticed a link between Vitamin D and ASD for years. A new study explains how a lack of the vitamin could lead to problems in fetal and neonatal brain development, creating the symptoms of autism spectrum disorder.
 
Rhonda Patrick and Bruce Ames of Children's Hospital Oakland Research Institute showed that vitamin D is essential for the synthesis of serotonin in the brain. They also show that it may be important for the making the precursor to oxytocin, as well as for the formation of the oxytocin receptor and vasopressin receptors. All three of these chemicals, which are both neurotransmitters and hormones that regulate body functions, are crucial for social behavior.
 
What Patrick's and Ames's study adds is an explanation for just how the lack of Vitamin D "turns off" serotonin production:
 
Vitamin D activates the gene that makes an enzyme that converts tryptophan into serotonin in the fetal brain.
 
Serotonin in the fetal and neonatal brain influences the structure and wiring of the brain.
 
Serotonin also acts as a neurotransmitter.
 
In the post-natal brain, serotonin affects social behavior.
 
In other words, Patrick says, "In order to make the hormone, you have to make this protein first." And it's vitamin D that allows the body to make the proteins that in turn create oxytocin, vasopressin and serotonin.
 
Patrick thinks the lack of enough serotonin in the fetal and neonatal brain could cause it to form in a way that causes the symptoms of ASD. She says, "During early fetal development, serotonin is a brain morphogen -- it's a growth factor for the brain. It guides the structure and some of the way that the neuronal connections are made."
 
Even before the fetal brain begins making its own serotonin, she adds, serotonin from the mother's body enters the fetus through the placenta and guides some brain development. Therefore, a vitamin D deficiency in the mother could also cause ASD.
 
In 2009, Swedish researchers studying the rise in autism spectrum disorder among Somali immigrants posited that it was because the dark-skinned immigrants weren't producing enough Vitamin D when exposed to the weak northern sun. (In fact, the Somali Swedes called autism "the Swedish disease.")

 
Deficits in oxytocin and vasopressin have also been linked to ASD, and Patrick thinks that, if the genes to produce their precursor proteins have similar responses to Vitamin D, it's possible that these two neurochemicals also are part of the puzzle. But this paper focuses on serotonin and its precursor, the essential amino acid tryptophan.
 
Patrick says that it's easy to create a temporary deficit of tryptophan in humans, and studies in the lab have shown that people whose tryptophan is depleted begin to have trouble decoding people's facial expressions, a prime symptom of autism.
 
Meanwhile, preventing autism could be as simple as adequate vitamin D supplementation for pregnant and nursing women and making sure young children have adequate levels of vitamin D. The paper concludes, "Supplementation with vitamin D and tryptophan would be a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder."
 
While people over 60 are commonly tested by their doctors to make sure they have adequate levels of vitamin D, Patrick thinks this should also be standard for pregnant women. "I think it needs to be up there with folic acid in terms of prenatal care," she says.
 
For parents looking for help now, Patrick says, "I wouldn’t rush out and give a child high doses of tryptophan. I certainly would get the vitamin D levels tested; it's a very simple test to do."
 
CHORI is beginning clinical trials looking at the effects of micronutrients on diseases. Patrick also is working with organizations involved in ASD research and treatment to design clinical trials to see if vitamin D could reduce autism symptoms. Patrick and Ames will set up a website to act as a resource for parents of children with ASD. They also hope to do clinical trials. To find out whether Patrick and Ames will start testing of kids with ASD or clinical trials of the vitamin to ameliorate symptoms, keep an eye on BruceAmes.org.

For more details about the study, read the Science Daily article.

PHOTO: HealthGauge
 

There's been plenty of research showing that when people inhale oxytocin, they tend to have more positive social behavior: trust, generosity, empathy and communication. But if taking one whiff of oxytocin can make you nicer, will taking oxytocin regularly keep you nicer? If you take a bigger dose, will it make you even nicer?

U.C. Davis researchers wanted to find out the long-term effects of taking oxytocin, so they studied prairie voles, the monogamous rodents that first demonstrated the positive effects of this brain chemical.

 The U.C. Davis research team, led by Karen L. Bales, treated a group of 89 male prairie voles with low, medium or high doses of inhaled oxytocin. The medium dose was roughly equivalent to the amount given to human subjects in lab studies.

They began giving the prairie voles one daily dose of oxytocin when they were weaned at 21 days old, and continued to give it to them through day 42, the time they reach sexual maturity.

"We were trying to approximate ages 12 to 17 in humans," Bales told me in an email. Because so many parents of children with autism spectrum disorder are turning to oxytocin products they've bought over the internet in hopes of increasing their kids' sociability, the short-lived voles offer a way to model the possible effects of long-term dosing of an adolescent.

 The study also wanted to look at possible dose-dependent differences: If one dose creates an effect, it doesn't necessarily follow that a different dose will create the same effect. In fact, she cites research showing that in schizophrenic patients, 20 IU of oxytocin increased emotion recognition, while a dose of 10 IU actually decreased it.

There was one troubling result: The male voles treated with low or medium doses of oxytocin were actually less likely to bond with a female -- and this effect lasted two weeks after treatment stopped. That could be equivalent to years in a human life.

 The female voles in the study also seemed to be less interested in mothering.

 Bales thinks that this effect could be attributable to down-regulation of the oxytocin receptors or oxytocin-producing neurons; that is, with external oxytocin flooding the receptors, they might become desensitized, while the oxytocin-producing brain cells might lower their production because it's not needed. It also could be attributable to changes in the vasopressin system, she suggests. Vasopressin is another brain chemical very similar to oxytocin that seems to be more important in male bonding.

 She says, "I originally thought that we would see the most changes with the highest dose of oxytocin, and that would be because of flooding oxytocin receptors and binding to vasopressin receptors.  But since we had the most changes at the lowest dose, that seems less likely.  Males do seem to be especially sensitive to developmental exposure to oxytocin...perhaps because they rely less on it normally?"

 Bales' work is with prairie voles, not people. But so far, what vole research taught us about oxytocin is quite applicable to humans. We think we're so different from this tiny, humble creature. But in fact, the genetic difference between Homo sapiens and other mammals is very small.

 It's not clear how applicable the results of this study might be to older humans, but certainly the body's receptors are constantly in a state of flux, responding to external changes. And it's well known that treatment with a hormone can cause the body to produce less of it.

 Bales plans to do more studies using voles of different ages, and also to look at different lengths of treatment.

 Meanwhile, if you are self-experimenting with oxytocin, it's a good idea to keep your dosing acute: once in a while with plenty of time for your body to go back to its natural state.

 Here's the ref: Bales, K.L. et al. Chronic Intranasal Oxytocin Causes Long-Term Impairments in Partner Preference Formation in Male Prairie Voles. Biological Psychiatry 2012.

A paper to be presented at the 2012 international Society for Autism Research used fMRI to find that a single dose of inhaled oxytocin increased activity in areas of the brain that process social activity.

The researchers' conclusion:

These results provide the first, critical steps towards devising more effective treatments for the core social deficits in autism which may involve a combination of validated clinical interventions with an administration of oxytocin. Such a treatment approach will fundamentally alter for the better our understanding of autism and its treatment.

LeftBrainRightBrain has more info and a link to the study, led by I. Gordon at Yale.

Larry Young, one of the early researchers on oxytocin and bonding in prairie voles, applied for a patent on using Melanotan II to enhance the effects of oxytocin used during psychotherapy. Co-applicant is Meera E. Modi, a member of Young's lab at Emory University.

The patent application "relates to methods of improving social cognition in a subject in need thereof including administering a compound that stimulates oxytocin (OT) release in the brain. Typically, the compound that stimulated OT release is a melanocortin receptor agonist. The compound, in certain embodiments, is melanotan II or derivative thereof."

Melanotan II is a synthetic version of melatonin.

Young and Modi point out that there are melanocortin receptors located on nerve cells that produce oxytocin. So, instead of having a patient inhale oxytocin directly, he or she could be given melanotan II or something like it, which would cause the brain to release oxytocin.

A bit of scientific inside-baseball: Larry Young and Sue Carter got a lot of attention for their work showing oxytocin's effects on prairie voles, but they seemed to quickly get left behind when researchers, most notably Paul Zak, began dosing humans. So, it's interesting to see Young getting in this game.

Also, I'm not a patent expert, nor a researcher, but the Young-Modi patent application is based on studies done with prairie voles. In the early days, Young and Carter were careful to say that they didn't know if their research applied to humans. Turned out it did. But I wonder if a patent would be granted for human treatment based on animal studies. Any experts out there want to weigh in?

You can read the patent application here: http://www.freshpatents.com/-dt20120503ptan20120108510.php

Marina Biotech has applied for a patent on the methods of using carbetocin to treat symptoms of autism. Carbetocin is an artificial form of oxytocin.

Eric Hollander of the Seaver Institute, the researcher who, with Jennifer Bartz, first showed oxytocin's efficacy in reducing the symptoms of autism, also had applied for a patent on such.

He was working with Nastech, a now-defunct biotech company that had developed new ways of delivering drugs via inhalant. Hollander originally administered oxytocin to adults with ASD intravenously.

Nastech also had applied for a patent on using carbetocin to treat symptoms of autism. In my 2005 blog post on this, I mistakenly said it had received the patent. I should have said its patent application was published. That application is no longer available on the USPTO site.

I will leave it to patent nerds to figure out if there's any connection between Marina Biotech and Nastech, and where Hollander's application stands -- and fits in. Here's info on the Marina patent on FreshPatents.

A new study found that inhaling oxytocin once a week for two weeks helped adolescents understand facial expressions.  Adam Guastella, of the Brain & Mind Research Institute at the University of Sydney, led the experiment.

Eric Hollander and Jennifer Bartz did the first studies of oxytocin as a treatment for symptoms of autism spectrum disorder. They gave it intravenously to adults, and found improvements in the ability to recognize the emotional content of speech improved for up to two weeks after treatment.

A French study of adults found the same improvement when adults with autism inhaled oxytocin. This is the first study of adolescents. It's possible that oxytocin could help them improve their ability to read social cues, and that the effect could last their lifetimes.

Guastella has been studying the effects of oxytocin on humans without diagnosed disorders. He's found that men who inhale oxytocin tend to remember photos of smiling faces more than those who haven't had a dose. He's also tested whether oxytocin could make couples more open during psychotherapy.
He has grants to test oxytocin as a therapy for schizophrenia and Prader-Willi Syndrome, as well.

Do newborns imprint on the mother, just like baby ducklings attach themselves to the first thing they see, whether that's the mother duck or Konrad Lorenz? Could autism begin when the newborn fails to imprint?

I was ready to dismiss this Psychology Today blog post by Bill Ahearn out of hand. But it's too well-reasoned -- and also, Ahearn is director of research at the New England Center for Children, a private nonprofit educational facility for children with autism.

Ahearn is not arguing that newborn humans have the same, simple kind of imprinting mechanism that baby birds do. But he does argue that a lack of response to the initial "social" cues of the mother's smell and nipple may interfere with the normal brain and physiological development that takes place after birth.

He writes,

... one of the earliest indicators that an ASD may be present is atypicality, at birth, in primitive reflexes, like rooting and sucking. As I mentioned above, imprinting establishes the significance of a cue and if that cue is not imprinted to, it does not have this same significance. Is it possible that something is going wrong in social learning that is akin to an imprinting error? Well, one thing we know about individuals with autism relative to people without it is that social cues do not hold the same significance for people with ASDs.

This is a fascinating article that takes some attention to read, but will reward the attention.