From extending lifespan to bolstering the immune system, the drug’s effects are only just beginning to be understood.
Scientists find that the hormone improves sociability in a mouse model of autism.
January 21, 2015|
V. ALTOUNIAN/SCIENCE TRANSLATIONAL MEDICINEMutant mice that exhibit many of the characteristics of human autism spectrum disorders, including social deficiency, have more interactions with fellow mice when given a dose of oxytocin, according to a report published today (January 21) in Science Translational Medicine. The beneficial effect was also apparent when the mice’s own oxytocin production was increased—which may be important for translating such a treatment to humans.
“It’s very exciting. They created a mouse model of autism . . . that had social deficits, and they found that if they gave oxytocin, it would rescue those social deficits,” said Larry Young who studies social neuroscience at Emory University and was not involved in the work.
The model mouse lacks a functional gene for contactin-associated protein-like 2 (Cntnp2). In humans, mutation of this gene causes cortical dysplasia and focal epilepsy (CDFE) syndrome; at least 70 percent of CDFE patients also display symptoms of autism spectrum disorders. Importantly, the characteristics of the mice—including their deficiencies in social behavior—are highly similar to those of humans with the CNTNP2 mutation.
Dan Geschwind’s team at the University of California Los Angeles Center for Autism Research and Treatment tested different drugs in the Cntnp2 mutant mice “to see if we could find a compound that would reverse or ameliorate this social behavior,” he explained, “with the hope that it would help us understand what’s going on in the mice and in the human patients.”
“There were a bunch of compounds and drugs that had been suggested to [target] potential mechanisms in social dysfuntion,” Geschwind told The Scientist. For each compound, the team injected a dose into untreated mice, waited roughly half an hour, and then tested the animals’ sociability.
Only two drugs increased the number of social interactions of the test mice: oxytocin and its structural relative, vasopressin. The team went on to show that vasopressin most likely exerts its effect by cross-reacting with the oxytocin receptor: blocking the oxytocin receptor prevented the behavioral improvements seen with either compound, while blocking the vasopressin receptor did not.
Geschwind’s team also showed that the brains of Cntnp2-mutant mice had fewer oxytocin-expressing neurons than those of wild-type animals and, as a result, lower levels of the hormone. Giving the mutant mice a single dose of oxytocin increased sociability for just a few hours. Encouragingly, however, if the team gave daily doses of oxytocin for two weeks in very young pups, the number of neurons expressing oxytocin increased and the improved social behavior lasted at least nine days after treatment was stopped.
Geschwind suggested that there might be a window of treatment opportunity soon after birth for obtaining such long-lasting effects. But how this relates to human development is unclear. “The earlier we start interventions, the better,” said neurologist Shafali Jeste of the Semel Institute for Neuroscience and Human Behavior in Los Angeles, who was not involved in the study. “But we do know that brain circuitry [in young children] is constantly evolving and developing based on experience and environment, so there is no reason to think that an intervention a bit later in childhood would not be effective.”
Geschwind and his colleagues were also able to improve social behavior in the mice by pharmacologically increasing the release of the animals’ own oxytocin. This result was “even more exciting,” said Young. Evidence already exists that oxytocin could help humans with autism spectrum disorders, he explained, but the documented improvements in symptoms have so far been small. “We are getting a hint of an effect,” he said, “but not enough that doctors should start prescribing it now.” Young said he thinks the reason for the limited benefits is because oxytocin “doesn’t easily pass the blood-brain barrier.” Thus, the finding that boosting oxytocin release improves behavior in mice suggests it is not necessary to give oxytocin itself. A smaller molecule, capable of entering the brain and stimulating release, might provide a stronger effect in mice and possibly humans, Young said.
A more significant effect might also be seen if clinical trials for oxytocin were targeted to the patients most likely to benefit—for example, those shown to have oxytocin deficits, suggested Jeste. Autism is “a very heterogeneous spectrum of disorders,” she explained, “and, from a clinical standpoint, the goal would be to provide more personalized treatments.” Geschwind’s study “represents the kind of work that we need in autism,” she added, “namely the search for targeted treatments that are mechanism based.”
O. Peñagarikano et al., “Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism,” Science Translational Medicine, 7:271ra8, 2015.
January 22, 2015
Interesting observation. So why not use some of this innocuous 'bonding' hormone in some kids with the problem. Why not promote more of the early practices, like papoosing infants, breast feeding, and en face talking, which promote oxytocin in infants. And turn off the tablets, Iphones and other devices that rob our infants from this kind of stimulation, and the TV which replaces it with flat faces that overwhelm our infants facial recognition centers by shifting every 5 seconds.
January 26, 2015
A few years back, Ed Yong published a very interesting article called "The Dark Side of Love", pointing out research that showed oxytocin could make people (not mice) more xenophobic in social situations. I concluded from my reading that perhaps oxytocin makes us more bonded to those we know, but more distant from those we don't know... which could backfire in autistic persons who are being exposed to "mainstream" situations. I don't hear any of this caution in this article. I certainly hope due diligence is done in clinical trials to tease out these effects.
January 26, 2015
I have not studied oxytocin in over 40 years, but a quick check on the web revealed an association with gut inflammation and oxytocin release. This caused me to wonder if this small effect of administered oxytocin on autism symptoms may relate to the amelioration of symptoms in the autistic boy who became asymptomatic when he received chigger bites while at summer camp. Eventually, the boy's father and the boy's doctor infected him with T. suis and eliminated his symptoms. Could the gut inflammation caused by the parasites result in the release of of intrinsic oxytocin, resulting in the greater improvement in autism than that noted in the experiement descirbed in today's article? In all likelihood there are other mechanisms invovled, but perhaps this is a small pice of the puzzle on which to build.
January 30, 2015
As a mom of three children, two with ADHD (one without), and both of those labors being medically managed with oxytocin and the other a spontaneous labor resulting in a typical child, how much more do we need to see that this might be the reason that AS/ASD/ADHD disorder expresses. Since current research has ADHD and ASD sharing many variants with one another on the gemone, why isnt more being done to persue doing large studies curtail the what seems a perfunctory practice of oxytocin drips to "stimulate" the labor. Is very frustrating to have children in the current school system that is antiquated and leaves kids with these challenges further behind and home schooling not exactly being an alternative for it's common reputation for making mom or dad more of the manager and director of this child and ruining the parental child relationship. Oxytocin isn't innocuous IMHO. I do think that kids today are more or less forced to be indoors more these days and seeking social connection through their devices because if they run around the neighborhood they will be snatched or molested by the neighbor. It is a social problem for sure that might take several years of undoing what generations of polution, poor prenatal advice (dont eat fish while your pregnant) and politics have created.