How Oxytocin Might Help Cure Autism

News about autism is almost always controversial, but the latest report that has people abuzz—about researchers who have successfully treated some symptoms of the disorder using a nasal spray of oxytocin—shouldn't come as much of a shock. Scientists have been experimenting with oxytocin as an autism treatment for years. In the new study, conducted by French researchers, 13 subjects with "high-functioning autism" (a.k.a. Asperger syndrome) became more trusting and socially engaged under the hormone's influence. It's a small study, but it has big implications, and it tracks with findings from other researchers. Mary Carmichael spoke with one of those scientists, Eric Hollander, who is the director of the compulsive, impulsive, and autism spectrum disorders program at the Montefiore Medical Center in New York. Excerpts below, with our easier-to-understand translation:

What is the oxytocin spray actually doing in the brains of these patients?
Hollander: In patients with autism, the fusiform gyrus doesn't seem to light up in response to human faces. They light up an adjacent region called the inferior temporal gyrus, which normally gets lit up when people are looking at man-made objects. But we seem to get more recruitment of the fusiform gyrus when we administer oxytocin.

This means: Unlike a healthy brain, an autistic one may not recognize human faces as something special—it puts them in the same category as regular objects. By boosting levels of oxytocin, researchers may be able to fix that problem, causing the autistic brain to respond to faces in a more normal way.

Hollander: We've seen effects in another region, called Brodmann Area 25, which is very active in individuals who have treatment-resistant depression. High-functioning adults with autism also have a very active Area 25, and in response to the oxytocin, there's a big reduction in activity.

This means: Oxytocin tamps down activity in a part of the brain that's linked to depression and stress. "Area 25" activates the "fight-or-flight response." If it malfunctions and starts firing all the time, it causes people to feel chronically stressed out. By calming down the activity in Area 25, oxytocin also calms down patients.

Do people with autism have abnormally low levels of oxytocin?
Hollander: It's challenging to measure the blood-plasma levels of oxytocin—it can be released in blips throughout the day, so it varies—but studies in children have found abnormalities in the plasma levels, and the subgroup of children with autism who are the most socially aloof tend to have the lowest levels of oxytocin. There are also studies in monkeys that have measured oxytocin levels in the spinal fluid as well as in the plasma. These studies show if you inhibit nurturing behaviors early in life, the spinal fluid and plasma levels of oxytocin are low, and they stay low throughout life.

This means: The data isn't perfect, but children with autism, especially severe cases, seem to have low oxytocin levels. Primate research, which is in some ways more rigorous, has shown that monkeys deprived of maternal love as infants tend to have chronically low levels of oxytocin throughout their lives.

Monkeys deprived of love have low oxytocin levels, and so do kids with autism? Doesn't that sound an awful lot like the discredited “refrigerator mother” hypothesis?
Hollander: In extreme cases of maternal deprivation, like children raised in orphanages without any early maternal behavior, there can be a long-lasting effect on oxytocin that's associated with social deficits. However, that probably is not the case with good or bad mothering. These are extreme cases of total lack of nurturing.

This means: This research does not mean that autism can be blamed on bad parents. The only time there might be links between parenting, oxytocin, and autismlike behavioral problems is in cases when a child has had no meaningful interaction with caregivers whatsoever.

Some behavioral therapies seem to help people with autism, especially if they're delivered early in life. Is it possible that these therapies work by increasing oxytocin levels?
Hollander: Those therapies are really important—that's the whole point of diagnosing autism early, because the therapies can really improve the long-term developmental trajectory—but nobody has specifically measured oxytocin in response to them. I can tell you that there are things we know of that can enhance oxytocin levels. Deep pressure massage does it, and breast-feeding, and sexual intercourse. We also know that patients with autism tend to calm down by doing certain physical activities, like lying underneath a mattress or using Temple Grandin's  squeeze machine."

This means: Nobody knows how behavioral therapies for autism affect oxytocin levels. We do know that in healthy people, affectionate physical contact increases oxytocin, which is a "calming" hormone. We also know that many people with autism find that being "squeezed" (albeit not by people) is calming.

The study looked at oxytocin's effect on social behaviors. You've also found it can affect other symptoms of autism, as well as other disorders. What are those effects?
Hollander: There is a group of behaviors that are self-stimulatory. When patients with autism are bored, they start to do things like hand-flapping or rocking back and forth to get up to their optimal level of stimulation. You actually see this in other species if you restrict input of sensory signals—if you put a tiger in a small cage, for instance, it will start to pace back and forth. With those types of behaviors, we saw a big decrease in response to the oxytocin. There are other, anxiety-related behaviors that seem to respond better to very low doses of SSRIs. We've also looked at patients with borderline personality disorder (BPD), who are exquisitely sensitive to social rejection. What we found was that when they got a single dose of the intranasal oxytocin in a situation where they had stress, like if they had to do a mathematical computation in front of other people who were evaluating them, there was a normalized cortisol response. But patients with BPD also have impairment in their social decision making, so in situations where they should be cooperating, they tend to defect, and in situations where it would make sense to defect, they try to cooperate. Paradoxically, the oxytocin made that abnormal decision making even worse. It's possible that the oxytocin was stimulating their vasopressin receptors.

This means: When they're given oxytocin, patients with autism aren't as likely to engage in some odd behaviors typical of the disorder (hand-flapping, rocking), which are thought to keep them from getting bored. But they do still tend to engage in other behaviors (hand-washing, compulsively putting things in order), which are more about staying calm. This second group of behaviors can be decreased by giving low doses of antidepressants. Oxytocin also has an interesting effect on patients with another illness, borderline personality disorder—it helps them by making them less stressed out but hurts them by causing them to make very bad social decisions, possibly because it accidentally binds to receptors in the brain linked to aggression.

How long do the effects of the oxytocin last?
Hollander: Even though it's staying in the plasma for a very brief period of time, we were getting effects in terms of enhanced social memories that seemed to persist two weeks later. Some of it is binding to central oxytocin receptors, and by stimulating those, it's allowing for the laying down of new social memories. Once those are laid down they seem to persist. So, we had people listen to neutral sentences, like "The boy went to the store," but we read those sentences with different tones—happy, sad, angry, or indifferent—and they had to recognize each tone. They developed an expertise in that. They were better at identifying the tones two weeks after the oxytocin was given. We don't know whether it's permanent.

This means: When it comes to correctly identifying others' emotions and recognizing social cues, oxytocin's effects last at least two weeks—possibly because while the oxytocin levels are artificially increased, the brain is better at creating new, long-lasting memories.

What would happen if nonautistic people used an oxytocin spray?
Hollander: When you show people threatening faces, they have a marked activation of the amygdala. If you then give those people oxytocin, they don't get as much amygdala activation, so there's less of this fight-or-flight, threat, fear response. And normally, you'd get an elevation in blood pressure, clammy skin. You don't get as much of that either.

This means: They'd be less scared of things, and probably less stressed.

Do you worry that an oxytocin nasal spray would end up being abused by healthy people if the FDA approved it for treating autism?
Hollander: We're still far away from getting this approved in the U.S. for the treatment of autism. You'd need to do a large-scale trial, which hasn't been done yet. But the idea of people using this as a spray to enhance performance—I certainly wouldn't want to advocate that. I'm not sure it would be used in a recreational fashion. It has the potential for decreasing the sensation of social threat, and for enhancing social reward and reinforcement and facilitating trust, but I'm not sure it makes people feel euphoric or high. There are medicines that are on the market for the treatment of social anxiety disorder, and they don't seem to be abused in a recreational fashion. I don't see people who are a little shy going out and using SSRIs at parties. On the other hand, a lot of them do self-medicate with alcohol.

This means: Well, what he said. We think this message is pretty clear.

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