Hug the Monkey

Oxytocin Spray Helps Adolescents with ASD

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.

Autism an Imprinting Error?

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.

Pipe Oxytocin Into the Senate Chamber?

A Washington Post reader has a great idea.

French Confirm Nasal Oxytocin Helps ASD

A new French study of 13 high-functioning adults with autism spectrum disorder found that inhaling oxytocin made the subjects more social and open to relating to others.

According to the London Times, Elissar Andari, of the Institut des Sciences Cognitives, a French government centre for neuroscience research presented the findings at a conference.

The article doesn't say how long improvements lasted; in the first study of oxytocin for autism, Eric Hollander and Jennifer Bartz of the Seaver Centers for Autism found they lasted up to two weeks.

Good Interview with Eric Hollander on Oxytocin and ASD

-- with Jasvir Singh

Writer James Ottar Grundvig, who has an autistic child, spoke with Hollander about his past research, in which he showed that oxytocin could improve some of the symptoms of autism spectrum disorder, as well as what he plans for the future.

Hollander recently moved from the Seaver and New York Autism Center of Excellence at Mt. Sinai School of Medicine to the Child Psychiatry Annex at the Montefiore Medical Center University Hospital for Albert Einstein College of Medicine.

 The interview recaps Hollander's ground-breaking studies showing that intravenous or intranasal oxytocin  improved emotions, strengthened trust bonds, and reduced or eliminated repetitive behavior in healthy adults with ASD -- with improvement lasting two weeks after a single dose.

 Hollander also comments on other studies showing that oxytocin may help with schizophrenia and social anxiety disorder.

 Dr. Hollander is a clinical psychiatrist who spearheaded autism research at Mount Sinai School of Medicine and chairs the Advisory Board of icare4autism. He believes that doing oxytocin studies on ASD (Autism Spectrum Disorder) children is over two years away. More evidence and safety needs to be obtained before the FDA approves that phase of research. Until then, studies will focus on young adults, according to the interview.

 You can read the entire interview here in the Epoch Times.

Oxytocin Gene Methylation Clue to Autism

with Jasvir Singh

Scientists have found many genetic markers for autism, including evidence that malfunction of the genes that influence oxytocin receptors may be at fault. A new study by Duke Department of Medicine researcher Simon Gregory identified a different culprit: epigenetics.

We used to think of genes as a deck of cards, shuffled at conception, that determined our physical development. If you had the genes for blue eyes, your eyes were blue. But now, we know that genes may switched on and off throughout fetal development and even throughout our lives. Even physical traits like hair color are not completely pre-determined. A group of molecules on top of our DNA, the epigenome, tells genes when to turn on or off. Epigenetics is basically a mediator between nature and nurture—it can activate some genes while inhibiting others. Once the gene is turned off epigenetically, the DNA has typically been methylated.

Most studies of the genetic basis of autism have focused on genes or missing genetic material in the DNA sequence. But a link between DNA methylation and autism has been described by Gregory in the journal BMC Medicine.

Gregory and his colleagues looked at how oxytocin relates to social interaction in those with autism disorders. They examined an oxytocin receptor gene, called OXTR, and found that 70 percent of the autistic people in a study had a methylated OXTR, in comparison to only 40 percent of those without symptoms of autism.

Those with autism often have their OXTR gene turned off, which could be why they have a greater difficulty in relating to others than those without autism.

Gregory thinks that methylation-modifying drugs might be a new area to explore for autism treatments. It seems as though finding a way to turn the oxytocin receptor gene back on might be a step in the right direction for treating autism.

Read more about Gregory's study, and other work on epigenetics, in the Washington Post.

NIH: More Studies of Oxytocin for Autism

The National Institutes of Mental Health Strategic Plan for ASD Research is ready for public comment, two years after congress re-established the the Interagency Coordinating Committee (IACC) and required that the IACC develop and annually update a strategic plan for ASD research.

You can read the draft of the strategic plan yourself. It includes  not only treatment options, but also important issues such as estate planning, so that an adult on the spectrum who can't function independently can be sure of  getting the care and support he or she needs.

The plan has a pretty succinct summary of treatment options, and it does mention oxytocin as something that needs further study.  Here's  the entirety:

Medications to improve some of the symptoms associated with autism have been studied. However, thus far, no medication has been shown in controlled trials to enhance social behavior or communication. In 2006, risperidone became the first Food and Drug Administration (FDA)-approved pharmacologic therapy for certain symptoms of autism.
August 15, 2008 Draft for Public Comment.
Budgetary requirements not included pending IACC discussion in November 2008. - 17 -
First introduced in 1993 as medication used to treat symptoms of schizophrenia, risperidone has now been shown to be effective as a treatment of irritability and aggression seen in some children with ASD. Selective serotonin reuptake inhibitors have had mixed results in decreasing certain repetitive and stereotyped behaviors (Kolevzon et al., 2006). Other biological and pharmacological treatments that have been investigated in small studies and may warrant fuller attention include omega-3 fatty acids, memantine, oxytocin, and pioglitazone (Ammiger et al., 2007; Chez et al., 2007; Hollander et al., 2007; Boris et al., 2007)

Short-term research goals mentioned include testing widely used treatments that haven't been studied in a controlled way; conducting five trials of interventions for infants and toddlers by  2011; and  three randomized studies of treatments for  school-aged kids by 2012.

I wonder if Eric Hollander and his team at Mt. Sinai Hospital, the group that showed improvements in communication in adults after treatment with oxytocin, will be able to nab a grant under this program.

New Evidence for Oxytocin Gene Defect in Autism

Because a major characteristic of autism spectrum disorder, or ASD, is a lack of affectionate interactions, many researchers are looking into impairments of the oxytocin system. A team of researchers looked at the genes of a large group of children with autism and found irregularities in the  prolactin gene, and the genes that produce receptors for prolactin and oxytocin. 

According to the press release, the researchers  have registered a possible association between some of the genes identified in animal studies as controlling affiliative behaviors in ASD.” No more details in the release, but the fact that the journal, Biological Psychiatry, issued a press release means they think this is big news.

I think the study may also give weight to the role of oxytocin in human love.

“Genes Controlling Affiliative Behavior as Candidate Genes for Autism” by Carolyn M. Yrigollen, Summer S. Han, Anna Kochetkova, Tammy Babitz, Joseph T. Chang, Fred R. Volkmar, James F. Leckman and Elena L. Grigorenko. The article appears in Biological Psychiatry, Volume 63, Issue 10 (May 15, 2008), published by Elsevier.

Gray and White Matters

There seems to be a flood of brain research lately that helps illuminate how the brain responds to social stimuli.

An intriguing new area is looking at two kinds of tissue in the brain: white matter and gray matter.  We usually think of gray matter as the stuff we use for cognition; more grey matter tends to equal a higher IQ, for example. White matter, on the other hand, is the connective nerve tissue thought to be used for "wiring together" different parts of the brain.

Of course, it's not that simple.  Too much gray matter in some regions has been linked to trauma.

Two studies released today looked at the relationship between volume of white or gray matter and behavior.

First, a team led by Manzar Ashtari of the Children's Hospital of Philadelphia in Pennsylvania looked at the brains of autistic kids. They found more gray matter than normal in parts of the brain dealing with social interactions. They think this could be related to abnormal function of the mirror neuron system.

Mirror neurons are thought to be special kinds of nerve cells that fire when we watch others. It's still speculative in humans, but they've found that monkeys have what they call mirror neuron regions that fire when the monkey watches a researcher pick up a cup. This might be related to empathy, the ability to literally put oneself in another's place. See Mirror Neurons, Oxytocin and Autism for more.

According to the Science Daily story,

"In the normal brain, larger amounts of gray matter are associated with higher IQs," Dr. Ashtari said. "But in the autistic brain, increased gray matter does not correspond to IQ, because this gray matter is not functioning properly."The autistic children also evidenced a significant decrease of gray matter in the right amygdala region that correlated with severity of social impairment. Children with lower gray matter volumes in this area of the brain had lower scores on reciprocity and social interaction measures.

Another study by James Cantor of the Centre for Addiction and Mental Health in Toronto  found significantly less white matter in the brains of pedophiles than in the brains of non-sexual offenders. The article says,

The study, published in the Journal of Psychiatry Research, challenges the commonly held belief that pedophilia is brought on by childhood trauma or abuse. This finding is the strongest evidence yet that pedophilia is instead the result of a problem in brain development.

I don't understand why they draw this conclusion. Plenty of studies have shown abnormalities in brain development in children who've been neglected, abused or traumatized. In fact, Victor Carrion of Stanford has found more gray matter in the prefrontal cortexes of the brains of children with PTSD. He's also found decreased total volume in the PFCs of adults and children with PTSD.

He recently told me that it's difficult to identify exactly what these differences mean when it comes to brain function and behavior. He said, "It seems like in some regions, there's a problem if you have more volume ...  in others, it's problematic if you don't have enough."

It seems to me that Cantor's study provides further evidence for two things: that early trauma affects brain development, and that this abnormal brain development leads to abnormal behavior later.

I've contacted the Centre for Addiction and Mental Health to more information on this statement. I'll post if and when they get back to me.

 

Mirror Neurons, Oxytocin and Autism

What's the relationship between mirror neurons and oxytocin? Science isn't even clear yet on what mirror neurons do, but news from the annual meeting of the Society for Neuroscience sparks some intriguing ideas.

Mirror neurons seem to fire when we perform an action and also when we watch someone else perform it. Most studies have been done with monkeys: They map which neurons fire when the monkey grasped an apple, and saw the same neurons become active when the monkey watched someone else hold the apple.

According to the press release from the conference, several researchers presented brain imaging studies comparing mirror neuron activity between children with autism and those with normal functioning.

Jaime Pineda, PhD, at the University of California, San Diego, did studies showing that the mirror neuron system is well-developed by the time a child is seven years old. His UCSD colleague, Lindsay Oberman, used EEG to monitor mirror neuron activity in ASD kids. She found that the system did work to some extent, and she saw normal activation of the mirror neurons when the children watched videos of family members, but not of strangers.

She suggests that people with normal brain function are able to generalize that all people are "like me," and therefore to understand them and have empathy for them, while kids on the spectrum are not able to make that leap. From the press release:

This evidence for normal mirror neuron activity in autistic children may indicate that mirror system dysfunction in these cases reflects an impairment in identifying with and assigning personal significance to unfamiliar people and things, Oberman suggests. Whether deficits in relating to unfamiliar people that are characteristic of autism are the cause or the result of a dysfunctional mirror neuron system is unclear.

This leads back to the oxytocin system. Many researchers think that ASD is due to dysfunction in the oxytocin system -- something is wrong with the brain's ability to produce or respond to oxytocin in social situations. Oxytocin influences generosity, increases empathy, and alleviates some of the symptoms of autism.   

Maybe oxytocin is necessary for the mirror neurons to fire; maybe it causes them to fire in response to social cues. Or perhaps, because oxytocin and dopamine are involved in social memory -- keeping track of who my family and friends are -- it's possible that the problem is in the oxytocin system, and the lack of appropriate social memory is what's keeping the mirror neurons to trigger.

This is all speculation; none of the scientists is working on this. Because human studies are so slow, costly and laborious, it seems that it's very difficult for scientists across disciplines to connect their work.

For a more detailed discussion of the research on mirror neurons, Ed Yong of Not Exactly Rocket Science has an excellent post. See Broken chains and faulty mirrors cause problems for autistic children.