A new study from Duke University Medical Center found a "genetic signature" that correlates autism with deficiencies in how the brain process oxytocin. Oxytocin researchers for a long time have suspected that there's some connection, because some of the key symptoms of autism spectrum disorder, or ASD, involve reduced abilities to interact socially with other people.

Instead of mutations in genes, the Duke researchers found differences in the methylation of genes that regulate the expression of oxytocin receptors. Methylation of some proteins in the oxytocin receptors of people diagnosed with ASD was about 70 percent, compared to approximately 40 percent in the general population.

"These results provide a possible explanation of why social isolation forms part of the autism spectrum -- because an autistic individual's ability to respond to oxytocin may be limited," [said co-lead author Simon G. Gregory, Ph.D., assistant professor in the Duke Department of Medicine]. " Oxytocin has been tied to levels of trust and ability to read social cues."

The study was reported by Science Daily today. 

Methylation is a molecular process that "switches off" or "switches on" genes. Remember that are genetic makeup is not constant. Genes may be expressed, that is, activated, by experience after birth. Those experiences include external events as well as molecular events.

To my mind, this gives some weight to the theory that a cause of autism -- or a contributor -- might be the extra dose of oxytocin usually given to women in labor. The theory is that all this extra oxytocin, in the form of a pitocin drip, hitting the baby's brain during labor may cause the oxytocin receptors in his brain to lower their receptivity, that is, to down-regulate, just like you'd lower the thermostat in your house when it's too warm.

Here's the citation, with a link to the abstract:

Simon G. Gregory, Jessica J. Connelly, Aaron J. Towers, Jessica Johnson, Dhani Biscocho, Christina A. Markunas, Carla Lintas, Ruth K. Abramson, Harry H. Wright, Peter Ellis, Cordelia F. Langford, Gordon Worley, G. Robert Delong, Susan K. Murphy, Michael L. Cuccaro, Antonello Persico and Margaret A. Pericak-Vance. Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Medicine, 2009; (in press)

I really respect Michael Odent for helping to spread the word about the importance of natural childbirth. But I find it hard to accept his reasoning that men shouldn't feel pressured to be present for the birth of their babies.

Odent made these statements more than a year ago, and he's still at it. In advance of an address at the Royal College of Midwives' conference next month, Odent is continuing to say that not only should men not feel that they should be there, they probably shouldn't be there even if they want to.

He told The Observer,

"The ideal birth environment involves no men in general. Having been involved for more than 50 years in childbirths in homes and hospitals in France, England and Africa, the best environment I know for an easy birth is when there is nobody around the woman in labour apart from a silent, low-profile and experienced midwife – and no doctor and no husband, nobody else."

Odent also told The Observer's Denis Campbell that seeing a woman in childbirth can ruin the man's sexual attraction for her. This is so disappointing. As we understand the connection between sex, love for a mate, childbirth and love for one's children, we see how oxytocin is central to each of these experiences. Therefore, they're really all part of the same thing, one big wheel of love within the family. Why would you want to leave a father out of part of this?

Certainly, a laboring woman needs to feel secure and safe. And, unfortunately, sometimes we don't feel really safe and secure with our mates. This is tragic, and if you're bringing a baby into this situation, it might be better for the man not to be there. 

But I think Odent goes way too far in saying that men have no place in the labor room.

I really respect Michael Odent for helping to spread the word about the importance of natural childbirth. But I find it hard to accept his reasoning that men shouldn't feel pressured to be present for the birth of their babies.

Odent made these statements more than a year ago, and he's still at it. In advance of an address at the Royal College of Midwives' conference next month, Odent is continuing to say that not only should men not feel that they should be there, they probably shouldn't be there even if they want to.

He told The Observer,

"The ideal birth environment involves no men in general. Having been involved for more than 50 years in childbirths in homes and hospitals in France, England and Africa, the best environment I know for an easy birth is when there is nobody around the woman in labour apart from a silent, low-profile and experienced midwife – and no doctor and no husband, nobody else."

Odent also told The Observer's Denis Campbell that seeing a woman in childbirth can ruin the man's sexual attraction for her. This is so disappointing. As we understand the connection between sex, love for a mate, childbirth and love for one's children, we see how oxytocin is central to each of these experiences. Therefore, they're really all part of the same thing, one big wheel of love within the family. Why would you want to leave a father out of part of this?

Certainly, a laboring woman needs to feel secure and safe. And, unfortunately, sometimes we don't feel really safe and secure with our mates. This is tragic, and if you're bringing a baby into this situation, it might be better for the man not to be there. 

But I think Odent goes way too far in saying that men have no place in the labor room.

When they hear about how oxytocin lets us connect with others while it keeps us healthy and happy, most people ask, "How can I get more?"

We'd all love to be able to pop a pill to instantly boost our oxytocin. Wouldn't it be great if whenever we felt lonely or disconnected, we could quickly get an oxytocin buzz? Unfortunately, as I tell people, there is not instant fix. However, science shows that it's very possible to naturally boost oxytocin levels.

The key is to practice behavior that tend to provoke the oxytocin response. For some people, that's as easy as calling someone on the phone or going into a social situation. For shyer people, like me, sometimes being around strangers can produce anxiety instead of connection.

A wonderful antidote to shyness is helping others. In Paul Zak's experiments, inhaling oxytocin made people more generous. And Stephanie Brown of the University of Michigan found that elderly people who cared for a spouse who was ill significantly reduced their risk of death; she thinks that's because of increased levels of oxytocin.

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Jett asked me about WAY-267,464, after finding this Wikipedia entry on it. After looking through my archives, I found that I had discussed this potential drug that Wyeth is working on with Dr. Robert Ring, Head of Molecular Neurobiology, Depression & Anxiety Disorders, Discovery Neuroscience, Wyeth Research.

The original draft of my book, The Chemistry of Connection, contained a whole chapter about potential oxytocin therapies. Unfortunately, my publisher didn't want much of this in the book. But there's immense interest in oxytocin drugs, and I believe that oxytocin is going to be the wonder drug of this decade -- or maybe next decade.

In February 2007, I interviewed Wyeth's Robert Ring about the potential for oxytocin therapies. Below is the section of the chapter discussing WAY 267,464, with some additional comments.

The delivery method -- how to get a drug inside someone -- is a huge issue for oxytocin. The nasal spray stings and doesn't last very long; injections hurt; IVs are cumbersome and unpleasant; pills break down in the digestive system before they have a chance to work.

That's why pharmaceutical companies will likely produce drugs containing proprietary oxytocin-like molecules, instead of bio-identical oxytocin. These designer molecules will bind with oxytocin receptors, but they'll have other characteristics that make them more effective or limit what they do.

Robert Ring, head of molecular neurobiology, depression and anxiety disorders, discovery neuroscience for drug giant Wyeth Pharmaceuticals, is unusual among drug company executives for being willing to discuss oxytocin drug development.

"We're blown away at the various diverse range of functions oxytocin seems to be acting on," he says. "Working at a drug company, you can't ignore the fact that oxytocin seems to be a multifunctional anti-stress peptide -- and it seems to be a potent analgesic as well."

One hot prospect is Wyeth's WAY 267,464. It's not a peptide like oxytocin is, which means that it won't degrade into other neurologically active substances. Instead, it's an oxytocin agonist, that is, it increases the effects of oxytocin. The advantage of treating with an agonist instead of simply trying to supplement the brain's natural supply is that often, when docs dose someone with a hormone, it further inhibits the body from producing it. WAY 267,464 also is less likely to cross over and bind to vasopressin receptors. This is important because, while scientists haven't nailed down vasopressin's role in human bonding and social interaction, it definitely seems to be important. So, the less you get in there and muck with unknown systems, the better.

In animal studies, the substance, known as 464, behaves much like oxytocin in reducing anxiety, and it also has some promise as an anti-psychotic.

Eric Hollander of the The Seaver Center for Autism Research and Treatment, Mount Sinai Medical Center, would seem to have a patent lock on teating symptoms of autism spectrum disorder, or ASD, and other disorders using oxytocin. Wyeth isn't concerned about Hollander's patents; it hopes to develop a unique molecule that binds to oxytocin receptors but has better properties for a drug. Neither is it working on an autism drug -- at least, Ring wouldn't say it is.

He pointed out that, although there's intense interest in using oxytocin to treat ASD symptoms. Because oxytocin and oxytocin-like drugs are a novel category, the path to FDA approval isn't clear. It might not be easy to demonstrate positive outcomes using standard methodologies.

Oxytocin's broad reach, relieving pain, reducing stress and soothing anxiety, could be an extra benefit for conditions with complex pathologies. Depression, for example, may go along with anxiety, chronic pain or physical illness. Oxytocin could potentially relieve these "co-morbid" conditions, Ring says. Easing any one of them would be important. Anxiety itself, he adds, is "a huge market."

Another promising area for the industry might be an antidepressant without the sexual side effects of selective serotonin-reuptake inhibitors like Prozac and Paxil. Over time, as these drugs increase the level of serotonin in the brain, prolactin also rises. Among its many roles in the body, prolactin induces the feeling of sexual satiety after orgasm. Chronically high levels of prolactin therefore can make you feel you've had enough sex, even if you aren't having any at all. An apathetic sex life is a common complaint among people on SSRIs.

Although oxytocin release is often promoted by serotonin, oxytocin also helps regulate sexuality, and it seems to be involved in erections of the penis and, presumably, the clitoris. So, it's possible that an oxytocin-based antidepressant could actually improve someone's sex life, as well as his frame of mind. Dr. Ring told me, "It's one thing to treat male erectile dysfunction, but there's a much bigger market for therapeutics for female dysfunction." While lubrication or engorgement problems may be neurological, oxytocin might be important for the motivational side of things. For example, if some aspect of sexual dysfunction had to do with anxiety about interacting with your partner, anything that would lower that anxiety might help.

(My editorial comment: For most women, anxiety about potential sexual partners is protective and a good thing. Ideally, any of these potential drugs would only be given to women with anxiety disorders. We hope.)

But don't expect 464 to turn into a pharmacological silver bullet. While its action in the body is remarkably like oxytocin's, Ring cautioned that this molecule may lack some of the properties of a good medicine. A successful oxytocin mimic should be able to be taken orally, and ideally, just once a day.

Wyeth Research is, of course, focusing on developing drugs to treat psychiatric disorders. But if a drug like this comes out, it may, like SSRIs or Provigil, also be taken up by people who haven't been diagnosed with a disorder but are just hoping to warm up their lives a bit.

This July 2009 paper in Neuropharmacology details tests of WAY-267464 on mice.

Receptor and behavioral pharmacology of WAY-267464, a non-peptide oxytocin agonist. 

And here is the Wyeth patent application for using oxytocin receptor agonists to treat schizophrenia and anxiety disorders.

Chalk up still another important role for oxytocin: It may be the key to why women gain too much weight during pregnancy. 

A study at Otago University found that oxytocin and prolactin seem to act as on/off switches for the appetite. Oxytocin contributes to satiety after meals -- as well as to milk let-down, trust, generosity and love. Increased prolactin may switch off oxytocin's satiation factor, encouraging the pregnant woman to eat more in order to support the developing fetus and milk production.

But Dr Colin Brown, a physiology researcher at Otago University, said more than 40 per cent put on too much weight - putting themselves and their babies at greater risk of birthing complications, and the children at increased risk of obesity and other health problems later in life.

Understanding this mechanism could help women who pack on the pounds, endangering their own health and increasing the chances the baby will grow up to be tubby, as well, according to the docs.