Hug the Monkey

Oxytocin No Longer the "Shy Hormone"

with Jasvir Singh

Thinking about oxytocin, once known as the shy hormone, has made a 360 degree turn. Michel Odent, a practitioner who introduced the concept of birthing pools and focuses on the long-term consequences of early experiences, writes that oxytocin is now showing up as the social hormone.

 

Odent claims that since the discovery of oxytocin a century ago by Henry Dale, we have been trying to understand its effects. Through the combination of various experiments and observations, oxytocin came to be known as the “shy hormone” (maybe before it became the "cuddle hormone"), because it resembled a shy person who does not appear in the presence of strangers or observers.

 

Couples would isolate themselves to make love, as if they knew the shy hormone would be released. Women would isolate themselves during breastfeeding and childbirth for the same reason. Women would protect the birthing experience from men as if they knew that oxytocin was shyer in a male than in a female environment.

 

However, this slowly changed, according to Odent. Not only have we forgotten that oxytocin is a shy hormone, but furthermore we are sending the opposite message. It is now encouraged to have coaches and support teams in birthing rooms; privacy is no longer a priority. We’ve reversed most of our ideas and are promoting a new generation of studies about oxytocin release.

 

This new generation of studies seems to make sense, though. We had to wait until the 1970s to discover that a newborn human baby needs its mother. . We’ve learned that the germs of the mother should be the first to colonize the baby’s body. Ad we know that mothering actually influences the sensitivity and distribution of oxytocin receptors in the baby's body.

 

You can read Odent’s entire article here: http://www.midirs.org/development/MIDIRSEssence.nsf/article/81B0FC4867DC184A8025768200528739?OpenDocument&utm_source=twitterfeed&utm_medium=twitter

 

For more information on Michel Odent, visit www.michelodent.com

The Peptide That Binds: Overview of Human Research

UC Berkeley researchers just published a review of human oxytocin studies in the Harvard Review of Psychiatry. Behavioral Health Central has a brief report. In a nutshell:

The researchers concluded: "Key conclusions are (1) human research with intranasal oxytocin has uniquely enhanced our understanding of the microstructure and function of the human social brain, and (2) the oxytocin system is a promising target for therapeutic interventions in a variety of conditions, especially those characterized by anxiety and aberrations in social function."

The paper is called The peptide that binds: a systematic review of oxytocin and its prosocial effects in humans.

Your Baby's Smile Is a Real Rush

with Jasvir Singh

It's not exactly late-breaking news that seeing your baby smile is one of life's simplest but deepest pleasures. But a Baylor College professor used brain scans to show just how rewarding it is.

Lane Strathearn, an assistant professor of pediatrics at at the Baylor College of Medicine and Texas Children’s Hospital, and a research associate in BCM’s Human Neuroimaging Laboratory, found that the reward centers in mothers' brains were activated when they saw their babies smile. (For you science geeks, those areas were the ventral tegmental area/substantia nigra regions, the striatum, and frontal lobe regions, all of which are involved in emotion processing, cognition and motor/behavioral outputs.) The activation was similar to those activated by drug addiction.

Strathearn has conducted research for the past nine years aimed to develop a better understanding of the pervasive problem of child neglect. A goal of his research has been to link early experiences in mothers with the relationship they develop with their children, and understand the biological mechanisms underlying this connection. An earlier study of his found that women who breastfed were less likely to neglect their children.

According to a story from Queensland University's media office about his work (Strathearn is a graduate):

"Our subsequent study showed that the hormone, oxytocin, which is involved in breastfeeding, is also related to secure attachment in mothers and to brain 'reward' activation when they view pictures of their baby," Dr Strathearn said. The study addresses the importance of this initial mother-infant relationship.

 Now, he's doing a study to see whether inhaling oxytocin influences how their brains respond to their babies.

Strathearn thinks that increasing demands for mothers to balance family and work life has caused the basic needs of children to fall lower and lower on the priority list. Unfortunately, physical and emotional neglect is often the result.

 

The Case for Harm from Pitocin in Labor

Christof Plothe is a doctor of osteopathy who works at a pediatric clinic in Alzy, Germany.

His paper, in press for 2010 publication in the International Journal of Prenatal and Perinatal Psychology and Medicine, reviews the scientific literature on oxytocin in relation to bonding between mother and child, and then examines studies showing effects of oxytocin or Pitocin (a synthetic brand) used during labor.

Plothe writes,

"For over 50 years Oxytocin has been used in modern obstetrics during  birth. Whilst the physiological aspects of the hormone have been  studied intensely the psychological mechanisms of its function have  only started to be known since the nineties of the last century. I  have been working with newborns for over a decade now and observed  fundamental differences after the oxytocin related births in the  babies, later in the adolescents and even in the adults. The  article is a summary of the contemporary research  of Oxytocin and hypothesizes that Oxytocin can have a lifelong   imprinting on the psyche when used during the delivery. 

He has observed that some children seem "oxytocin-imbalanced." These kids may be insecure, have difficulty with school work, and problems with relationships within the family. Plothe has been treating some with oxytocin, and found that such symptoms improved or even disappeared.

He calls for more studies and discussion among health professionals and researchers to try to determine how much modern birth practices may have lifelong consequences.

You can read the entire paper here: The perinatal application of oxytocin and its potential influence on the human psyche.

The Penis, Arousal and Oxytocin

As you know if you've been reading my blog, oxytocin is not just the cuddle hormone, nor is it just a girl thing. It's also necessary for sexual arousal, and studies have charted its effects specifically on penile erection. (They have not to my knowledge tested whether oxytocin is necessary for the engorgement of the clitoris -- aka female arousal -- but I sure bet it is.)

The Neurotopia blog covers an interesting study showing that oxytocin levels rise inside the penis as excitement increases, specifically in the corpus cavernosa, the spongy center of the penis. It also rises in the circulating blood -- until full erection. According to Neurotopia:

During sexual arousal and the formation of an erection, oxytocin levels went up in both the systemic blood and the cavernosa blood. But as the penis reached full rigidity, oxytocin continued to rise in the penis, but flattened off in the systemic circulation. Then, during the soft-off, blood levels of oxytocin the penis dropped (as expected), but rose AGAIN in the systemic circulation.

I wonder if this leveling off and then new increase in the amount of oxytocin circulating in the blood correlates with oxytocin levels inside the brain. (In fact, many studies assume that it does, measuring blood levels to make a guess at brain levels.) Is this how sex remains, well, sexy, while the emotional charge comes afterward?

Autism Gene Linked to Empathy

A variation in a gene for the oxytocin receptor helps determine how much empathy a person has, according to a new study.

Sarina Rodrigues, assistant professor of psychology at Oregon State University and  Laura Saslow, a UC Berkeley psychology graduate student, compared four variations in the OXTR gene. They found that people who inherited one specific combo were much more likely to be able to identify emotions in the "mind-reading" test, and also described themselves as generally mellow and less likely to get stressed.

From the UC Berkeley press release:

All humans inherit a variation of this gene or "allele" from each parent. The UC Berkeley study looked at the three combinations of gene variations of the oxytocin receptor. The most empathetic – able to get an accurate read on others' emotions – had two copies of the "G allele." In contrast, members of the AA and AG allele groups were found to be less capable of putting themselves in the shoes of others and more likely to get stressed out in difficult situations.

This study is a counterpoint to the recent research from Duke University showing that differences in the methylation of genes that regulate the expression of oxytocin receptors correlated with autism.

WAY-267464: The Love and Connection Drug?

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.

Oxytocin may be key to pregnancy weight gain: Herald News

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.

Mothering and Fathering Influence Bonding in Adult Voles

Larry Young and Todd Ahern of the Yerkes Primate Center at Emory found that "early life nurturing impacts later life relationships."

It's still another data point in the enormous body of evidence showing how important it is for kids to get early nurturing, love and care. Larry Young was one of the second wave of oxytocin researchers working on the monogamous prairie voles. This research showed that oxytocin was crucial for the prairie voles' ability to form pair bonds.

In this experiment, also with prairie voles, Young and Ahern compared prairie vole pups raised by a single mother with those raised by a male and female couple. In the wild, prairie voles mate for life in a system described as social monogamy. That is, the couples live together and cooperate in raising offspring; they may engage in some extra-pair copulation, the rodent version of affairs.

The pups raised by a single mother got a lower level of care than those raised by a cooperating couple.  And when they reached adulthood, they weren't as enthusiastic parents.

According to the press release,

"These results suggest naturalistic variation in social rearing conditions can introduce diversity into adult nurturing and attachment behaviors. S[ingle-mother]-raised pups were slower to make life-long partnerships, and they showed less interest in nurturing pups in their communal families," says Young.

Oxytocin Could Be Weaponized, Expert Warns

Malcolm Dando's op-ed piece in Nature this week has gotten attention for his warning that biologists seldom understand the military implications of their research.

Analee Newitz on io9 quotes Dando using oxytocin sprays as an example of this:

Some companies are already marketing oxytocin on the back of studies showing that a nasal squirt of the hormone increases trust in humans. Even though the effectiveness of commercial sprays is doubtful, such research opens up the possibility of a drug that could be used to manipulate people's emotions in a military context. Discussions with more than 2,000 practising life scientists in 13 countries over the past few years have taught me that few have considered such possible uses of their work.

Red Orbit has another article about Dando's op-ed.

In writing my book about oxytocin's role in human emotion, I spoke to most of the top oxytocin researchers. They were well aware about people's self-experimentation. Sue Carter of the University of Illinois said at that their clinic, which treats kids with autism spectrum disorder, many parents told her they'd tried over-the-counter oxytocin sprays, or else asked about it.

Awareness of the issue of self-dosing and entrepreneurial companies using biology research for profit and/or military weapons development isn't much use, of course. Biologists have to do the basic experimentation; the best way they can protect their research is to patent whatever they can.