(Image caption: Neurons of love: A newly discovered type of brain cell responds to oxytocin and so regulates female mice’s interest in males, but only when the females are in heat. These star-shaped neurons (above) are shown within a brain region called the medial prefrontal cortex.)

Newly discovered brain cells explain a prosocial effect of oxytocin

Oxytocin, the body’s natural love potion, helps couples fall in love, makes mothers bond with their babies, and encourages teams to work together. Now new research at Rockefeller University reveals a mechanism by which this prosocial hormone has its effect on interactions between the sexes, at least in certain situations. The key, it turns out, is a newly discovered class of brain cells.

“By identifying a new population of neurons activated by oxytocin, we have uncovered one way this chemical signal influences interactions between male and female mice,” says Nathaniel Heintz, James and Marilyn Simons Professor and head of the Laboratory of Molecular Biology.

The findings, published today in Cell (October 9), had their beginnings in a search for a new type of interneuron, a specialized neuron that relays messages to other neurons across relatively short distances. As part of her doctoral thesis, Miho Nakajima began creating profiles of the genes expressed in interneurons using a technique known as translating ribosome affinity purification (TRAP) previously developed by the Heintz lab and Paul Greengard’s Laboratory of Molecular and Cellular Neuroscience at Rockefeller. Within some profiles from the outer layer of the brain known as the cortex, she saw an intriguing protein: a receptor that responds to oxytocin.

“This raised the question: What is this small, scattered population of interneurons doing in response to this important signal, oxytocin?” Nakajima says. “Because oxytocin is most involved in social behaviors of females, we decided to focus our experiments on females.”

To determine how these neurons, dubbed oxytocin receptor interneurons or OxtrINs, affected behavior when activated by oxytocin, she silenced only this class of interneurons and, in separate experiments, blocked the receptor’s ability to detect oxytocin in some females. She then gave them a commonly used social behavior test: Given the choice between exploring a room with a male mouse or a room with an inanimate object – in this case a plastic Lego block – what would they do? Generally, a female mouse will go for the non-stackable choice. Legos just aren’t that interesting to rodents. But Nakajima’s results were confusing: Sometimes the mice with the silenced OxtrINs showed an abnormally high interest in the Lego, and sometimes they responded normally.

This led her to suspect the influence of the female reproductive cycle. In another round of experiments, she recorded whether the female mice were in estrus, the sexually receptive phase, or diestrus, a period of sexual inactivity. Estrus, it turned out, was key. Female mice in this phase showed an unusual lack of interest in the males when their receptors were inactivated. They mostly just sniffed at the Lego. There was no effect on mice is diestrus, and there was no effect if the male love interest was replaced with a female. When Nakajima tried the same alteration in males, there was also no effect.

“In general, OxtrINs appear to sit silently when not exposed to oxytocin,” says Andreas Görlich, a postdoc in the lab who recorded the electrical activity of these neurons with and without the hormone. “The interesting part is that when exposed to oxytocin these neurons fire more frequently in female mice than they do in male mice, possibly reflecting the differences that showed up in the behavioral tests.”

“We don’t yet understand how, but we think oxytocin prompts mice in estrus to become interested in investigating their potential mates,” Nakajima says. “This suggests that the social computation going on in a female mouse’s brain differs depending on the stage of her reproductive cycle.”

Oxytocin has similar effects for humans as for mice, however, it is not yet clear if the hormone influences the human version of this mouse interaction, or if it works through a similar population of interneurons. The results do, however, help explain how humans, mice and other mammals respond to changing social situations, Heintz says.

“Oxytocin responses have been studied in many parts of the brain, and it is clear that it, or other hormones like it, can impact behavior in different ways, in different contexts and in response to different physiological cues,” he says. “In a general sense, this new research helps explain why social behavior depends on context as well as physiology.”

Oxytocin promotes social behavior in infant rhesus monkeys

The hormone oxytocin appears to increase social behaviors in newborn rhesus monkeys, according to a study by researchers at the National Institutes of Health, the University of Parma in Italy, and the University of Massachusetts, Amherst. The findings indicate that oxytocin is a promising candidate for new treatments for developmental disorders affecting social skills and bonding.

Oxytocin, a hormone produced by the pituitary gland, is involved in labor and birth and in the production of breast milk. Studies have shown that oxytocin also plays a role in parental bonding, mating, and in social dynamics. Because of its possible involvement in social encounters, many researchers have suggested that oxytocin might be useful as a treatment for conditions affecting social behaviors, such as autism spectrum disorders. Although oxytocin has been shown to increase certain social behaviors in adults, before the current study it had not been shown to do so in primate infants of any species.

Working with infant rhesus monkeys, the NIH researchers found that oxytocin increased two facial gestures associated with social interactions— one used by the monkeys themselves in certain social situations, the other in imitation of their human caregivers.

“It was important to test whether oxytocin would promote social behaviors in infants in the same respects as it appears to promote social interaction among adults,” said the study’s first author, Elizabeth A. Simpson, Ph.D., postdoctoral fellow of the University of Parma, conducting research in the Comparative Behavioral Genetics Section of the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. “Our results indicate that oxytocin is a candidate for further studies on treating developmental disorders of social functioning.”

The study was published online in Proceedings of the National Academy of Sciences.

The researchers began by gauging the ability of rhesus macaques to imitate two facial gestures: lip smacking and tongue protrusion. In lip smacking, the lips are protruded and open, then smacked together repeatedly. The study authors wrote that rhesus mothers will engage in this facial gesture with their infants in the first month after giving birth. Tongue protrusion involves a brief protrusion and retraction of the tongue. Although this gesture is seen in other primates and typically not seen in macaques, macaques will imitate it when their human caregivers display it, the study authors added.

By observing the monkeys’ ability to imitate the two gestures, the researchers sought to determine if oxytocin could promote social interaction through a gesture that was natural to them as well as through a gesture not part of their normal communication sequence.

The researchers tested the infants in the first week after birth. Three times a day, every other day, the caregivers would demonstrate the facial gestures in sequence to the infant monkeys, while the animals’ responses were recorded on video. At this phase of the study, the researchers found that some of the monkeys mimicked their caregivers’ gestures more frequently than did other monkeys. The researchers referred to the monkeys who gestured more frequently as strong imitators.

Beginning in the second week of life, the researchers tested the monkeys on two separate days. The infant monkeys inhaled an aerosolized dose of oxytocin in one session, and a dose of saline in the other. In each session, the dose was delivered through an inhalation mask held gently over the animal’s face.

Overall, the monkeys were more communicative after receiving oxytocin, more frequently making facial gestures, than they were after receiving the saline. The monkeys were more likely to engage in lip smacking than tongue protrusion, but were more likely still to engage in either of these gestures after oxytocin than after the saline. There also were differences in the frequency of gesturing among the individual monkeys, with the strong imitators becoming even stronger imitators after receiving oxytocin.

After oxytocin exposure, the strong imitators were more likely to look at caregivers and stand close to them than they were after the saline. Looking into a caregiver’s face and remaining in close proximity to a caregiver are indicators of social interaction and social interest, Dr. Simpson said.

In another test, the researchers found that after exposure to oxytocin, monkeys had lower levels of cortisol in their saliva. Cortisol is produced by the adrenal glands in response to stress. Lower cortisol levels after oxytocin exposure indicate that oxytocin may also function to diminish anxiety, the researchers wrote.

Can ‘love hormone’ protect against addiction?

Researchers at the University of Adelaide say addictive behaviour such as drug and alcohol abuse could be associated with poor development of the so-called “love hormone” system in our bodies during early childhood.

The groundbreaking idea has resulted from a review of worldwide research into oxytocin, known as the “love hormone” or “bonding drug” because of its important role in enhancing social interactions, maternal behaviour and partnership.

This month’s special edition of the international journal Pharmacology, Biochemistry and Behavior deals with the current state of research linking oxytocin and addiction, and has been guest edited by Dr Femke Buisman-Pijlman from the University of Adelaide’s School of Medical Sciences.

Dr Buisman-Pijlman, who has a background in both addiction studies and family studies, says some people’s lack of resilience to addictive behaviours may be linked to poor development of their oxytocin systems.

"We know that newborn babies already have levels of oxytocin in their bodies, and this helps to create the all-important bond between a mother and her child. But our oxytocin systems aren’t fully developed when we’re born - they don’t finish developing until the age of three, which means our systems are potentially subject to a range of influences both external and internal," Dr Buisman-Pijlman says.

She says the oxytocin system develops mainly based on experiences.

"The main factors that affect our oxytocin systems are genetics, gender and environment. You can’t change the genes you’re born with, but environmental factors play a substantial role in the development of the oxytocin system until our systems are fully developed," Dr Buisman-Pijlman says.

"Previous research has shown that there is a high degree of variability in people’s oxytocin levels. We’re interested in how and why people have such differences in oxytocin, and what we can do about it to have a beneficial impact on people’s health and wellbeing," she says.

She says studies show that some risk factors for drug addiction already exist at four years of age. “And because the hardware of the oxytocin system finishes developing in our bodies at around age three, this could be a critical window to study. Oxytocin can reduce the pleasure of drugs and feeling of stress, but only if the system develops well.”

Her theory is that adversity in early life is key to the impaired development of the oxytocin system. “This adversity could take the form of a difficult birth, disturbed bonding or abuse, deprivation, or severe infection, to name just a few factors,” Dr Buisman-Pijlman says.

"Understanding what occurs with the oxytocin system during the first few years of life could help us to unravel this aspect of addictive behaviour and use that knowledge for treatment and prevention."

‘Love hormone’ oxytocin carries unexpected side effect

The love hormone, the monogamy hormone, the cuddle hormone, the trust-me drug: oxytocin has many nicknames. That’s because this naturally occurring human hormone has recently been shown to help people with autism and schizophrenia overcome social deficits.

As a result, certain psychologists prescribe oxytocin off-label, to treat mild social unease in patients who don’t suffer from a diagnosed disorder. But that’s not such a good idea, according to researchers at Concordia’s Centre for Research in Human Development. Their recent study — published in Emotion, a journal of the American Psychological Association — shows that in healthy young adults, too much oxytocin can actually result in oversensitivity to the emotions of others.

With the help of psychology professor Mark Ellenbogen, PhD candidates Christopher Cardoso and Anne-Marie Linnen recruited 82 healthy young adults who showed no signs of schizophrenia, autism or related disorders. Half of the participants were given measured doses of oxytocin, while the rest were offered a placebo.

The participants then completed an emotion identification accuracy test in which they compared different facial expressions showing various emotional states. As expected, the test subjects who had taken oxytocin saw greater emotional intensity in the faces they were rating.

“For some, typical situations like dinner parties or job interviews can be a source of major social anxiety,” says Cardoso, the study’s lead author. “Many psychologists initially thought that oxytocin could be an easy fix in overcoming these worries. Our study proves that the hormone ramps up innate social reasoning skills, resulting in an emotional oversensitivity that can be detrimental in those who don’t have any serious social deficiencies.”

As Cardoso explains, “If your potential boss grimaces because she’s uncomfortable in her chair and you think she’s reacting negatively to what you’re saying, or if the guy you’re talking to at a party smiles to be friendly and you think he’s coming on to you, it can lead you to overreact — and that can be a real problem. That’s why we’re cautioning against giving oxytocin to people who don’t really need it.”

Ultimately, however, oxytocin does have the potential to help people with diagnosed disorders like autism to overcome social deficits.

But, says Cardoso, “The potential social benefits of oxytocin in most people may be countered by unintended negative consequences, like being too sensitive to emotional cues in everyday life.”

Researchers identify gene that influences the ability to remember faces

New findings suggest the oxytocin receptor, a gene known to influence mother-infant bonding and pair bonding in monogamous species, also plays a special role in the ability to remember faces. This research has important implications for disorders in which social information processing is disrupted, including autism spectrum disorder. In addition, the finding may lead to new strategies for improving social cognition in several psychiatric disorders.

A team of researchers from Yerkes National Primate Research Center at Emory University in Atlanta, the University College London in the United Kingdom and University of Tampere in Finland made the discovery, which will be published in an online Early Edition of Proceedings of the National Academy of Sciences.

According to author Larry Young, PhD, of Yerkes, the Department of Psychiatry in Emory’s School of Medicine and Emory’s Center for Translational Social Neuroscience (CTSN), this is the first study to demonstrate that variation in the oxytocin receptor gene influences face recognition skills. He and co-author David Skuse point out the implication that oxytocin plays an important role in promoting our ability to recognize one another, yet about one-third of the population possesses only the genetic variant that negatively impacts that ability. They say this finding may help explain why a few people remember almost everyone they have met while others have difficulty recognizing members of their own family.

Skuse is with the Institute of Child Health, University College London, and the Great Ormond Street Hospital for Children, NHS Foundation Trust, London.

Young, Skuse and their research team studied 198 families with a single autistic child because these families were known to show a wide range of variability in facial recognition skills; two-thirds of the families were from the United Kingdom, and the remainder from Finland.

The Emory researchers previously found the oxytocin receptor is essential for olfactory-based social recognition in rodents, like mice and voles, and wondered whether the same gene could also be involved in human face recognition. They examined the influence of subtle differences in oxytocin receptor gene structure on face memory competence in the parents, non-autistic siblings and autistic child, and discovered a single change in the DNA of the oxytocin receptor had a big impact on face memory skills in the families. According to Young, this finding implies that oxytocin likely plays an important role more generally in social information processing, which is disrupted in disorders such as autism.

Additionally, this study is remarkable for its evolutionary aspect. Rodents use odors for social recognition while humans use visual facial cues. This suggests an ancient conservation in genetic and neural architectures involved in social information processing that transcends the sensory modalities used from mouse to man.

Skuse credits Young’s previous research that found mice with a mutated oxytocin receptor failed to recognize mice they previously encountered. “This led us to pursue more information about facial recognition and the implications for disorders in which social information processing is disrupted.” Young adds the team will continue working together to pursue strategies for improving social cognition in psychiatric disorders based on the current findings.

A single spray of oxytocin improves brain function in children with autism

A single dose of the hormone oxytocin, delivered via nasal spray, has been shown to enhance brain activity while processing social information in children with autism spectrum disorders, Yale School of Medicine researchers report in a new study published in the Dec. 2 issue of Proceedings of the National Academy of Sciences.

“This is the first study to evaluate the impact of oxytocin on brain function in children with autism spectrum disorders,” said first author Ilanit Gordon, a Yale Child Study Center adjunct assistant professor, whose colleagues on the study included senior author Kevin Pelphrey, the Harris Professor in the Child Study Center, and director of the Center for Translational Developmental Neuroscience at Yale.

Gordon, Pelphrey, and their colleagues conducted a double-blind, placebo-controlled study of 17 children and adolescents with autism spectrum disorders. The participants, between the ages of 8 and 16.5, were randomly given either oxytocin spray or a placebo nasal spray during a task involving social judgments. Oxytocin is naturally occurring hormone produced in the brain and throughout the body.

“We found that brain centers associated with reward and emotion recognition responded more during social tasks when children received oxytocin instead of the placebo,” said Gordon. “Oxytocin temporarily normalized brain regions responsible for the social deficits seen in children with autism.”

Gordon said oxytocin facilitated social attunement, a process that makes the brain regions involved in social behavior and social cognition activate more for social stimuli (such as faces) and activate less for non-social stimuli (such as cars).

“Our results are particularly important considering the urgent need for treatments to target social dysfunction in autism spectrum disorders,” Gordon added.

Oxytocin gene partly responsible for how adolescents feel in company

Loneliness: could there be a genetic explanation for it? Yes, to some extent! At least in the case of young female adolescents who, it appears, are more likely to feel lonely in everyday life if they have a specific variant of the gene that regulates how oxytocin – also known as the ‘bonding hormone’ – is received in the brain. Boys who carry this variant are not lonelier but, like girls, respond more strongly to a negative social environment. These findings were published this week in the academic journal PlosONE.

Oxytocin is a hormone with an important role in social behaviour. In the period following birth, it is an important factor in the bonding process between mother and baby, but it also has an influence on other relationships. The gene that regulates oxytocin-sensitivity in the brain varies between one person and another. Some people are less sensitive to oxytocin and therefore more likely to feel lonely. Various indicators have already suggested this. This prompted a group of behavioural researchers in Nijmegen to carry out a fresh and in-depth study of oxytocin effects in a group in which ‘belonging’ is of paramount importance: young adolescents.

A large group, frequently surveyed

The study involved 278 adolescents, 58 per cent of whom were girls. They were contacted via their smartphones nine times a day over a six-day period and asked to report how they felt and who they were with. The presence of the variant of the oxytocin receptor gene OXTR was also determined. ‘This is a new approach to researching the interaction between gene variation and the environment,’ explains Eeske van Roekel, the lead author of the article published online in PlosONE on Monday 4 November. ‘By asking the subjects nine times a day “How do you feel? Who are you with? What do you think of the people you are with?,” we managed to put together a clear picture of how adolescents feel in everyday life. These real-time reports are more reliable than responses after the event.’

Lonelier with specific OXTR variant

‘Our most important finding was that girls who carried a certain variant of the oxytocin gene in their DNA felt lonelier than girls who did not. Boys with this variant were also adversely affected by negative company at the weekend: their feelings increased the longer they were in such company, while boys without this variant were unaffected. These findings apply to both boys and girls.’ The measured effects are small but still relevant, says Van Roekel. ‘These methods reveal more about actual everyday experiences than methods that ask people once at a later date to describe how they felt.’ Heightened sensitivity to negative company in the case of this specific variant was only visible at weekends. How can that be explained? ‘We surmise that it’s because you have more freedom in the weekend to choose the people you mix with than through the week,’ says Van Roekel. ‘Then it makes a deeper impression if they treat you in a negative manner.’

New trend

No-one knows yet exactly how the receptor gene works. ‘We still don’t know how it translates into, for example, oxytocin levels in the brain,’ says Van Roekel. ‘So more research is needed on that front.’ Research on connections between genes and behaviour is developing gradually. ‘We think that our approach, which takes multiple measurements in the daily life of adolescents, has a lot to offer when it comes to discovering connections.’ Van Roekel conducted her research in the group of Professor Rutger Engels at the Behavioural Science Institute of Radboud University Nijmegen.