MEDICAL NEWS& PERSPECTIVES

Scientists Probe Oxytocin Therapyfor Social Deficits in Autism, Schizophrenia
INCREASING SALIENCE

Bridget M. Kuehn

In the past several years, scientists havelearned that oxytocin plays an important reinforcing role in social interactions that goes far beyond the previously documented effects of thehormone in female reproduction.
Oxytocin has long been known as a
key factor in bonding between a motherand infant. It also has important physiological effects on pregnant women
during and after delivery. A syntheticversion of oxytocin is widely used to induce or augment labor. Intranasal oxytocin has also been used to promote therelease of breast milk.
Now, basic research on an unusual
animal model has allowed scientists tounderstand the wider physiological effects of oxytocin.
Carter began working with prairie
voles with a field biologist and colleague, Lowell Getz, PhD, at the University of Illinois, in Urbana-Champaign, who was studying them in thewild. Field evidence on the voles suggested they live in lifelong pairs, andCarter brought them into the labora-E

oxytocin plays an important role inhuman social interactions, andpreliminary clinical studies suggest thehormone may help improve social functioning in individuals with autism orschizophrenia. But experts caution thatmuch remains to be learned about oxytocin and its physiological effects before
it is ready for clinical use.
Oxytocin has long been known tohelp facilitate mother and infant bonding. Research on the socially monogamous prairie vole has demonstrated thatthe hormone plays a much wider rolein helping to establish social bonds
among animals. The animal findings
have led to studies in humans to assess how exposure to the hormone affects human interactions, including
early clinical studies in individuals withsocial impairments related to such disorders as autism and schizophrenia.
Still, a host of questions remain about
the hormone’s wider physiological effects on humans, which range from aiding lactation to potentially promoting
healing, noted Sue Carter, PhD, professor of psychiatry and co-director of
the Brain-Body Center at the University of Illinois, in Chicago. In addition, data on the safety and effects ofchronic use of oxytocin are limited because many human studies have involved only a single intranasal dose or
several weeks of administration.
“Oxytocin research is exciting andpromising, but how the information
should be applied is not clear,” Carter
said in an interview. “What we have
now are fragments of knowledge, andwe can’t yet see the full picture.”

Studying the social
interactions of prairie
voles has led
scientists to believethat oxytocin plays animportant role inmediating social
bonds. Preliminary
clinical studies
suggest the hormone
might benefit
individuals withdisorders that involvesocial deficits.

Todd Ahern, PhD/Emory University

MERGING EVIDENCE INDICATES THAT

tory to study the physiology behind thisbehavior, hoping to gain insights thatmight be relevant to human relationships. Other groups also began working with the animals, which became alaboratory model for understanding theendocrinology behind sociality, according to Carter.
The voles are one of the few species
besides humans with a complex family structure, according to Larry J.
Young, PhD, director of the Center forTranslational Social Neuroscience at
Emory University, in Atlanta, who summarized this area of research at the Society for Neuroscience annual meeting in San Diego in November. In aninterview, he explained that whilestrong bonds between mother and offspring are common in many species,
few species form lasting bonds between the mother and father.
“The male and female prairie voles
work as a team [to raise their offspring], as humans do,” Young said.
Carter’s group was able to demonstrate that giving oxytocin to a female
vole promotes bonding with her mate,©2011 American Medical Association. All rights reserved.

(Reprinted) JAMA, February 16, 2011—Vol 305, No. 7

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MEDICAL NEWS & PERSPECTIVESand that blocking the oxytocin receptors in females prevents them fromforming bonds with their mates (CarterCS et al. Prog Brain Res. 2008;170:331336). Such work led some to refer tooxytocin as “the love hormone,” butboth Young and Carter say that is a misnomer because the hormone actually
has a much broader role in social
interaction.
In studies of mice without oxytocin receptors, Young and his teamfound that oxytocin enables mice torecognize one another. The mice
without the receptors could not recognize mice they had previously
met—a state Young called “socialamnesia.” Other work has verified
that oxytocin helps mice to focus onsocial signals.
“We realized that oxytocin isn’t
just a bonding hormone,” he said.
“Oxytocin tunes the brain in to socialcues.”
Human studies have solidified
oxytocin’s role in social interactions(Ross HE and Young LJ. Front Neuroendocrinol. 2009;30[4]:534-547).
Humans exposed to intranasal oxytocin make more eye contact (whichis essential to reading social cues),
feel increased trust in social interactions, and are better able to infer
emotions from other people’s facialexpressions.
“All of this is telling us that oxytocin increases the saliency of social
stimuli,” Young said.
BOOSTING SOCIAL BEHAVIOR

Oxytocin’s role in enhancing social interaction led researchers to wonder
whether it might be a useful therapy for
individuals with disorders that involve social deficits. For example, patients with autism spectrum disorders
often fail to pick up on social cues,
Young noted.
Preliminary evidence suggests thehormone may benefit such patients.
For example, one study comparedsocial behaviors in 13 adult patientswith Asperger syndrome or highfunctioning autism receiving intranasal oxytocin or a placebo with such660

behaviors in 13 matched healthy controls (Andari E et al. Proc Natl Acad Sci
U S A. 2010;107[9]:4389-4394). The
researchers found that while playing agame in which some players are cooperative and others are less so, thepatients treated with oxytocin weremore likely than untreated patients toexhibit preferential treatment toward
helpful players. In another task,
treated patients spent more time gazing at human faces, especially the eyes,
than untreated patients. However, thetreated patients still spent less timelooking at the faces than healthy controls. Another randomized, blinded
controlled trial of 16 male patients
aged 12 to 19 years with an autism
spectrum disorder found that intranasal oxytocin improved patients’ performance on the Reading the Mind in theEyes Task, a test of patients’ ability torecognize emotion in people’s faces(Guastella AJ et al. Biol Psychiatry.
2010;67[7]:692-694).
Eric Hollander, MD, clinical professor of psychiatry at Albert Einstein
College of Medicine and director of
the Compulsive, Impulsive, andAutism Spectrum Disorder Program at
the Montefiore Medical Center, inBronx, NY, reviewed studies of oxytocin in patients with autism spectrum
disorders (Green JJ and Hollander E.
Neurotherapeutics. 2010;7[3]:250257). He noted that studies havefound that oxytocin may also havebeneficial effects on the irritability
and repetitive behaviors seen inpatients with autism. “The findings
are very consistent,” he said in aninterview.
Other studies have suggested thatboth intranasal oxytocin and endogenous oxytocin may improve somesymptoms of schizophrenia. In a studyof 23 women and 27 men with schizophrenia, a team led by Leah H. Rubin,
PhD, a research assistant professor at
the University of Illinois at Chicago,
found that higher levels of endogenous oxytocin were associated withless severe positive symptoms andreduced psychopathology (based on
the Positive and Negative Syndrome

JAMA, February 16, 2011—Vol 305, No. 7 (Reprinted)

Scale [PANSS]) in female patients,
while higher endogenous oxytocinlevels were associated with more desirable social behaviors in both sexes(Rubin LH et al. Schizophr Res. 2010;
124[1-3]:13-21). A recent randomized
controlled crossover trial of oxytocin
as an adjunct to antipsychotic medications in 19 patients with schizophrenia found that, based on PANSS
scores and Clinical Global ImpressionImprovement Scale scores, oxytocin
reduced symptoms compared withplacebo after 3 weeks of treatment
but not at earlier time points (Feifel Det al. Biol Psychiatry. 2010;68[7]:678680).
Despite these promising effects, Hollander cautioned that further study isnecessary. He noted that so far, datafrom trials and clinical use of oxytocin suggest that it is well tolerated, butlarge-scale safety and efficacy studies areneeded for specific indications. Additionally, scientists must develop andvalidate outcome measures that can beused to study the effects of oxytocin onsocial cognition.
“This is new territory because there
are not treatments for things like social cognition,” he said.
But given the promising results sofar, particularly in older patients,
Hollander was optimistic about thetherapeutic potential of oxytocin inpatients with autism spectrum disorders. “It could be used in older individuals to target core symptoms, or inyounger individuals to enhance development. If such treatment improvedsocial interaction, it might have positive effects on the overall trajectory,”he said.
Young, too, was optimistic about
the potential therapeutic benefit ofoxytocin in autism, but he noted it isunlikely to correct symptoms associated with autism other than socialdeficits. Additionally, he suggested
that its use might be most beneficialin specific settings.
“I think it will be most effective when
paired with socially reinforced behavioral therapies,” he said. For example,oxytocin might be administered shortly©2011 American Medical Association. All rights reserved.

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MEDICAL NEWS & PERSPECTIVES

before a therapy session so that a patient receives the benefit of the drug ininterpreting social cues from the therapist, such as eye contact.
Young noted that studies areneeded to determine if direct administration of oxytocin is the best
approach or whether treatments that

increase endogenous oxytocin levels
would be better. He added that
research is also needed to determine
whether chronic administration ofoxytocin might lead to a decrease inoxytocin receptors. Until such issues
are worked out, he cautioned against
the use of oxytocin by individuals

without physician supervision. Some
web sites claim to market oxytocin
for use in boosting trust in relationships. “It’s important for [individuals] to realize it’s not the time forthem to start taking these drugs
without a physician,” he said. “Wedon’t know the safety issues.” 䊐Guideline Cites Appropriateness Criteria
for Performing Tonsillectomy in Children
chair of otolaryngology at the Long Island College Hospital in Brooklyn, NY.
“The big surprise is seeing how many

Mike Mitka

P. Marazzi, MD/www.sciencesource.com

PROMPTED BY A LACK OF CONSENsus on surgical indications andperioperative management fortonsillectomy in children in the UnitedStates, the American Academy of Otolaryngology–Head and Neck Surgery
has issued the first-ever guideline on thetopic.
The clinical practice guideline,
released January 3, provides evidencebased guidance in identifying children who may benefit from tonsillectomy and offers recommendations
intended to optimize the perioperative management of children undergoing the procedure (Baugh RF et al. Otolaryngol Head Neck Surg. 2011;
144[1][suppl]:S1-S30). The document
also provides guidance on how to improve counseling and education of parents of children who may be candidates for tonsillectomy and suggests
ways to reduce inappropriate or unnecessary variations in care.
Tonsillectomy is the third most common surgery in US children younger
than 15 years, with more than 530 000
performed annually, primarily for recurrent throat infections and sleepdisordered breathing. Evidence gathered by the guideline authors suggeststhat tonsillectomy may be overused asa treatment for throat infections and underused for sleep-disordered breathing, said Richard M. Rosenfeld, MD,
MPH, a coauthor of the document andThe first-ever guideline for tonsillectomy inchildren addresses a variety of topics, such as
considering removal of enlarged tonsils whencertain comorbid conditions are present.

kids with frequent throat infections get
better on their own without surgery,showing us how high the bar should be
set to get a worthwhile benefit for tonsillectomy,” Rosenfeld said.
The guideline authors set the bar forconsidering tonsillectomy at at least 7
episodes of documented sore throat in
the preceding year, at least 5 episodes
over each of the proceeding 2 years, orat least 3 episodes in each of the previous 3 years. In addition, either a temperature exceeding 38.3°C, cervicallymphadenopathy, tonsillar exudate, ora positive culture for group A ␤hemolytic streptococcus should be©2011 American Medical Association. All rights reserved.

documented with each episode. For
children who do not meet that standard, “tonsillectomy seems to offer little
benefit over watchful waiting,” Rosenfeld said. And there are possible harms
and adverse events associated with tonsillectomy, including hospitalization,
the risks of anesthesia, prolonged throat
pain, bleeding, and financial costs.
In commenting on the guideline,
Scott R. Schoem, MD, chair of theAmerican Academy of Pediatrics section on otolaryngology–head and necksurgery, said that clinicians who referchildren who do not meet the criteria
to an otolaryngologist for tonsillectomy may be missing opportunities tosuccessfully treat those children. Specialists who see children referred tothem “after just 3 streps in a row will
not do anything except say that if it continues, then tonsillectomy will beconsidered,” explained Schoem, director of pediatric otolaryngology at Connecticut Children’s Medical Center inHartford.
As for sleep-disordered breathing, theguideline states that if the condition coexists with tonsil hypertrophy and there
are comorbid conditions such as growth
retardation, poor school performance,enuresis, and behavioral problems, tonsillectomy may be appropriate. Performing tonsillectomy for sleepdisordered breathing is increasing
because the condition’s prevalence is on
the rise due to its association with obesity—a condition that is also increas-(Reprinted) JAMA, February 16, 2011—Vol 305, No. 7

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