An imbalance in blood levels of oxytocin may be associated with certain forms of autism spectrum disorders (ASDs). "I think that this is an important area for future development to understand the underlying root cause of ASDs and develop treatments to help manage symptoms," said Eric Hollander, MD, chair of psychiatry and director of the Seaver and New York Autism Center of Excellence at Mount Sinai School of Medicine.
The oxytocin receptor mediated by certain single nucleotide polymorphisms (SNPs) may be a culprit, according to C. Sue Carter, PhD, professor in the Department of Psychiatry and codirector of the Brain-Body Center at the University of Illinois, Chicago. Use of pitocin to induce labor is also coming under scrutiny.
Carter1 was a coauthor of a study that confirmed a link between the oxytocin receptor and ASDs in white persons in relation to the SNP rs2254298. Her research was conducted in response to a study of members of the Chinese Han population2 that showed an association between ASDs and certain SNPs, including rs2254298.
The results of Carter and colleagues' study were similar to those of the study by the Chinese research team, although only SNP rs2254298 was implicated and the G allele—rather than the A allele—was found to be overexpressed in probands of the study participants with ASDs. In speaking with Applied Neurology, Carter also cited research linking low levels of oxytocin to ASDs.3,4
Other recent studies led by Hollander showed that oxytocin therapy using intravenous pitocin significantly reduced repetitive behaviors and improved speech comprehension in patients with ASDs for up to 2 weeks.5,6 The group is now studying treatment with an intranasal form of pitocin in high-functioning adults with ASDs. "We're seeing that oxytocin delivered through the nose twice a day over a 6-week period has resulted in a reduction of self stimulatory behaviors and an improvement in social cognition," said Hollander.
"Patterns of oxytocin, even in blood of nonautistic persons, are not well described. We don't understand the developmental effects of oxytocin very well, and it is possible that the most important effects of oxytocin on ASDs occur in the prenatal or early postnatal period," Carter commented.
Hollander and colleagues7 have hypothesized that excess oxytocin—perhaps associated with the use of pitocin during birthing—might be a potential cause of ASDs. "In some individuals whose oxytocin system could be genetically vulnerable, a strong environmental early hit while the brain is still developing could down-regulate the oxytocin system, leading to developmental problems. But this is only a hypothesis that has been observed by association," Hollander said.
Empirical work on the relationship between the use of pitocin and ASDs is too scarce to draw conclusions, said Carter. Furthermore, research in this area is challenged, because pitocin is given very frequently during birthing, making it increasingly difficult to find groups that have not been exposed to it.
"I think it is often assumed that pitocin does not reach the infant in amounts that would directly affect the baby. Increasing amounts of pitocin are being given in some hospitals, though. In our most recent research in animals, a little extra oxytocin given directly to newborns facilitated certain forms of social behavior, but larger amounts were disruptive," said Carter.
1. Jacob S, Brune CW, Carter CS, et al. Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett. 2007;417:6-9.
2. Wu S, Jia M, Ruan Y, et al. Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biol Psychiatry. 2005;58: 74-77.
3. Modahl C, Green L, Fein D, et al. Plasma oxytocin levels in autistic children. Biol Psychiatry. 1998;43:270-277.
4. Green L, Fein D, Modahl C, et al. Oxytocin and autistic disorder: alterations in peptide forms. Biol Psychiatry. 2001;50:609-613.
5. Hollander E, Bartz J, Chaplin W, et al. Oxytocin increases retention of social cognition in autism. Biol Psychiatry. 2007;61:498-503.
6. Hollander E, Novotny S, Hanratty M, et al. Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger's disorders. Neuropsychopharmacology. 2003;28:193-198.
7. Hollander E, Cartwright C, Wong CM, et al. A dimensional approach to the autism spectrum. CNS Spectrums 1998;3:22-39.