Pam Harrison

May 27, 2014

ATLANTA ― A novel vasopressin 1a receptor antagonist, similar to oxytocin, modifies core symptoms of social cognition in high-functioning adults with autism spectrum disorder (ASD) compared with placebo, new research shows.

Investigators at Albert Einstein College of Medicine, New York City, found that affective speech recognition was substantially improved following infusion of the vasopressin 1a receptor antagonist compared with placebo in high-functioning adults with ASD who had good verbal skills.

"We've previously shown improvements in affective speech comprehension following infusions with oxytocin where there seemed to be a long-term effect on the laying down of social memories," lead investigator Eric Hollander, MD, professor of psychiatry and behavioral sciences, told Medscape Medical News.

"And that's what we found with this vasopressin 1a antagonist as well, where we again see these delayed effects, which we think may be related to social memory or social learning," he added.

The study was presented here at the 13th Annual International Meeting for Autism Research (IMFAR).

Lust and Fear

For the study, 19 high-functioning adults with ASD were studied before and after a 2-hour infusion with either the vasopressin 1a antagonist or placebo. Infusions were separated by at least 1 week, and each patient received a 2-hour infusion of both active and control treatments.

At baseline, investigators correlated results of Affective Speech Recognition (ASR), Reading the Mind in the Eyes (RMET), and olfaction measures with measures of functioning on both the Vineland and Autism Diagnostic Observation Schedule as well as IQ.

The ASR assesses individuals' ability to recognize different emotions in spoken language. In this study, patients were exposed to 6 different "neutral" sentences, but each sentence was read in 8 different emotional tones, including anger, fear, and lust. The ability to recognize different emotions was documented before and after each of the 2 infusions.

"It turned out that there was a significant difference between subjects in their ability to recognize 2 emotions in particular," said Dr. Hollander ― lust, which correlates with sexual signaling, and fear, which is associated with social threat signaling.

"These 2 emotions in particular on the ASR scale seemed to differ to a great extent while on the vasopressin 1a receptor medication, and they were relatively large effect sizes of 0.7 and 0.8, so there was a potent difference between the 2 treatments," said Dr. Hollander, who is also director of the Autism and Obsessive Compulsive Spectrum program at the college and at Montefiore Medical Center in New York City.

The investigators also found that blocking the vasopressin 1a receptor with the antagonist had some "mild" antianxiety effects, although treatment was not associated with sedation.

Interestingly, results also showed that the same novel antagonist affected olfaction.

Study participants who had an impaired sense of smell at baseline performed more poorly on the ASR measure, suggesting that olfaction influences social cognitive function in ASD, said Dr. Hollander.

"Across a number of different emotions, including lust and fear, those subjects who had more impaired olfaction [at baseline] had more difficulties with social signaling so that not only did they do more poorly on affective speed recognition, but they did more poorly on some other scales that looked at social cognition, such as Reading the Mind in the Eyes task," he added.

Both oxytocin and vasopressin play a critical role in social cognition and social signaling deficits of ASD, the researchers note.

Different studies have suggested that there are abnormalities in the vasopressin 1a receptor in individuals with ASD.

Animal studies also have related the vasopressin 1a receptor to sociability in different species.

By blocking vasopressin 1a receptors with this specific antagonist, investigators hoped that they could induce even temporary positive changes in social cognition in adults with ASD.

The fact that the antagonist did seem to affect patients' ability to lay down social memory and social learning well beyond the pharmacokinetic effects of the compound is promising, Dr. Hollander suggested.

Indeed, the VANILLA study, a multicenter, ongoing follow-up study, is currently evaluating the ability of an oral formulation of the same vasopressin 1a antagonist to affect potential long-term changes in social cognition in adults with ASD.

"Enormously" Exciting

Asked to comment on the study, Robert Ring, PhD, chief science officer, Autism Speaks, New York City, told Medscape Medical News that he felt that findings from this study are "enormously exciting" and represent one of the "surprisingly underreported highlights" from IMFAR this year.

"Vasopressin and oxytocin are the product of the same primordial gene, are very similar to one another in structure, and even share the same family of receptors in the brain," he observed.

Although the hormonal effects in the periphery of these neuropeptides are profoundly different, "in the brain, they act on very similar neural systems to influence many of the same brain functions, especially social behavior."

Importantly, each neuropeptide's effects on brain function are often the opposite of one another, as Dr. Ring pointed out, meaning that vasopressin 1a antagonists probably work in ways similar to oxytocin receptor agonists in terms of their effects on social behavior.

"Individuals with autism may or may not want treatments that change the effects of autism on social behavior, and this is fine," Dr. Ring said. "But we believe that the community as a whole should have options, and this trial and this molecule are potentially bringing families closer to having those choices."

Nevertheless, Dr. Ring cautioned that no medication developed to address core symptoms of ASD are going to work in isolation and that they must be used within the context of a child's development and alongside of behavioral interventions, training, and education.

The study was funded by Roche. Dr. Hollander reports that he has served on the scientific advisory board at Roche. Dr. Ring reports no relevant financial relationships.

13th Annual International Meeting for Autism Research (IMFAR). Abstract 176.111. Presented May 17, 2014.


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