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Neurology Today:
doi: 10.1097/01.NT.0000411149.89241.c7
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Oxytocin Found to Temporarily Improve Social Behaviors in Frontotemporal Dementia

Talan, Jamie

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Oxytocin had already taken an intriguing course out of the labor and delivery room after scientists identified one of its most intriguing roles: social affiliation. It's been tried successfully in autism and now, scientists at the University of Western Ontario have given a single dose of oxytocin to patients with frontotemporal dementia (FTD) — who often become withdrawn, emotionally blunted, and inappropriate — and showed that it can help to temporarily boost social behavior in FTD.

EXAMPLE TRIALS FROM ...
EXAMPLE TRIALS FROM ...
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Elizabeth C. Finger, MD, an assistant professor in the department of clinical neurological sciences, told Neurology Today there is growing evidence from healthy volunteers and people with autism that oxytocin enhances features of relatedness. It is thought to work on the brain regions that govern social cognition.

In a study published in 2011 in Brain, Dr. Finger and her colleagues found that a single dose of oxytocin tested in a double-blind crossover trial in patients with FTD altered performance on a number of neuropsychological tests as well as caregiver rating scales. The hormone positively affected social cognition and behavior.

“It is too early to say that this will be a symptomatic treatment for FTD,” said Dr. Finger. “But it is potentially promising.” The investigators have now launched a study to test different doses of the hormone and to extend the length of time patients are taking the hormone.

Dr. Finger and her colleagues noted that many of the deficits in autism overlap with FTD. Patients have difficulty with facial expression recognition and understanding the mental state of others, a concept called “theory of mind.”

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STUDY PROTOCOLS

The investigators enrolled 20 patients with mild to moderate FTD. The study design enabled them to test the effects of the hormone against a dose of intranasal saline in the same patients two weeks apart. The initial screening visit included an extensive neuropsychological battery, including tests of memory, language, and executive function. They were randomized to receive the hormone or saline at their first testing day and two weeks later they were given the other blinded dose.

The investigators used a 24 IU dose of intranasal oxytocin (three puffs per nostril). At both testing days they were asked to complete a number of tasks to assess their ability to process emotional stimuli. Testing began 20 minutes after administration of either substance. They were also asked to look at faces and listen to voices and rate the type and intensity of the emotion. Their caregivers were also asked to rate the behavior of the patients on the testing days. The scientists then compared the responses of the two sessions to see if oxytocin made a difference.

When patients were taking the oxytocin they showed reduced recognition of angry expressions compared with their placebo dose (p<0.05). There was also a signal that the patients had poorer recognition of fear following the dose of the hormone.

Oxytocin did not seem to improve vocal affect recognition scores. Patients also performed worse on tests designed to tap “theory of mind.”

DR. ADAM BOXER Its a...
DR. ADAM BOXER Its a...
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Dr. Finger said that the administration of the hormone was associated with an average 13 percent improvement from baseline testing on the Neuropsychiatric Inventory compared to 3 percent when they were on saline.

Caregivers filled out the Frontal Behavioral Inventory and reported a 9 percent improvement in behavior following oxytocin compared to a 1.0 percent improvement following the placebo dose.

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WHAT DOES IT MEAN FOR PATIENTS?

“Neuropsychiatric behaviors are improved by oxytocin,” the study authors said. “However, the results of the current study are not sufficient to warrant the use of oxytocin as a treatment for FTD at present.”

Oxytocin is produced in the hypothalamus and sent out through projections to the amygdala, which is damaged in FTD. The thought is that the hormone may boost the signal to damaged neurons. Its effects may aid social cognition but it would not have an impact on the pathology of the disease or its degenerative course.

“Oxytocin may enhance positive cues in the environment and reduce negative ones and lead to reduced threat sensitivity,” Dr. Finger said.

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EXPERTS COMMENT

“It's an exciting proof of concept study,” said Adam Boxer, MD, associate professor of neurology and director of the Frontotemporal and Alzheimer's Diseases Clinical Trials Program at the University of California, San Francisco. “The fact that they found this compound could potentially ameliorate the key features of FTD is encouraging. If oxytocin can restore some social interactions with the family it would be a huge step forward.”

Dr. Boxer said that there are a number of experimental compounds in development for FTD, including substances that target the deposition of the tau protein that accumulates in the brains of some patients with the disease. There are also medicines that target the growth hormone progranulin that seems to accumulate in the brain of FTD patients with a mutation in the gene that makes the hormone. Progranulin plays an important role in inflammation.

FTD offers clues to personality and social connectedness. The disease begins attacking brain regions that are important for different aspects of social functioning. “The hope is to find disease-modifying agents that show the degeneration,” said Dr. Boxer. “We think that ultimately with medicines in hand we can do prevention studies on genetic forms of the disease.”

“This is an interesting line of research,” said Brad Dickerson, MD, associate professor of neurology at Harvard Medical School and director of the FTD unit at Massachusetts General Hospital. “It makes a lot of sense that oxytocin can promote more social behavior. There is a signal there. This disease is in desperate need of a treatment. Even if it ameliorated some of the symptoms it would be very meaningful.”

“If we can give oxytocin chronically would there be a persistent benefit? Further tests are necessary to answer this question,” said Dr. Dickerson. He will be offering a course on understanding social behavior and diagnosing FTD at the AAN annual meeting in April in New Orleans.

Want to hear more about the role of oxytocin in social behavior? Tune in to a podcast interview with study author Elizabeth C. Finger, MD: http://bit.ly/zv6bt5

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REFERENCE:

Jesso S, Morlog D, Finger EC, et al. The effects of oxytocin on social cognition and behaviour in frontotemporal dementia. Brain 2011;134(Pt 9):2493-501. E-pub 2011 Aug 22.

©2012 American Academy of Neurology

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