Is oxytocin a means for restoring social behaviour in FTD?

Oxytocin, a brain peptide, promotes positive social behaviour in humans and other mammals. It promotes maternal behaviours, and its administration facilitates responsiveness to social cues and co-operative behavior in healthy adults and individuals suffering autism – a developmental disorder featuring handicaps in socialization and communication. It is plausible oxytocin will improve social behaviour in FTD, where abnormalities of conduct, temperament and communication are central features and cause handicap and suffering.

Distribution of oxytocin

The brain cells that produce oxytocin reside in nuclei (collections of brain cells) located in the posterior aspect of the hypothalamus, a brain structure that controls bodily states such as hunger, thirst, sleep and body temperature. Oxytocin is transferred to the pituitary gland (another region regulating metabolism), and then to the blood stream for circulation. It is also delivered to the brain regions in the frontal and temporal lobes involved in modulating emotions, processing and interpreting social cues, responding to incentives and rewards, and managing voluntary behaviour.

Developing oxytocin as a treatment for FTD

Since oxytocin has prosocial effects in healthy adults, and in those suffering autism, it may help those suffering FTD. A few years ago, a group of investigators in Canada conducted a ‘proof of concept’ study of this idea in a clinical trial. The results were mixed: improvements in emotional reasoning were seen 8 hours after the single dose, but disappeared within a week. The trial had used a single intranasal dose of oxytocin, as there was little safety information to go on and few formulations to work with.
The same group, working with new collaborators in the United States, recently completed a follow-on study to clarify the safety and adverse effects of different doses of intranasal oxytocin. Four doses were tested (placebo, 24, 48, and 72 IU), each administered in both nostrils twice daily for a week. The trial utilized a randomized and blinded design and enrolled 23 patients suffering behavioral variant FTD or semantic dementia. Firstly oxytocin was well tolerated in most respects, but a third of those receiving the drug developed unexpected sexual behaviours of mild severity. Secondly, some subjects seemed to gain relief from apathy and insensitivity – although these effects did not reach the significance threshold when treatment groups were compared to the placebo group.

Summary

Treatment development is a high priority for the FTD community. We pursue three varieties of treatment – curative, for halting neurodegeneration, ameliorative, for reducing dysfunction and suffering, and rehabilitative, for promoting function and adaptation. Oxytocin, uniquely among pharmacological agents, promises ameliorative and rehabilitative effects. Several years ago a small trial suggested clinical value. A new study now provides the data to guide dosing, as well as assurance that repeated administration is safe and feasible. The stage is now set, at last, for the large-scale trial that we hope will provide definitive measurements of its effects in FTD.

References

Jesso S, Morlog D, Ross S, Pell MD, Pasternak SH, Mitchell DGV, Kertesz A. Finger EC. The effects of oxytocin on social cognition and behaviour in frontotemporal dementia. Brain 2011, 134:2493–2501.

Onyike C. F1000Prime Recommendation of Evaluation Jesso S et al., Brain 2011, 134(Pt 9):2493-501. In F1000Prime, 18 Nov 2011: F1000Prime.com/13370989#eval14741095

Finger EC, McKinley J, Blair M, Oliver LD, Jesso S, Tartaglia MC, Borrie M, Wells J, Dziobek I, Pasternak S, Mitchell DGV, Rankin K, Kertesz A, Boxer A. Oxytocin for frontotemporal dementia: a randomized dose-finding study of safety and tolerability. Neurology 2015, 84:174–181.

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