Oxytocin and Social Cataplexy

In this episode of Talking Sleep, host Dr. Seema Khosla welcomes Dr. Carrie Mahoney, a neuroscientist and faculty member in the Department of Neurology at Harvard Medical School and Beth Israel Deaconess Medical Center, to discuss her groundbreaking research on how oxytocin may regulate social cataplexy in narcolepsy.

With FDA approval of new narcolepsy medications, understanding the neural mechanisms underlying cataplexy has never been more clinically relevant. Dr. Mahoney's research began with a simple but profound clinical observation: cataplexy attacks occurred reliably when patients laughed with close friends and family members, but rarely when joking with coworkers or strangers. This pattern of emotion-triggered muscle weakness in social contexts prompted investigation into whether oxytocin—the hormone associated with bonding and social connection—might play a role.

Dr. Mahoney explains social cataplexy and discusses whether most cataplexy episodes occur in social contexts. She traces how she came to hypothesize oxytocin's involvement, moving from clinical observation to basic science investigation. The research explores how the amygdala—typically associated with fear—also processes other emotional responses including the joy and bonding feelings that characterize close relationships.

The episode walks through her research methodology. Using orexin knock-out mice (which model narcolepsy), Dr. Mahoney observed increased cataplexy during social interactions. She then systematically investigated oxytocin signaling in the amygdala to understand the mechanism. She employed advanced neuroscience techniques including chemogenetics and optogenetics—tools that allow precise manipulation and observation of specific neural circuits. The conversation clarifies what these approaches reveal about oxytocin's role in triggering muscle atonia during emotional social situations.

A crucial ethical question emerges: If oxytocin facilitates social bonding but also triggers cataplexy, would blocking oxytocin eliminate this important neurochemical? Dr. Mahoney addresses whether targeted intervention might be possible without sacrificing the neurochemical foundation of human connection and social behavior.

The research faced significant setbacks during COVID-19, affecting experimental timelines and animal studies. Dr. Mahoney discusses how she navigated these disruptions and the collaborative nature of validating complex neuroscience findings. She co-published this work wit