Chronic social isolation has debilitating effects on mental health in mammals–for example, it is often associated with depression and post-traumatic stress disorder in humans. Now, a team of Caltech researchers has discovered that social isolation causes the build-up of a particular chemical in the brain, and that blocking this chemical eliminates the negative effects of isolation. The work has potential applications for treating mental health disorders in humans.
The work, led by postdoctoral scholar Moriel Zelikowsky, was done in the laboratory of David J. Anderson, Seymour Benzer Professor of Biology, Tianqiao and Chrissy Chen Leadership Chair, Howard Hughes Medical Institute Investigator, and director of the Tianqiao and Chrissy Chen Institute for Neuroscience. A paper describing the research appears in the May 17 issue of the journal Cell.
Confirming and extending previous observations, the researchers showed that prolonged social isolation leads to a broad array of behavioral changes in mice. These include increased aggressiveness towards unfamiliar mice, persistent fear, and hypersensitivity to threatening stimuli. For example, when encountering a threatening stimulus, mice that have been socially isolated remain frozen in place long after the threat has passed, whereas normal mice stop freezing soon after the threat is removed. These effects are seen when mice are subjected to two weeks of social isolation, but not to short-term social isolation–24 hours–suggesting that the observed changes in aggression and fear responses require chronic isolation.
“Humans have an analogous Tac2 signaling system, implying possible clinical translations of this work,” says Zelikowsky. “When looking at the treatment of mental health disorders, we traditionally focus on targeting broad neurotransmitter systems like serotonin and dopamine that circulate widely throughout the brain. Manipulating these systems broadly can lead to unwanted side effects. So, being able to precisely and locally modify a neuropeptide like Tac2 is a promising approach to mental health treatments.”