Brain researchers uncover how social isolation alters social behavior

South Korean researchers have identified the mechanism by which short-term social isolation alters social decision-making.

The Korea Brain Research Institute (KBRI) announced Sunday that a joint research team led by Kim Jeong-yeon of its Emotional and Cognitive Disease Research Group and Chae Se-hyeon, a professor at Gangwon National University, found that just one day of social isolation is enough to increase the expression of a specific serotonin receptor in the brain. That change shifts how the brain assigns value to social targets, causing isolated individuals to prefer familiar companions over new ones.

Loneliness and social isolation are well-established risk factors for a range of mental illnesses, including depression and anxiety disorders. How brief periods of isolation affect social decision-making, and the brain mechanisms behind such changes, had not been fully understood.

The research team set out to examine how short-term social isolation affects social preference and to determine the role of the lateral habenula (LHb), a structure located in the epithalamus, in that process.

The team isolated mice individually for 24 hours, then exposed them simultaneously to a familiar companion and a new one. While mice normally show greater interest in unfamiliar individuals, the socially isolated mice did the opposite, approaching the familiar companion more frequently. The researchers said this suggests that social isolation does not simply alter sociability in general, but changes the very criteria by which the brain evaluates social targets.

Analysis of the isolated mice's brains revealed that expression of the 5-HT4 receptor (5-HT4R), a type of serotonin receptor, in the lateral habenula had increased by more than 2.5 times compared with non-isolated mice. Serotonin is a neurotransmitter known to play a key role in regulating emotion and mood.

The team also found that serotonin signaling to the lateral habenula decreased during social isolation, and that the elevated 5-HT4R expression represented an adaptive response by the brain to compensate for the reduced serotonin input.

When the researchers administered a drug that activates the 5-HT4 receptor, synaptic plasticity — the ability of neurons to regulate their connections — impaired by social isolation was restored, and abnormally elevated neuronal excitability returned to normal levels.

The study suggests that the lateral habenula could serve as a new therapeutic target for mental illnesses accompanied by impaired social functioning, including depression, social anxiety disorder, autism spectrum disorder and schizophrenia. "Even a brief period of isolation can change the way a person perceives their social relationships," Kim said. "We hope this research provides new insights into understanding and treating mental health problems caused by loneliness and social isolation."

The findings were published in the international journal Cell Reports.