Brain molecule may determine antisocial behavior

If you hate meeting new people and have a tendency to avoid eye contact, you can now blame a specific molecule in your brain for your antisocial tendencies.

This same molecule could also play a part in your ability to venture out of your comfort zone and make difficult social move, like moving out of your parents’ home, getting a divorce or changing jobs or apartments, new research at the Weizmann Institute of Science says.

The research, reported this week in Nature Neuroscience, suggests that a molecule involved in regulating stress in the brain may help determine how willing one is to leave the safety of one’s social group and strike up new relationships.

In a study performed in mice, the researchers identified a stress mechanism that appears to act as a “social switch”: It caused mice either to increase interactions with “friends” and “acquaintances” or, in contrast, to reduce such interactions and seek instead to meet strangers. Since a similar stress system operates in the human brain, the findings suggest that a similar mechanism may regulate how humans cope with social challenges.

Disruptions in this mechanism might be responsible for difficulties with social coping in people affected by social anxiety, as well as autism, schizophrenia and other disorders, the researchers said.

“Most social contacts involve a certain level of social stress or anxiety, even when we interact with people we know well — for example, during a holiday meal with extended family,” said Dr. Yair Shemesh, who co-led the study at the Weizmann’s Neurobiology Department. “In fact, from the point of view of evolution, moderate levels of social apprehension are essential for safe and successful social engagement.”

Of mice and men

The scientists used two behavioral setups to study how mice cope with the challenge of interacting with other mice. One was a “social maze,” in which a mouse can choose whether to interact through a mesh with familiar mice or with strangers, or even to avoid interaction at all. The other was a special arena, in which a group of mice was tracked with video cameras and the observations were analyzed with a computer algorithm created for this purpose. This setting allowed the researchers to study the various types of interactions – such as approach, contact, attack or chase – among the mice over several days.

“In social environments, an individual’s interests often clash with the group’s needs and expectations,” said Prof. Alon Chen, who runs the laboratory. “So the individual must maintain what’s known as a socioemotional balance: between the processing of social signals and his or her emotional response to such pressure.”

The results showed that a molecular mechanism involved in stress management in the brain of mice determines their behavior toward other mice. The mechanism involves a small signaling molecule, Urocortin-3, and a receptor on the surface of neurons to which this molecule binds. Both Urocortin-3 and the receptor are part of the corticotropin-releasing factor, or CRF system, which plays a central role in coping with stress, and both are prominently expressed in a brain region called the medial amygdala, known to be associated with social behavior in mice.

Mice that had high levels of Urocortin-3 in the brain actively sought out contacts with new mice behind the net, even ignoring their own group. But when the activity of Urocortin-3 and its receptor were blocked in their brains, the mice chose to socialize mainly within the group, avoiding contacts with the strangers.

“In nature mice live in groups, and the social challenges they face within the group differ from their relationship with intruders. It therefore makes sense for a brain mechanism to produce different types of social coping in these two situations,” said Oren Forkosh, who co-led the study. “In humans, this mechanism might be involved whenever we consider moving out of our parents’ home, getting a divorce or changing jobs or apartments.”