Anxiety in monkeys is linked to hereditary brain traits

Anxiety can run in families. Key differences in how an anxious monkey’s brain operates can be passed along too, a large study suggests.

By finding a pattern of brain activity linked to anxiety, and by tracing it through generations of monkeys, the results bring researchers closer to understanding the brain characteristics involved in severe anxiety — and how these characteristics can be inherited.

“We can trace how anxiety falls through the family tree,” which parents pass it on to which children, how cousins are affected and so on, says study coauthor Ned Kalin of the University of Wisconsin School of Medicine and Public Health in Madison. The newly identified brain activity pattern takes the same path through the family tree as the anxious behavior, Kalin and colleagues report July 30 in the Journal of Neuroscience.

Kalin and colleagues studied rhesus monkeys that, as youngsters, displayed an anxious temperament. Human children with this trait are often painfully shy, and are at much higher risk of going on to develop anxiety and depression than other children, studies have shown.

Monkeys can behave similarly. Researchers measured anxious temperament by subjecting young monkeys to a stressful situation: An intruder entered their cage and showed only his or her profile to the monkey. “The monkey isn’t sure what is going to happen, because it can’t see the individual’s eyes,” Kalin says. Faced with this potential threat, monkeys freeze and fall silent. By measuring the degree of this response, as well as levels of the stress hormone cortisol, the researchers figured out which monkeys had anxious temperaments.

In addition to collecting these behavioral measures for 378 young monkeys from 2007 to 2011, the researchers subjected the monkeys to brain scans under anesthesia. Monkeys with outsized stress responses to the intruder showed a crucial difference in the extended amygdala — a brain structure and its surroundings known to be heavily involved in fear and threat detection.

Two parts in particular — the central nucleus and the bed nucleus of the stria terminalis — behaved in lockstep. When the activity of one was high, for instance, so was the activity of the other, functional magnetic resonance imaging scans showed. This tight link in activity between those two parts of the brain was also passed down from parents to offspring, along with anxious temperament, family trees revealed.

The study wasn’t designed to show whether the differences in brain behavior actually caused the anxious behavior in the monkeys. To do that, researchers will need to alter the activity of the amygdala and its surrounding parts and see whether changes in anxious behavior result.

Still, the results are “very relevant to the human condition,” says psychiatrist and chief scientific officer Kerry Ressler at McLean Hospital in Belmont, Mass. These same brain structures are also thought to be heavily involved in human anxiety.

This study and others like it are revealing details of how the brain operates to create certain psychiatric disorders — information necessary for designing targeted treatments, Ressler says. Even so, there’s much more work to be done before the results can help people with anxiety. Understanding brain areas involved in anxiety, “while critical, is still many steps away from knowing the best way to intervene,” Ressler cautions.  

Kalin and colleagues are performing similar studies on children, though the researchers won’t be able to collect the same sort of data on multiple generations.