Researchers have discovered an inherited brain pathway that increases the risk of anxiety in monkeys, and if the research translates to humans, it could have huge implications for treating overwhelming anxiety.
While it's true that anxiety disorders are one of the most pervasive and debilitating mental disorders that we know of – affecting millions of people worldwide – that doesn't mean we fully understand them.
Scientists know that anxiety disorders can be brought about by both environmental and genetic factors, but when it comes to heritability, we still don't know much about how they are handed down from generation to generation.
Now, an intriguing new animal study offers a little more insight into how anxiety develops, how it changes the brain, and how it is transmitted from parents to children.
"When we began this research, we knew so little about the brain regions involved, especially in primate species," said one of the researchers, psychiatrist Jonathan Oler from the University of Wisconsin.
"This study speaks to how important it is to study animals that are related to humans as they allow us to learn about the causes of human anxiety and by so doing we can potentially develop better treatment and hopefully prevention strategies."
Using functional magnetic resonance imaging (fMRI), the study examined the brains of hundreds of related pre-adolescent rhesus macaques with various levels of anxious temperaments.
The focus was specifically on extreme anxiety temperaments (AT) because these are a significant risk factor for anxiety disorders and depression in human children. The idea was to create a non-human primate model of AT, which is thought to be about 30 percent heritable among rhesus monkeys.
Examining the results, the researchers found neural connections between two regions of the amygdala - the brain's fear centre - that are related to anxiety in pre-adolescent rhesus macaques. The continuum of neurons was found to be heritable and extends between the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the extended amygdala.
The findings are further supported by a previous study from the same authors that demonstrated metabolic changes associated with anxiety in the same circuitry using positron emission tomography (PET).
There are plenty of known limitations when using PET and fMRI to study neurobiology, but taken together, the two studies suggest that the same genes underlying the connectivity of the new-found circuit also underlie AT.
"The way we measure this alteration in monkeys is very similar to the method that we use to measure this circuit in our studies of anxiety in human children, so this research is highly translational," said senior author and biological psychiatrist, Ned Kalin.
"Looking first at the monkeys has provided us with clues about which systems to focus on in our studies of at risk young children."
This isn't to say that this particular circuit is fully responsible for AT. Like anxiety disorders, AT and other related constructs are a combination of heritable and environmental factors. But that doesn't mean the new findings are trivial, either.
Extreme early-life anxiety is one of the biggest risk factors for anxiety disorders and depression, yet most current treatments address symptoms rather than the underlying problem. The more researchers learn about the pathophysiology of anxiety disorders, the more likely it is that future treatments can stop the disorder from developing.
"In data from a species closely related to humans, these findings strongly point to alterations in human brain function that contribute to the level of an individual's anxiety," said Kalin.
"Most importantly these findings are highly relevant to children with pathological anxiety and hold the promise to guide the development of new treatment approaches."
The authors of the new study hope that their findings will assist future research on anxiety disorders in at-risk children.
"We are continuing to discover the brain circuits that underlie human anxiety, especially the alterations in circuit function that underlie the early childhood risk to develop anxiety and depressive disorders," said Kalin.
The study was published in the Journal of Neuroscience.