The brain function that underlies anxiety and depression is inherited, a new study finds — but there is still plenty of space for experience and environment to reduce the risk of a full-blown mental disorder.



The research focused on rhesus monkeys. Like humans, some young rhesus monkeys have what's called an "anxious temperament." Expose them to a mildly stressful situation, like being in a room with a stranger, and the monkeys will stop moving and stop vocalizing while their stress hormones skyrocket. Extremely shy children do the same, said Dr. Ned Kalin, a psychiatrist at the University of Wisconsin–Madison.



Kalin and his colleagues scanned the brains of young monkeys, anxious and not, and found three brain regions associated with anxiety that also showed evidence of heritability. About 30 percent of the variation in early anxiety is explained by family history, the researchers reported Monday (July 6) in the journal Proceedings of the National Academy of Sciences.



Early temperament



Anxiety and depression are widespread disorders. According to the National Institute of Mental Health (NIMH), about 18 percent of U.S. adults have experienced an anxiety disorder in the past year, and about 7 percent have had a major depressive episode. The average age of onset for anxiety disorders is 11. [7 Thoughts That Are Bad for You]



Kids with extremely anxious temperaments are at a 50 percent risk of developing a mental disorder later in life, Kalin told Live Science. He and his colleagues are trying to figure out the brain basis of this temperament, in hopes of developing early interventions that can nudge kids away from anxiety and depression.



The researchers used PET scanning to image the brains of 592 young rhesus monkeys at the Wisconsin National Primate Research Center. These monkeys are raised in pairs at the center and vary in their levels of anxiety, Kalin said.



During the scanning, a stranger entered the room and did not make eye contact with the monkey. This is a mildly stressful scenario for the monkeys, enabling the researchers to watch what happens in the animals' brains during an anxiety-inducing encounter.



(Animal rights activists and others have criticized and even tried to stop Kalin's work with rhesus monkeys, though at least one petition against his research has erroneously suggested that Kalin subjected the monkeys to extreme stress and solitary confinement, according to the University of Wisconsin–Madison's response to the petition.)



Anxious brains



Because the researchers know exactly how all the monkeys in their colony are related, they were able to trace the inheritance of anxious behaviors through the family tree. They found that 35 percent of the variation in anxiety could be explained by the genes passed down by mom and dad.



But the researchers took this finding one step further. They looked at specific brain regions that activated during stressful situations, and then matched those up with brain regions whose structure and function were inherited in the same pattern as the anxiety. They found that structure did not seem to affect an anxious temperament. But the function of three brain regions was both heritable and involved in anxiety.



The first, the orbitofrontal cortex, sits behind the forehead and is the most evolutionarily advanced part of the brain, Kalin said. The next was the amygdala, an almond-shaped region deep in the middle of the brain that is involved in fear and emotion. The third was the limbic system, which sits at the very base of the brainstem and is a part of even the most primitive reptile brains.



"What we find is more activity" in the anxious brains, Kalin said. It's as if the parts of the brain that have evolved to deal with normal threats have gone supercritical, responding to mild threats as if they were major, he explained. [The 10 Most Controversial Psychiatric Disorders]



"We believe that our study shows that the overactivity of that system is inherited from our parents," Kalin said. This overactivity may then leave a person vulnerable to developing depression and anxiety later. But given that nearly 70 percent of the variation in risk of these disorders is not genetic, there is a lot of hope for treatment and intervention, Kalin said.



"This now focuses us on very early childhood, to be thinking about alterations in brain function in children and ideally to be developing ideas that are new about what we can do to help kids that have this brain overactivity," Kalin said.



The next step is to continue using rhesus monkeys to understand the brain systems and molecular interactions that lead to hyperactive fear regions, he said. The researchers are also following young children over a period of years, scanning their brains to determine what makes the difference between the half of anxious-temperament children who develop a mental disorder and the half who don't. A separate line of research has already found that a secure attachment to a caregiver helps prevent later mental disorders for extremely shy kids.



"These are very serious illnesses that are common and affect lots and lots of the population," Kalin said. "We need to understand better what causes them, what the genetic underpinnings are and come up with new treatments to reduce suffering and hopefully do this early in life."



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