Although scientists have long known that anxiety runs in families, exactly how this risk is passed from one generation to the next has remained somewhat of a mystery. But now, researchers believe they may have found the key to unlocking this mystery.
By studying the behavioral patterns of rhesus monkeys, researchers at the University of Wisconsin-Madison found that elevated levels of activity in particular areas of the brain, which were inherited from generation to generation, may set the stage for the development of anxiety and depression in the future.
The research, published this week in the Proceedings of the National Academy of Sciences, showed that young monkeys, like humans, have what is called an “anxious temperament.” When exposed to a mildly stressful situation, such as being in a room with a stranger, the monkeys stop moving and vocalizing, while their stress hormones skyrocket, said senior author Dr. Ned Kalin, chair of psychiatry at the UW School of Medicine and Public Health.
Using advanced imaging to monitor activity in the monkeys’ brains, Dr. Kalin and colleagues discovered that an overactive circuit connecting three regions of the brain was responsible for the anxious temperament seen in some young monkeys. What’s more, the researchers also found evidence that this overactive circuitry is a heritable trait that had been passed on through multiple generations of monkeys.
“Over-activity of these three brain regions are inherited brain alterations that are directly linked to the later life risk to develop anxiety and depression,” Dr. Kalin said in a press release. “This is a big step in understanding the neural underpinnings of inherited anxiety and begins to give us more selective targets for treatment.”
Genetic factors account for 35 percent of anxiety disorder risk
Anxiety and depression top the list of the most common mental health conditions in the United States. According to the National Institute of Mental Health (NIMH), about 18 percent of U.S. adults — nearly 40 million people — have experienced an anxiety disorder in the past year, and about 7 percent, or 16 million people, have had a major depressive episode. Over the course of a lifetime, an estimated one in four Americans will be affected with one or both of these disorders.
Previous studies have shown that many people who suffer from anxiety disorders have a biological vulnerability to stress, making them more susceptible to environmental stimuli than the rest of the population. According to Dr. Kalin, about half of children with extremely anxious temperaments end up developing a mental disorder later in life. He and his colleagues are trying to figure out the neural basis of this temperament, in hopes of developing early interventions that can nudge kids away from anxiety and depression.
For this latest study, the researchers imaged the brains of 592 young rhesus monkeys using positron emission tomography brain scans (PET), which monitor metabolism in specific mood-related brain areas. During the scanning, the monkeys were placed under mild stress by having an experimenter intrude into their space without making eye contact — an experience similar to what a child would encounter. The researchers also monitored the monkeys’ behavioral responses to the situation.
The results showed that the monkeys that reacted more strongly to the anxiety-producing situation — by freezing up or becoming less communicative — were also more likely to show overactive metabolism in those brain scans, indicating that the circuit was working overtime. Those anxious monkeys often inherited this type of brain function from their ancestors. 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, Dr. 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.
New possibilities for early intervention
The brains of anxious monkeys were characterized by over-activity in the three aforementioned regions, as if the parts of the brain that have evolved to deal with normal threats have gone into overdrive, responding to mild threats as if they were major, the researchers explained. This over-activity may then leave a person vulnerable to developing depression and anxiety later in life.
“Basically, we think that to a certain extent, anxiety can provide an evolutionary advantage because it helps an individual recognize and avoid danger, but when the circuits are over-active, it becomes a problem and can result in anxiety and depressive disorders,” Dr. Kalin said.
However, it’s important to point out that although having an anxious temperament increases the risk of developing more serious mental health disorders down the line, it doesn’t seal our fate. Indeed, given that an estimated 65 percent of the variation in risk of these disorders is not genetic, there is a lot of hope for treatment and intervention.
And with these new findings, there may now be entirely new possibilities for early intervention, patient education, and even preventive efforts targeting high-rick individuals. Patients who know they have a higher risk of developing breast cancer, for example, are more likely to seek regular checkups by their doctor and stay invested in their health. Similarly, if patients knew they were more likely to develop anxiety-related disorders, they too may feel empowered to stay ahead of the disease by seeking counseling or lowering daily stress levels.