Anxiety: Hereditary brain chemistry explored

By investigating the brains of hundreds of genetically related monkeys, researchers have identified the brain regions and networks involved in anxiety. They have also shown that changes in connectivity between them are heritable.

Anxiety disorders are a considerable global concern. Affecting almost 1 in 5 adults, they can significantly impact an individual's quality of life.

Characterized by intense feelings of worry, anxiety disorders can also produce physical symptoms, such as an increased heart rate and shaking.

As with many disorders of the mind, little is known about the nuts and bolts — for example, which cells, regions, and pathways are to blame. Because of this, medications tend to attack the symptoms rather than the source of the issue.

A recent study helps pad our understanding of the brain chemistry behind anxiety disorders; it forms another rung in the ladder toward better treatment.

Building on previous findings, researchers from the University of Wisconsin School of Medicine and Public Health in Madison investigated anxiety in a population of almost 400 rhesus monkeys. Using MRI scanning technology, they shine a light on the dimly lit pathways involved in anxiety. Their results were published recently in the journal JNeurosci.

Anxiety networks unraveled

The scientists, led by Dr. Ned Kalin, focused on behavioral inhibition and anxious temperaments that appear at a young age. These traits are of interest because they strongly predict the development of anxiety disorders later in life.

Understanding the basis of these characteristics could offer insight into how and why anxiety disorders develop.

In earlier MRI-based studies, Dr. Kalin and his team pinpointed brain networks that play a part in producing overly anxious behavior. Of particular note is the central extended amygdala, which is part of the brain's reward system; this network encompasses an array of nuclei, all of which connect to the amygdala.

Two of the primary divisions of the central extended amygdala are the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST). Metabolism in these tightly interconnected regions has been correlated with variation in anxious temperament; in other words, the amount of activity in the Ce and BST predicts how anxious a particular person will be.

To investigate further, the researchers first assessed each young primate's natural anxiety level; they did this by exposing them to a human intruder and noting their behavior — more anxious individuals moved around less and made fewer vocalizations. The scientists also measured cortisol levels as a measure of stress.

As expected, monkeys with higher levels of anxiety were found to have increased activity in the Ce and BST.

Heritable connectivity

The animals used in the study came from the same pedigree and were, therefore, all related to different degrees. Because their breeding had been carefully documented, the investigators knew who was related to whom and how closely. This allowed the team to calculate how heritable anxiety is and whether the heritability matches up with changes in brain activity.

They found that the levels of connectivity between the Ce and BST were, indeed, strongly heritable; as the authors explain:

"In the current study, co-heritability analyses demonstrated that Ce-BST functional connectivity and [anxious temperament] are passed down the family tree together [...], supporting the hypothesis that Ce-BST functional connectivity and [anxious temperament] share molecular underpinnings."

These results support the theory that interplay between the Ce and BST are important in trait anxiety; they also add further evidence that anxiety is heritable and point to new avenues of research.

Although no new treatments for anxiety disorders will come directly from these findings, it is a step forward. Because early-life anxiety predicts mental health in later life, understanding how it develops could be an important step toward intervening and preventing it from developing further.