Scientists have long believed that a disposition toward anxiety can be genetic and passed on through generations. Now, by conducting PET scans on our evolutionary cousin the rhesus monkey, researchers have determined that an overactive brain circuit involving three particular brain areas may set the stage for anxiety and depressive disorders.

According to research out of the Department of Psychiatry and the Health Emotions Research Institute at the University of Wisconsin-Madison, elevated activity in the prefrontal-limbic-midbrain circuit may be involved in mediating the risk of extreme anxiety in early childhood.

"Overactivity of these three brain regions are inherited brain alterations that are directly linked to the later-life risk to develop anxiety and depression," said Dr. Ned Kalin, senior author, and chair of psychiatry at the UW School of Medicine and Public Health, in a statement.
By studying nearly 600 young rhesus monkeys from a large multi-generational family, the research team determined that about 35 percent of variation in anxiety-like tendencies is explained by family history.

"This is a big step in understanding the neural underpinnings of inherited anxiety and begins to give us more selective targets for treatment," said Kalin.

Using PET/CT the researchers measured brain activity when the monkeys were subjected to what the authors called "a mildly threatening situation that a child would also encounter" a stranger who does not make eye contact. If metabolism increased, it was indicative of increased anxiety.

The three regions affected were located in the brain stem, the most primitive part of the brain; the amygdala, the limbic brain fear center; and the prefrontal cortex, which is responsible for higher level reasoning and is fully developed only in humans and their primate cousins.

"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 overactive, it becomes a problem and can result in anxiety and depressive disorders," said Kalin.

The researchers noted that the size of the brain structures was not responsible for the genetic transfer of anxious temperament, just the functions.

"Now that we know where to look, we can develop a better understanding of the molecular alterations that give rise to anxiety-related brain function," said Kalin.

The research is being published in this week's Proceedings of the National Academy of Sciences.

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