Anxiety and depression affect millions of people worldwide, yet scientists know very little about how associated symptoms affect the brain. Researchers from Cambridge University recently discovered the brain region that links stress-related disorders and cardiovascular disease as well.

The findings were recently published in the journal Nature Communications. In the paper, the team describes an emotional region of the brain known as the subgenual anterior cingulate cortex (sgACC) within the ventromedial prefrontal cortex.

For the lab experiments, the team chose the tiny marmoset due to the similarities in brain regions with humans. The sgACC of the primate brains were given small doses of a drug to over-activate the brain region "without damaging or disrupting function in other brain regions," said the authors. Heart rate and blood pressure were also measured via a small implanted wireless device to an artery.

Stress-Related Disorders and Cardiovascular Problems

Activity in the sgACC affected people with depression and anxiety by increased negative emotions, reduced pleasure known as anhedonia and increased heart disease risk. Despite sharing the same brain region, symptoms also varied in response to drug therapies such as antidepressants.

The sgACC also promotes cortisol production. The stress hormone that triggers the "fight-or-flight" response explained Dr. Laith Alexander, instead of the "rest-and-digest" response over-activating the cardiovascular system. Understanding brain activity associated with enhanced negative emotions would help researchers develop better treatments, noted by the authors.

The over-activation of the sgACC increased the marmoset's response to a threat and showed symptoms of depression and anxiety. Professor Angela Roberts said that the results revealed how threat processing affected a different brain region than reward processing. "This is key because the distinct brain networks might explain the differential sensitivity of threat-related and reward-related symptoms to treatment."

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Anxiety and Threat Processing

To understand more about anxiety and threat processing, the marmosets were trained to associate a sound with a threat in the form of a rubber snake. The monkeys were then observed how they would regulate their response to fear when threatened. When their sgACC was over-activated when faced with an unexpected threat in the form of an unfamiliar person, they had elevated levels of anxiety.

Stress-Related Disorders and Cardiovascular Problems Share the Same Brain Region
(Photo: © Laith Alexander)

Heart rate levels that changed between predicting a reward or punishment and facing an unfamiliar threat were similar to cardiac dysfunction seen in stress-related disorders.

Their previous research has revealed how ketamine can alleviate symptoms of anhedonia due to its antidepressant properties. However, the same drug did not improve anxiety associated with the sgACC.

The results showed evidence of how specific symptoms of depression and anxiety respond to different treatments. Professor Robers said that "anhedonia-like behavior was reversed by ketamine; on the other, anxiety-like behaviors were not."

The sgACC is just one brain region affecting stress-related disorders that have symptoms of anxiety that have been observed to affect other regions of the prefrontal cortex. The scientists shared that further studies are needed to identify the various causes of depression and anxiety and treatments to improve these conditions.

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