It is well established that chronic stress can lead to anxiety and depression. Now, researchers from Rockefeller University in New York, NY, have shed light on the structural brain changes stress causes to produce this outcome. Furthermore, there may be a way to prevent it.

[A stressed woman]Share on Pinterest
Researchers found chronic stress leads to brain changes in the amygdala brain region.

According to a 2015 survey from the American Psychological Association (APA), around 75 percent of Americans report experiencing at least one symptom of stress in the past month, such as irritability, anxiety, fatigue, and depression.

Previous studies have shown that stress can cause alterations to the hippocampus (resource no longer available at www.nature.com) – the part of the brain responsible for memory and emotion – which may trigger anxiety and depression.

However, the team involved in this latest research notes that few studies have investigated how stress affects the amygdala – a brain region involved in fear and anxiety.

Lead author Carla Nasca and colleagues decided to further investigate this association, focusing on how chronic stress affects the amygdala of mice.

They recently published their findings in the journal Molecular Psychiatry.

To induce prolonged stress in mice, the researchers periodically confined the rodents to a small space for 21 days.

At the end of the confinement period, the team analyzed the behavior of the mice. Specifically, they looked at whether the mice started to display behaviors related to anxiety and depression, such as avoiding social interaction.

Additionally, the researchers assessed the rodents’ nerve cells, or neurons, in certain areas of the amygdala, including the medial and basolateral regions.

While neuronal branches in the basolateral region lengthened and became more complex in response to prolonged stress – a positive sign, indicating flexibility and adaptation – nerve cells in the medial region did the opposite.

The team found that the branches of nerve cells in the medial region – which are important for communication between other areas of the brain – shrank in response to prolonged stress (resource no longer available at www.nature.com).

According to the researchers, this can be damaging to the brain, reducing its ability to accommodate new experiences, which can trigger anxiety and depression.

“Chronic stress is linked to a number of psychiatric conditions, and this research may offer some new insights on their pathology.

It seems possible that the contrasting responses we see within the amygdala, and the limbic system in general, may contribute to these disorders’ differing symptoms, which can range from avoiding social contact to experiencing vivid flashbacks.”

Bruce S. McEwen, study co-author

But it is not all bad news; the researchers also found that it might be possible to prevent this process.

The researchers repeated the 21-day stress-inducing experiment in another group of mice.

This time, they treated some of the mice with acetyl-l-carnitine 3 days before the end of the experiment.

Fast facts about stress
  • Money worries are a leading cause of stress among Americans
  • Stress plays a role in around 60 percent of human disease and illness
  • Stress may increase the risk of heart disease by around 40 percent.

Learn more about stress

Acetyl-l-carnitine is a molecule naturally produced by both humans and mice. Studies have shown that animals susceptible to depression are more likely to be deficient in acetyl-l-carnitine, and it is currently being tested as an antidepressant.

Compared with untreated mice, the team found those that received acetyl-l-carnitine demonstrated greater neuronal branching in the medial region of the amygdala.

What is more, the treated mice were more sociable at the end of the experiment than the untreated mice.

Based on their results, the researchers suggest acetyl-l-carnitine might have the ability to prevent some harmful brain changes that occur in response to stress.

The researchers note that their study also included mice that were more prone to stress-induced anxiety and depression – just as some people are more vulnerable to these conditions in response to stress.

These mice also benefited from treatment with acetyl-l-carnitine, suggesting the molecule may prevent stress-induced brain changes in humans who are at greater risk of anxiety and depression.

Next, the team plans to investigate whether humans with depression have lower levels of acetyl-l-carnitine than those without the condition.

Learn how mood and stress reduce lifespan.