This single brain region links depression, anxiety, and heart disease

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Over-activity in a single brain region called the subgenual anterior cingulate cortex (sgACC) underlies several key symptoms of mood and anxiety disorders, but an antidepressant only successfully treats some of the symptoms.

In a new study, researchers found that sgACC is a crucial region in depression and anxiety, and targeted treatment based on a patient’s symptoms could lead to better outcomes.

They found that increased activity in sgACC—a key part of the emotional brain- could underlie increased negative emotion, reduced pleasure, and a higher risk of heart disease in depressed and anxious people.

More revealing still is the discovery that these symptoms differ in their sensitivity to treatment with an antidepressant, despite being caused by the same change in brain activity.

The research was conducted by a team at the University of Cambridge.

Depression is a debilitating disorder affecting hundreds of millions of people worldwide, but people experience it differently.

Some mainly have symptoms of elevated negative emotions like guilt and anxiety; some have a loss of ability to experience pleasure (called anhedonia); and others a mix of the two.

In the study, the team used marmosets, a type of non-human primate, to study the brain region.

They infused tiny concentrations of an excitatory drug into sgACC to over-activate it.

The researchers found that sgACC over-activity increases heart rate elevates cortisol levels and exaggerates animals’ responsiveness to threat, mirroring the stress-related symptoms of depression and anxiety.

This suggests that over-activity in sgACC promotes the body’s ‘fight-or-flight’ rather than ‘rest-and-digest’ response, by activating the cardiovascular system and elevating threat responses.

The team also found by over-activating sgACC, marmosets stayed fearful for longer as measured by both their behavior and blood pressure, showing that in stressful situations their emotion regulation was disrupted.

Similarly, when the marmosets were confronted with a more uncertain threat in the form of an unfamiliar human, they appeared more anxious following the over-activation of sgACC.

The team found over-activation of sgACC increased activity within the amygdala and hypothalamus, two key parts of the brain’s stress network.

By contrast, it reduced activity in parts of the lateral prefrontal cortex—a region important in regulating emotional responses and shown to be under-active in depression.

The researchers have previously shown that ketamine—which has rapidly acting antidepressant properties—can ameliorate anhedonia-like symptoms.

But they found that it could not improve the elevated anxiety-like responses the marmosets displayed towards the human intruder following sgACC over-activation.

The research shows that the sgACC may sit at the head and the heart of the matter when it comes to symptoms and treatment of depression and anxiety.

One author of the study is Dr. Laith Alexander.

The study is published in the journal Nature Communications.

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