The researchers used brain imaging to examine other brain regions affected by sgACC overactivity during the threat. Overactivation of sgACC increased activity in the amygdala and hypothalamus, two important parts of the brain’s stress network. In contrast, it reduced activity in parts of the lateral prefrontal cortex – a region that is important in regulating emotional responses and has been shown to be underactive in depression. “The regions of the brain that we identified as affected during threat processing were different from those that were affected during reward processing.” said Professor Angela Roberts of the Department of Physiology, Development and Neuroscience at Cambridge University, who led the study. “This is key as the different brain networks could explain the different sensitivity of threat and reward-related symptoms to treatment.” Photo credit: Laith Alexander
Overactivity in a single region of the brain called the subgenual anterior cingulated cortex (sgACC) underlies several key symptoms of mood and anxiety disorders, but an antidepressant is effective in treating only some of the symptoms. A new study published today in the journal Nature Communications suggests that sgACC is a critical region for depression and anxiety, and targeted treatment based on a patient’s symptoms could lead to better outcomes.
Depression is a debilitating disorder that affects hundreds of millions of people worldwide, but is experienced differently. Some mainly have symptoms of increased negative emotions such as guilt and anxiety; Some have a loss of the ability to experience pleasure (called anhedonia). and others a mixture of both.
Research at the University of Cambridge found that increased activity in sgACC – a key element of the emotional brain – may be underlying increased negative emotion, decreased pleasure, and a higher risk of heart disease in depressed and anxious people. Even more telling is the discovery that these symptoms differ in their sensitivity to antidepressant treatment, even though they are caused by the same change in brain activity.
Using marmosets, a type of non-human primate, the research team infused sgACC with tiny concentrations of an excitatory drug to overactivate it. Marmosets are used because their brains have important similarities to humans and it is possible to manipulate regions of the brain to understand causal effects.
The researchers found that overactivity of sgACC increased heart rate, increased cortisol levels, and transmitted the animals’ response to threats, reflecting the stress-related symptoms of depression and anxiety.
“We found that overactivity in sgACC promotes the body’s ‘fight or flight’ response rather than the ‘resting and digestive response’ by activating the cardiovascular system and increasing threat responses,” said Dr. Laith Alexander, one of the first study authors from the Institute of Physiology, Development and Neuroscience at Cambridge University.
“This builds on our previous work showing that overactivity also decreases anticipation and motivation for rewards, reflecting the loss of the ability to experience the pleasure seen in depression.”
To study threat and anxiety processing, researchers trained marmosets to associate a sound with the presence of a rubber snake, an immediate threat that marmosets find naturally stressful. Once marmosets found out about this, the researchers erased the association by presenting the sound without the snake. They wanted to measure how quickly the marmosets can dampen and regulate their fear response.
“Because of the overactivation of sgACC, marmosets remained anxious for longer, measured by their behavior and blood pressure, which shows that their emotion regulation was disturbed in stressful situations,” said Alexander.
Similarly, when confronted with a more uncertain threat in the form of an unknown human, the marmosets appeared more anxious after overactivating sgACC.
“The marmosets were much more cautious about an unknown person after overactivating this key brain region – they kept their distance and displayed alert behavior,” said Dr. Christian Wood, a lead study author and senior postdoctoral fellow in the Cambridge Physiology, Development and Neuroscience Department.
The researchers used brain imaging to examine other brain regions affected by sgACC overactivity during the threat. Overactivation of sgACC increased activity in the amygdala and hypothalamus, two important parts of the brain’s stress network. In contrast, it reduced activity in parts of the lateral prefrontal cortex – a region that is important in regulating emotional responses and has been shown to be underactive in depression.
“The regions of the brain that we found to be affected during threat processing are different from those we showed earlier and are affected during reward processing,” said Professor Angela Roberts of the Institute of Physiology, Development and Neuroscience Cambridge University who directed the study.
“This is key as the different brain networks could explain the different sensitivity of threat and reward-related symptoms to treatment.”
The researchers previously showed that ketamine – which has fast-acting antidepressant properties – can relieve anhedonia-like symptoms. However, they found that it failed to improve the increased fear-like responses the marmosets showed to the human intruder after overactivating sgACC.
‘We have clear evidence of the different sensitivity of different clusters of symptoms to treatment – on the one hand, the anhedonia-like behavior was reversed by ketamine, on the other hand, the fear-like behavior was not, “explained Professor Roberts.
“Our research shows that the sgACC can be at the forefront and focus in relation to symptoms and treatment of depression and anxiety.”
The Marmoset Study provides insights into the loss of pleasure in depression
Nature communication (2020). DOI: 10.1038 / s41467-020-19167-0 Provided by the University of Cambridge
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