Although depression and anxiety affect millions of people worldwide, there’s still much we don’t know about them. In fact, we still don’t fully understand which brain regions are involved in depression and anxiety, and how they differ between people with varying symptoms. Understanding how or why these differences occur is fundamental to developing better treatments.
So far, we know that part of the brain’s frontal lobe, the prefrontal cortex, often shows activity changes in people with depression and anxiety. Parts involved in cognition and regulating emotions are underactive, whereas other parts involved in emotion generation and internal bodily functions are over-active.
One key region shown to be over-active in people with depression and anxiety is the subgenual anterior cingulate cortex (sgACC), thought to be involved in emotional responses. However, neuroimaging studies only show correlation and don’t tell us that the over-activity causes any of the symptoms. But our new research has found over-activating the sgACC induces symptoms of depression and anxiety, highlighting causality.
For our study, we used marmosets (a type of primate) because their brain closely resembles a human’s brain. We found over-activity in this region causes several key features of mood and anxiety disorders, particularly how reactive they are to threat. Their reaction to threat is important, as patients with depression and anxiety tend to perceive and react to situations more negatively.
To over-activate sgACC, we implanted tiny hollow tubes – called cannulae – into the marmosets’ brains. We then infused small amounts of a drug into sgACC to increase excitability without damaging or disrupting function in other brain regions. We also implanted a small wireless device into an artery to measure blood pressure and heart rate.
But before over-activating sgACC, we trained the marmosets to associate a specific tone with the presence of a rubber snake, which marmosets find threatening. After learning this association, the marmosets exhibited fear and had higher blood pressure when hearing the tone. We then presented the tone without the snake to break this association. This allowed us to measure how quickly the marmosets could dampen their fear response with and without sgACC over-activation.