Understanding how or why these differences occur is fundamental to developing better treatments.
Treatment response
Source 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 sgACCthought to be involved in emotional responses.
But our new research has found over-activating the sgACC induces symptoms of depression and anxiety, highlighting causality. 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.
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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 Depression And Anxiety And Depression 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.
Heart disease and depression
Without over-activation, marmosets gradually regulated their threat response within minutes when hearing the tone without the snake. But after over-activating sgACC, marmosets exhibited fearful behaviour and higher blood pressure for much longer. They also remained anxious around other types of threat in the form of an unfamiliar human. This reaction showed they could no longer dampen down their threat responses. Being unable to regulate emotions is also seen in many patients with anxiety and depression.
These findings build on our earlier work that showed over-activity of sgACC reduces anticipation and motivation for rewards, mirroring the anhedonia inability to feel pleasure seen in depression. This suggests sgACC over-activity can cause two of the core symptoms seen in depression — negative emotions including anxiety and lack of pleasure. Another outstanding question is why people with depression also have increased risk of heart disease. Heart rate variability is an important measure of how rapidly the heart can adapt to changes in the environment, especially cues which predict reward or punishment.
These changes mirror some of the cardiac dysfunction seen Depression And Anxiety And Depression depression and anxiety.
We also used brain imaging to investigate the other regions affected by sgACC over-activity in threatening situations. By contrast, reduced activity was seen in parts of the lateral prefrontal cortex, which regulates emotional responses and is underactive in depression. These changes were very different to those seen following over-activation during a rewarding situation. Knowing these differences may be key to us understanding which treatments will be most effective depending on the symptoms exhibited by a patient.]
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