There is no argument that millions of people are still affected by depression and anxiety – prominent mental health disorders – affecting at least more than 300 million people globally. Strangely, there is very little we know about these disorders. Aside from that, we don’t fully understand the brain areas responsible for anxiety and depression and their differing symptoms for sufferers.
As far as we know, the prefrontal lobe which is a part of the brain’s frontal lobe depicts activity changes in people struggling with depression and anxiety. The areas responsible for cognition and emotional regulation are usually unexcited whereas other areas responsible for generating emotions and bodily reactions are over-excited or over-active.
A basic region which has shown over-activity in depressed and anxious people is the subgenual anterior cingulate cortex (sgACC) – involved in emotional responses or behaviours. Neuroimaging studies have over the time only shown a correlation between depression, anxiety and sgACC, but do not tell if the over-activity or excitation of sgACC causes depression and anxiety symptoms. However, a new research has discovered that the over-activity of the sgACC causes depression and anxiety symptoms.
The new research employed marmosets (primate animal) as subjects of experiment. Marmosets were used because of their brain composition similarity with that of humans. In the study, it was found that over-activity in the sgACC region caused common symptoms of mood and anxiety disorders – more importantly, their reaction to threats. Marmosets’ reaction to threats is important in the study since anxious and depressed people tend to negatively perceive and react to threatening situations.
To over-stimulate the sgACC, cannulae – tiny hollow tubes were implanted into the marmosets’ brains. Then, a small quantity of drugs was infused into the sgACC to increase the excitability. These drugs wouldn’t disrupt the functioning of the other regions of the brain, just the sgACC. Small wireless devices were also implanted into the artery to measure both the blood pressure and heart rate.
Before over-activating the sgACC, the marmosets were first conditioned to associate a tone to the presence of a rubber snake (threat). Usually, marmosets see snakes as threats. After pairing snakes with marmosets, the subjects displayed high emotional response (fear) and high blood pressure to the sound of the tone. Then the pairing /association was deconditioned by continuously presenting the noise without the presence of the snake. This allowed the researchers to measure how quickly the marmosets regulated fear responses with or without sgACC over-stimulation.
When the marmoset’s sgACC is not activated, they gradually regulate their responses to threats within minutes when they hear just the tone but not the rubber snake. On the contrary, when the marmoset’s sgACC is activated, with the tone and snake’s present, they showed fearful emotional response and much higher levels of blood pressure. The marmosets were also anxious around other types of threats such as the presence of strange humans. This showed they could no longer reduce or regulate their threat responses.
In line with previous studies, inability to regulate one’s emotions is prevalent among people suffering from depression and anxiety. Therefore, this recent study builds on the literature suggesting that over-activity of sgACC mitigates anticipation and motivation for rewards – something similar to the inability to experience pleasure (anhedonia), as seen in cases of depression. The study then concluded that over-activation of sgACC can cause the symptoms of depression and anxiety such as negative affect/emotion and lack of pleasure.
Heart disease and depression
The other category we are concerned about is why people with depression have a high risk of cardiovascular problems like heart disease. Although lifestyle, behavioural, and socioeconomic factors are strong explanations, the recent study examined whether sgACC over-activity could affect cardiovascular functioning. This was tested because the heart is connected to the brainstem – which is an area that regulates the heart rate and blood pressure.
It was discovered that sgACC over-excitation did not only significantly increase the blood pressure of the marmosets when presented as a threatening stimulus, it increased the heart rate while also reducing the heart rate variability when at rest. The heart rate variability explains how quickly the heart can adapt to various environmental changes, especially when dealing with cues associated with rewards and punishment.
The findings corroborate the findings in depression and anxiety studies. Increased heart rate and reduced heart variability imply that over-activity in the sgACC supports the body’s response to fight or flight, emotions which if persists for a certain period, often puts the heart under stress and may explain the prevalence of heart disease among people struggling with depression.
Heart disease and depression
In recent study, brain imaging response was also used to investigate other areas of the brain affected by sgACC over-activity when presented with a threatening situation. Increased activity was discovered in two fundamental parts of the brain – the amygdala and hypothalamus – which are the brain’s stress network. By comparison, reduced activity was detected in the lateral prefrontal cortex – an area regulating emotional responses. Previous research has shown that the lateral prefrontal cortex is underactive in depression. The changes were different from those found in over-activation during reward events.
Identifying these differences may help us to understand the type of treatment which will be most effective in treating symptoms of patients. This result further led to the investigation about why some certain individuals respond to drugs like antidepressants and why others don’t. For example, an antidepressant is selective reuptake inhibitors (SSRIs). Obviously more than one-third of those who take antidepressants report no significant improvement in symptoms. And this calls for new treatment.
Ketamine is another drug with promising results used in combating treatment-resistant depression – taking effect in less than 2 hours to relieve depressive symptoms. Earlier study had shown ketamine effectiveness in treating anhedonia after sgACC was over-activated.
However, in this study, it was discovered that ketamine couldn’t improve the anxiety levels of marmosets when presented with unfamiliar humans. This shows that some levels of depression and anxiety symptoms react differently to various kinds of antidepressants or treatments. As shown in an instance, ketamine reversed anhedonia, but on the other hand did not reduce anxiety.
Clearly, over-activation of the sgACC may likely be an underlying cause of depression and anxiety symptoms in people while other areas may have altered activity in different brain regions associated with anxiety. There is still research needed regarding finding the different casualties of depression and anxiety and the kinds of treatments required to improve them. But this research indicates that for some sufferers of depression and anxiety, targeting over-activity of the sgACC may be efficient in alleviating their symptoms.