You don’t need to be a mental health expert to know that depression is more than just feeling sad. From low self-esteem and a lack of motivation to physical changes across the body, the mental health condition can be truly all-encompassing.

But at the root of many of these issues is depression’s impact on the brain. While you might be familiar with the serotonin theory of depression – that depression is caused by a lack of the ‘feel good’ hormone serotonin in the brain – the changes that occur in the brain during a period of depression are a lot more complicated.

That means that more research is needed to understand exactly what’s going on, but experts do have some understanding of the mechanisms at play.

So, to give you a clearer idea of how depression impacts the brain, we spoke to Dr Romayne Gadelrab, a consultant psychiatrist at South London and Maudsley NHS Foundation Trust and the private mental health centre The Soke.  

While the impact of depression on the brain is incredibly complex, Dr Gadelrab says a good place to start is focusing on three key areas: system dysfunction, inflammation and structural changes.

1. System dysfunction

Depression can wreak havoc on several key systems within the brain, impacting various neurotransmitters and communication pathways in the process.

Serotonin is one of these neurotransmitters, Dr Gadelrab says. “The question of whether or not serotonin is involved in depression has been talked about in the media and has become quite controversial, but I think it’s fair to say that enough research has shown that it is involved in some way,” she says.

In short, low serotonin levels may not cause depression, but there’s definitely something going on there – and more research is needed to figure out exactly what that is. For example, Dr Gadelrab suggests that it could have something to do with the ‘serotonin system’, which controls and regulates the presence of serotonin throughout the body.

The second area of the brain that is affected is the hypothalamic-pituitary-adrenal axis, or HPA axis for short. Depression can lead to this axis becoming dysregulated, stopping it from working optimally. And this can have a knock-on effect across the body.

“The HPA axis is a really important communication system in the body which helps to regulate our responses to stress,” she says. “And this means the dysregulation of the HPA axis can affect things like mood, energy levels and even the immune system.”

In particular, the dysregulation of the HPA axis can lead to elevated levels of the stress hormone cortisol, which, among other things, can deplete serotonin levels and wreak havoc on the circadian rhythm (the body’s internal clock). It’s for this reason that depression is often associated with disrupted sleep. Dr Gadelrab adds: “In depression, we often see changes and difficulties with sleeping. People will find it difficult to fall asleep, stay asleep or, very commonly, wake up early in the morning and not be able to get back to sleep. And this can all be related to high levels of cortisol.”

The third key area that depression can affect is the autonomic nervous system, which controls a lot of those things we don’t think about all that often: our breathing, heart rate and stress response. The autonomic nervous system feeds back to the brain but is present in nerves that thread all around the body, including the all-important vagus nerve. It’s this part of the autonomic nervous system that controls our sympathetic and parasympathetic systems, which are responsible for the ‘fight or flight’ and ‘rest and digest’ responses.

In people with depression, this system often isn’t functioning correctly. That means they might be more easily stressed out or find it hard to relax.

2. Inflammation

Research into the link between inflammation and depression has identified a strong link between the two, with a large-scale study published in the American Journal Of Psychiatry in 2021 concluding that inflammation is a “core feature” of the mental health condition.

While experts still aren’t quite sure whether depression causes inflammation or vice versa, we know that chronic inflammation has been shown to trigger or exacerbate depression, and that the brain scans of people with depression show high levels of inflammation.

This paves the way for exciting developments in the treatment of depression, Dr Gadelrab says, as anti-inflammatory medications and diets could be used alongside traditional treatments to ease symptoms.

3. Structural changes

Last, but by no means least, depression can also lead to structural changes in the brain, Dr Gadelrab explains. “Again, there are more and more studies in this area,” she says. “These are looking at brain scans and changes in connection within the brain, and in people with depression, they have seen some reductions in key areas like the frontal cortex, which is involved in our reward pathways, mood and decision making.”

It’s for this reason that experts are now looking into the link between childhood adversity and depression, Dr Gadelrab adds. “It could be that those structural factors are causing depression or that the depression itself causes them,” she says. 

Images: Getty