How to treat the three key types of depression, according to a neuroscientist

Telegraph

3 days ago

The ICD-10, a diagnostic manual used in Britain and elsewhere, lists nine symptoms of depression, and 'you only need five to receive a diagnosis', says Prof Roiser. Some symptoms, such as sleep disturbance, can manifest as either an increase or a decrease. 'This means there are potentially hundreds of different combinations of symptoms in people with depression.'
Crucially, 'there is no particular reason to believe that those symptoms share the same cause', Prof Roiser argues. The serotonin theory of depression, which suggests this complex condition is caused by a chemical imbalance, is 'a very outdated idea from the 1960s, and even then it was understood to be a massive oversimplification', he says.
Instead, it appears there are several different 'dimensions in brain function', changes in which may lead to different symptoms.
The three key types of depression
A new study from Washington University School of Medicine in St Louis, published in June, identified three main types of depression experienced in the general population and explored how they manifest in patients' brains and daily lives.
Though the study was conducted in the US, it used data from the UK Biobank, which tracks the health of half a million British volunteers over their lifetimes. Low mood without low motivation, low motivation without low mood and a combination of both are all common.
1. Low mood (without low motivation)
People who primarily struggle with low mood might experience:
A persistent feeling of sadness, tearfulness, numbness or emptiness lasting at least two weeks.
Becoming easily frustrated, irritated, or angry over things that never used to bother them (a symptom of anxiety, which often co-occurs with low mood).
Excessive or inappropriate feelings of guilt or shame over things they didn't do or weren't responsible for.
A consistent and extreme negative view of themselves and their abilities, or feelings of worthlessness.
2. Low motivation (without low mood)
People who primarily struggle with low motivation might experience:
Persistent tiredness despite sleeping well.
Cognitive impairment (brain fog), which can appear as difficulty concentrating or making decisions.
Trouble completing everyday tasks like work, housework or admin.
A sharp decrease in sex drive.
A loss of interest in other people, as well as activities and hobbies they once enjoyed.
3. Low mood and low motivation
People who struggle with a mix of low mood and low motivation may experience a combination of these symptoms.
The study's participants differed not only in their symptoms but also 'in their neurobiology', says Dr Janine Bijsterbosch, the lead scientist, in a press release.
In other words, different symptoms correlated with different changes in the brain. At the same time, however, people with similar symptom profiles sometimes showed different underlying brain patterns. This is part of why most neuroscientists 'have lost faith in the idea that there is a single explanation for depression at the level of the brain', says Prof Roiser.
'It is a condition defined by its symptoms, so there is an inherent circularity there.'
Despite its complexity, these findings align with Prof Roiser's own decades of experience studying depression as a neuroscientist. He explains there appears to be 'a set of different brain circuits that underlie motivation, linked to symptoms like loss of energy as well as brain fog.'
Meanwhile 'another circuit in the brain deals with negative emotions'. Both can 'interact with and affect each other', but the fact that there are some general trends in people with different clusters of symptoms 'mean that we might soon be able to target them with different types of intervention.'
It's also difficult to determine whether these brain changes are a cause or a consequence of depression. Scientists currently estimate that the heritability of depression is between 40 and 50 per cent, suggesting a strong genetic component, alongside life experiences that can increase vulnerability to the condition.
There is one new theory that may underlie depression in all its forms.
'A substantial number of people with depression also seem to have high levels of inflammation in their bodies, which could drive changes in the brain', says Prof Roiser. This might explain why both exercise and antidepressants, some of which have anti-inflammatory effects, can be effective in treating the various symptoms of depression.
'It's currently just a hypothesis. There are several rigorous studies currently underway to investigate the role of inflammation in depression, and in five years we may have some answers.'
The best treatments for different kinds of depression
This is why Prof Roiser's work on brain imaging is so crucial.
'An MRI scan of neurobiology may have the potential to predict clinical outcomes that depression symptom screening alone cannot capture', says Dr Yvette Sheline, who also contributed to the Washington University study.
While doctors may not yet fully understand what depression is or why it occurs, brain scans could help tailor treatments to the unique symptoms of different types of depression.
A number of treatments for depression are currently available on the NHS, while others are being explored by researchers as potential therapies. There is limited evidence, however, to indicate which treatments work best for specific types of depression.
'The important thing is not to lose hope', says Prof Roiser. 'There are a number of different treatments that are effective for depression, so if one proves not to work well for you, you should certainly go back to your doctor and ask about different options.' Different treatments are likely to work for different people, due to the different brain circuits driving their depression.
Best for low mood without low motivation
Antidepressants
Antidepressants, such as SSRIs, appear to work best for 'negative affect', in other words, low mood and anxiety, says Prof Roiser. Although their effects on brain chemistry are well understood, 'we don't know exactly how they work in terms of brain circuits. One important idea is that they change the emotional response to the negative thought patterns that characterise depression. We do know that SSRIs are especially effective at blunting the experience of negative emotions.'