Mental Health Overhaul

Nobody needs reminding that just a few years ago we were all plunged into a state of maximal uncertainty.

We didn’t know what was going on, we couldn’t predict what would happen next, and the lockdowns were completely disruptive to normal life.

“Difficulty in responding to uncertainty lies at the core of many mental health difficulties, and it’s very telling that since the pandemic there’s been a twenty-five percent global increase in people diagnosed with depression and anxiety," says Rebecca Lawson, Professor of Neuroscience and Computational Psychiatry in the University of Cambridge’s Department of Psychology.

Drug treatments and therapies for depression and anxiety do exist - but they’re only effective in 50% of people so it’s a ‘try and see’ approach, often with side-effects along the way. The problem, says Lawson, is that mental health conditions are diagnosed by the symptoms people experience, because there’s no other way.

"We don’t have blood tests or brain scans that will give us an indication of whether you have a mental health condition or not"

says Lawson, adding: "We just have a reference manual listing behavioural symptoms which if you have enough of, you get your diagnosis and a plan of action.”

This approach to mental health considers the symptoms to be the condition - low mood as part of depression, for example. This is very different from physical health conditions where a symptom like a cough could be caused by many things, from a common cold, to asthma, to cancer – each needing a very different treatment.

“We're lacking that mechanistic understanding of the different routes to causing the symptoms of mental health conditions,” says Lawson, adding: “That means we can't predict who treatments will be effective for – and for the most part we don't actually know how the treatments work.”

Mental health problems are complex, and idea of a ‘one size fits all’ treatment is outdated. Lawson compares the current state of understanding to cancer research twenty years ago: “We had a very poor understanding of the different mechanisms that could cause breast cancer, for example,” she says.

With greater understanding, cancer treatment has moved to a precision medicine approach where treatment is often tailored to the individual. Lawson wants to achieve the same for mental health.

She’s creating computational models of the behaviour of people with mental health conditions - breaking it down into its constituent parts.

The aim is to be able to assess someone to produce their unique ‘computational fingerprint’ – resulting in a personalised approach to treatment based on the underlying cause of their symptoms.

“People with depression have a tendency to put negative interpretations on things, and there are lots of reasons why this might be happening,” she says.

“Maybe at the visual end you see things differently, or maybe you have difficulty perceiving positive events in the world, or maybe you're not updating your beliefs in response to your experiences. The idea is that by trying to get closer to the mechanisms that drive the behaviour, we might be able to actually understand how the treatments work, and who they work for.”

A large, competitively-won Wellcome Mental Health Award is now allowing Lawson and her team to investigate the mechanisms underlying depression and anxiety – in particular, how people process uncertainty.

She wants to see how two different treatment approaches – antidepressant medication and Cognitive Behavioural Therapy - change a person’s computational fingerprint, and change their intolerance of uncertainty.

“We’ll do a head-to-head trial of these two different treatments to understand how they're different mechanistically – the hope being that we could then use knowledge of the underlying mechanism to guide the most effective treatment approach on a personalised basis.”

We tend to talk about anxiety and depression much more openly since the pandemic, but this openness doesn’t yet to extend to all mental health conditions – and that can mean many people still don’t seek the support they need.

“There's much less stigmatisation now around saying that you have an anxiety disorder or depression than there used to be,” says Amy Milton, Professor of Behavioural Neuroscience in the University of Cambridge’s Department of Psychology, “but there’s still a strong stigma attached to drug addiction, which is my opinion is unfair, because it’s also largely driven by biological mechanisms.”

Milton is studying disorders including drug addiction, post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder, all of which seem to be driven, at least in part, by malfunctions in emotional memories - those where our brain links an emotional response to an experience.

We’re more likely to remember emotionally charged images, like someone shouting at us, than neutral ones. But when they’re formed under very traumatic circumstances this can leave lasting damage – even years later when there’s no longer any danger, particular stimuli can trigger the memories and cause the same strong emotional response. This is what happens in PTSD; Milton is trying to work out what’s going on in a bid to stop it. She says:

"Our memories aren’t fixed – we know they drift and change, and under the right conditions they can be updated. If emotional memories contribute to the persistence of PTSD, can we target them in some way?"

Memories are very stable when they’re in an inactive state not being used, and they switch to an active state as we do something that uses them. As they move between the two, they destabilise.

“Our idea is that if we give a person with PTSD a reminder of their trigger stimulus to activate the associated emotional memory, together with a drug that blocks that memory from restabilising, then the memory will disappear," says Milton. "We already know it works in rats. If we could get rid of a person’s distressing emotional reaction without them forgetting the event, that’s really exciting.”

Milton has found that problems with emotional memory are also involved, in different ways, in drug addiction and obsessive-compulsive disorder. While they are just one component of all three disorders, she says that targeting the mechanism of the emotional memories could become an important part of wider treatment packages.

“It may be that the same mechanisms are affected in different mental health disorders,” she says. “Our ideal approach would be to try and work out which symptoms are causing problems for any individual patient, and treat the processes that give rise to those symptoms. Similar to Rebecca’s approach this is more flexible and personalised, and should have much better outcomes.”

Read more about the University's research on Mental Health and Illness

Article published: 4 October 2024

_{The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License}