IMAGINE you are a doctor before the advent of modern medical tests and your patient is gasping for breath. Is it asthma, a chest injury, or are they having a heart-attack? You don't know and have no idea how best to help them.
Some would argue that's what it's like for doctors trying to diagnose mental health problems today. There are no blood tests or brain scans for mental illnesses so diagnoses are subjective and unreliable.
The issue came to a head one year ago this month, with the latest edition of psychiatry's "bible", the Diagnostic and Statistical Manual of Mental Disorders. The US National Institute for Mental Health (NIMH) said the DSM-5 had so many problems we effectively need to tear it up and start again. The way forward, it said, is a new research programme to discover the brain problems that underlie mental illnesses.
That research is now taking off. The first milestone came earlier this year, when the NIMH published a list of 23 core brain functions and their associated neural circuitry, neurotransmitters and genes – and the behaviours and emotions that go with them (see "The mind's 23 building blocks"). Within weeks, the first drug trials conceived and funded through this new programme will begin.
While just a first draft, the list arguably represents the future of neuroscience-based mental healthcare. "This is the Rosetta stone for characterising human mental function," says Andrew Krystal at Duke University in Durham, North Carolina.
Criticism of psychiatry has been growing for years – existing treatments are often inadequate, and myriad advances in neuroscience and genetics have not translated into anything better. Vocal opponents are not confined to the US. Last week, the new UK Council for Evidence-based Psychiatry launched a campaign claiming that drugs such as antidepressants and antipsychotics often do more harm than good.
What's more, many suspect that commonly used labels, such as depression and schizophrenia, merely group together people sharing some superficial symptoms, when their underlying brain disorders are quite different.
Genetic studies, for instance, suggest that schizophrenia and bipolar disorder, supposedly distinct conditions, involve mutations in many of the same genes. And diagnostic confusion between the disorders is common (see "What's in a name").
"We are just playing semantic games," says Sami Timimi, a psychiatrist at the University of Lincoln, UK, who leads a campaign called No More Psychiatric Labels. "It's as if calling it 'bipolar disorder' reveals some essential truth – it reveals more about the subjective preferences of the diagnoser," he says.
Although the NIMH has now admitted the DSM-5 is the best approach we currently have, its research programme is an attempt to go back to the drawing board. "Let's not try to study each 'disorder' but rather, the neural systems themselves, and study how they become dysregulated," says Bruce Cuthbert, who heads the NIMH's programme.
So what do the mind's 23 building blocks consist of? The best mapped-out anatomically is the brain's fear circuitry, thanks to years of scaring volunteers as they lie in fMRI scanners. This system is probably involved in phobias and post-traumatic stress disorder.
Another is the related circuitry that deals, not with present danger, but with vaguer fears that something bad might happen in future. "That circuit is very relevant to rumination and anxiety," says Cuthbert.
Another five neural systems are components of the brain's reward circuitry, which is active when we find something pleasurable – like eating or sex – and drives us to repeat the experience. These can malfunction when people are addicted to drugs or alcohol.
The reward system, says Cuthbert, is very powerful because one of the most important things that organisms need to learn is to seek out things like food and water. "Drug abuse hijacks that system so the cues create urges that are very hard to resist," he says.
A malfunctioning reward system may also lie behind two of the commonest forms of mental illness: depression and anxiety. Some people with these conditions have a symptom called anhedonia, a failure to enjoy usually pleasurable activities. Someone who was once a keen gardener, say, would lose all interest in their hobby, says Krystal, who is leading the NIMH's efforts to develop drugs that treat it. The first trial in humans of one such compound is about to begin.
Most of the other neural systems on the NIMH list – which include attention, perception, working memory, arousal and social communication – do not tie in neatly with specific mental disorders, at least not as we currently define them. Instead, they cut across many different disorders, for example, problems with memory are seen in anxiety, depression and schizophrenia. This lack of a one-to-one correspondence between the disorders and the brain systems lends weight to the idea that existing diagnostic labels are flawed.
Only with a better understanding of these brain circuits can we develop ways to monitor them objectively using tools such as brain scans and EEGs, where electrodes on the scalp record the brain's electrical activity. A recent refinement of EEG is the ability to record , a measure of the brain's response to specific stimuli. Electrodes on the face can also measure how much we twitch after an unexpected noise, for example, to probe activity in the brain's fear circuitry. This is thought to go awry in people with anxiety disorders.
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