Target faulty brain circuits to treat mental illness

IT HAS been more than a decade in the works, but finally we know the main changes that will be introduced next May, when the American Psychiatric Association publishes the next edition of its Diagnostic and Statistical Manual of Mental Disorders, known as DSM-5.

Those changes, which could influence the way millions are treated, include new definitions of autism and related conditions, and a shift in the criteria for depression to include some people grieving after bereavement.

Debate over DSM-5 seems likely to rumble on. But now there is a deeper problem to ponder: while discoveries about the genes and brain circuits that underlie human behaviour are accumulating rapidly, they haven't led to major clinical advances.

That's largely because these findings don't map well on to the constellation of conditions described in the DSM. When the last major revision was completed in 1994, its authors hoped that neurobiologists would soon home in on specific disruptions to brain circuitry involved in the main psychiatric disorders. "I was naive enough to think that it was just a matter of time," says Michael First of Columbia University in New York City. It hasn't worked out that way. Take schizophrenia: what was once considered to be a distinct psychotic disorder actually seems to cover a variety of disruptions to normal brain functioning. This suggests that many of psychiatry's diagnostic labels do not describe coherent conditions with common underlying causes. No wonder, then, that many conditions are so hard to treat.

Some critics argue that it's time to rip up the manual and start again - with wider input. In the coming weeks, organisers of a petition to reform DSM-5 backed by 14,000 mental health professionals plan to launch an online forum to debate a new diagnostic system.

In the long run, the best hope for psychiatric diagnosis may come from the US National Institute of Mental Health, whose Research Domain Criteria project started up this year. Rather than giving people labels such as schizophrenic or depressed, the project aims to develop biological and behavioural measurements reflecting underlying alterations to brain circuitry that can trigger mental illness. Crucially, the measurements will include sliding scales that recognise a continuum between "normality" and ill health - rather like measurements of blood pressure, used to diagnose hypertension.

It could be years before doctors routinely use such measurements, but there are hints at how it could shape the future of psychiatry. For instance, people diagnosed with depression may lose interest in activities they used to enjoy. This symptom is also seen in some other disorders and is linked to disruption in the brain's mesolimbic dopamine circuitry. Being able to measure and treat these disruptions could help people across a broad range of psychiatric illnesses, suggests Bruce Cuthbert, the project's co-ordinator.

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