(Image: AP Photo/Cliff Owen)

A REVOLUTION is under way in psychiatry. The science underpinning this discipline has in the past shifted from psychology to pharmacology, and now it is changing again. We are starting to build it on genomics and neuroscience, thanks to advances in DNA sequencing and functional imaging.

The next decade should see all of these strands intertwined into a more holistic approach. People are beginning to recognise that depression and schizophrenia, for example, are brain disorders related to physiological changes rather than simply behavioural ones.


What does it mean to think of mental illnesses in this way? Is psychiatry really just part of neurology? Many disorders of neurology, such as stroke, involve damage to a specific site in the brain. But psychiatric disorders may be more usefully thought of as brain circuit problems – what researchers have called “connectopathies”. You could make an analogy with heart conditions. The behaviour and ways of thinking seen in a mental illness are symptoms of an underlying disorder in a brain circuit – a brain “arrhythmia”, but a straight neurological disorder would be more like a heart attack.

Teething problems

The problem is that even though there have been thousands of studies looking for biological markers of mental health problems such as depression or schizophrenia, none has proven clinically actionable. And, in truth, little has been replicable even in a research setting. So some psychiatrists understandably reason that this approach offers no advantage, but large costs.

This is premature. Consider the recent history of cancer research. More than a decade ago, doctors realised that they needed to reconsider their diagnostic approach. Molecular genetics has revealed that tumours once labelled as “breast cancer” or “lung cancer” are actually many different forms. Traditional diagnostic criteria – such as what a tumour looks like or its location – lacked the precision to select the best treatment for each form. Better diagnosing information based on biomarkers is now allowing better treatment and prognosis for patients.

A similar process has just begun in psychiatry, with one of the vanguards being the US National Institute of Mental Health’s Research Domain Criteria (RDoC) project, which aims to collect genomic, cellular, imaging, social and behavioural information on large numbers of people with what are often termed “mental disorders”. Rather than trying to map this on to the behaviourally defined categories that clinical psychiatry uses, RDoC will ask the data to define the categories, just as scientists have done with cancer. We already consider “depression”, “schizophrenia” and “autism” as more than single conditions; perhaps a decade hence, biological and other qualifiers will be essential to identify a specific condition and the best way to deal with it.

One example is recent work on suicidality. Researchers have found biomarkers for suicidal behaviour that seem significant across many of the current diagnostic categories of mental illness (see “Suicidal behaviour predicted by blood test showing gene changes“). In addition, studies of psychosis, mood disorders and developmental disorders are beginning to deconstruct those groups by using biomarkers and innovative tests of cognition, which may prove to be the most powerful biomarker for such conditions.

Tectonic shift

Objective diagnostic categories that are reliable and biologically valid are long overdue in this field. For people under 50, psychiatric disorders cause more disability, have higher mortality rates and incur greater costs than any other group of disorders. If the path to better outcomes in cancer and other medical specialities requires precision medicine, then certainly the best hope for easing the morbidity, mortality and cost of psychiatric conditions will be to develop tests to identify precise diagnostic groups within what we now call mental disorders.

Such a tectonic shift could ultimately improve the lives of many millions of people.

This article appeared in print under the headline “A different way of thinking”