Building a biological model of mental illness

Conceptual computer artwork of a DNA (deoxyribonucleic acid) double helix Image copyright SPL
Image caption The DEFINE Consortium aims to build on a growing understanding of the genetics of brain function

A team of scientists based at Cardiff University who found that a handful of genes are implicated in a wide range of debilitating neurological conditions have won £5m for further research.

"So the animal has actually gone to the wrong panel. He's swum to the long black panel first and had to change direction to find the platform."

Deep in the bowels of Cardiff University's Behavioural Neuroscience Laboratory, Dr Julie Dumont is putting a rat through its paces in a water maze.

It is a classic test of spatial awareness and memory, but because the rat has been bred to incorporate a set of specific gene variants associated with serious psychological disorders in humans, it is also a useful model for studying the impact of conditions ranging from schizophrenia and bipolar disorder to autism and ADHD.

The experiment is one of the first in a new initiative that aims to build on recent advances in genetics to develop a better understanding of the biological basis of brain function and mental illness.

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Media captionProf Peter Kinderman: To say that suicide is caused by a deficit in serotonin is kind of crazy

Earlier this year, researchers based at Cardiff and the Massachusetts General Hospital in Boston demonstrated that five of the major psychiatric disorders - schizophrenia, bipolar disorder, major depression, autism and ADHD - shared common genetic risk factors. In particular, two genes involved in the regulation of calcium in the brain seemed to play a role across all five disorders.

In a paper published in the Lancet and on the Today programme, one of the lead authors of the study, Prof Nick Craddock, argued that it could be used to help re-write the definitions of psychological conditions, reclassifying them on the basis of their causes rather than the descriptions of symptoms used today.

That process has now begun with the award of a £5.2m grant from the Wellcome Trust. Led by the professor of psychiatry at Cardiff University, Mike Owen, the DEFINE Consortium aims to build on the growing understanding of the genetics of brain function with insights from imaging studies, stem cell research and animal models, to create a biological model of mental illness.

"Recent findings in genetics have advanced our understanding of mental illness and psychiatric disorders in important new ways," says Professor Owen.

"The next step is to take the genetic findings and trace them into how the brain functions and influences behaviour."

A key component of this new biological model of mental illness comes from the analysis of neural cellular activity. Recent advances in the field of stem cells have enabled cell biologists like Prof Adrian Harwood to derive neurones from patients suffering from acute mental disorders like schizophrenia and study them in the laboratory.

"The genes that we've identified cause changes in proteins, and the proteins cause changes in cell behaviour. That's the arena where the important things are happening, so to understand these debilitating psychological conditions we really need to understand what's happening, the processes and biochemistry, in the context of the cell."

Image copyright SPL
Image caption A computer screen display showing the colour-coded peaks of spectra showing genetic sequences

But not everyone is impressed with the idea of a biological model for mental illness. While Peter Kinderman, professor of clinical psychology at the University of Liverpool, accepts that "every single thought anyone has ever had must have involved neuro-chemical processing in the brain," he argues that neuroscience has consistently over stated the statistical significance of its findings and marginalised the vital role played by social and environmental factors.

"The problem is that we're relying on a very reductionist way of looking at what the brain does," he says. "To say that the biochemistry is the driving force or cause of behaviour is taking the interpretation too far. Suicide rates have risen significantly since the financial crisis began, but to say that suicide is caused by a deficit in serotonin is kind of crazy."

If neuroscience has been guilty of biological reductionism in the past, Prof Owen says that is not the intention behind the Cardiff DEFINE Consortium. Building a better model of mental illness, and developing better treatments for conditions like schizophrenia, bipolar disorder and autism will require insights from both biological and psychological approaches.

"It's not just the brain it's the mind as well, but we have to accept that understanding the biology, the neuroscience, is going to be a prerequisite for making progress on these conditions and in developing more effective treatments. It's necessary but it won't be sufficient," he says.