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The promise and challenges of biomarkers for mental illnesses

Each of the 100 billion nerve cells in the brain makes an average of 1,000 connections with other neurons. Zachary Veach

The human brain is the location of personality, emotion, learning and wisdom in a unique individual.

It contains 100 billion nerve cells – roughly the same number as there are galaxies in the observable universe. Each cell makes, on average, 1,000 connections with other neurons, representing the potential for 100 trillion simultaneous information transactions.

In such a complex and dynamic structure, there’s plenty of room for biochemical processes to go astray. Mental illnesses such as Alzheimer’s disease, Parkinson’s disease, schizophrenia or bipolar disorder can be the end results of this dysfunction.

As a community, we are generally used to the concept of chronic, as yet incurable diseases. In contrast, we struggle with the concept of mental illnesses. We’re uncomfortable with people whose reality is different from ours, especially when that was not always the case.

We’re confronted and overwhelmed by the challenges of individuals who are losing their minds as a result of their illness – who slip away from their lifetime experience, their personality, their creativity, their dreams, their relationships and their ability to love and feel loved.

At present, we have little to offer these people. Our methods of diagnosis are complex and, to a degree, subjective. Our therapeutic options are sparse – the few drugs that are available to treat patients with mental illnesses are typically old and only partially effective. And we have no effective strategies to prevent mental illness.

I believe the discovery of new “biomarkers” for different forms of mental illness may transform this frustrating situation.

Every biological process creates a biological signal – the molecular product or products of a biochemical reaction. An aberrant biological process must create a signal that is different in some way from normal processes. These signals are inherently detectable in one or more of the body’s biological fluids.

In searching for a biomarker, scientists are trying to find the proverbial needle in the haystack. They must be found among the background chemical noise arising from normal biological functions.

New biomarkers will not just provide a new, objective way of diagnosing mental illness. They may also assist in treatment of conditions such as Alzheimer’s disease, where early diagnosis could allow therapeutic intervention to take place before the onset of irrecoverable mental decline.

Biomarkers could play a key role in the development and deployment of new drugs, patient management strategies and, ultimately, could lead to new population health initiatives to prevent mental illness.

A fundamental challenge in biomarker discovery is to look in the right direction. To identify useful biomarkers we must study not only individuals who have a defined mental illness but, most critically, individuals who will one day develop mental illness, well before their symptoms become apparent.

Australia is well placed to do this. We have one of the world’s leading prospective cohort studies of Alzheimer’s disease in the form of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL).

The AIBL study has recruited over 1000 participants aged over 60 and includes healthy controls, individuals with mild cognitive impairment and individuals who have been diagnosed with Alzheimer’s disease. Other important prospective cohort studies include the WA Family Study of Schizophrenia and the famous Geelong Osteoporosis Study, which is now yielding valuable information about other medical conditions such as depression.

These are real assets for Australian science. And it’s very pleasing to note that the consultation paper recently released as part of the McKeon review of health and medical research recognises the importance of the biobanks that are created in this type of research.

To be most useful to researchers, prospective studies must be executed with extraordinary rigour in subject management and sample collection. This is essential to reduce noise, so that we can detect faint, but real biological signals – the equivalent of astronomers heading far away from city lights so they can see distant objects more clearly.

While we have a long way to go before we can prove the value of particular biomarker discoveries, the search might ultimately lead us to a biochemical pathway that we can modify with a new drug, or perhaps with something as simple as a dietary supplement or lifestyle modification.

This may sound like an ambitious goal but we see as our benchmark the outstanding successes of cardiovascular medicine over the past decades. The discovery of simple biomarkers, such as blood pressure and blood cholesterol, have transformed medical practice by enabling doctors to measure risk and response to intervention effectively, both in individuals and at the level of the population.

New products and new approaches to clinical management and disease prevention would potentially benefit millions of individuals around the world and generate ongoing social and economic benefits for Australia.

This article is based on a longer speech given by Professor Ian Cooke at the Cooperative Research Centre breakfast with the Health Minister Tanya Plibersek at Parliament House Canberra, in August 2012.

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