From depression to obesity

Obesity and depression, the two curses of our time that continue to confound modern medicine, may have a disturbing link: it is possible that treatment of one may trigger the other.After two decades of research exploring the mysteries cloaking these debilitating conditions  which now account for a massive burden of disease  two Canberra-based researchers from Brazil believe they have found the evidence of an insidious connection.Professor Julio Licinio, a medical researcher and his wife, Professor Ma-Li Wong, have pursued a career-long hunt for the links between obesity and depression.Licinio, who heads the John Curtin School of Medical Research, says widespread use of anti-depressants may explain why obesity rates have continued to climb in the past decade  a trend he does not believe can be solely attributed to bad diets and sedentary lifestyles."I think it is probably one of the missing pieces of this puzzle, that psychiatric drugs have long-term effects that we are not watching."The pair, along with researchers at John Curtin and the University of Miami, have published new findings suggesting an interplay between obesity and anti-depressant medicines. The team found in tests with laboratory rats that short-term anti-depressant treatment may be an enduring cause of obesity, even a long time after treatment is discontinued.Wong says the perspective she and Licinio have on the anti-depressant-obesity link is "a bit unusual and a lot of people will not agree with it".The scale of the challenge is illustrated by the widespread use of anti-depressants  they are now among the most prescribed drug in the US, she says, and many would say over-prescribed. But there is meagre information on what proportion of patients taking them become obese.Anxiety and depression together represent the second most common cause of ill-health in Australia, while obesity plays a frequent role in lethal conditions like coronary heart disease and diabetes."There is a lot of difficulty in understanding depression. It is a complex disease. Studies of depression are not easy to replicate."On the other hand, obesity is not seen as a psychiatric disorder, she says.Licinio and Wong have held professorships in related fields at UCLA and Miami University. Yet for somebody of his research background, it is notable that Licinio holds deep scepticism about the efficacy of medical treatments for diseases including diabetes, cancer, psychiatry and rheumatoid arthritis."Today we look back 150 years ago when people were treated with leeches and think it is craears' time people will look back [at today's treatments] and think the same thing."For some psychiatric disorders, he says, "We really don't completely understand why the drug acts and what we are doing. Some people respond to the drug you give and some people don't. Some people have terrible side-effects and other people don't. Some people just are not touched by the drug."The range of responses depend on an individual's genetic "markers" or make-up. In many cases drug treatment "is all guess work", he says.

Is he suggesting that the widely accepted espousal of evidence-based medicine is a modern myth?

"It is not going to make me very popular but I think it is."

There are several factors behind this apart from the numerous biological differences between humans, including research biased towards selected patient groups and the complexity of reactions between drugs.According to an American survey, the average geriatric patient is on 14 different medicines.But amid the profusion of drugs available, Licinio points to the singular lack of real advance in psychiatric medication.Serious depression represents a substantial problem in Australia, with 1.4 million sufferers each year. "Yet nothing we use to treat psychiatric patients suffering depression and other psychiatric illness today is based on anything discovered in the past 40 years  even though there has been an explosion in neuroscience."This brings Licinio to his latest project  the establishment this month of an online learned journalTranslational Psychiatry. Like another internationally recognised publication, Molecular Psychiatry, that he pioneered, the latest is part of the prestige Nature stable.Translational psychiatry is the emerging science aimed at translating ideas into research. Translation of the enormous effort in neuroscience into psychiatric therapy has vast potential, Licinio says.The two branches of the study of the brain had drifted apart over the decades with psychiatry tending towards the primary care of mental illness while neuroscience went towards high end technology and molecular discovery."I think it is one of the areas of medicine where there is a big gap between the excitement of discoveries about the brain but very little in terms of new treatment.Licinio and Wong came to Canberra from the United States, he as director of John Curtin School of Medical Research and she as a research group leader there.

From their early days together in New York in the mid-1980s, they have collaborated on much of their research. Wong's career mission is "to unravel the biology of major depression", while Licinio's interests tend towards analysing the consequences. Over two decades they have explored the relationship between brain and appetite, which despite its widespread implications for western health, remains steeped in uncertainty over treatment and drug impacts.Licinio knows a little about translating an exciting idea into successful therapy. When he was working at the University of California, Los Angeles, he pioneered the treatment of four patients whose genetic deficiency in the hormone leptin had left them morbidly obese and facing the prospect of early death.Administered a synthesised version of leptin, the four patients shed much of their fat and dramatically improved their health. It was, says Licino, "the highlight of my career"."When will investigators in psychiatry feel the same type of elation as they bring perfectly happy and productive lives to patients with autism, Alzheimer's, depression, bipolar disorder or schizophrenia?"It is important to bring people together who understand neuroscience and people who understand diseases. It sounds so simple but it is not the way it is done now."Licinio, the foreigner, has thrown his support strongly behind the campaign to protect Australian research funding against budget cuts."Medical research is something this country is very competitive at." He rattles off several research areas at John Curtin  a potential vaccine for tuberculosis, cancer treatments, neurology and a robotic eye  which he said had potential for commercial development if the money was available.Professor Ian Hickie, the director of Sydney University's Brain and Mind Research Institute, says the recruitment of Licinio and Wong is "a major acquisition" for Australian psychiatry and medical research.Their work is an example of the potential for research into mental health and behavioural medicine to deliver "major advances to health care", Hickie says.Though it is little-known outside Canberra, the John Curtin school, based at the Australian National University, has been associated with three Nobel prize winners: the neurologist Sir John Eccles, and the immunologists Professor Peter Doherty and Rolf Zinkernagel.A former director, the late Frank Fenner, pioneered myxomatosis use against rabbits and led the successful international drive to rid the world of smallpox.With that illustrious past, Licinio ponders how the school can have a tomorrow that is better than its past."Welcome to my job."

Courtesy- MARK METHERELL

Sydney Morning Herald