Researchers search for cause of schizophrenia

19 December 2016

It remains one of the most misunderstood diseases in Australia, but a collaboration of researchers is picking through the circuitry of the brain to find the causes of schizophrenia. Psychiatrists and neuroscientists are teaming up in Brisbane to understand the early changes to the brain that eventually trigger a debilitating and often life-long psychosis in one in 100 young people. Neuroscientist Dr James Kesby, working with teams from the Queensland Brain Institute and the Queensland Centre for Mental Health Research, is hunting for early biomarkers for schizophrenia, looking notably for changes to particular neurotransmitters, and especially at the role of dopamine. “Dopamine is heavily involved in schizophrenia,” said Dr Kesby. “Our antipsychotic drugs work by blocking dopamine receptors, but they’re not very effective. However, they give us an idea of what the underlying causes could be.” Dopamine is one of the neurotransmitter chemicals that sends signals around the brain. Different levels of dopamine are associated with both addiction and schizophrenia, but the neurotransmitter’s role in triggering schizophrenia is still unclear. “Once we better understand how changes in dopamine progress to schizophrenia, we might be able to find better tests that can give us an idea of who might go on to develop schizophrenia.” said Dr Kesby. There’s a big push underway within the Brisbane Diamantina Health Partners, a collaboration of Brisbane hospitals and medical research institutes, to look for early markers for schizophrenia in children and young adults before they get psychosis. If early biomarkers in the brain can be identified, it may be possible to predict who’s at greatest risk of developing schizophrenia and treat them before the damage is done. The onset of schizophrenia most commonly appears in young men between 15 to 25, and young women between 20 and 30. The risk of schizophrenia is known to be associated with a number of factors, including genetics and even a lack of developmental Vitamin D, but how the disease develops remains a complicated picture. Dr Kesby believes dopamine could be key, because drugs such as marijuana and amphetamines that change levels of dopamine can also induce schizophrenia-like psychosis in young people. The antipsychotic drugs used to treat schizophrenia work by suppressing dopamine. Dopamine is also important in the brain development of adolescents and young adults, encouraging risk taking, and it’s in those years that most people who develop schizophrenia have their first psychotic episode. “In my research, I’m saying, ‘Let's have a look at what specific neurotransmitter might the common aspect in all these diverse risk factors’,” said Dr Kesby. “But it’s a complex picture.” Schizophrenia includes a range of symptoms, including the psychosis, which can be marked by hallucinations, delusions, and disordered thinking, as well as other symptoms such as impaired cognition and memory. “There is a lot of great work researching these other symptoms, but we can't treat them well until we understand how those impairments originated,” he said. “One constant in schizophrenia is the psychotic element. No two people tend to have the same group of symptoms, but they will generally have a psychotic event, making it a common factor in this very complicated disease. So, understanding how people progress to psychosis may give us some clues as to how these other symptoms develop and how they can be better treated. Maybe, if we could do something earlier to prevent psychosis, we could also prevent some of those other problems happening.” Dr Kesby recently won the Advance Queensland Research Fellowship to pursue his research, which involves a collaboration of clinicians and neuroscientists to identify behaviour that may point to early biomarkers for schizophrenia. “You've got to be embedded in someone else's research, more than just sitting on meetings, to understand the disease from different perspectives,” said Dr Kesby, a neuroscientist who’s working with clinical psychiatrists, including Associate Professor James Scott. “Simple questions from psychiatrists such as James Scott can help me think about neurobiology from a different clinical perspective,” he said, “and that helps everyone better understand schizophrenia.” “These translational teams, forming big multi-disciplinary networks, are really the key to this sort of thing, but putting them together takes time. It takes investments in building those relationships, which I think is what has been lacking previously. Now we're starting to say, ‘Okay this is going to be a bigger task’.” With no new drugs developed in the last 30 years, it’s hoped a better understanding of the triggers of schizophrenia will lead to early interventions that could reduce, or even prevent, the symptoms. “If you can get in really early and try to focus on cognitive tasks, for instance, and help manage a person’s environment, and maintain friendships and all those support networks, you might help delay or prevent schizophrenia in some cases,” said Dr Kesby. “And for other people with more severe symptoms, we need to develop better treatments.”

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