Institute Research Awarded $2.2M

RESEARCH NEWS

Institute Research Awarded $2.2M

The Schizophrenia Research Institute is pleased to announce that research supported by the Institute was recently rewarded with five National Health and Medical Research Council (NHMRC) Project Grants, totaling an investment of over $2.2 million. This funding reflects the quality and relevance of the Institute’s research program.

Congratulations to Dr Murray Cairns, Dr Paul Tooney, Prof. Rodney Scott, Prof. Xu-Feng Huang, Dr Chao Deng, Prof. Cyndi Shannon Weickert, Dr Jan Fullerton, Prof. Peter Schofield and Dr Melissa Green.

The NHMRC is Australia’s peak body for supporting health and medical research, and to receive an NHMRC grant is seen as a measure of excellence in the medical research
community. To the recipients it means that their Australian research peers have assessed their research proposals as among the most likely to produce significant benefit to the community. The grant recipients and research projects are:

Molecular and cellular characterisation of schizophrenia associated dysfunction in microRNA biogenesis.
Cairns, M, Scott R, Tooney P, Rostas J, Brichta A.
The Institute’s Univeristy of Newcastle group have identified substantial changes in the biogenesis of microRNA in schizophrenia. These small non-coding molecules derived from “junk” DNA, play a significant role in genetic regulation, with each one capable of silencing hundreds of target genes. This has major implications for schizophrenia, which is known to involve substantial changes in gene activity. The project will identify the molecular basis of this alteration in gene silencing, and its biological implications for schizophrenia.

Cognitive and affective schizophrenia symptom intervention.
Huang XF, Deng C.
Atypical antipsychotic drugs such as olanzapine, clozapine and risperidone are commonly used to treat mental illness. While these drugs are effective, their side effects of obesity and metabolic disorders are a major hurdle leading to a serious lack of compliance in taking medication. This project, conducted by the Institute’s University of Wollongong team will define the mechanism leading to these side effects and will help to identify pharmaceutical targets for the better treatment of mentally ill patients.

Neuregulin dependent neuronal migration and schizophrenia.
Shannon Weickert C, Garner B, Fullerton J.
Schizophrenia will affect 1 in 100 Australians and is responsible for $2.2 billion in health costs, disables thought and emotion and is devastating to the individual, the family and the community. We need to develop drugs able to reverse the root cause of schizophrenia. We know that schizophrenia is caused by risk genes and environments and impacts brain maturation. The Schizophrenia Research Laboratory team will test how one such gene, neuregulin, acts to derail the normal development of the human cerebral cortex in patients who suffer.

Imaging genetics in schizophrenia and bipolar disorder: Adjudicating neurocognitive endophenotypes.
Green M.

Sialyltransferase in the bipolar and schizophrenic brain: examining the role of a novel generalised susceptibility gene.
Schofield P, Fullerton J, Shannon Weickert C, Donald J.

Congratulations also to Institute CEO Prof. Vaughan Carr and affiliates Dr Helen Stain, Terry Lewin, A/Prof. Robyn Langdon and Prof. Bryan Mowry on the award of NHMRC Grants for schizophrenia and other mental health research that have not recevied direct support from the Institute. These include:

Living in a rural community: A longitudinal study of the course and outcome of mental health and wellbeing.
Kelly B, Stain H, Lewin T, Carr V, Fragar L, Perkins D, Fuller J.

The effects of oxytocin on social cognition in schizophrenia.
Guastella A, Langdon R, Redoblado Hodge M, Ward P, Scott E.

Reducing impulsive behaviour in repeat violent offenders using a Selective Serotonin Reuptake Inhibitor.
Butler T, Schofield P, Greenberg D, Weatherburn D, Wilhelm K, Carr V, D’Este C, Jones A.

Studying the molecular basis of schizophrenia in a large, globally competitive Indian sample.
Mowry B, Thara R, Jorde L, Nyholt D.

Identifying eQTLs and endophenotyping known CNVs in a large Australian schizophrenia sample.
Mowry B.

Christmas is coming…help us find a cure

GENERAL NEWS

Christmas is coming…help us find a cure

A present with meaning

Nearly $1billion is spent on unwanted Christmas presents in Australia. This year give a gift that will be appreciated by all those affected by schizophrenia, the third largest cause of disability in young people.

Buy a charity gift card ($25 or $50) from Woolworths, Big W, Australia Post and Dick Smith stores or online and activate it at www.everydayhero.com.au by selecting the Schizophrenia Research Institute as your charity of choice.

Thank you for your kindness this Christmas.

Charity Christmas Cards

Order your personalized corporate Christmas cards and 40% per card will be donated to the Schizophrenia Research Institute.

Minimum order 50 cards, card cost from $1.29 each. www.christmascards4charity.com.au/sri

If you do not want to order online, please download and use the following order form.

Schizophrenia Research Institute Christmas Cards

Novel Targets for Schizophrenia Drug Development

RESEARCH NEWS

Novel Targets for Schizophrenia Drug Development

Institute scientist Dr Murray Cairns finds further evidence that microRNA could be involved in the development of shizophrenia.



Dr Murray Cairns.

microRNA specialist, Dr Murray Cairns, from the Schizophrenia Research Institute’s centre at the University of Newcastle, has made great steps of discovery in the molecular biology of schizophrenia by finding further evidence that miRNA could be involved in the development of the disorder.

miRNAs are exceptionally small pieces of RNA derived from non-coding genetic material. Their only function is to control the activity of other genes. Despite their size, these small molecules have a powerful influence, with a single microRNA having the capacity to subtly affect thousands of genes. They are very important in the development of the brain and are also involved in neural function and plasticity, which underpins the brains ability to learn and adapt to challenges.

In a recent study published in Molecular Psychiatry, Dr Cairns discovered widespread changes in microRNA production and expression throughout several regions of brains of people with schizophrenia. These elevated levels of miRNA would regulate the expression of many genes implicated in the illness. The magnitude of miRNA changes and their wide sphere of influence is another important step towards understanding the basis of a pathological influence in the development of schizophrenia.

The evidence supports the idea that schizophrenia could occur because of change in the regulation of many genes rather than specific gene mutations. Importantly, microRNA could be novel targets for drug development.

Institute to Offer New Resource to Community

RESEARCH NEWS

Institute to Offer New Resource to Community

World first Schizophrenia Library to open in March 2010.

Professor Vaughan Carr had a vision to create a one stop shop for all information on schizophrenia for researchers, clinicians, government and the general public. His vision will soon become a reality and a world first in March 2010 when the Institute will launch the Schizophrenia Library.

With support from NSW Health, this service to the community will be a free encyclopedia on all things to do with schizophrenia.

“We have a real need to collate and store information, to have it openly accessible for researchers, clinicians, policy makers, people affected by this disease and the general public,” said Professor Carr.

The library examines existing published reviews of information sourced from existing medical databases and all evidence is assessed and graded. There will be a number of different categories, including treatment, risk factors, course and outcome, central nervous system
anomalies, signs and symptoms, diagnosis, co morbid conditions, families and a population perspective.

Institute Scientist Leads New Study

Dr Melissa Green investigates shared genetics basis between schizophrenia and bipolar disorder

Dr Melissa Green.

Dr Melissa Green, who has worked with the Institute for over 10 years, was recently named as an Australian Research Council Future Fellow, with her project attracting close to $700,000 funding over four years from the federal government. She is leading a significant new study at the University of New South Wales, investigating the shared genetics basis between schizophrenia and bipolar disorder.

The study which requires over 300 people with schizophrenia, bipolar, schizoaffective disorder and healthy controls, is being conducted in collaboration with researchers at the Schizophrenia Research Institute, the Black Dog Institute, the Prince of Wales Medical Research Institute, and Leiden University, The Netherlands.

The work is being conducted as revisions to psychiatric diagnostic manuals are being undertaken and it is being considered whether schizophrenia and bipolar disorder should be grouped together.

“It’s very controversial. There’s not been enough evidence so far to support that change – this study will provide good quality evidence on this issue,” said Dr Green.

The research will also aid the early detection of cognitive vulnerability to psychosis in adolescence, facilitating early intervention and the development of new treatments that can be personalised according to genotype.

Dr Green and her team will integrate data from genetics, functional neuroimaging, cognitive testing and physiological measurements to pinpoint shared genetic susceptibility to the conditions, which may manifest in common cognitive and frontal brain dysfunctions.

Trial Continues to Give Hope

The Institute’s first clinical trial has commenced at the Schizophrenia Research Laboratory



Cyndi Shannon Weickert

Professor Cyndi Shannon Weickert, her drive for research and her personal story of her twin brother were the focus for the ABC’s Australian Story in May breaking this year’s record as the most viewed show with over 1 million Australians watching.

Professor Shannon Weickert is the Macquarie Group Foundation Chair of Schizophrenia Research and was recruited by the Schizophrenia Research Institute and partners to set up the Schizophrenia Research Laboratory* in 2007. In just over 2 years she has already translated her science from the benchtop to the patient and the Institute’s first clinical drug trial commences this year.

“We now know that this brain receptor doesn’t work in the normal way for people with schizophrenia. With this drug trial we can begin to stimulate it and try and get the neurodevelopmental program back on track. For some patients we could see improvements in language and memory,” she explains.

The trial commenced in July with an initial group of 12 volunteers. A total of 88 male and female patients with schizophrenia will ultimately receive this new therapy in addition to their ongoing medication. For six weeks, patients will take a drug called raloxifene, a hormonal modulator that stimulates the oestrogen receptor in the brain. The aim is to learn how this hormonal modulator can influence thought processing in schizophrenia and determine whether it could be used as a novel therapeutic treatment for cognitive problems in patients.

This drug is already used for cancer and osteoporosis and this is the first time it will be used in males with schizophrenia and in patients with schizophrenia under 40 years of age.

The Institute would like to acknowledge healthcare call centre experts McKesson Asia Pacific, who kindly donated teams of personnel to help the Institute cope with the huge number of calls received from volunteers wishing to join the trial.

Many thanks to all our supporters who have kindly sent a gift since the broadcast. We are still raising funds for Cyndi’s work and every donation counts. Congratulations also go to Cyndi and her team for being the only Australian researchers in 2009 to receive not just one but two Neuropathology Research Grants from the Stanley Medical Research Institute in the USA.

NSW Health Supports Clinical Trial

NSW Health provided the initial funding to establish Australia’s first ever Chair of Schizophrenia Research and recruit Prof. Shannon Weickert to Sydney. The Institute is extremely grateful to NSW Health for once again supporting this research with further funding of over $200,000 for the next three years to support the clinical trial.

You can help Professor Cyndi Shannon Weickert, star of ABC’s Australian Story.

To donate to the Schizophrenia Research Laboratory click here.

* The Schizophrenia Research Laboratory is a joint initiative of the Schizophrenia Research Institute, University of New South Wales, Prince of Wales Medical Research Institute, the Macquarie Group Foundation and is supported by NSW Health.

Australia’s Largest Brain Research Project

RESEARCH NEWS

Australia’s Largest Brain Research Project

The Australian Schizophrenia Research Bank to open in 2010

The core ASRB investigators (L-R): Prof. Ulli Schall, Kathryn McCabe, Prof. Bryan Mowry, Prof. Frans Henskens, Dr Carmel
Loughland, Prof. Stan Catts, Prof. Vaughan Carr, Prof. Chris Pantelis, Prof. Rodney Scott, Prof. Pat Michie and Prof. Assen
Jablensky.

The Australian Schizophrenia Research Bank is grateful to all our volunteers. This vast project of gaining a rich research bank of up to 4,000 people will be officially open for access by Australian researchers in July 2010.

With over 1,000 enquiries, volunteer assessment is now well underway and to date more than 650 people from across Australia have completed the assessment program, which includes MRI brain scans, blood samples and detailed clinical information.

As the bank continues to grow into a valuable data and sample resource for research in schizophrenia, we are pleased to announce another level of research support that it will provide. Based on the Institute’s successful Schizophrenia Research Register, which has supported close to 100 projects in NSW since 1998, researchers will also be able to apply to the bank to recruit schizophrenia patients and healthy controls for other research projects. This will significantly increase our capacity to support schizophrenia research across the nation. Without the generous support of our volunteers and supporters, this exciting project would not be possible.

Viertel Foundation Supports Australian Schizophrenia Research Bank

The Sylvia and Charles Viertel Charitable Foundation has been a long-term supporter of the Schizophrenia Research Institute over the last ten years, and once again the Foundation has come to the aid of schizophrenia research with a grant of $210,000 over three years to provide funding for a second Clinical Assessment Officer for the Bank in Queensland. Anna Stiller has joined Sandra Diminic in the Brisbane office, which will greatly enhance the capacity for recruitment and assessment of volunteers in Queensland.

The Global Value of Our ‘Bank’

The Australian Schizophrenia Research Bank is poised to play a valuable role on the stage of global research. However, this is a complex and challenging task, which is also being undertaken in other countries with greater populations.

As a reminder of this, the journal Nature recently reported findings of Genome-Wide Association Studies (GWAS) conducted on a total of 8,000 cases of schizophrenia and 19,000 controls. Although combined results from three studies showed that a segment of genes on chromosome 6 coding for proteins involved with immune functions were significantly associated with schizophrenia, surprisingly, none of the previously identified susceptibility genes were confirmed and no clear genetic markers of schizophrenia emerged.

What can the Australian Schizophrenia Research Bank contribute in this context? As well as the ability to confirm or refute these findings, and to contribute our data to international databases, the Bank has several important dimensions.

Diagnoses are rigorously determined and we have the capacity to apply several different diagnostic systems. Clinical and demographic characterization is comprehensive and multi-dimensional. Cognitive functioning is systematically assessed, and brain structure is measured using MRI scans. Our Bank therefore has the capacity to identify more uniform subgroups of schizophrenia according to diagnostic, clinical, cognitive and structural criteria. It is important to treat schizophrenia not as a single disease entity but as a syndrome comprising two or more entities or relatively homogeneous subgroups.

By enabling different approaches to the data, the Bank places the Schizophrenia Research Institute in a strong position to make significant contributions to future discoveries of the genetic aspects of schizophrenia.

Adolescents’ Vulnerability with Cannabis Use

The Institute partners with ANSTO to examine link between cannabis and psychosis



The ANSTO team L-R: Hongqin Wang, Dr Victoria Dalton, Dr Mathieu Verdurand, and Dr Katerina Zavitsanou.

Although one of the Institute’s newest centres, the group led by Dr Katerina Zavitsanou at ANSTO’s Radiopharmaceutical Research Institute has quickly gathered momentum. After several years with the Institute’s centre at the University of Wollongong, Katerina established an independent research group when awarded an ANSTO Senior Research Fellowship. Through a funding partnership with ANSTO, the Institute now employs two postdoctoral Research Officers under Katerina’s guidance: Dr Victoria Dalton joined the Institute in 2007 from Ireland, and Dr Mathieu Verdurand has arrived more recently from France – bringing expertise from around the world.

Research at this centre is investigating how cannabis use can lead to psychosis development, focusing particularly on the period of vulnerability during adolescence. This work aims to pinpoint the mechanisms underlying schizophrenia and drug-induced psychosis, and is using animal models to shed light on what makes some individuals more susceptible to developing psychotic disorders.

Nuclear Technology for Brain Research

ANSTO’s unique, cutting-edge facilities allow investigation of the brain’s messaging system through radiopharmaceutical labelling, which can map the distribution and highlight the action of specific neurotransmitters and receptors throughout the brain.

In a recent study, autoradiography was used to examine brain changes in rats following administration of drugs targeting cannabinoid CB1 receptors, thereby mimicking the main actions of marijuana or hashish. Short and long-term treatment with a cannabinoid CB1 receptor agonist had a profound and complex effect on the densities of these receptors throughout the brain. Strong decreases in cannabinoid CB1 receptor binding were seen in several areas of the brain involved in emotion and learning/ memory. These findings indicate that in certain brain regions, the effects of cannabis are only evident after repeated, long-term use. Recent studies also indicate that the adolescent brain responds differently to cannabinoid administration than the adult brain.

The team is continuing this research by examining other neurotransmitters, including the serotonin and dopamine systems, to determine how they are affected by cannabis use. In ongoing research, these affected systems will then be explored in-depth using the cutting edge imaging technology PET/SPECT to examine changes in the action of these neurotransmitters in the living animal brain.

The research team at ANSTO is bringing us closer to understanding schizophrenia and the role of drug use in psychosis development.

Grant Success for Institute Scientists

Five prestigious US grants worth over $US400,000 awarded to Schizophrenia Research Institute scientists

The US-based National Alliance for Research on Schizophrenia and Depression (NARSAD) is the largest non-government, donor-supported organisation that distributes funds for brain disorder research.



Dr Tim Karl, Dr Murray Cairns & Dr Jonathon Arnold.

The NARSAD Young Investigator Award Program offers up to US$30,000 a year for up to two years to enable promising investigators to either extend their research fellowship training or to begin careers as independent research faculty.

In 2009, two hundred NARSAD Young Investigator Awards were given to researchers from across the world, with only five awarded to Australian scientists. Three of these awards were obtained by Schizophrenia Research Institute scientists.

At the University of Sydney, Dr Jonathon Arnold will study the role of ABC transporter in resistance to antipsychotic therapy and cannabinoid-antipsychotic drug interactions.

Dr Murray Cairns will continue his research using a neurodevelopmental model of schizophrenia-associated changes in gene silencing at the Institute’s University of Newcastle centre.

At the Institute’s centre located at the Prince of Wales Medical Research Institute, Dr Tim Karl will investigate the role of cannabis in animals genetically predisposed to schizophrenia.

This is the second time that Dr Cairns and Dr Karl have been successful in obtaining support from NARSAD.



Prof. Cyndi Shannon Weickert.

The Stanley Medical Research Institute (SMRI) is a nonprofit organisation supporting research on the causes of, and treatments for, schizophrenia and bipolar disorder. Since it began in 1989, SMRI has supported more than $300 million in research in over 30 countries around the world.

SMRI supports a research grants program that covers a wide spectrum of approaches to research on schizophrenia and bipolar disorder, including neuropathology research that utilises samples from the Stanley Brain Collection.

In 2009, only eight neuropathology grants were awarded across the world. Prof. Cyndi Shannon Weickert’s group has been successful in obtaining two of these grants, the only Australian researchers who were successful in their applications.

The Schizophrenia Research Institute warmly congratulates all successful grantees. These grant successes reflect positively on the quality and relevance of the Institute’s research program.

New Steps Towards Schizophrenia Diagnosis

RESEARCH NEWS

New Steps Towards Schizophrenia Diagnosis

Institute research offers hope of an earlier diagnosis

Researchers at the Schizophrenia Research Institute are closer to finding a new way of detecting schizophrenia. In a recent study to be published in Schizophrenia Bulletin*, scientists have focused on a specific brain response, called mismatch negativity (MMN).

Results in schizophrenia patients show a deficiency in MMN is linked to a thinning of the brain’s grey matter in regions that govern communication, social cognition and planning of tasks.

At present schizophrenia diagnosis can only be made after intensive psychiatric assessment and can be hard to distinguish from other conditions in its early stages. As MMN is specific to schizophrenia and not present in other illnesses like bipolar disorder, this sound test may prove to be a biological index for the disease. Institute scientists are now investigating MMN in young people judged to be at risk of developing schizophrenia.

These new findings provide further evidence of MMN.