About APRN

APRN aims to establish an Australian collaborative research network for psychotic disorders that:

• builds pathways for discovery, from gene to therapy, by vertical integration of scientific activity across each level of research expertise and resource
• achieves critical mass within each level of research expertise by horizontal integration of collaborating research centres across institutions, and across states and territories
• actively engages consumers and carers, clinicians and policymakers, and the general public, in the promotion and development of psychosis research

Currently available treatments for psychosis are non-specific, affecting only the secondary symptoms. For major improvements in clinical outcomes, we must move from non-specific to specific treatments that directly target the primary underlying disorders. To do this, research findings at the level of cellular and molecular neuroscience and genetics must be related to clinical research into psychotic disorders – indicating the need for collaboration between basic scientists and clinical researchers.

The fields that are relevant to psychosis research include molecular and cellular neuroscience, epidemiological genetics, neuroimaging, drug design, cognitive neuroscience, and therapeutics. These fields go from the ‘micro’ (molecular neuroscience) through to the ‘macro’ (therapeutics). Pathways for treatment discoveries are built by vertical integration of these levels of research, so that there is a tightly interlocking chain of research supporting the application of fundamental (basic) research findings to the development of therapeutics.

Translational Research and SPOREs

The US National Institutes of Health (NIH) have highlighted the need to better link research to clinical practice, and have developed the notion of translational research. Translational research seeks to translate advances from the bench or animal laboratory into clinical application.

In relation to cancer research, NIH developed funding models called Specialised Programs of Research Excellence (SPOREs). SPOREs conduct translational research that requires interdependence between basic and clinical investigators in both the planning and implementation of research and emphasise the application of basic research findings to patients and populations. SPOREs must demonstrate effective integration of basic and applied research that translates into areas of early detection, diagnosis, therapy, and prevention. They must represent all the required levels or areas of research expertise and infrastructure.

If the SPOREs model is to be applied to psychotic disorders, it will need to include genomics, proteomics, anatomical and chemical neuropathology, structural and functional neuroimaging, in vivo chemical imaging including spectroscopy, drug design, endophenotypic measurement, clinical assessment, and novel therapeutics.

Bigger studies = better results

Typically, psychosis research is carried out on small groups of patients – often groups as small as 10 to 20 are compared with similar sized groups of healthy subjects. This research is useful in looking for promising leads. But because of the low precision of clinical measurement and the high complexity of psychotic disorder, major advances require multi-centre recruitment of much larger samples – with hundreds or even thousands of subjects per group. The assessment of these large samples includes clinical ratings, neuropsych- -ological testing, functional brain mapping, and genotyping.

To permit carriage of large-scale studies using multi-modal assessments, centres expert in these techniques must horizontally integrate within each specialised knowledge area to ensure standardisation of measurement across centres and regions. This will drive collaborative networking of these and clinical centres to ensure uniform clinical assessment with across-centre reliability; standardisation of imaging data acquisition equipment and sequences, and analysis software, across magnetic resonance imaging (MRI) sites; integration of large-scale databases; and, centralised genotyping and genetic analysis procedures.

Focus on the genes

APRN will seek to build up research programs around the genes that have been recently implicated in the development of the psychotic disorder s – and their likely functional roles in terms of synaptic plasticity. By gathering converging evidence from each of the levels of research about the functional significance of these genes, this project will contribute to the international effort to define the precise role of the genes in psychotic disorder.

Viewed from a global perspective, this nationally coordinated project would be ideally equipped to participate in international research collaborations, and well positioned to benefit from overseas funding and technology transfer.

From research to better practice

Because the time required for translation of a fundamental research discovery into an advance in therapeutics can be in the order of a decade, APRN will include research with potential near-term improvements by seeking to extract therapeutic value from existing knowledge.

An example of this is the investigation of whether clinical outcomes can be improved by varying the order or combination of currently available treatments, especially studies of combined antipsychotic drug and psychosocial intervention or adjunctive pharmacological therapies. Studies such as these will ensure that the work is relevant to today’s patient, as well as to those of the next generation. Hence, a range of research projects that offer a mix of nearterm, medium-term, and long-term outcomes will be included.

In a related fashion, the proposal will have a focus on the dissemination of evidence-based practice to support rapid translation of new ideas from research into clinical application. This activity has been called Research into practice and involves efforts in continuing education for clinicians and managers in addition to evaluation of the effectiveness of strict adherence to agreed-upon treatment guidelines and protocols.

Finally, a national research collaboration of the scale and scope proposed requires well developed scientific management and meeting processes. Indeed, regular meetings of the scientists will be the creative powerhouse for the entire endeavour. This thinking must also be informed by consumer and community concerns.