Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD): 10 Years of Australia's First Virtual Research Institute

Abstract

Objective: To review the first 10 years of operation of the Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), Australia's first virtual research institute.

Method: Narrative description of the evolution of NISAD.

Results: Since inception in 1996, NISAD has developed a wide range of activities to enhance existing efforts and develop new initiatives in schizophrenia research, initially throughout New South Wales, but increasingly on a national scale. This involved the initial development of critical research infrastructure to provide the foundation, with the subsequent focus on developing a multidisciplinary programme of schizophrenia research, across the basic to applied research spectrum. While the primary focus has been the scientific domain, NISAD has also played a leading role in increasing public awareness of schizophrenia as a disease amenable to scientific investigation.

Conclusion: NISAD has succeeded in building a framework to apply the latest developments in neuroscience to the study of schizophrenia and has formed a multidisciplinary network of clinicians and neuroscientists who are actively collaborating on a range of research initiatives. The ‘virtual institute’ structure of NISAD has proven cost-efficient and consistent with innovative thinking about research resource management.

Keywords

institute network psychosis research schizophrenia

The development of the Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD) has been unique in the Australian research landscape, being the first virtual medical research institute – or ‘institute without walls’ – in the country. This has meant that NISAD's research programme has been network-focused rather than edifice-based.

March 2006 marked NISAD's 10 year anniversary. This milestone seemed an appropriate time to document this first period of the institute's existence. There had initially been some doubt about the proposed structure of NISAD and the aim to create an open, statewide research network. Ten years later, NISAD has confirmed its adherence to this vision and helped to create a vibrant and productive community of schizophrenia researchers in NSW.

This review describes NISAD's evolution, including the formation of the institute, the early focus on research infrastructure, the development and refinement of an integrated schizophrenia research programme and future directions.

Establishment of NISAD

In the early 1990s, little schizophrenia research was being undertaken in NSW. The few investigators involved were poorly resourced, had little access to research infrastructure, and communication and collaboration was minimal. Feelings of frustration regarding the lack of research activity were expressed by patients and carers, and there was a consciousness of missed opportunities for schizophrenia research in NSW.

At the 1991 Schizophrenia Fellowship of NSW Symposium, Stanley Catts presented the results of a survey of scientists and clinical specialists, which concluded that a lack of infrastructure was the major barrier to the advancement of schizophrenia research in NSW.

It was also apparent that private/corporate philanthropy and increased public support would occur only if government provided a lead. He proposed the formation of a research institute to encourage the application of the brain sciences to schizophrenia research. The Schizophrenia Fellowship of NSW endorsed this proposal. Meanwhile, NISAD's “champion” Don McDonald was gathering political support and secured the endorsement of the NSW Labor Council. A final proposal was released in March 1994, which called for the establishment of an ‘institute without walls’ to provide infrastructure for networking and collaboration between existing neuroscience centres and schizophrenia researchers in NSW.

Critically, these years of cooperative planning resulted in firm partnerships being forged between patients, carers and the research community, with excellent collegial relationships emerging between neuroscientists and clinicians. This coalition provided a persuasive body of opinion arguing for the establishment of NISAD.

In association with the Schizophrenia Fellowship of NSW, researchers sought bipartisan support from the State Government and Opposition. The proposal was adopted by the NSW Labor Party, then in opposition, with a pledge to provide $2m over 5 years to establish NISAD. Upon winning office in 1995 this pledge was honoured and NISAD was officially born.

Why a virtual institute? Benefits and challenges

A virtual institute was determined to be cost-efficient and consistent with innovative thinking about research resource management. Participating scientists remained in their usual academic, clinical and technical environments, maintaining access to laboratory space, equipment and expertise in their respective centres. NISAD supported the application of these research resources to schizophrenia. That is, NISAD enhanced the work of participating research centres in relation to schizophrenia, without incurring costly administrative and capital overhead expenses, thereby obtaining maximum value from each research dollar.

From a scientific perspective, a multidisciplinary approach was thought to provide the best opportunity to expedite the research process by providing a framework to obtain confirmation from convergent evidence, rather than replication. Although major improvements in measurement have benefited schizophrenia research, results are generally difficult to replicate and can be considered inconclusive. The NISAD model recognized that before major discoveries could be made, research into complex diseases required the development of model systems, convergent experimental approaches, and availability of infrastructure of relevant scale and measurement resolution. The NISAD virtual structure supported this method of conducting research, with scientists and clinicians working across multiple disciplines, under a flexible thematic research and infrastructure-focused panel structure, with oversight and direction provided by a Research Council of senior scientists.

The virtual structure also allowed for a high degree of flexibility in the way NISAD conducted and supported research. The needs of individual centres vary greatly depending on a range of factors, including location, current level and type of funding support, access to local infrastructure etc. NISAD tailored support to suit the needs of the centres and exercised flexibility in changing this support as the priorities of individual centres changed. This type of flexibility would not have been possible in a traditional institute structure.

One of NISAD's first major challenges was to engage internationally renowned Australian neuroscientists and clinicians, many of whom had little interest in schizophrenia research and harboured reservations about the virtual structure. Buy-in was initially achieved by providing a broad funding base and building the research programme around the expertise, interests and skills of the senior scientists at each particular site. However, this meant that there was little strategic direction and convergence in the research programme. Although this model was appropriate initially, the downside was an inability to focus project aims in the early years. This diversity and lack of focus was a key criticism raised during NISAD's external review in 2001. A tighter focus was required and a more strategic approach to research planning has since been adopted. This has included the progressive development of an overarching theme and research strategy that grew out of a series of meetings aimed at achieving consensus among scientists. Subsequently, financial incentives were used to re-direct work into areas within the redefined focus. The direct employment of scientists by NISAD, as opposed to distributing funds to host organizations or secondment of existing staff, also assisted in shaping the research programme through performance review and setting annual goals and objectives. However, refinement of the research programme remains a work in progress.

The decision to focus on infrastructure development during the formative years meant that research productivity and related outcomes were lower than would have been the case had NISAD initially invested more heavily in existing research enterprises. This decision has now been vindicated with significantly increased productivity from NISAD-supported research in 2002–2006 (130 papers published/in press, $4.2m direct grant funding, $10m indirect grant funding, 33 research higher degrees awarded and 320 conference presentations) compared to 1996–2001 (10 papers published, $0.4m direct grant funding, $1.8m indirect grant funding, two higher degrees awarded and 80 conference presentations). The increased productivity is almost entirely based on the platform of infrastructure developed in the early years.

Scientific governance and leadership has been another challenge for the virtual institute model. The NISAD research programme is overseen by a Research Council of senior scientists who all receive NISAD support. Therefore, to address potential conflict of interest issues, an independent Scientific Advisory Committee was created in 2001 to advise the NISAD Board on the institute's research programme. The position of scientific director within a virtual structure also calls for a non-traditional approach with the position more one of facilitation than direction. The structure also requires a research manager to operate across the large research programme, helping to bring researchers together and develop the multidisciplinary programme.

The virtual model also requires innovative communication strategies to overcome the loss of collegial corridor conversations that would otherwise enhance collaborative research. Email and other modern communication technologies are essential in maintaining communication between NISAD scientists. Regular teleconferences and scientific summits also help to address this issue. The best evidence that NISAD researchers are effectively communicating is the wide range of collaborative research projects undertaken across disciplines and sites.

The virtual structure means that NISAD is dependent on infrastructure support from partner organizations where NISAD employees are located and research is conducted. Formal research agreements were developed with all institutions where NISAD research takes place to secure these arrangements. These agreements cover all aspects of NISAD research at partner organizations and also include items such as intellectual property, indemnity, ethics etc.

The virtual structure has limited NISAD's capacity to obtain and administer NHMRC grant funding, with the institute being unable to satisfy all the criteria needed to be awarded NHMRC Accredited Independent Medical Research Institute status until 2004. This status allows NISAD to receive infrastructure support on NHMRC grants administered by the institute. Another limiting factor in this respect was NISAD's decision to administer NHMRC grants awarded to its employees only if they were multi-institutional; all other grants are administered by the employees’ host institutions.

Infrastructure building: the first 5 years

This first period of NISAD's existence was successful in building research capacity, initiating research centres, developing collaborative links and increasing the number of scientists participating in schizophrenia research in NSW.

NISAD Schizophrenia Research Register

To overcome the lack of access to clinical populations of sufficient size who were willing to participate in research, the NISAD Schizophrenia Research Register was launched in 1998. Based at the University of Newcastle, the Register has recruited more than 1200 volunteers. Approximately 600 people have participated in more than 50 schizophrenia research studies in NSW, Queensland and Victoria. This has resulted in 25 publications in peer-reviewed journals since 2001. Reviews and comparisons of the data collected from Register volunteers have been published [1–4].

New South Wales Tissue Resource Centre

NISAD was instrumental in supporting the establishment of the New South Wales Tissue Resource Centre (NSW TRC), a facility that collects, stores and distributes well-characterized fixed and frozen post-mortem human brain tissue, for projects related to schizophrenia (and alcohol-related disorders) [5]. Located at the University of Sydney, the NSW TRC currently holds more than 450 cases and has supported more than 65 schizophrenia-related studies throughout Australia, Japan, Belgium and Canada. This has resulted in 30 publications in international peer-reviewed journals since 2000. A review of the NSW TRC has been published [6].

Gift of Hope Brain Donor Programme

To augment the NSW TRC, NISAD developed the Gift of Hope (GoH), a volunteer brain donor programme, which allows people to consent to post-mortem donations of their brains for schizophrenia research. Donors take part in a range of assessments, thus providing brain tissue with an unprecedented depth of accompanying clinical, neuropsychological and neuroradiological data. The GoH programme currently lists over 350 volunteers and a review of the programme has been published [7]. Although public perception regarding brain donation appears to be negative, a study examining the responses from families of deceased persons to the question of brain donation found the opposite, with a 60% permission rate [8].

Hunter DNA Bank for Schizophrenia and Allied Disorders

A limiting factor in genetic schizophrenia research has been obtaining large samples to perform analyses of sufficient statistical power. The Hunter DNA Bank for Schizophrenia and Allied Disorders was established in 2002 to facilitate genetic research by providing researchers with access to DNA, RNA and lymphocytes, cross-referenced with clinical and neuropsychological data from people with schizophrenia [9]. To date the DNA Bank holds more than 175 samples.

NISAD Virtual Brain Bank

The NISAD Virtual Brain Bank commenced in 2004 and currently holds 200 magnetic resonance imaging (MRI) scans from people with schizophrenia at various stages of their disease. These scans are analysed using a novel technique, which preserves individual gyral anatomy, developed by the Laboratory of Neuro Imaging, University of California Los Angeles [10] and brought to Australia by NISAD. Once analysed, the images can be grouped together and subtle regional changes detected in cortical structures with high accuracy.

Other research infrastructure

Together with the development of the core infrastructure facilities described here, NISAD has been instrumental in supporting NSW researchers via the development of infrastructure for implementing functional magnetic resonance imaging (fMRI) studies, establishment of collaborative centres for human brain research to provide safe environments for neurobiological research using post-mortem tissue and assisting in the establishment of an animal behaviour phentoyping facility.

Highlights of the NISAD research programme: 1996–2006

NISAD's research programme has largely been conducted at the University of NSW, University of Newcastle, University of Sydney, University of Wollongong, Macquarie University, Liverpool Hospital, Westmead Hospital, Royal North Shore Hospital, Garvan Institute of Medical Research and Prince of Wales Medical Research Institute. Major interstate collaborations have involved the Queensland Centre for Mental Health Research, University of Queensland, Centre for Clinical Research in Neuropsychiatry and the University of Western Australia. International collaborations have involved the University of California Los Angeles and the University of Duisburg-Essen.

Cognitive Neuroscience Panel

The Cognitive Neuroscience Panel focuses on research in cognition, computational modelling, and cognitive neuroscience aimed at understanding the neural systems implicated in schizophrenia.

Executive functioning in schizophrenia

NISAD researchers used the Tower of London (TOL) paradigm to measure executive functioning in fMRI and positron emission tomography environments [11]. Different patterns of fMRI neural activation in chronic schizophrenia suggested impaired recruitment of neural networks underlying executive function [12]. Structural and functional MRI data were integrated in the one analysis, demonstrating a correlation between areas of reduced regional cortical thickness and impaired brain function in first-episode schizophrenia [13].

Auditory processing in schizophrenia

Reduction in the amplitude of an early auditory event-related brain potential (ERP) in schizophrenia, mismatch negativity (MMN), has been proposed as a biological marker of vulnerability for schizophrenia. NISAD researchers have demonstrated an appropriate functional neuroimaging model of MMN in healthy subjects, confirming the notion of a fronto-temporal neural network subserving auditory sensory memory processing [14], with reduced activation observed in this network in chronic schizophrenia, in line with MMN data [15]. Other NISAD research utilizing MMN has demonstrated that deficits in temporal processing in particular are evident in the early stages of the disorder [16], and occur over a range of time scales [17] and temporal contexts [18].

Attention in schizophrenia

NISAD researchers investigated the higher-order cognitive control processes involved in switching attention between tasks in healthy populations [19, 20], showing generalized response slowing and impaired attentional control in schizophrenia [21]. Investigation of the recovery cycle of the auditory N100 ERP component, which measures attention, supported the hypothesis of altered inhibitory processing of auditory stimuli in both schizophrenia and bipolar disorder [22, 23].

Visual/emotion processing in schizophrenia

Using visual scanpath technology NISAD scientists demonstrated restricted scanpaths in schizophrenia, most pronounced for positive and neutral compared to negative expressions [24], with similar but attenuated restriction of scanpaths in first-degree biological relatives [25], a finding not seen in affective disorder [26]. This provides evidence that visual scanpath dysfunction may be a trait marker in familial transmission of schizophrenia. Further research demonstrated differential effects on visual scanpaths and recognition accuracy between patients on atypical and typical antipsychotic medications [27], specific aberrations in the viewing of threat-related faces in association with delusions [28], and reduced attention to contextual information when interpreting the meaning of ambiguous facial expressions [29].

Studies using a neural network model [30] and healthy subjects performing a facial emotion categorization task [31] suggested that a generalized deficit at the earliest stages of processing could account for the negative emotion recognition impairments in schizophrenia. Subsequent research in schizophrenia populations provided additional confirmation that facial perception processing is disrupted at the very earliest ‘encoding’ stage, prior to activation of elaborate emotion recognition mechanisms [32, 33].

Integration of fMRI with measures of autonomic arousal [34, 35], have been used to explore a variety of networks in response to fear in healthy controls [36–38], suggesting that the negative emotions (e.g. fear, anger, disgust) may engage distinct responses within limbic and arousal systems, with common activation of the medial prefrontal cortex [39]. Schizophrenia patients displayed a dysjunction between arousal and limbic–medial prefrontal responses to negative emotion [40] and a loss of the normal functional connectivity in these systems during fear perception [41, 42]. These findings suggest that a lack of coordination in orienting, perceptual processing and prefrontal regulation of fear stimuli may contribute to a cycle of misattribution about incoming signals of potential threat in schizophrenia.

NISAD researchers have also used fMRI to investigate emotion processing in bipolar disorder, with separate functional routes in the evaluation of emotional stimuli demonstrated, via the recruitment of additional subcortical limbic systems when more advanced prefrontal cortical processing could no longer be engaged [43, 44].

Theory of mind and delusions in schizophrenia

There may be multiple pathways to poor insight, one of which is a theory of mind (ToM) difficulty that impairs capacity to simulate other perspectives for the purpose of critically evaluating beliefs [45]. Such ToM impairment interferes with empathy and comprises social functioning [46]. Studies of orienting to gaze indicate that ToM difficulties in schizophrenia co-occur with social hyperarousal/vigilance and impaired controlled/inferential processing [47], a combination that may augment paranoid ideation. NISAD scientists have developed a new tool to assess persecutory ideation [48] and have found low covert self-esteem, high need for closure and a self-defensive wariness of others in paranoid schizophrenia [45, 49–51].

Neurobiology Panel

The Neurobiology Panel targets human and animal brain systems to identify the abnormally functioning neurons and neurotransmitters that could be responsible for schizophrenia, as well as attempting to identify the genetic factors that contribute to the development of schizophrenia. The Panel also undertakes behavioural studies of animal models relevant to schizophrenia.

Post-mortem human brain research

Immunohistochemical studies identified the distribution of neurokinin NK₁ and NK₃ receptors in prefrontal and visual cortex [52] and NK₁ receptors in the amygdala [53] of control subjects, with markedly increased levels of NK₁ receptors observed in the prefrontal cortex in schizophrenia [54]. A subsequent study found increased density of NK₁ receptors in the forebrain cortex of guinea pigs chronically treated with haloperidol [55], suggesting that the above human brain alterations may be due to antipsychotic medication effects. Immunohistochemistry was also used to characterize neuronal populations that principally produce gamma-amniobutyric acid (GABA) as their output in several brain regions that have previously been linked to schizophrenia, including the anterior thalamus [56–58], posterior cingulate cortex [59], posterior hypothalamus [60] and prefrontal cortex [61]. However, no evidence of schizophrenia-specific alterations was found.

Using ligand binding and receptor autoradiography, changes in receptor density have been shown in the anterior and posterior cingulate cortex for glutamate [N-mthyl-D-aspartate (NMDA), L-α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)] [62, 63], cannabinoid (CB1) [64, 65], serotonin (5HT-2) [66], GABA-A [67] and muscarinic (M1/M4) receptors [67, 68] in schizophrenia. However, no change in muscarinic (M2/M4) receptors was observed [67, 69], suggesting a therapeutic potential for muscarinic M1 receptor agonists in schizophrenia [70]. Studies of the superior temporal gyrus (STG) showed similar changes for muscarinic (M1/M4) [71] and GABA-A receptors [72] in schizophrenia.

Genomic research in schizophrenia

Using microarray techniques, alterations have been observed in human blood lymphocytes for a number of genes with known functions in the brain, such as myelination, receptor regulation and metabolism [73]. Further analysis of this sample has identified distinct age-related gene expression profiles for subgroups of schizophrenia. Examination of post-mortem human amygdala tissue has identified dysregulation of genes involved in presynaptic function, myelination and cellular signalling, implicating dysfunction of the cytomatrix active zone of amygdala synapses in schizophrenia [74].

A number of genes involved in brain development and function have been shown to be significantly altered in laboratory animals treated with anti-manic and anti-psychotic medications [75, 76]. Subsequently, results from the anti-manic (lithium) study were brought together with human genetic data to implicate a gene called FAT and its protein partners in a molecular pathway involved in the pathogenesis of bipolar disorder [77].

NISAD researchers conducted the first proteomic analysis of post-mortem human anterior cingulate tissue in schizophrenia. Proteins involved in metabolism, oxidative stress, the cytoskeleton and the synapse were significantly altered in schizophrenia, representing the products of 36 unique genes [78] and suggesting possible mechanisms of action in disease pathogenesis. A proteomic examination of the striatum of acute methamphetamine-treated rats, a model suggested to be related to the neuroadaptive processes involved in schizophrenia, has identified a number of altered proteins [79].

Animal models of relevance to schizophrenia

Results from a behavioural study of a heterozygous neuregulin (Nrg1) knockout mouse, which included the effects of environment (housing conditions) and age, suggested the Nrg1 knockout is a useful model for investigating schizophrenia-related phenomena [80]. The age and environmental effects observed in Nrg1 mutant mice, were consistent with the pathophysiology and neurodevelopmental theory of schizophrenia.

Intrinsic somatosensory deprivation, induced by neonatal capsaicin administration in rats, produced brain changes resembling those found in schizophrenia patients, including reduced cortical thickness, larger ventricles and increased neuronal density in several cortical areas [81]. Sensory input dysfunctions have the potential to affect processing of all input information, and it is thought that this model could account for the varying severity and range of symptoms in schizophrenia.

NISAD researchers have pioneered an oral antipsychotic administration method in animal models [82] demonstrating extrapyramidal side-effects (EPS) and effects on anxiety and motor activity during treatment with haloperidol and risperidone [83]. Furthermore, chronic risperidone treatment accompanied by an EPS-like behavioural phenotype resulted in alterations in the rat striatal protein profile, possibly subsequent to blockade of dopaminergic systems [84]. Related animal studies have shown regional changes in neuropeptide Y gene expression and serotonin receptor (5-HT2a and 5-HT2c) mRNA expression following treatment with antipsychotics in rats [85, 86]. Regional alterations in muscarinic (M2/M4) and serotonin (5-HT2a and 2c) receptor densities following diets high/low in different fatty acid types have also been observed [87, 88].

Psychopharmacology and Therapeutics Panel

This panel focuses on research investigating the effects of medication and/or pharmacological probes in schizophrenia patients and at-risk populations. It also provides a platform for initiating trials of new interventions, both pharmacological and non-pharmacological.

Substance use and schizophrenia

Using fMRI techniques, NISAD researchers have discovered similar patterns of reduced brain activation in first-episode schizophrenia patients (not cannabis-using) and chronic cannabis users, suggesting the possibility of shared pathological processes in these conditions [89]. Further research has shown that peripheral fatty acid alterations in relation to stress were differentially evident in schizophrenia patients according to cannabis use history [90], contributing to evidence linking enndocannabinoid abnormalities, cannabis use and stress in schizophrenia.

NISAD researchers have made a range of recommendations in regards to smoking interventions [91], and identified associations between substance use and depression/reality distortion symptoms, while lower personal disability was found in treatment seekers compared to epidemiological samples [92]. A subsequent randomized controlled trial (RCT) demonstrated the utility of an intervention comprising nicotine replacement therapy, motivational interviewing (MI) and cognitive behaviour therapy (CBT) in smokers with a psychotic disorder [93]. However, another RCT that used a combined MI/CBT intervention to reduce substance use among people with psychotic disorders was associated with only modest, short-term improvements in cannabis use and depression [94].

Remediation and recovery from schizophrenia

An intensive, single training session with a new computer-based remediation tool, demonstrated significantly improved recognition of facial expressions of emotion in schizophrenia [95]. The integration of eye movement data has demonstrated increased visual attention to important facial features following training [96], suggesting that computer training tools may be useful in remediation of facial emotion recognition impairments.

NISAD scientists developed a five-stage consumer-oriented model of measuring recovery from schizophrenia [97], which led to the development of a new measure of recovery called the Stages of Recovery Instrument (STORI). Investigation of the STORI has demonstrated preliminary support for a stage model of recovery, and validation of the instrument as a measure of patient definition of recovery [98].

Pathways to care in early psychosis

A NISAD study investigating the pathways by which young people first accessed treatment found an extended timeline, with approximately 50% of contacts made during periods of acute psychosis not leading to appropriate treatment [99]. Comorbid substance abuse further lengthened the time to receive appropriate treatment.

The future

NISAD research has grown by supporting the establishment of a broad range of groups in NSW, with expertise in a range of techniques and approaches to schizophrenia research. However, NISAD's focus is increasingly turning to national collaborative research.

Significant advances in schizophrenia research have been limited by the difficulty in achieving sufficiently large samples of cases for studying the causal role of multiple genetic factors. In 2005–2006, NISAD was awarded an NHMRC enabling grant and a Pratt Foundation grant to establish the Australian Schizophrenia Research Bank (ASRB), in collaboration with investigators at the Universities of Queensland, Western Australia and Melbourne. The ASRB aims to recruit a large sample of volunteers with schizophrenia (n = 2000) and healthy controls (n = 2000). Data collection will include clinical and cognitive characterization, blood banking involving DNA extraction and the establishment of immortal cell lines, and structural MRI brain scans using standardized imaging and analysis methodology. This will provide Australian researchers with access to a facility containing comprehensive, cross-referenced data, able to support schizophrenia research across the clinical, cognitive, genetic, brain imaging and linked domains. This will enable research questions that require large sample sizes to be addressed by Australian researchers, particularly those who would not normally have ready access to clinical populations.

NISAD has partnered with the University of New South Wales and Prince of Wales Medical Research Institute to create the NISAD Chair of Schizophrenia Research. The Chair will be in the field of the developmental neurobiology of behaviour and cognition related to schizophrenia, entailing research at the molecular and cellular levels and in animal behavioural phenotypes of relevance to schizophrenia. The Chair will be supported by NISAD's existing expertise in genetics, neurobiology, cognitive neuroscience, and pharmacology and therapeutics.

NISAD is also playing a leading role in a national coalition of psychosis researchers and organizations seeking funding to establish the Australian Psychosis Research Network (APRN). The aim of APRN is to provide strategic direction and coordination for a national programme of clinical, neuroscience, and genetic research into psychotic disorders. This national effort will coordinate the application of technical and clinical infrastructure, promote standardization of measurement across research centres, support multicentre studies of large representative clinical cohorts and their long term follow up, enable integration of research databases nationally, and establish multidisciplinary meeting processes for scientific exchange (see www.aprn.net.au).

Conclusion

NISAD has succeeded in building a framework to apply the latest developments in neuroscience to the study of schizophrenia, using a non-traditional virtual institute model. While the primary focus has been the scientific domain, NISAD has also played a role in increasing public awareness of schizophrenia as a disease amenable to scientific investigation.

NISAD has provided infrastructure for much of the schizophrenia research effort in NSW. This infrastructure has directly led to major federal funding for a variety of schizophrenia research projects and ensured that NISAD's research productivity has achieved a level comparable to other major research institutions. The institute has played a major role in creating a vibrant, multidisciplinary network of more than 100 clinicians and neuroscientists in NSW who are actively collaborating on a range of schizophrenia research initiatives. Increasingly, NISAD's focus is turning to collaborative research on a national scale.

Footnotes

Acknowledgements

We acknowledge the support of the people with schizophrenia and their carers, who have been NISAD's staunchest supporters. We also acknowledge the pivotal and ongoing support of the Schizophrenia Fellowship of NSW. The authors acknowledge all the scientists who have been involved in the work of NISAD, both past and present. Thanks to Therese Garrick, Carmel Loughland, Ulrich Schall and Paul Tooney for comments on the manuscript. We are indebted to NISAD's ‘founding fathers’: Jim and Carmel Breene, Jack and Judy Gibson, Don McDonald and Alan Tunbridge – all of whom have had much personal experience of the challenges and trauma that schizophrenia can bring.

NISAD is supported by infrastructure funding from NSW Health. Major direct supporters have included (in alphabetical order): Alma Hazel Eddy Trust, Andrew Thyne Reid Trust, Australian Rotary Health Research Fund, Baxter Charitable Foundation, Cecilia Kilkeary Foundation, Ian Potter Foundation, J.S. Love Trust, Macquarie Bank Foundation, Myer Foundation, National Alliance for Research on Schizophrenia and Depression, National Health and Medical Research Council, Perpetual Foundation, Pratt Foundation, Rebecca Cooper Medical Research Foundation, Ron and Peggy Bell Foundation, Ronald Geoffrey Arnott Foundation, St George Foundation, Sylvia and Charles Viertel Charitable Foundation, Telstra Foundation. We gratefully acknowledge the continued support from the Construction Forestry Mining Energy Union (CFMEU) and the many generous corporate and private supporters, who are too many to mention individually.

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