Youth Mental Health Facility

This new purpose built facility is designed to provide the most innovative research environment in the nation for studying the genetic, epigenetic and related developmental paths to adult mental illness. It will be located immediately behind and linked to the six-storey building that houses our basic science laboratories (Building G) as well as immediately adjacent and linked to the seven-storey clinical and translational research facilities (Building F) of the Brain and Mind Research Institute.

The combination of major advances in small animal models of psychiatric disorder with new insights from human genetics, epigenetic processes and environmental impacts on the later stages of adolescent and early adult brain development will allow the specific testing of new models of pathways to adult psychiatric illness. The facility will also permit expansion of the current clinical services suites (through the link to Building F) to focus on enhanced care for those with the most-treatment resistant psychotic and major mood disorders.

This $16 million building has been funded by the NSW State Government and is due to be completed by February 2009.

Level 0: Below ground: Medical Cyclotron and car park

Level 1: Entrance and Basic Genetics Laboratories

Level 2: Basic Research Laboratories for epigenetic studies

Level 3: Clinical Science Laboratories for investigating cellular changes during the onset of adult mental illness

Level 4: Specialised Clinical Practice for treatment-resistant psychiatric illness

Uncovering developmental paths to adult mental illness and substance abuse
The search for new pathways to adult psychiatric illness has shifted focus in recent years from simplistic models of genetic predetermination. More complex interactive models are currently being investigated between at-risk genetic factors that are inherited across generations and key environmental exposures during critical periods of brain development (e.g. intrauterine, early childhood years and early and late adolescence). While these environmental exposures may include traditional factors such as stressful intrauterine environments, birth trauma or head trauma it is increasingly clear that they may also include novel infective factors (e.g. viral agents), exposure to illicit drugs (e.g. cannabis, amphetamines and other stimulant drugs) and other environmental stressors during late adolescence or early adult life.

The mechanisms by which such environmental factors interact with genetic predispositions to cause critical changes in development of the adult brain are only just starting to be elaborated. Further, it is increasingly likely that some of these changes not only affect the individual with the illness but may also lead to basic changes in their genetic structure which may then be passed onto future generations by traditional genetic or novel epigenetic mechanisms.

If it is possible to characterise these new pathways to adult psychiatric illness, the possibility emerges of prevention of the onset of these most disabling conditions even in those who are genetically susceptible. Much research in recent decades has been overly pessimistic about the possibility of identifying such paths which can be halted in the late childhood or early adolescent years. These previous paths have assumed that little active pathology occurs after the neonatal or early childhood period. Current neuroimaging and clinical and neuropsychological research, however, indicates that active processes within the brain that are relevant to the onset of these disorders are occurring right through to early adulthood and that some can already be slowed or reversed by active therapeutic approaches.

On almost a daily basis, new genetic targets related to brain development or key aspects of brain physiology are being proposed as vulnerability factors to major mental illness. However, the real neurobiological consequences of these genetic risk factors has been poorly characterised and the implications for prevention or treatment practice has not been determined. The basic biology of epigenetic processes, and their relevance to neurobiology, awaits clear delineation. Both of these key areas require major investments in mouse models of illness, where one is able to study the direct interactions between altered genetic status and exposures to key environmental toxins (e.g. viruses, drugs, social deprivation) or environmental enhancements (e.g. diet, social manipulations, enriched environments).

Our basic science program in genetics, epigenetics and the brain effects of critical novel environmental exposures will be strongly linked with our NHMRC-supported national program of basic and clinical research for early intervention in major psychiatric disorders (led by Professor Pat McGorry at Orygen Youth Health and the University of Melbourne). We will establish a genuine novel program of linked animal and human research where the developments in either domain are quickly translated into further detailed neurobiological and disease prevention research programs. At this stage, this linkage does not occur elsewhere in the nation.

Research programs
The research program of this new building integrates the basic animal research elements with the cellular research labs that are necessary to understand the ways in which interactions between at risk genotypes and toxic environmental factors result in alterations in signal transmission within the cells of the central nervous system. To conduct this work, researchers needs access to a range of genetically-altered mice, longer-term mouse breeding programs and sustained environments for studying the effects of alternate toxic factors at different stages of brain and social development. Additionally, related laboratories then study the ways in which the various range of brain cell signalling systems (neuronal, astrocytes, immunologically-activated microglia) are affected by these various combinations of genetic and environmental factors.

Relevant biological specimens are not only collected from the specific mouse models of illness but also from humans with the major psychiatric disorders (via blood and related-cellular testing) and their immediate family members. These specimens are used to look not only at indicators of genetic and environmental risk to psychiatric illness but also factors that are related to preferential response to available pharmacological and other novel neurobiological and immunological therapies. As these specimens are collected from a unique national cohort of young persons in the early stages of illness they have the potential to be considerably more informative than samples collected from those in later or chronic stages of illness.

Clinical focus
In addition to the basic and applied animal and human neurobiology programs of the complex, additional areas will be devoted to the expansion of novel treatment programs for those with treatment resistant psychotic and major mood disorders. Patients with these disorders are often neglected and new treatment approaches are often not linked with novel neurobiological research programs.