Abstract
ASC01 PROGRESSIVE BRAIN STRUCTURAL CHANGES AT THE ONSET OF PSYCHOSIS
Chris Pantelis
Recent structural imaging studies suggest that progressive changes occur early in the course of psychosis. Our initial longitudinal MRI findings in young people at ultra-high risk (UHR) for psychosis identified progressive left-sided temporal, orbitofrontal and bilateral cingulate changes in those converting to psychosis versus non-converters (Pantelis et al, Lancet, 2003). In the context of a staging model of psychosis (McGorry et al, Aust N Z J Psychiatry, 2006) we have undertaken a further series of longitudinal studies from ultra-high risk for psychosis and first-episode psychosis (FEP).
MRI follow-up studies: Using novel automated analyses, we assessed subtle longitudinal changes in cortical grey matter. 35 UHR (12 converters vs 23 non-converters) were scanned at least 12 months apart; 16 patients with first-episode schizophrenia (FES) and 14 controls were scanned at baseline and 2–4 years later. We examined surface retraction at the CSF-grey matter boundary. Neuropsychological follow-up study: In a second study, we undertook a 10-year follow-up study of FEP patients and controls, to assess changes in brain structure and function. We report initial data from 30 FEP and 25 controls on measures of executive function.
Compared with non-converters, UHR converters showed significantly greater brain contraction in prefrontal cortex. Compared with controls, FES showed significantly greater surface retraction in dorsal frontal and parietal lobes, with global changes suggesting accelerated grey matter loss. Data from the 10-year FEP follow-up study found progressive cognitive decline in attentional set-shifting ability; in contrast, other functions relevant to the prefrontal cortex, including spatial working memory, showed an enduring deficit from before onset of illness.
These brain structural and neuropsychological changes will be discussed in the context of normal and abnormal brain maturational trajectories. We suggest that the onset of schizophrenia and psychosis disrupts the normal maturational trajectory, which is most prominent in the prefrontal cortex during adolescence and young adulthood. Such disruption may explain the observed changes observed from before the onset of a first psychotic episode (Pantelis et al, Schizophr Bull, 2005; Pantelis et al, Int Rev Psychiatry, 2007; Wood et al, Schizophr Bull, in press).
ASC02 THE USE OF TRANSCRANIAL MAGNETIC STIMULATION IN THE STUDY AND TREATMENT OF SCHIZOPHRENIA
Paul Fitzgerald
Schizophrenia remains disorder which is poorly understood and for which we have only partially effective treatments. Although transcranial magnetic stimulation (TMS) techniques are best known for their use in the treatment of depression, a significant body of research has developed around the use of TMS to study schizophrenia and potentially modulate the symptoms of this disorder. In regards to the first area, a considerable number of studies have been done using TMS to explore the function of cortical circuitry, in particular inhibitory neurons and neuronal plasticity. These studies have indicated that patients with schizophrenia display a deficit in cortical inhibition and that there is a corresponding abnormality in the capacity of cortical circuits to adapt in a normal manner to stimulation. Further research is under way investigating these deficits of cortical inhibition across a variety brain regions. In parallel to this investigative research, a considerable body of studies has been conducted investigating the use of TMS in the treatment of schizophrenia. The studies have predominantly focused on the use of low frequency stimulation in temporoparietal cortex to target hallucinations and high-frequency stimulation applied to prefrontal cortex in the treatment of negative symptoms. This research suggests that TMS has the capacity to ameliorate the frequency and intensity of hallucinations and may have possible benefits in improving negative symptoms. Further research is required to understand the link between symptoms and some of the core physiological deficits in this disorder and to better refine treatment paradigms.
ASC03 SCHIZOPHRENIA IS A WHOLE OF BRAIN DISEASE INVOLVING ALTERED COMMUNICATIONS BETWEEN NEURONS AND NEUROGLIA
Brian Dean
ASC04 WHY SCHIZOPHRENIA EPIDEMIOLOGY NEEDS NEUROSCIENCE – AND VICE VERSA
John McGrath
In recent years the epidemiology of schizophrenia has become much more interesting. It is now clear that the incidence of schizophrenia varies widely between sites, and varies according to a range of demographic variables such as sex, urbanicity of place of birth, paternal age, migrant status, and season of birth. Cannabis appears to be a risk-modifying factor for schizophrenia. Left to its own devices, there is a danger that schizophrenia epidemiology will engage in ‘circular epidemiology’ (replication studies that do not substantially advance knowledge). I argue that epidemiology needs to build stronger links with molecular, cellular and behavioural neuroscience. By way of demonstration, cross-disciplinary projects related to low prenatal vitamin D and paternal age will be outlined. Such dialogues can be rewarding for all parties. We need to build shared research platforms that encourage greater cross-fertilization between schizophrenia epidemiology and neuroscience.
ASC05 Mythbusting
Gordon Parker
It has been suggested that research is like sex – it has a function but it's not what attracts us. Researchers vary in their motivations and approaches, and such variegation adds to the overall research endeavour. I was distracted from clinical work by tentatively pursuing a dominant myth in the early 70s – that parents'caused’ most psychiatric disorders. At first pass concepts such as the'schizophrenogenic mother’ strained credulity, and I elected to determine the structural model underpinning parental style, develop a measure of the key constructs (the Parental Bonding Instrument or PBI came to pass) and obsessively examine the relevance of parenting to all disorders listed in DSM-II (and some not listed). It became clear that anomalous parenting was of antecedent causal relevance to some disorders, more a consequence (aka'high expressed emotion’) of problems in the child in other disorders, and irrelevant to other conditions.
This led to a longstanding approach to psychiatric research. In essence, what is the theory, what is the underlying model and, if the model appears limited or inappropriate, how might it be improved?
The most consistent track I've explored has been the classification of mood disorders, but my research has also suggested a simple model for modelling and measuring personality disorders (along dimensions of co-operativeness and effectiveness), and challenged much of the logic underpinning the treatment of'depression’ (especially the view that any treatment – be it drug or psychotherapy – should be modelled as having'universal’ relevance.
ASC06 Do you want to be right or do you want to be effective? ICD-11 and DSM-V for anxiety and depressive disorders
Gavin Andrews
The American Psychiatric Association and the World Health Organization have begun to revise their classifications of mental disorders. There are four issues: the structure of the classifications, the relation between categories and dimensions, the sensitivity of categorical thresholds to definitions, and maximizing the utility and validity of the diagnostic process.
There is now sufficient evidence to replace the present groupings of disorders with an empirically based structure that reflects the actual similarities among disorders. For example, the present depression and anxiety disorders would be best grouped as internalizing disorders, with bipolar disorder grouped with other psychoses.
Most mental disorders exist on a severity dimension. A diagnosis of a disorder is an expert opinion that the disorder is present. Clearly the disorder was present before the clinician made the diagnosis, and will still be present when treatment has reduced the symptoms. The reliability and validity of the classification would be improved if we accepted the dimensional nature of disorders while retaining the use of categorical diagnoses to enhance clinical utility.
Definitions of the thresholds that define categories are susceptible to detail. In ICD-11 and DSM-V, disorders about which there is agreement should be identically defined, and disorders in which there is disagreement should be defined differently, so that research can identify which definition is more valid.
The present diagnostic criteria are too complex to have acceptable clinical utility. We propose a reduced criterion set that can be remembered by clinicians and an enhanced criterion set for use with decision support tools.
ASC07 The emerging genetics of the mood disorders
Phillip Mitchell
In the last few years there have been major advances internationally in the molecular genetics of both depression and bipolar disorder. This presentation will present recent findings from our group in Sydney which have been undertaken in collaboration with colleagues Schofield, Wilhelm, Donald and Fullerton.
Depression: In 2006, we replicated the finding of a gene-environment interaction between the serotonin transporter gene and multiple stressful life events. We extended prior reports in demonstrating this interaction to be responsible for the first onset of depression, and not to be mediated by neuroticism. We have recently studied the expectations and understanding of this genetic test for study participants-a critical issue as such tests will be promoted for the clinical arena in coming years.
Bipolar disorder: We have recently completed a genome scan on 69 Australian families and will present linkage findings from that, focusing particularly on gene-gene interactions. We compare these findings with results from recent genome-wide association studies from the UK and US.
ASC08 Oxidative biology; new mechanism of disease and new therapeutic opportunities
Michael Berk
There is an increasing body of evidence that there are central and peripheral reductions in glutathione levels as well as changes in other primary free radical defences systems.
ASC09 A BIPOLAR VIEW OF THE WORLD
Gin Malhi
In recent years the term bipolar disorder has firmly supplanted manic-depression and the illness is known more widely than ever before. Clinically, its detection and diagnosis pose considerable difficulties and despite the emergence of effective pharmacological and psychological treatments the neurobiological basis of bipolar disorder remains an enigma. Against this backdrop both structural and functional neuroimaging have been promising and have unveiled a number of interesting findings. For instance, sophisticated structural neuroimaging studies hat have used aspects of Magnetic Resonance Imaging (MRI) have found differences in the size of key brain nuclei and cortical regions in patients with bipolar disorder. Similarly, functional imaging studies that have examined bipolar brain processing using functional MRI (fMRI) have implicated abnormalities in neural networks that involve in particular the limbic system and prefrontal cortex. A synthesis of the various neuroimaging findings along with putative models is proposed and considered along with the application of newer technologies and potential future directions.
ASC10 STUDYING PROBLEM BEHAVIOURS
Paul Mullen
Clinically we deal not just with psychiatric syndromes but with a range of problem behaviours from molesting children, to disordered eating. The approach adopted by the current DSM and ICD systems, and consequently in research and clinical practice, is to reconstruct such behaviours exclusively as the reflection of an underlying psychopathology. This can have utility but equally it can lead to unproductive debates such as whether a pattern of behaviour reflects delusion (as in morbid jealousy) or an extreme variant of the normal. The reluctance to take behaviour as our prime focus has legitimate roots in not wishing to become agents of social control. Constantly obfuscating problem behaviours by converting them immediately into putative mental disorders (paedophilia, impulse control disorder, sadism etc) is however theoretically and clinically unwise.
The presentation will take the example of querulous behaviour in the form of the insistent pursuit of claims and grievances which is not only out of proportion to the alleged injustice but positively destructive of the complainants own interests. An approach to research and clinical management will be advanced which gives priority to the behaviour as a problem not simply as a symptom.
ASC11 PSYCHOLOGICAL TREATMENTS AND RECOVERY IN EARLY PSYCHOSIS: RECAPITULATING THE PAST
Henry Jackson
This paper reviews progress as regards the role of psychological treatments in the schizophrenia and early psychosis domain over the past 40 years. Treatments and models from the psychodynamic, behavioural and the cognitive eras are reviewed. In the current era of cognitive therapy it is ironic that the most striking success of cognitive behavioural therapy for positive symptoms has been with chronic schizophrenic patients with lengthy illness histories and not with first-episode psychosis patients. Possible reasons for this will be discussed. This author argues that in the realm of early psychosis, efforts may be better placed for the greater good in terms of restoration of social and occupational functioning, rather than focussing on delusions and hallucinations per se. This harkens back to the days of the behavioural era which focussed on disability and addressing negative symptoms, rather than on hallucinations and delusions. Cognitive treatment of positive symptoms in first-episode psychosis may be better reserved for those people evincing poor responsiveness to medication and those with depression, anxiety disorders and demoralisation. This author advocates a recovery model in which positive symptoms and other morbidity are viewed as impediments to social and occupational participation rather than an end in themselves.
ASC12 EARLY-ONSET VERSUS LATE-ONSET DEPRESSION: IMPLICATIONS FOR PUBLIC HEALTH CAMPAIGNS AND HEALTH SYSTEM REFORM
Ian Hickie
A great deal of clinical assessment and research practice focuses on the sub-classification of the major affective disorders. Currently, there is a need to rationalise this activity and place greater emphasis on the key distinction between early and late-onset cases. Late-onset depressive disorders have specific genetic, vascular and other medical risk factors that can guide preventative, early-intervention and treatment approaches [1, 2]. These strategies maximise preservation of key cortical, subcortical and white matter structures. By contrast, many early-onset disorders share genetic risk factors with the anxiety disorders and are associated with a different pattern of response to medical and psychological treatments. Preventative and early-intervention approaches for these disorders emphasise recognition not only of different psychosocial risk factors but also early use of a wide range of educational, psychological and behavioural interventions. Increasingly, such interventions can be delivered via collaborative care models, e-health technologies or well-trained primary care workforces [3]. Development of effective preventative strategies is now a high priority for early-onset cases, as is minimizing co-morbid alcohol or other early substance misuse. Providing effective treatments for many more persons with mild or moderately severe depressive disorders can be expected to lead to further reductions in deaths due to suicide [4], medical complications [5] or lives lived with prolonged disability [6]. Co-ordinated national campaigns that increase awareness of depression as an illness can assist to achieve these goals [7].
ASC13 EARLY INTERVENTION IN PSYCHOTIC AND MOOD DISORDERS IN YOUNG PEOPLE
Patrick McGorry
Mental and substance use disorders are among the most important health issues facing society. They are by far the key health issue for young people in the teenage years and early twenties, and if they persist, they constrain, distress and disable for decades. Epidemiological data indicate that 75% of people suffering from an adult-type psychiatric disorder have an age of onset by 24 years of age, with the onset for most of these disorders – notably psychotic, mood, personality, eating and substance use disorders – mainly falling into a relatively discrete time band from the early teens up until the mid 20s, reaching a peak in the early twenties.
In recent years, a worldwide focus on the early stages of psychotic disorders has improved the prospects for understanding these complex disorders and improving their short term and longer term outcomes. This reform paradigm has also illustrated how a staging model may assist in interpreting and utilising biological data and refining diagnosis and treatment selection. There may be broader lessons for psychiatric research and treatment, particularly in the field of mood disorders. This brief overview will focus on the need for a new approach to youth mental health with special emphasis on psychotic and severe mood disorders. The contribution of Australian research to this process will be highlighted.
ASC14 THE IMPACT OF GENDER ON MENTAL ILLNESS
Jayashri Kulkarni
The history of the treatment of women with mental illness is bleak and shameful and currently treatments remain “gender-blind” to a large extent. Medicine still generally assumes that the archetypal patient and physician are men although women constitute the greatest percentage of the population receiving treatments for mental illness in most societies. Psychiatric illnesses may present very differently in men and women because of gender differences in social responsibilities and expectations.
Using schizophrenia as a paradigm, gender differences in the epidemiology and psychopathology will be presented. Gender sensitive drug treatments for schizophrenia, hormone treatments and psychosocial therapies will be explored in the presentation.
The recent shift in recognizing estrogen's effect on the brain has generated interest in its effect on cognition, emotion, and other non reproductive brain functions. Women have a considerably less severe course of schizophrenia and better social adaptation compared to men. With respect to treatment response, research has demonstrated that, early in their illness, women respond more quickly and more thoroughly than men to antipsychotic medication. Data will be presented demonstrating efficacy of hormonal modulation in the treatment of mental illness in women.
The best treatment for pregnant women with psychotic symptoms is still unclear. Biopsychosocial factors involved in the optimal care of pregnant women with schizophrenia will be discussed. This area is of great importance in preventing mental illness as much as possible in future generations and also in preventing secondary morbidity in women with schizophrenia.
ASC15 SYNTHESIS AND SENSIBILITY
Vaughan Carr
The traditional approach to investigator led research involving individual scientists or small teams of researchers competing with each other for limited resources, while capable of producing good science, is limited by inherent inefficiencies and fragmentation of research effort when it comes to answering the big questions concerning mental disorders. Consideration of the vast complexities of brain functioning, the breathtaking intricacies of molecular genetics and the myriad permutations by which environmental influences interact with both over time in the development of mental disorders, make most current research approaches look puny by comparison. The sheer scale of the discovery effort required demands a new approach, one that entails very large networks of scientists, collaboration rather than competition, coordination rather than fragmentation, bold planning rather than serendipity. Such an approach holds great promise but entails formidable challenges, not least of which is whether sensibility can triumph over sensibilities.
ASC16 SCHIZOPHRENIA: SCIENTIFIC CHALLENGES FOR THE 21ST CENTURY
Assen Jablenski
Despite a century of research, the nature and causes of schizophrenia remain largely cryptic, and the field abounds in inconsistent empirical findings and conceptual controversies. How far can genetics take us in understanding its causes and what is the role of the environment? Is the disorder rooted in neurodevelopment or in neurodegeneration? Can we bridge the gap between the objective measurement of brain function and the subjective phenomenology of schizophrenia? These, and other unresolved fundamental issues, are again leading to questions about the status of schizophrenia as a putative disease entity and to attempts at its “deconstruction”.
The Western Australian Family Study of Schizophrenia (WAFSS) has set out to address some of these problems by combining a detailed examination of the phenotype of schizophrenia, using a multi-domain approach to the dissection of cognitive processes, and a biological systems approach to its genetic analysis, supported by novel genotyping technologies. In this research, schizophrenia emerges as a complex disorder of impaired corticogenesis and synaptic plasticity whose phenotypic and pathogenetic heterogeneity is not captured in the current diagnostic classifications.
ASC17 Towards identifying genetic risk factors for schizophrenia
Bryan Mowry
ASC18
ASPR Organon Award Winner
Abstract not available at time of printing.