Abstract
PL01 - Understanding impaired cognition and emotion in schizophrenia
Professor of Psychiatry and Psychology, U.C. Davis Imaging Research Center & the Center for Neuroscience, University of California at Davis
References
1. Minzenberg MJ et al. Arch. Gen. Psychiat. 2009;66:811–822.
2. Yoon JH et al. Am. J. Psychiat. 2008;165:1006–1014.
3. Lewis DA et al. Am. J. Psychiat. 2008;165:1585–1593.
4. Cho RY et al. Proc. Natl. Acad. Sci. U.S.A. 2006;103:19878–19883.
PL02 - Environmental risk factors for schizophrenia: Does developmental vitamin d deficiency play a role?
1 Queensland Centre for Mental Health Research
2 Queensland Brain Institute, University of Queensland
There is robust evidence showing that winter birth, migrant status and urban birth are associated with an increased risk of schizophrenia. We proposed that developmental vitamin D (DVD) deficiency may underlie these features. In order to explore this hypothesis, we undertook a program of research linking risk factor epidemiology and neurobiology. Firstly, we mapped the receptor and key enzyme in the human brain. In vitro and whole animal studies demonstrated that DVD deficiency is associated with a range of structural and functional neurobiological outcomes of interest to schizophrenia research. In order to assess the association between developmental vitamin D status and risk of schizophrenia, we examined cohorts in Finland and the US. Results from a recent Danish study based on neonatal dried blood spots have allowed us to refine our hypothesis. This research demonstrates how translational epidemiology (linking clues from epidemiology to neuroscience) can uncover previously unsuspected brain mechanisms. While much more work needs to be done, this research suggests that the incidence of schizophrenia could be reduced via simple, safe and cheap nutritional supplements.
PL03 - Neuroimaging of schizophrenia: From maps to mechanisms
Central Institute of Mental Health (CIMH), Mannheim, Germany
We discuss a research strategy where the integration of neuroimaging data with information from genetics and epidemiology provides mechanistic insights not only into the cognitive neuropsychology, but also into the molecular pathophysiology and aetiology of schizophrenia that create a basis for novel treatments.
While much has been learned in schizophrenia from studies in patients, moving the level of inquiry back to causal antecedents of the disorder may be more promising to guide future intervention and prevention. In genetics, recently discovered genome-wide significant risk variants for psychotic disorders (ZNF804A, CACNA1C) have been discovered that afford an opportunity to establish neural mechanisms linked to genetic risk for schizophrenia and bipolar disorder through an imaging genetics approach. In addition, neuroimaging is now beginning to provide a neural basis for the understanding of environmental risk factors such as social status, social stress, and urbanicity.
We find that genome-wide significant variants impact on the brain connectome, partially recapitulating phenotypes observed in patients at risk and with overt disease. Disturbances of connectivity are likely part of the core neurogenetic risk architecture of schizophrenia. We also present data that the processing of environmental risk factors is linked to prefrontal regulatory circuits of the limbic system. Treatment implications of these discoveries are discussed.
PL04 - Social cognition in schizophrenia
University of North Carolina-Chapel Hill, Chapel Hill, NC, USA
Social cognition refers to the cognitive processes that underlie and potentially support social interactions. Over the past 15 years, there has been great interest in the role of social cognition in schizophrenia. It is thought that impairments in social cognition may contribute to the development of schizophrenia, as well as social and functional impairments that are a consequence of this disorder.
This presentation begins with an overview of social cognition in schizophrenia. Three keys areas of social cognition are identified: 1) emotion perception; 2) theory of mind; and 3) attributional style. A summary of extant research in these domains is reviewed. This is followed by a discussion of the role of social cognition in contributing to social functioning impairments in schizophrenia. This part of the presentation concludes with a description of a conceptual model for how social cognition may impact social functioning in schizophrenia.
The second half of the presentation will focus more on translating basic research in social cognition into treatment applications. This will begin with a brief overview of previous research that has examined social cognition training in schizophrenia. I will then describe our own social cognition treatment program: Social Cognition and Interaction Training (SCIT). An overview of SCIT will follow. The presentation will conclude with a review of preliminary research that has examined the effectiveness of SCIT for individuals with schizophrenia as well as future research directions for the field.
PL05 - Functional recovery in early psychosis: Something old somewhere new
Centre for Youth Mental Health, The University of Melbourne & Orygen Youth Health Research Centre
While there have been debates about which definition actually constitutes recovery in psychotic illness, nearly all definitions of recovery now include some focus on the need for functional recovery – the attainment or reattainment of the ability to live independently in society. This covers a number of domains although the most frequently mentioned is recovery in the vocational domain. Vocational recovery has been seen as important for a long time and various different approaches have been used in order to help people with schizophrenia try to get back to work. Many of the early approaches used a train and place model. More recently efforts have concentrated on place and support models, mostly gathered under the rubric of supported employment. While there is a lot of evidence for the efficacy of these models in established schizophrenia, until recently there has been little to no attention given to vocational recovery in the early phase of psychotic illness. There are many good reasons for focussing on the early phase of illness, not least of which is that the onset of illness tends to occur in the key vocational development phase of life. Disruption to this development has far reaching implications in terms of future employability and career attainment. This presentation will review the work in this and other functional domains, highlighting progress and drawing attention to areas which still need to be developed.
PL06 - The nosological entity in psychiatry: An historical illusion or a real moving target?
Centre for Clinical Research in Neuropsychiatry, The University of Western Australia, Perth, Australia
The protagonist of modern psychiatric nosology Emil Kraepelin wrote, late in his career, that “it is now necessary to turn away from arranging illnesses in orderly, well defined groups and to set ourselves instead the undoubtedly higher and more satisfying goal of understanding their essential structure”. Nine decades later, both the arrangement of psychiatric disorders and the understanding of their essential structure remain an unending quest. Today, both DSM-IV and ICD-10 are essentially classifications of diagnostic concepts, and not of ‘natural kinds’, such as people or diseases. The basic construct underlying current psychiatric classifications remains that of nosological entity, despite growing evidence that most mental disorders are not separated by natural boundaries that would support the validity of diagnostic categories. Most diagnostic concepts in psychiatry have not been shown to be valid in this sense, though many possess clinical utility by virtue of the information about outcome, treatment response and aetiology which they convey. However, researchers are increasingly assuming that variation in symptomatology is continuous and therefore questioning the validity of contemporary classifications. Although the evidence is far from being consistent or definitive, recent proposals to deal with phenotypic and biological heterogeneity by linking genomics with neural circuitry analyses that cut across conventional disease categories resonate surprisingly with Kraepelin's late views on “registers” of continuous variation replacing the “natural disease entity” concept.
PL07 - Update on the australian national survey of high impact psychosis (ship)
1 The University of Western Australia, Perth, Australia
PL08 - Schizophrenia, psychosis and cognition: Back to the future
Institute of Psychiatry, King's College London and King's Health Partners, London, UK
The illness now called schizophrenia started its origins as ‘dementia praecox,’ a deteriorating cognitive disorder. The first few decades the focus was on its cognitive and associative aspects until the discovery of antipsychotics. For the last half century schizophrenia has been focussed on the study of psychotic symptoms with significant progress. The talk will review our current understanding of the pathophysiology of schizophrenia with a special emphasis on the dopamine system. The emerging data supports the view that the major dopaminergic abnormality is a presynaptic one, that this abnormality precedes the onset of psychosis. However, we may have pushed the dopamine model as far as it can in terms of new therapeutics – and the problem of cognition in schizophrenia is still largely unaddressed. New approaches are needed. How does the cognitive dysfunction of schizophrenia relate to the psychotic dysfunction of the illness? What, precisely, is wrong with cognition in schizophrenia? Is it a multitude of distinct dysfunctions or is it a single common factor? Does one know enough about the pathophysiology of cognitive dysfunction to design rational treatments? What have been the results of early treatment efforts? Is a drug-treatment of cognition in the context of schizophrenia even a sensible goal? If not, what should it be? The talk will raise and partially address these questions and finish with a model of schizophrenia which embraces both psychosis and cognition and ties it with what is known about psychosis and its treatment.
PL09 - The path to developing better schizophrenia treatments
1 Schizophrenia Research Institute, Sydney, Australia
2 Neuroscience Research Australia, Sydney, Australia
3 University of New South Wales, Sydney, Australia
The causes of schizophrenia are best understood in the context of the developing and maturing brain. The majority of schizophrenia cases are first recognized in adolescence, which is a unique and challenging time of life for humans. Indeed, evidence suggests that the most dysfunctional region of the brain in schizophrenia, the reason-centered prefrontal cortex, is one of the last to mature in late adolescence and early adulthood. In normal teens, we have identified that the prefrontal cortical inhibitory system and the cortical dopamine system are still undergoing maturational changes which can result in shifts in the control of the output of cortical glutamate neurons. Thus, biological changes that are normally occurring in a teenage cortex and help guide the individual from using juvenile strategies of behavior to more adult strategies of behavior can be influenced by perturbations in environmental and hormonal signals. In schizophrenia, deleterious forms of genes and damaging environments can interact to derail the normal maturational program of the cerebral cortex in adolescence. Indeed, evidence from our laboratory and others around the world suggests that genes and environments that increase risk for developing schizophrenia can interfere with the ability of the prefrontal cortex to recognize and respond to growth factors, sex hormones and stress hormones. Furthermore, we have evidence that the cortical inhibitory neurons and dopamine signaling system may be held in a state of immaturity in people with schizophrenia. This suggests that, for at least some forms of schizophrenia, the pathology can be viewed as a delay in certain aspects of cortical development. From this perspective, it becomes clear that we need to develop new treatments that can stimulate the healthy growth and maturation of the cortical neurons in people with schizophrenia. It also suggests that interventions may be more effective if used early in the course of the development of schizophrenia.