- Email: [email protected]
14:30 COMPLETE GENOME SEQUENCE BASED GENETIC ANALYSIS OF MONOZYGOTIC TWINS DISCORDANT FOR SCHIZOPHRENIA
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Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
ORAL PRESENTATIONS 4
Oral Presentation GENETICS AND ENVIRONMENT Chairpersons: Dan Rujescu and John McGrath Tuesday, 17 April 2012 2:00 pm – 4:00 pm
14:00 COMMON POLYGENIC VARIATION CONTRIBUTING TO SCHIZOPHRENIA RISK EXPLAINS VARIATION IN TOTAL BRAIN VOLUME Afke Terwisscha van Scheltinga 1 , Steven Bakker 1 , Neeltje van Haren 1 , Heleen Boos 1 , Wiepke Cahn 1 , Markus Nothen 2,3 , Marcella Rietschel 4 , Sven Cichon 2,3,5 , Hilleke Hulshoff Pol 1 , Roel Ophoff 6 , Rene Kahn 1 1 University Medical Centre Utrecht, Utrecht, Netherlands; 2 University of Bonn, Bonn, Germany; 3 Life & Brain Center, University of Bonn, Bonn, Germany; 4 University of Heidelberg, Mannheim, Germany; 5 Research Center Juelich, Juelich, Germany; 6 University of California Los Angeles, CA, USA Background: Schizophrenia patients have, on average, 3% reduced brain volumes on magnetic resonance imaging (MRI) scans. Brain volume reductions in schizophrenia are associated with cognitive decline and poor outcome. The factors underlying these volume changes may therefore influence the core features of the disorder. Brain volume in general and its reduction in schizophrenia are highly heritable. The aim of our study was to investigate if a large set of single nucleotide polymorphisms (SNPs) associated with schizophrenia is also associated with brain volume, both in patients and controls. Methods: Subjects were genotyped using the Illumina HumanHap550 beadchip. After quality control and removal of SNPs in linkage disequilibrium 122,462 SNPs were used in the analysis. In the discovery sample (568 schizophrenia patients and 511 controls) we performed a GWAS and then defined sets of SNPs with p-values below different thresholds (PT ’s). For each individual in de target sample of 159 schizophrenia patients and 145 healthy controls with MRI scans we counted the number of possitively associated (“score”) alleles. Individual polygenic schizophrenia scores (PSS) were calculated for every PT -SNP set by weighting the number of score alleles by the logarithm of the odds ratio from the GWAS (conform Purcell et al., 2009). Total brain, gray matter, white matter, lateral and third ventricle volume were measured on a 1.5 Tesla MRI scan and corrected for age, sex and intracranial volume. We then performed linear regressions using brain volumes as dependent variable and PSS as independent variable. The analyses were repeated including also disease status and disease*PSS interaction as independent variables. Results: The polygenic schizophrenia score was significantly associated with total brain volume (variance explained 0.03, p=0.001, using the 30% highest ranking SNPs to calculate the score). When taking the association between the polygenic score and schizophrenia disease into account, the effect of this score on brain volume remained significant (variance explained0.024, p=0.003).Similar effects of PSS were seen on all other brain volume measures, with the largest effect on third ventricle volume (R2 =0.066, p=0.002). The association is also significant in the patient group only, but not in the control group only. Discussion: The results indicate that schizophrenia and total brain volume have a substantial shared genetic component. Using highly heritable, quantitative phenotypes such as brain volume may facilitate the identification of genetic factors involved in schizophrenia and possibly also in other complex genetic disorders.
14:15 PERSISTENCE OF THE EXTENDED PSYCHOSIS PHENOTYPE IN YOUNG PEOPLE: LINK BETWEEN VULNERABILITY AND CLINICAL NEED 1,2
1
3
Johanna T.W. Wigman , Wilma A.M. Vollebergh , Alison R. Yung , Evert Thiery 4 , Caterine Derom 5 , Jim van Os 2,6 1 Utrecht University, Utrecht, Netherlands; 2 Maastricht University, Maastricht, Netherlands; 3 ORYGEN Youth Health, Melbourne, Victoria, Australia;
Association for Scientific Research in Multiple Births, Ghent, Belgium; Catholic University Leuven, Leuven, Belgium; 6 Institute of Psychiatry, London, United Kingdom 5
Background: The pathway from the earliest and mildest expressions of psychosis to clinical disorder is highly variable and heterogeneous. A better understanding of the psychosis phenotype and how early states develop into clinical disorder is important, since this offers opportunities for early intervention or primary prevention of psychotic disorders. Methods: Using latent growth modeling in three general population samples, we investigated the development of subclinical expression of psychosis over time in healthy individuals. Two of these samples were adolescents (Study 1: N=2230 and Study 2: N=881, followed-up for respectively 6 and 3 years), and one consisted of young adult female twins (Study 3: N=566, followed-up for 2 years). In all studies, subclinical positive psychotic experiences were assessed at three time points with the Community Assessment of Psychic Experiences (CAPE). Results: Differential developmental trajectories of subclinical psychotic symptoms were found. In all three samples, the large majority of participants reported low levels of psychotic experiences over time. In both adolescent samples but not in the young adult sample, smaller subgroups of participants reported increasing or decreasing levels of psychotic experiences over time. Additionally, in all samples a small subgroup of individuals was identified that reported persistently high levels of psychotic experiences over time. Compared to individuals with low levels of psychotic experiences over time, these clinically relevant subgroups also reported higher levels of depression/anxiety (Study 1: p<001; Study 2: p<0.001), attentional problems (Study 1: p<0.001) and service use at the last follow-up (Study 1: p<0.001). They functioned worse, both socially (Study 1: p<0.001) and in general (Study 2: p<0.001), and applied more non-adaptive coping styles (Study 2: p<0.001). Parents of adolescents in this subgroup also reported higher levels of thought problems in their child (Study 1: p<0.001). In adolescents (Study 1), persistence of psychotic experiences was associated with risk factors such as trauma (OR 2.18, 95% CI 1.66-2.85), negative life events (OR 1.80, 95% CI 1.41-2.29), cannabis use (OR 1.80, 95% CI 1.06-3.05) and familial loading for psychotic disorder (OR 3.72, 95% CI 1.0712.98). The subgroups reporting increasing or decreasing levels of psychotic experiences scored intermediate on psychopathology and functioning, suggesting a continuous expression of liability for psychosis. In young adult twins (Study 3), persistence of psychotic experiences was also predicted by trauma (OR 3.26, 95% CI 1.77-6.00) and by having a monozygotic twin with persistent psychotic experiences (OR 9.32, 95% CI 4.73-18.45). Discussion: In sum, the subclinical expression of psychosis is present and dynamic in adolescence; this expression is less pronounced and more stable in young adulthood. This early expression of psychosis develops in a context of psycho(patho)logical functioning, observable illness, risk factors for psychiatric illness and genetic liability. Studying longitudinal patterns of subclinical psychotic experiences over time may help us to understand how the extended psychosis phenotype actually runs its highly variable course. Persistence of psychotic experiences may be a more fruitful, stable phenotype to study compared to cross-sectionally assessed experiences, because these are both common and dynamic in nature. The phenotype of persisting experiences, being intermediate in its psychotic expression between incidental subclinical psychotic experiences in healthy individuals and high-risk status for psychosis, may form the bridge that covers the gap on the hypothesized psychosis continuum between general and clinical populations.
14:30 COMPLETE GENOME SEQUENCE BASED GENETIC ANALYSIS OF MONOZYGOTIC TWINS DISCORDANT FOR SCHIZOPHRENIA Christina A. Castellani 1 , Sujit Maiti 1 , Richard L. O’Reilly 2 , Shiva M. Singh 1 1 The University of Western Ontario, Department of Biology, London, Ontario, Canada; 2 The University of Western Ontario, Department of Psychiatry, London, Ontario, Canada Background: Human genome variation profiles are currently both ill-
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
defined and poorly understood. The link between the major mental health disorders and genetics has received considerable research attention; results in the field however, have offered only limited insight. When combined with genetic relationships, individual sequences add unrivaled proficiency. During the last few years it has become apparent that monozygotic twins do differ for a number of genetic and epigenetic features. Given the near identical genetic structure of monozygotic twins, any difference between monozygotic twins discordant (MZD) for a disease will have a high likelihood of being causal. With this in mind I have sequenced the DNA of six individuals, which includes two pairs of MZ twins discordant for schizophrenia and one set of parents. Methods: Sequencing of monozygotic twins (n=4) discordant for schizophrenia and one set of parents (n=2) was carried out using the Complete Genomics Analysis system. The Complete Genomics platform has a 99.999% sequencing accuracy, 47.27 to 50.25-fold coverage and >99% of the reference genome is called. The sequences were further assessed for accuracy in relation to Affymetrix SNP Array 6.0 results. The genome sequences are currently being analyzed to identify de novo genetic and epigenetic differences between co-twins and the origin of those changes. Results: Genome wide variations including SNPs, indels, CNVs and microRNAs were assessed. It has allowed for the evaluation of similarities and differences across unrelated individuals, parents and children, as well as between MZ twins. The results show that an individual carries approximately 3.7 million SNPs, 150 CNVs, 400,000 indels and 220 microRNA variants. Also, two unrelated individuals differed for 1.5-1.8 million SNPs ( 45%), a parent and child differed for 0.9-1.0 million SNPs ( 30%) and a pair of MZ twins differed for 100,000 ( 3%) SNPs. Differences in the identity of CNVs for the three comparisons were 45%, 30% and 4%, respectively. Interestingly, CNV and SNP differences between MZD twins affect a set of genes enriched in neurodevelopmental genes, as well as genes that have been already implicated in Schizophrenia. Discussion: The results identify patient specific genetic changes that may lead to schizophrenia. The novel results re-enforce that individual genomes harbor extensive variability, some inherited and others acquired during parental meiosis and/or mitosis. There is no single human genome sequence. Even monozygotic twins are not identical and each individual may be a mosaic, potentially carrying different sequence variations in different cells. This is supported by a high mutation rate and the persistence of genetic diseases with a severely reduced fecundity in all human populations.
14:45 NOVEL DATA FROM A LARGE POPULATION PREVALENCE SURVEY: A UNIQUE OPPORTUNITY TO INFORM PSYCHOSIS RESEARCH DIRECTIONS AND MENTAL HEALTH REFORM Vera A. Morgan 1 , Anna Waterreus 1 , Assen Jablensky 1 , Andrew Mackinnon 2,10 , John J. McGrath 3,11 , Vaughan Carr 4 , Robert Bush 3 , David Castle 2 , Martin Cohen 5,9 , Carol Harvey 2 , Cherrie Galletly 6 , Helen Stain 5 , Amanda L. Neil 12 , Patrick McGorry 2,10 , Barbara Hocking 7 , Suzy Saw 8 1 School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, WA, Australia; 2 The University of Melbourne, Melbourne, VIC, Australia; 3 The University of Queensland, Brisbane, QLD, Australia; 4 The University of New South Wales, Sydney, NSW, Australia; 5 The University of Newcastle, Newcastle, NSW, Australia; 6 University of Adelaide, Adelaide, SA, Australia; 7 SANE Australia, Melbourne, VIC, Australia; 8 Australian Government Department of Health and Ageing, Canberra, ACT, Australia; 9 Hunter New England Mental Health, Newcastle, NSW, Australia; 10 Orygen Youth Health Research Centre, Melbourne, VIC, Australia; 11 Queensland Brain Centre, Brisbane, QLD, Australia; 12 Health Economic Consultant, Brisbane, QLD, Australia Background: Recently, Australia undertook its second national prevalence survey of psychosis across all public treatment sectors (inpatient, outpatient, community). The survey builds on data collected in the first national psychosis survey in 1997-98, with a substantial collection of new and updated information using a much expanded interview and assessment package. These data provide a comprehensive snapshot of multiple facets of the lives of people living with psychosis, extending and deepening our understanding of clinical presentation, living circumstances, social partic-
S73
ipation and needs in this population. Many data elements are unique in that they have not been collected previously in the context of a large, epidemiological survey. ?The survey included items on: psychopathology; physical health including fasting blood tests; premorbid/current cognitive ability; disability; at-risk behaviors; education; employment and income; accommodation; service utilisation and need. These data have been assessed contemporaneously and in depth in a large, unbiased sample. Blood was provided for DNA extraction. Methods: The survey covered 62,000 square kilometres and 1.5 million people aged 18-64 years, approximately 10% of the Australian population in this age group. A two-phase design was used: 7,955 people who were screen positive for psychosis and eligible in Phase 1 were randomised; 1,825 were interviewed and assessed in Phase 2. Results: The one month treated prevalence of psychosis was 3.5 cases per 1,000 population. The majority (63.0%) of participants met ICD-10 criteria for schizophrenia or schizoaffective disorder and 17.5% for bipolar affective disorder. Symptoms reported over a 12 month period included: delusions (60.9%), hallucinations (55.8%), elevated or irritable mood (23.5%), anxiety (59.8%) and depression (54.5%). Some 85.2% reported at least one negative symptom and 22.0% reported five or more. ?The majority (91.6%) were on psychotropic medication. Polypharmacy was common: 63.4% were on more than one class of medication and 27.4% of those on antipsychotics were using two or more. ?Current cognitive ability was markedly impaired compared to population norms. Mean estimated premorbid IQ, although lower than population norms, was within the normal range. This suggests some cognitive impairment in people with psychosis prior to illness onset that is amplified in the years following diagnosis. ?Half (49.9%) met criteria for metabolic syndrome. Rates for other physical health conditions were markedly higher in people with psychosis compared to the general population. ?The proportion currently smoking was 66.1%. Half (50.5%) had a lifetime history of alcohol abuse/dependence and 54.5% had a lifetime history of illicit drug abuse/dependence. ?Two-thirds were impaired in their capacity to socialise over the past year and one third had impaired ability to care for themselves over the past four weeks. ?Educational achievement was low and only 32.7% had any paid employment in the past year. The proportion of homeless people was high. ?Replication of questions from the first survey provides a rare opportunity to assess change over time. Inclusion of a range of psychotic disorders enables detailed analysis by diagnostic grouping. Discussion: People with a psychotic illness face multiple challenges related to physical health, employment, income, housing, self-care and social contact, in addition to their mental health issues. These challenges highlight the importance of an integrated approach to service provision to ensure that their living requirements and needs for social participation are met, as well as their very considerable mental and physical health needs.
15:00 ABSOLUTE RISK OF SUICIDE FOLLOWING FIRST HOSPITAL CONTACT WITH MENTAL DISORDER Merete Nordentoft 1 , Carsten B. Pedersen 2 , Preben B. Mortensen 2 Psychiatric Centre Copenhagen, Copenhagen, Denmark; 2 National Centre for Register-based Research, Aarhus, Denmark 1
Background: Schizophrenia and other severe mental disorders are associated with increased risk for suicide. Previous estimates of lifetime risk of suicide in mental disorders were based on selected samples with incomplete follow-up. We wanted to estimate, in a national cohort, the absolute risk to die from suicide within 36 years after first psychiatric contact. Methods: We carried out a prospective study of incident cases followed up to 36 years. Median follow-up was 18 years. Individual data were drawn from Danish longitudinal registers. A total of 176,347 persons born in 19551991, were followed from their first contact to secondary mental health services after age 15 until death, emigration or disappearance, or end of 2006. For each participant, five matched controls were included. The main outcome measure was absolute risk of suicide in percent up to 36 years after the first contact. Included diagnostic categories were: Schizophrenia, schizophrenia-like psychosis, bipolar affective disorder, unipolar affective disorder, substance abuse and anorexia. Results: Among men, the percent of absolute risk of suicide was highest for bipolar disorder, 7.77 (95% CI: 6.01-10.05), followed by unipolar
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
ORAL PRESENTATIONS 4
Oral Presentation GENETICS AND ENVIRONMENT Chairpersons: Dan Rujescu and John McGrath Tuesday, 17 April 2012 2:00 pm – 4:00 pm
14:00 COMMON POLYGENIC VARIATION CONTRIBUTING TO SCHIZOPHRENIA RISK EXPLAINS VARIATION IN TOTAL BRAIN VOLUME Afke Terwisscha van Scheltinga 1 , Steven Bakker 1 , Neeltje van Haren 1 , Heleen Boos 1 , Wiepke Cahn 1 , Markus Nothen 2,3 , Marcella Rietschel 4 , Sven Cichon 2,3,5 , Hilleke Hulshoff Pol 1 , Roel Ophoff 6 , Rene Kahn 1 1 University Medical Centre Utrecht, Utrecht, Netherlands; 2 University of Bonn, Bonn, Germany; 3 Life & Brain Center, University of Bonn, Bonn, Germany; 4 University of Heidelberg, Mannheim, Germany; 5 Research Center Juelich, Juelich, Germany; 6 University of California Los Angeles, CA, USA Background: Schizophrenia patients have, on average, 3% reduced brain volumes on magnetic resonance imaging (MRI) scans. Brain volume reductions in schizophrenia are associated with cognitive decline and poor outcome. The factors underlying these volume changes may therefore influence the core features of the disorder. Brain volume in general and its reduction in schizophrenia are highly heritable. The aim of our study was to investigate if a large set of single nucleotide polymorphisms (SNPs) associated with schizophrenia is also associated with brain volume, both in patients and controls. Methods: Subjects were genotyped using the Illumina HumanHap550 beadchip. After quality control and removal of SNPs in linkage disequilibrium 122,462 SNPs were used in the analysis. In the discovery sample (568 schizophrenia patients and 511 controls) we performed a GWAS and then defined sets of SNPs with p-values below different thresholds (PT ’s). For each individual in de target sample of 159 schizophrenia patients and 145 healthy controls with MRI scans we counted the number of possitively associated (“score”) alleles. Individual polygenic schizophrenia scores (PSS) were calculated for every PT -SNP set by weighting the number of score alleles by the logarithm of the odds ratio from the GWAS (conform Purcell et al., 2009). Total brain, gray matter, white matter, lateral and third ventricle volume were measured on a 1.5 Tesla MRI scan and corrected for age, sex and intracranial volume. We then performed linear regressions using brain volumes as dependent variable and PSS as independent variable. The analyses were repeated including also disease status and disease*PSS interaction as independent variables. Results: The polygenic schizophrenia score was significantly associated with total brain volume (variance explained 0.03, p=0.001, using the 30% highest ranking SNPs to calculate the score). When taking the association between the polygenic score and schizophrenia disease into account, the effect of this score on brain volume remained significant (variance explained0.024, p=0.003).Similar effects of PSS were seen on all other brain volume measures, with the largest effect on third ventricle volume (R2 =0.066, p=0.002). The association is also significant in the patient group only, but not in the control group only. Discussion: The results indicate that schizophrenia and total brain volume have a substantial shared genetic component. Using highly heritable, quantitative phenotypes such as brain volume may facilitate the identification of genetic factors involved in schizophrenia and possibly also in other complex genetic disorders.
14:15 PERSISTENCE OF THE EXTENDED PSYCHOSIS PHENOTYPE IN YOUNG PEOPLE: LINK BETWEEN VULNERABILITY AND CLINICAL NEED 1,2
1
3
Johanna T.W. Wigman , Wilma A.M. Vollebergh , Alison R. Yung , Evert Thiery 4 , Caterine Derom 5 , Jim van Os 2,6 1 Utrecht University, Utrecht, Netherlands; 2 Maastricht University, Maastricht, Netherlands; 3 ORYGEN Youth Health, Melbourne, Victoria, Australia;
Association for Scientific Research in Multiple Births, Ghent, Belgium; Catholic University Leuven, Leuven, Belgium; 6 Institute of Psychiatry, London, United Kingdom 5
Background: The pathway from the earliest and mildest expressions of psychosis to clinical disorder is highly variable and heterogeneous. A better understanding of the psychosis phenotype and how early states develop into clinical disorder is important, since this offers opportunities for early intervention or primary prevention of psychotic disorders. Methods: Using latent growth modeling in three general population samples, we investigated the development of subclinical expression of psychosis over time in healthy individuals. Two of these samples were adolescents (Study 1: N=2230 and Study 2: N=881, followed-up for respectively 6 and 3 years), and one consisted of young adult female twins (Study 3: N=566, followed-up for 2 years). In all studies, subclinical positive psychotic experiences were assessed at three time points with the Community Assessment of Psychic Experiences (CAPE). Results: Differential developmental trajectories of subclinical psychotic symptoms were found. In all three samples, the large majority of participants reported low levels of psychotic experiences over time. In both adolescent samples but not in the young adult sample, smaller subgroups of participants reported increasing or decreasing levels of psychotic experiences over time. Additionally, in all samples a small subgroup of individuals was identified that reported persistently high levels of psychotic experiences over time. Compared to individuals with low levels of psychotic experiences over time, these clinically relevant subgroups also reported higher levels of depression/anxiety (Study 1: p<001; Study 2: p<0.001), attentional problems (Study 1: p<0.001) and service use at the last follow-up (Study 1: p<0.001). They functioned worse, both socially (Study 1: p<0.001) and in general (Study 2: p<0.001), and applied more non-adaptive coping styles (Study 2: p<0.001). Parents of adolescents in this subgroup also reported higher levels of thought problems in their child (Study 1: p<0.001). In adolescents (Study 1), persistence of psychotic experiences was associated with risk factors such as trauma (OR 2.18, 95% CI 1.66-2.85), negative life events (OR 1.80, 95% CI 1.41-2.29), cannabis use (OR 1.80, 95% CI 1.06-3.05) and familial loading for psychotic disorder (OR 3.72, 95% CI 1.0712.98). The subgroups reporting increasing or decreasing levels of psychotic experiences scored intermediate on psychopathology and functioning, suggesting a continuous expression of liability for psychosis. In young adult twins (Study 3), persistence of psychotic experiences was also predicted by trauma (OR 3.26, 95% CI 1.77-6.00) and by having a monozygotic twin with persistent psychotic experiences (OR 9.32, 95% CI 4.73-18.45). Discussion: In sum, the subclinical expression of psychosis is present and dynamic in adolescence; this expression is less pronounced and more stable in young adulthood. This early expression of psychosis develops in a context of psycho(patho)logical functioning, observable illness, risk factors for psychiatric illness and genetic liability. Studying longitudinal patterns of subclinical psychotic experiences over time may help us to understand how the extended psychosis phenotype actually runs its highly variable course. Persistence of psychotic experiences may be a more fruitful, stable phenotype to study compared to cross-sectionally assessed experiences, because these are both common and dynamic in nature. The phenotype of persisting experiences, being intermediate in its psychotic expression between incidental subclinical psychotic experiences in healthy individuals and high-risk status for psychosis, may form the bridge that covers the gap on the hypothesized psychosis continuum between general and clinical populations.
14:30 COMPLETE GENOME SEQUENCE BASED GENETIC ANALYSIS OF MONOZYGOTIC TWINS DISCORDANT FOR SCHIZOPHRENIA Christina A. Castellani 1 , Sujit Maiti 1 , Richard L. O’Reilly 2 , Shiva M. Singh 1 1 The University of Western Ontario, Department of Biology, London, Ontario, Canada; 2 The University of Western Ontario, Department of Psychiatry, London, Ontario, Canada Background: Human genome variation profiles are currently both ill-
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
defined and poorly understood. The link between the major mental health disorders and genetics has received considerable research attention; results in the field however, have offered only limited insight. When combined with genetic relationships, individual sequences add unrivaled proficiency. During the last few years it has become apparent that monozygotic twins do differ for a number of genetic and epigenetic features. Given the near identical genetic structure of monozygotic twins, any difference between monozygotic twins discordant (MZD) for a disease will have a high likelihood of being causal. With this in mind I have sequenced the DNA of six individuals, which includes two pairs of MZ twins discordant for schizophrenia and one set of parents. Methods: Sequencing of monozygotic twins (n=4) discordant for schizophrenia and one set of parents (n=2) was carried out using the Complete Genomics Analysis system. The Complete Genomics platform has a 99.999% sequencing accuracy, 47.27 to 50.25-fold coverage and >99% of the reference genome is called. The sequences were further assessed for accuracy in relation to Affymetrix SNP Array 6.0 results. The genome sequences are currently being analyzed to identify de novo genetic and epigenetic differences between co-twins and the origin of those changes. Results: Genome wide variations including SNPs, indels, CNVs and microRNAs were assessed. It has allowed for the evaluation of similarities and differences across unrelated individuals, parents and children, as well as between MZ twins. The results show that an individual carries approximately 3.7 million SNPs, 150 CNVs, 400,000 indels and 220 microRNA variants. Also, two unrelated individuals differed for 1.5-1.8 million SNPs ( 45%), a parent and child differed for 0.9-1.0 million SNPs ( 30%) and a pair of MZ twins differed for 100,000 ( 3%) SNPs. Differences in the identity of CNVs for the three comparisons were 45%, 30% and 4%, respectively. Interestingly, CNV and SNP differences between MZD twins affect a set of genes enriched in neurodevelopmental genes, as well as genes that have been already implicated in Schizophrenia. Discussion: The results identify patient specific genetic changes that may lead to schizophrenia. The novel results re-enforce that individual genomes harbor extensive variability, some inherited and others acquired during parental meiosis and/or mitosis. There is no single human genome sequence. Even monozygotic twins are not identical and each individual may be a mosaic, potentially carrying different sequence variations in different cells. This is supported by a high mutation rate and the persistence of genetic diseases with a severely reduced fecundity in all human populations.
14:45 NOVEL DATA FROM A LARGE POPULATION PREVALENCE SURVEY: A UNIQUE OPPORTUNITY TO INFORM PSYCHOSIS RESEARCH DIRECTIONS AND MENTAL HEALTH REFORM Vera A. Morgan 1 , Anna Waterreus 1 , Assen Jablensky 1 , Andrew Mackinnon 2,10 , John J. McGrath 3,11 , Vaughan Carr 4 , Robert Bush 3 , David Castle 2 , Martin Cohen 5,9 , Carol Harvey 2 , Cherrie Galletly 6 , Helen Stain 5 , Amanda L. Neil 12 , Patrick McGorry 2,10 , Barbara Hocking 7 , Suzy Saw 8 1 School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, WA, Australia; 2 The University of Melbourne, Melbourne, VIC, Australia; 3 The University of Queensland, Brisbane, QLD, Australia; 4 The University of New South Wales, Sydney, NSW, Australia; 5 The University of Newcastle, Newcastle, NSW, Australia; 6 University of Adelaide, Adelaide, SA, Australia; 7 SANE Australia, Melbourne, VIC, Australia; 8 Australian Government Department of Health and Ageing, Canberra, ACT, Australia; 9 Hunter New England Mental Health, Newcastle, NSW, Australia; 10 Orygen Youth Health Research Centre, Melbourne, VIC, Australia; 11 Queensland Brain Centre, Brisbane, QLD, Australia; 12 Health Economic Consultant, Brisbane, QLD, Australia Background: Recently, Australia undertook its second national prevalence survey of psychosis across all public treatment sectors (inpatient, outpatient, community). The survey builds on data collected in the first national psychosis survey in 1997-98, with a substantial collection of new and updated information using a much expanded interview and assessment package. These data provide a comprehensive snapshot of multiple facets of the lives of people living with psychosis, extending and deepening our understanding of clinical presentation, living circumstances, social partic-
S73
ipation and needs in this population. Many data elements are unique in that they have not been collected previously in the context of a large, epidemiological survey. ?The survey included items on: psychopathology; physical health including fasting blood tests; premorbid/current cognitive ability; disability; at-risk behaviors; education; employment and income; accommodation; service utilisation and need. These data have been assessed contemporaneously and in depth in a large, unbiased sample. Blood was provided for DNA extraction. Methods: The survey covered 62,000 square kilometres and 1.5 million people aged 18-64 years, approximately 10% of the Australian population in this age group. A two-phase design was used: 7,955 people who were screen positive for psychosis and eligible in Phase 1 were randomised; 1,825 were interviewed and assessed in Phase 2. Results: The one month treated prevalence of psychosis was 3.5 cases per 1,000 population. The majority (63.0%) of participants met ICD-10 criteria for schizophrenia or schizoaffective disorder and 17.5% for bipolar affective disorder. Symptoms reported over a 12 month period included: delusions (60.9%), hallucinations (55.8%), elevated or irritable mood (23.5%), anxiety (59.8%) and depression (54.5%). Some 85.2% reported at least one negative symptom and 22.0% reported five or more. ?The majority (91.6%) were on psychotropic medication. Polypharmacy was common: 63.4% were on more than one class of medication and 27.4% of those on antipsychotics were using two or more. ?Current cognitive ability was markedly impaired compared to population norms. Mean estimated premorbid IQ, although lower than population norms, was within the normal range. This suggests some cognitive impairment in people with psychosis prior to illness onset that is amplified in the years following diagnosis. ?Half (49.9%) met criteria for metabolic syndrome. Rates for other physical health conditions were markedly higher in people with psychosis compared to the general population. ?The proportion currently smoking was 66.1%. Half (50.5%) had a lifetime history of alcohol abuse/dependence and 54.5% had a lifetime history of illicit drug abuse/dependence. ?Two-thirds were impaired in their capacity to socialise over the past year and one third had impaired ability to care for themselves over the past four weeks. ?Educational achievement was low and only 32.7% had any paid employment in the past year. The proportion of homeless people was high. ?Replication of questions from the first survey provides a rare opportunity to assess change over time. Inclusion of a range of psychotic disorders enables detailed analysis by diagnostic grouping. Discussion: People with a psychotic illness face multiple challenges related to physical health, employment, income, housing, self-care and social contact, in addition to their mental health issues. These challenges highlight the importance of an integrated approach to service provision to ensure that their living requirements and needs for social participation are met, as well as their very considerable mental and physical health needs.
15:00 ABSOLUTE RISK OF SUICIDE FOLLOWING FIRST HOSPITAL CONTACT WITH MENTAL DISORDER Merete Nordentoft 1 , Carsten B. Pedersen 2 , Preben B. Mortensen 2 Psychiatric Centre Copenhagen, Copenhagen, Denmark; 2 National Centre for Register-based Research, Aarhus, Denmark 1
Background: Schizophrenia and other severe mental disorders are associated with increased risk for suicide. Previous estimates of lifetime risk of suicide in mental disorders were based on selected samples with incomplete follow-up. We wanted to estimate, in a national cohort, the absolute risk to die from suicide within 36 years after first psychiatric contact. Methods: We carried out a prospective study of incident cases followed up to 36 years. Median follow-up was 18 years. Individual data were drawn from Danish longitudinal registers. A total of 176,347 persons born in 19551991, were followed from their first contact to secondary mental health services after age 15 until death, emigration or disappearance, or end of 2006. For each participant, five matched controls were included. The main outcome measure was absolute risk of suicide in percent up to 36 years after the first contact. Included diagnostic categories were: Schizophrenia, schizophrenia-like psychosis, bipolar affective disorder, unipolar affective disorder, substance abuse and anorexia. Results: Among men, the percent of absolute risk of suicide was highest for bipolar disorder, 7.77 (95% CI: 6.01-10.05), followed by unipolar