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Poster #86 PREMATURE AGEING AS A PROPOSED EXPLANATION FOR EXCESS OF DEATH IN SCHIZOPHRENIA
S122
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
2000 in the Copenhagen County. All Children are screened for PLE by the Development and Well Being Assessment (DAWBA) section T, a web-based self-report questionnaire covering hallucinations, delusions and thought disorders. All children are invited to the clinic and examined with the “ToM Storybook Frederik”. Furthermore, the children are interviewed with the K-SADS-PL, using the screening section and the supplements on psychotic and affective symptoms in order to gain an observer-based rating of PLE during the past month and lifetime before Results: The presentation will include preliminary results on the relationships between PLE and ToM in general, and the association between the hypo- and hyper-functioning types of ToM deficits and the patterns of hallucinations, delusional thoughts, and thought disorders in the group of 506 children interviewed as of December 1st 2011. Deficits in ToM are expected to be associated with PLE in a dose-response relationship. Hyper-ToM will be more strongly associated to delusional thoughts than hypo-ToM. Discussion: The results will help in identifying early patterns of risk and contribute to the understanding of the early stages of the development of psychosis. These findings might increase the potential for successful preventive interventions.
population (6.05, 95% CI: 5.96; 6.15). To evaluate premature aging, we compared the respective age groups with 15 years older individuals of the general population and found that the risk differences were no longer significant as indicated by overlapping 95% confidence intervals up to the age of 54 years in patients with schizophrenia. For example, patients with schizophrenia as young as 25-29 years had the same risk of CV death (0.06/1000 PYR (95% CI: 0.02, 0.24)) as the 40-44 years in the general population (0.15/1000 PYR, 95% CI: 0.14; 0.16). The 50-54 years patients with schizophrenia had the same risk of CV of death (2.97/1000 PYR (95% CI: 2.45, 3.61)) as the 65-69 years (3.32/1000 PYR (95%CI: 3.26, 3.38)) in the general population. Discussion: Our findings support the hypothesis of premature aging by approximately 15 years in patients with schizophrenia with regard to cardiovascular mortality. If confirmed, it suggests, when initiating agedependent drug therapy of cardiovascular risk factors in this population, to add 15 years to the calendar age to obtain their proper biological age.
Poster #87 EFFECT OF GEOGRAPHICAL ANCESTRY AND ETHNICITY ON TARDIVE DYSKINESIA SEVERITY Poster #86 PREMATURE AGEING AS A PROPOSED EXPLANATION FOR EXCESS OF DEATH IN SCHIZOPHRENIA Dan Cohen 1 , Christiane Gasse 2 , Thomas Laursen 2 1 Mental Health Organization North-Holland North, Heerhugowaard, Netherlands; 2 National Centre for Register-Based Research, Aarhus, Denmark Background: Two findings point to abnormal ageing in schizophrenia. First, studies across countries have consistently shown that schizophrenia is accompanied by excess mortality from natural causes and by sizable reduced life expectancy suggesting a disease-related rather than treatment-related feature. Second, age-dependent type 2 diabetes mellitus in schizophrenia is increased, especially at younger ages. The common process of a parallel course of biological and calendar ageing seems to diverge in schizophrenia, with biological age antedating calendar age. We coined this process of more speedy biological ageing “premature ageing”. Objective: To test premature ageing of 15 years in patients with schizophrenia we compared (1) mortality rates due to cardiovascular disease (CVD) between the schizophrenic population and the general population of the same calendar age, and (2) the mortality rates due to CVD between the schizophrenic population and the 15 years older general population. Methods: We conducted a population-based cohort study linking Danish registry data. Among all persons living in Denmark at some point between 1996 and 2010 we identified individuals with schizophrenia (ICD8: 295 (exclusive 295.79), ICD10: F20). Cardiovascular (CV) mortality rates and 95% confidence intervals (CI) were calculated per 1000 person-years at risk (PYR), and adjusted for calendar period. Follow-up began at their 15th birthday or 1996 and ended at their 75th birthday or 2010. Results: CV mortality rates among persons with schizophrenia were increased across all age groups, e.g. 6-fold in 25-29 years (0.06/1000 person years at risk (95% CI 0.02, 0.24)) vs. 0.01/1000 person years at risk (95% CI: 0.01; 0.01) in the general population, to 3-fold increased in the oldest age group of 70-74 years (15.55 (13.13; 18.42) compared with the general
Table 1. Cardiac mortality rate in the general population, schizophrenia +15 years and schizophrenia Age group 25-29 30-34 35-39 40-44 45-45 50-54 55-59 60-64 65-69 70-74
General population
Schizophrenia population + 15 years
Schizophrenic population
0.01 (0.01, 0.01) 0.03 (0.03, 0.04) 0.07 (0.06, 0.07) 0.15 (0.14, 0.16) 0.30 (0.28, 0.31) 0.55 (0.53, 0.57) 0.93 (0.90, 0.96) 1.75 (1.72, 1.79) 3.32 (3.26, 3.38) 6.05 (5.96, 6.15)
– – – 0.06* (0.02, 0.24) 0.29* (0.14, 0.57) 0.60* (0.38, 0.92) 0.80* (0.56, 1.15) 1.37* (1.04, 1.81) 2.97* (2.45, 3.61) 4.02 (3.34, 4.83)
0.06 (0.02, 0.24) 0.29 (0.14, 0.57) 0.60 (0.38, 0.92) 0.80 (0.56, 1.15) 1.37 (1.04, 1.81) 2.97 (2.45, 3.61) 4.02 (3.34, 4.83) 6.99 (5.90, 8.28) 10.54 (8.88, 12.51) 15.55 (13.13, 18.42)
*No significant difference to general population.
Vincenzo De Luca, Clement Zai, Gary Remington, James L. Kennedy Camh, Toronto, ON, Canada Background: Tardive dyskinesia is a difficult-to-treat form of involuntary and repetitive body movements that can have slow onset. It frequently appears after long-term or high-dose use of antipsychotics drugs. Tardive dyskinesia is more common in African populations. Methods: We carried out a retrospective descriptive genetic study to determine prevalence and ethnic risk factors for tardive dyskinesia (TD) among psychotic patients treated with neuroleptics in 4 centers in Canada and USA using the AIMS as main outcome. The patients were from African and European backgrounds. We also analyzed the geographical ancestry using the program Structure. Results: Two-hundred patients were included in the final analysis. The African self-reported Ethnicity was associated with higher incidence of tardive diskinesia (p<0.05). Furthermore a statistically significant correlation was found between African ancestry and tardive diskinesia (p<0.05). Discussion: Overall the prevalence of TD in African patients is higher and in our sample this difference seems to be related to both the geographical ancestry and cultural factors.
Poster #88 CHILDHOOD INFECTION AND SCHIZOPHRENIA AND OTHER PSYCHOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF POPULATION-BASED STUDIES Golam M. Khandaker 1,2 , Glyn Lewis 3 , Christina Dalman 4 , Peter B. Jones 1,2 1 University of Cambridge, Cambridge, United Kingdom; 2 Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom; 3 University of Bristol, Bristol, United Kingdom; 4 Karolinska Institutet, Stockholm, Sweden Background: As the human brain continues to develop until early adulthood, developmental alterations during early life from infectious illnesses particularly that of the CNS, can potentially contribute to risk of adult schizophrenia. Despite decades of research question still remains whether an association between childhood CNS infection and adult psychotic illness really exist, or is this confined to a particular type of infection (such as viral, bacterial or specific infectious agent). Effects of common childhood infections not directly affecting the CNS are also unclear. We addressed these issues through a systematic literature review and meta-analyses. Methods: Electronic (PubMed and EMBASE) and manual search identified 7 studies that met the inclusion criteria. Included studies used population-based cohort or case-control designs, objective assessment of childhood infection at the individual level, and measured outcome of adult schizophrenia and other psychosis using standard methods. We calculated risk ratio for non-affective psychosis and schizophrenia in relation to childhood all CNS infection, viral and bacterial infection from all available samples, which was combined in random effect meta-analysis. Results: As a group, only CNS viral infection was found to be associated
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
2000 in the Copenhagen County. All Children are screened for PLE by the Development and Well Being Assessment (DAWBA) section T, a web-based self-report questionnaire covering hallucinations, delusions and thought disorders. All children are invited to the clinic and examined with the “ToM Storybook Frederik”. Furthermore, the children are interviewed with the K-SADS-PL, using the screening section and the supplements on psychotic and affective symptoms in order to gain an observer-based rating of PLE during the past month and lifetime before Results: The presentation will include preliminary results on the relationships between PLE and ToM in general, and the association between the hypo- and hyper-functioning types of ToM deficits and the patterns of hallucinations, delusional thoughts, and thought disorders in the group of 506 children interviewed as of December 1st 2011. Deficits in ToM are expected to be associated with PLE in a dose-response relationship. Hyper-ToM will be more strongly associated to delusional thoughts than hypo-ToM. Discussion: The results will help in identifying early patterns of risk and contribute to the understanding of the early stages of the development of psychosis. These findings might increase the potential for successful preventive interventions.
population (6.05, 95% CI: 5.96; 6.15). To evaluate premature aging, we compared the respective age groups with 15 years older individuals of the general population and found that the risk differences were no longer significant as indicated by overlapping 95% confidence intervals up to the age of 54 years in patients with schizophrenia. For example, patients with schizophrenia as young as 25-29 years had the same risk of CV death (0.06/1000 PYR (95% CI: 0.02, 0.24)) as the 40-44 years in the general population (0.15/1000 PYR, 95% CI: 0.14; 0.16). The 50-54 years patients with schizophrenia had the same risk of CV of death (2.97/1000 PYR (95% CI: 2.45, 3.61)) as the 65-69 years (3.32/1000 PYR (95%CI: 3.26, 3.38)) in the general population. Discussion: Our findings support the hypothesis of premature aging by approximately 15 years in patients with schizophrenia with regard to cardiovascular mortality. If confirmed, it suggests, when initiating agedependent drug therapy of cardiovascular risk factors in this population, to add 15 years to the calendar age to obtain their proper biological age.
Poster #87 EFFECT OF GEOGRAPHICAL ANCESTRY AND ETHNICITY ON TARDIVE DYSKINESIA SEVERITY Poster #86 PREMATURE AGEING AS A PROPOSED EXPLANATION FOR EXCESS OF DEATH IN SCHIZOPHRENIA Dan Cohen 1 , Christiane Gasse 2 , Thomas Laursen 2 1 Mental Health Organization North-Holland North, Heerhugowaard, Netherlands; 2 National Centre for Register-Based Research, Aarhus, Denmark Background: Two findings point to abnormal ageing in schizophrenia. First, studies across countries have consistently shown that schizophrenia is accompanied by excess mortality from natural causes and by sizable reduced life expectancy suggesting a disease-related rather than treatment-related feature. Second, age-dependent type 2 diabetes mellitus in schizophrenia is increased, especially at younger ages. The common process of a parallel course of biological and calendar ageing seems to diverge in schizophrenia, with biological age antedating calendar age. We coined this process of more speedy biological ageing “premature ageing”. Objective: To test premature ageing of 15 years in patients with schizophrenia we compared (1) mortality rates due to cardiovascular disease (CVD) between the schizophrenic population and the general population of the same calendar age, and (2) the mortality rates due to CVD between the schizophrenic population and the 15 years older general population. Methods: We conducted a population-based cohort study linking Danish registry data. Among all persons living in Denmark at some point between 1996 and 2010 we identified individuals with schizophrenia (ICD8: 295 (exclusive 295.79), ICD10: F20). Cardiovascular (CV) mortality rates and 95% confidence intervals (CI) were calculated per 1000 person-years at risk (PYR), and adjusted for calendar period. Follow-up began at their 15th birthday or 1996 and ended at their 75th birthday or 2010. Results: CV mortality rates among persons with schizophrenia were increased across all age groups, e.g. 6-fold in 25-29 years (0.06/1000 person years at risk (95% CI 0.02, 0.24)) vs. 0.01/1000 person years at risk (95% CI: 0.01; 0.01) in the general population, to 3-fold increased in the oldest age group of 70-74 years (15.55 (13.13; 18.42) compared with the general
Table 1. Cardiac mortality rate in the general population, schizophrenia +15 years and schizophrenia Age group 25-29 30-34 35-39 40-44 45-45 50-54 55-59 60-64 65-69 70-74
General population
Schizophrenia population + 15 years
Schizophrenic population
0.01 (0.01, 0.01) 0.03 (0.03, 0.04) 0.07 (0.06, 0.07) 0.15 (0.14, 0.16) 0.30 (0.28, 0.31) 0.55 (0.53, 0.57) 0.93 (0.90, 0.96) 1.75 (1.72, 1.79) 3.32 (3.26, 3.38) 6.05 (5.96, 6.15)
– – – 0.06* (0.02, 0.24) 0.29* (0.14, 0.57) 0.60* (0.38, 0.92) 0.80* (0.56, 1.15) 1.37* (1.04, 1.81) 2.97* (2.45, 3.61) 4.02 (3.34, 4.83)
0.06 (0.02, 0.24) 0.29 (0.14, 0.57) 0.60 (0.38, 0.92) 0.80 (0.56, 1.15) 1.37 (1.04, 1.81) 2.97 (2.45, 3.61) 4.02 (3.34, 4.83) 6.99 (5.90, 8.28) 10.54 (8.88, 12.51) 15.55 (13.13, 18.42)
*No significant difference to general population.
Vincenzo De Luca, Clement Zai, Gary Remington, James L. Kennedy Camh, Toronto, ON, Canada Background: Tardive dyskinesia is a difficult-to-treat form of involuntary and repetitive body movements that can have slow onset. It frequently appears after long-term or high-dose use of antipsychotics drugs. Tardive dyskinesia is more common in African populations. Methods: We carried out a retrospective descriptive genetic study to determine prevalence and ethnic risk factors for tardive dyskinesia (TD) among psychotic patients treated with neuroleptics in 4 centers in Canada and USA using the AIMS as main outcome. The patients were from African and European backgrounds. We also analyzed the geographical ancestry using the program Structure. Results: Two-hundred patients were included in the final analysis. The African self-reported Ethnicity was associated with higher incidence of tardive diskinesia (p<0.05). Furthermore a statistically significant correlation was found between African ancestry and tardive diskinesia (p<0.05). Discussion: Overall the prevalence of TD in African patients is higher and in our sample this difference seems to be related to both the geographical ancestry and cultural factors.
Poster #88 CHILDHOOD INFECTION AND SCHIZOPHRENIA AND OTHER PSYCHOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF POPULATION-BASED STUDIES Golam M. Khandaker 1,2 , Glyn Lewis 3 , Christina Dalman 4 , Peter B. Jones 1,2 1 University of Cambridge, Cambridge, United Kingdom; 2 Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom; 3 University of Bristol, Bristol, United Kingdom; 4 Karolinska Institutet, Stockholm, Sweden Background: As the human brain continues to develop until early adulthood, developmental alterations during early life from infectious illnesses particularly that of the CNS, can potentially contribute to risk of adult schizophrenia. Despite decades of research question still remains whether an association between childhood CNS infection and adult psychotic illness really exist, or is this confined to a particular type of infection (such as viral, bacterial or specific infectious agent). Effects of common childhood infections not directly affecting the CNS are also unclear. We addressed these issues through a systematic literature review and meta-analyses. Methods: Electronic (PubMed and EMBASE) and manual search identified 7 studies that met the inclusion criteria. Included studies used population-based cohort or case-control designs, objective assessment of childhood infection at the individual level, and measured outcome of adult schizophrenia and other psychosis using standard methods. We calculated risk ratio for non-affective psychosis and schizophrenia in relation to childhood all CNS infection, viral and bacterial infection from all available samples, which was combined in random effect meta-analysis. Results: As a group, only CNS viral infection was found to be associated