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Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring
3. Epidemiology
33
urban-rural comparison. Arch Gen Psychiatry 58:663-8., 2001 Yung AR, Phillips LJ, McGorry PD, McFarlane CA, Francey S, Harrigan S, Patton GC, Jackson HJ: Prediction of psychosis. A step towards indicated prevention of schizophrenia. Br J Psychiatry Suppt 172:1420, 1998
E L E V A T E D MATERNAL INTERLEUKIN-8 L E V E L S AND RISK OF SCHIZOPHRENIA IN
ADULT OFFSPRING V. Babulas,* A. S. Brown, J. Hooton, C. A. Schaefer,
H. Zhang, E. Petkova, M. A. Perrin, J. M. Gorman, E. S. Susser Psychiatry, Columbia University~New York State Psychiatric Institute, New York, NY, USA Many studies have implicated prenatal infection in the etiology of schizophrenia. Cytokines, a family of soluble polypeptides, are critically important in the immune response to infection, and in utero exposure to elevated cytokines is kaaown to damage the developing fetal brain. We aimed to determine whether second trimester levels of four cytokines that are plausible candidates for schizophrenlainterleukin-8 (IL-8), interleukin-I ~, (IL-t ~), interteukin-6 (IL-6), and tumor necrosis factor-a(TNF-~)- are increased in individuals who later developed schizophrenia. For this purpose, we conducted a nested case-control study of a large birth cohort, born from 19591967, and followed up for psychiatric disorders in 1997-1998. Cases (N=59) were birth cohort members diagnosed with schizophrenia and other schizophrenia spectrum disorders (SSD); 85% of SSD cases had schizophrenia or schizoaffective disorder. All cases had available second trimester maternal serum samples that were drawn during pregnancy, and subsequently frozen and archived. Controls (N=105) were members of the birth cohort, had not been diagnosed with a schizophrenia spectrum or major affective disorder, and were matched to cases on date of birth, gender, length of time in the cohort, and availability of maternal sera. The measures of exposure were maternal second trimester serum levels of IL-8, IL- 1~, IL-6, and TNF-~x. Cytokines were quantified in sera using the sandwich enzyme-linked immunosorbent assay; all assays were conducted blind to case/control status. We found that second trimester maternal IL-8 in SSD cases was significantly increased as compared to controls (%2=5.41, p=.02). There were no differences between cases and controls with respect to IL-113 (Z2=0.68, p=.41), IL-6 (Z2=0.46, p=.50) or TNF-o~ (Z2=.10, p=.75). In conclusion, infectious or inflammatory processes associated with increased levels of IL-8 during the second trimester may play a role in the etiology of schizophrenia. Studies attempting to replicate this finding are necessary. If confirmed, this finding may have important implications for identifying risk factors and pathogenic mechanisms involved in schizophrenia.
REDUCED RURAL INCIDENCE OF SCHIZOPHRENIA IS PRIMARILY A FEMALE PHENOMENON: THE CAVAN-MONAGHAN FIRST EPISODE STUDY AT SEVEN YEARS R A. Baldwin,* R J. Scully, J. E Quinn, M. G. M o r g a n , A. Kinsella, J. M. O w e n s , E. O ' C a l l a g h a n , J. L. W a d d i n g t o n
Stanley Research Unit, St.Davnet, Monaghan, Ireland There is an emerging body of evidence to indicate that the incidence of schizophrenia is reduced among those born in or having their ear-
ly upbringing in a rural as opposed to an urban environment. Greater understanding of this phenomenon is predicated on systematically collected, prospective data within an epidemiologically complete popnlation. Over 1995-2002, all first episode cases of psychosis, of whatever form, presenting to the catchment area of Cavan-Monaghan Psychiatric Service, a rural and socioeconomically homogenous region of rural Ireland, have been entered into the study. During this period, t46 cases of psychosis were accrued among a population of 103,054. Overall incidence of any DSM-IV psychosis at 6-month follow-up was 27.2/100,000 aged > 15, with risk being 1.6-fold greater in males [33.1] than in females [21.0, P<0.01]. Incidence of schizophrenia spectrum psychosis [schizophrenia, schizophreniform or schizoaffective disorder] was 9.9/100,000 aged > 15, with risk being 2.9-fold greater in males [14.5] than in females [5.0, P<0.001 ]. Incidence of schizophrenia, comprising first-episode schizophrenia and first episode schizophreniform disorder evolving into schizophrenia over 6-month follow-up, was 6.5/100,000 aged > 15; risk was 5.7-fold greater in males [l 0.9] than in females [1.9, P<0.001]. Among additional psychotic diagnoses, incidence of affective psychosis [bipolar disorder or major depressive disorder with psychotic features] was 10.1/100,000 aged > 15, with risk being similar in males [10.2] and females [9.9]. While incidence of bipolar disorder was 4.7/100,000 aged > 15, with risk being t.7-fold greater in males [5.8] than in females [3.4], incidence of major depressive disorder with psychotic features was 5.4/100,000 aged > 15, with risk being 1.5-fold greater in females [6.5] than in males [4.4]. For other psychoses [brief psychotic disorder, delusional disorder, psychosis due to a general medical condition, substance-induced psychotic disorder, psychosis not otherwise specified], incidence was 7.3/100,000 aged > 15, with risk being 1.4-fold greater in males [8.4] than in females [6.1]. Within this overwhelmingly rural region, reduced incidence of schizophrenia spectrum psychotic illness, and particularly of schizophrenia itself, appeared to be a phenomenon essentially of females, with only bipolar disorder evidencing ally comparable trend. These studies were supported by the Stanley Medical Research Institute.
THE INFLUENCE OF INEQUALITY ON THE INCIDENCE OF SCHIZOPHRENIA - AN ECOLOGICAL STUDY J. Boydell,* J. van Os, K. M c K e n z i e , R. M u r r a y
Psychological Medicine, Institute of Psychiatry, Denmark Hill, London, United Kingdom Background Socio-economic factors are known to be associated with schizophrenia but no previous work has investigated the effect of inequality on the incidence of the disorder. Objectives To determine whether neighbourhoods with greater inequality, i.e. where there is a wide range from deprivation to affluence within the locality, have a higher incidence of schizophrenia. Design Ecological design involving a case record study to determine the incidence of schizophrenia over a ten year period across 15 administrative areas (neighbourhoods) in South London. We calculated an index of inequality for each area using a composite deprivation score. Results There was no effect of inequality overall.In the group of deprived areas however the incidence of RDC schizophrenia increased significantly as inequality increased.The incidence rate ratio was 3.79 p=0.019 after adjusting for age, sex, absolute deprivation, ethnicity, proportion of ethnic minorities and the interaction between individual ehnicity and proportion of ethnic minorities. Conclusion Increased inequality is associated with increasing incidence of schizophrenia but only in the most deprived areas.This is independent of
International Congress on Schizophrenia Research 2003
33
urban-rural comparison. Arch Gen Psychiatry 58:663-8., 2001 Yung AR, Phillips LJ, McGorry PD, McFarlane CA, Francey S, Harrigan S, Patton GC, Jackson HJ: Prediction of psychosis. A step towards indicated prevention of schizophrenia. Br J Psychiatry Suppt 172:1420, 1998
E L E V A T E D MATERNAL INTERLEUKIN-8 L E V E L S AND RISK OF SCHIZOPHRENIA IN
ADULT OFFSPRING V. Babulas,* A. S. Brown, J. Hooton, C. A. Schaefer,
H. Zhang, E. Petkova, M. A. Perrin, J. M. Gorman, E. S. Susser Psychiatry, Columbia University~New York State Psychiatric Institute, New York, NY, USA Many studies have implicated prenatal infection in the etiology of schizophrenia. Cytokines, a family of soluble polypeptides, are critically important in the immune response to infection, and in utero exposure to elevated cytokines is kaaown to damage the developing fetal brain. We aimed to determine whether second trimester levels of four cytokines that are plausible candidates for schizophrenlainterleukin-8 (IL-8), interleukin-I ~, (IL-t ~), interteukin-6 (IL-6), and tumor necrosis factor-a(TNF-~)- are increased in individuals who later developed schizophrenia. For this purpose, we conducted a nested case-control study of a large birth cohort, born from 19591967, and followed up for psychiatric disorders in 1997-1998. Cases (N=59) were birth cohort members diagnosed with schizophrenia and other schizophrenia spectrum disorders (SSD); 85% of SSD cases had schizophrenia or schizoaffective disorder. All cases had available second trimester maternal serum samples that were drawn during pregnancy, and subsequently frozen and archived. Controls (N=105) were members of the birth cohort, had not been diagnosed with a schizophrenia spectrum or major affective disorder, and were matched to cases on date of birth, gender, length of time in the cohort, and availability of maternal sera. The measures of exposure were maternal second trimester serum levels of IL-8, IL- 1~, IL-6, and TNF-~x. Cytokines were quantified in sera using the sandwich enzyme-linked immunosorbent assay; all assays were conducted blind to case/control status. We found that second trimester maternal IL-8 in SSD cases was significantly increased as compared to controls (%2=5.41, p=.02). There were no differences between cases and controls with respect to IL-113 (Z2=0.68, p=.41), IL-6 (Z2=0.46, p=.50) or TNF-o~ (Z2=.10, p=.75). In conclusion, infectious or inflammatory processes associated with increased levels of IL-8 during the second trimester may play a role in the etiology of schizophrenia. Studies attempting to replicate this finding are necessary. If confirmed, this finding may have important implications for identifying risk factors and pathogenic mechanisms involved in schizophrenia.
REDUCED RURAL INCIDENCE OF SCHIZOPHRENIA IS PRIMARILY A FEMALE PHENOMENON: THE CAVAN-MONAGHAN FIRST EPISODE STUDY AT SEVEN YEARS R A. Baldwin,* R J. Scully, J. E Quinn, M. G. M o r g a n , A. Kinsella, J. M. O w e n s , E. O ' C a l l a g h a n , J. L. W a d d i n g t o n
Stanley Research Unit, St.Davnet, Monaghan, Ireland There is an emerging body of evidence to indicate that the incidence of schizophrenia is reduced among those born in or having their ear-
ly upbringing in a rural as opposed to an urban environment. Greater understanding of this phenomenon is predicated on systematically collected, prospective data within an epidemiologically complete popnlation. Over 1995-2002, all first episode cases of psychosis, of whatever form, presenting to the catchment area of Cavan-Monaghan Psychiatric Service, a rural and socioeconomically homogenous region of rural Ireland, have been entered into the study. During this period, t46 cases of psychosis were accrued among a population of 103,054. Overall incidence of any DSM-IV psychosis at 6-month follow-up was 27.2/100,000 aged > 15, with risk being 1.6-fold greater in males [33.1] than in females [21.0, P<0.01]. Incidence of schizophrenia spectrum psychosis [schizophrenia, schizophreniform or schizoaffective disorder] was 9.9/100,000 aged > 15, with risk being 2.9-fold greater in males [14.5] than in females [5.0, P<0.001 ]. Incidence of schizophrenia, comprising first-episode schizophrenia and first episode schizophreniform disorder evolving into schizophrenia over 6-month follow-up, was 6.5/100,000 aged > 15; risk was 5.7-fold greater in males [l 0.9] than in females [1.9, P<0.001]. Among additional psychotic diagnoses, incidence of affective psychosis [bipolar disorder or major depressive disorder with psychotic features] was 10.1/100,000 aged > 15, with risk being similar in males [10.2] and females [9.9]. While incidence of bipolar disorder was 4.7/100,000 aged > 15, with risk being t.7-fold greater in males [5.8] than in females [3.4], incidence of major depressive disorder with psychotic features was 5.4/100,000 aged > 15, with risk being 1.5-fold greater in females [6.5] than in males [4.4]. For other psychoses [brief psychotic disorder, delusional disorder, psychosis due to a general medical condition, substance-induced psychotic disorder, psychosis not otherwise specified], incidence was 7.3/100,000 aged > 15, with risk being 1.4-fold greater in males [8.4] than in females [6.1]. Within this overwhelmingly rural region, reduced incidence of schizophrenia spectrum psychotic illness, and particularly of schizophrenia itself, appeared to be a phenomenon essentially of females, with only bipolar disorder evidencing ally comparable trend. These studies were supported by the Stanley Medical Research Institute.
THE INFLUENCE OF INEQUALITY ON THE INCIDENCE OF SCHIZOPHRENIA - AN ECOLOGICAL STUDY J. Boydell,* J. van Os, K. M c K e n z i e , R. M u r r a y
Psychological Medicine, Institute of Psychiatry, Denmark Hill, London, United Kingdom Background Socio-economic factors are known to be associated with schizophrenia but no previous work has investigated the effect of inequality on the incidence of the disorder. Objectives To determine whether neighbourhoods with greater inequality, i.e. where there is a wide range from deprivation to affluence within the locality, have a higher incidence of schizophrenia. Design Ecological design involving a case record study to determine the incidence of schizophrenia over a ten year period across 15 administrative areas (neighbourhoods) in South London. We calculated an index of inequality for each area using a composite deprivation score. Results There was no effect of inequality overall.In the group of deprived areas however the incidence of RDC schizophrenia increased significantly as inequality increased.The incidence rate ratio was 3.79 p=0.019 after adjusting for age, sex, absolute deprivation, ethnicity, proportion of ethnic minorities and the interaction between individual ehnicity and proportion of ethnic minorities. Conclusion Increased inequality is associated with increasing incidence of schizophrenia but only in the most deprived areas.This is independent of
International Congress on Schizophrenia Research 2003