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Prenatal influenza, genetic susceptibility and schizophrenia
137
AN ASSOCIATION BETWEEN SCHIZOPHRENIC BlRTHS AND INFLUENZA DEATHS IN IRELAND LN THE YEARS 1921-1971 Mary Morris*, David Cotter, Noriyoshi Takei, Dermot Walsh, Conall Larkin, John L. Waddington, Eadbhard O’Callaghan St. John of God Psychiatric Services, Blackrock, Dublin, Ireland There is much debate about whether an association exists between prenatal exposure to influenza and later schizophrenic births. Prompted by such controversy, we investigated this hypothesis in an Irish population. The birth dates of 2846 schizophrenics (ICD-9), born between 1921 and 1971 admitted to hospital (1988/1989) were used for the analysis. In Ireland, only quarterly figures for the population birth rates were available for the same years. We estimated the monthly birth rate from recent Census data. Data relating to influenza deaths were obtained from the Central Statistics Office. We applied a generalized linear model to our data, in which the fluctuations in the general population birth pattern, and the long term and seasonal variations in schizophrenic births were allowed for. An inclusion of influenza deaths in the month, and in the previous month, of birth into the model reduced the scaled deviance by 6.66 (p
by the Health Research
SCHIZOPHRENIA CLASS Fiona Mulvaney*,
Board.
AND PARENTAL
SOCIAL
HISTORY OF ARREST, PSYCHOTIC DISORDERS AND SOCIAL CLASS: A COMPARISON BETWEEN SCHIZOPHRENIA AND OTHER PSYCHOSES Carles Muntaner*, Paula Wolyniec,
Ann E. Pulver
Laboratory of Socio-environmental Studies, NIMH. Room BIA-12 Federal Building, 7550 Wisconsin Avenue, Bethesda, MD 20892, USA The present study investigates differences in history of arrest between patients with Schizophrenia and other psychotic disorders (Bipolar Disorder, Psychoactive-Substance Induced Psychosis, and other “functional” psychoses). All admissions with psychotic disorders to fifteen hospitals providing inpatient psychiatric services in the Baltimore-Washington area were surveyed between 1983-1989 (The Maryland Epidemiology Sample; Pulver and Bale, 1989). Study participants were interviewed using a modified version of the DIS. After adjusting for age, gender, number of admissions, and social class, we found that patients admitted for psychoactive substance-induced psychosis were more likely to report having been arrested than patients with schizophrenia. There were no substantial differences in arrest history between patients with schizophrenia and bipolar disorder. The relationship between psychotic diagnosis and history of arrest was modified by so&demographic factors. In particular, psychotic patients with substance-induced diagnoses who originated from a lower social class were more likely to report prior arrests than others. Future studies should investigate whether perceived dangerousness of schizophrenic patients in the community might be accounted for by psychoactive substance use and social class.
Majella Byrne, Eadbhard O’Callaghan
St John of God Psychiatric Services, Blackrock, Co Dublin, Ireland The over-representation of people with schizophrenia, in the lower social classes has been consistently reported. However, reports examining paternal social class at the time of their schizophrenic son’s birth have not demonstrated the same degree of consistency in their findings. This study examined the birth registration records of 145 male schizophrenic (ICD 9) first admission patients to a community psychiatric service between 1960 and 1990. Paternal occupation of the next registered male birth in the district was also recorded and used as a matched control. Occupations were classified according to the Irish Census based Social Class Scale. The social class distribution of fathers of schizophrenic males did not differ from controls. No excess was found in the lowest social class category (Patients 19.4% Controls 16.3% p=O.3). Age at first admission was examined to assess its contribution to the drift hypothesis. A strong trend towards social class differences in age at first presentation was identified with patients in Social Class I displaying the youngest age at first admission (X=21.13+4.41, 95% C.I.= 19.69 - 24.57: Kruskal-Wallis oneway analysis of variance: C.S.= 10.6, p=O.O6).
PRENATAL INFLUENZA, GENETIC SUSCEPTIBILITY AND SCHIZOPHRENIA R.M. Murray*, N. Takei, P. Sham, E. O’Callaghan,
P Wright
Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK We have completed 4 studies in England of the relationship between influenza and schizophrenic births; all have shown that exposure to epidemics in the 5th or 6th month of gestation increases the risk of later schizophrenia. This effect is more noticeable for females than males, and an examination of births of female affective psychotics has shown a decrease in their births 5 months following influenza epidemics. This suggests that some females predisposed to affective psychosis are diverted instead, by prenatal influenza, to developing a schizophrenia-like illness. Prenatal viral illness may explain the higher rates of schizophrenia we found in city-born individuals and in Afro-Caribbean immigrants in England. We hypothesise that the mechanism is an auto-immune impairment of neurodevelopment, and are therefore examining maternal HLA antigens. If the ‘schizophrenia gene’ is involved in the immune response to viral infections, then this
138
could explain the persistence gene in the population.
of such a seemingly
disadvantageous
SCHIZOPHRENIC BIRTHS IN ENGLAND AND WALES AND THEIR RELATIONSHIP TO INFECTIOUS DISEASES Eadbhard O’Callaghan, Pak C. Sham, Noriyoshi Takei, Graham Murray, Gyles Glover, Edward Hare, Robin M. Murray Department of Psychological Medicine, Kings College Hospital and Institute ofPsychiatry, London, UK Some recent epidemiological reports suggest an association between prenatal exposure to influenza and schizophrenic births. We investigated whether or not there was an association between deaths from 16 infections (measles, rubella, diphtheria, varicella zoster, mumps, herpes simplex, scarlet fever, whooping cough, typhoid, paratyphoid, encephalitis, meningitis, broncho-pneumonia, lobar pneumonia, rheumatoid fever and polio) between 1937 and 1965 and the births of schizophrenics. We examined schizophrenic birth dates from two large data sets (12 UK Regions, 19761986 and a National data set 1970-1975). Using the program GLIM (Numerical Algorithms Group 1985) a generalized linear model was employed to test for statistical association. Both data sets demonstrated an association between deaths from bronchopneumonia and later schizophrenic births. No other consistent associations across the data sets were found. Individual associations were found for: varicella-zoster and schizophrenic births three months later and a negative effect for encephalitis nine months before birth. These data provide little evidence for an association between infectious diseases other than influenza and later schizophrenia.
SEASONAL EFFECTS ON CLINICAL FEATURES OF SCHIZOPHRENIA R. Persaud*, G. Der, N. Takei, D. Castle, S. Wessley, R. Murray Department RAF, UK
of Psychiatry,
Institute of Psychiatry,
London SE5
A summer peak for admissions for manic-depression and schizophrenia has been widely reported. Another recent finding has been a statistically significant summer peak of admissions for female schizophrenics but no seasonal effect on male admissions. Based on routine hospital statistics the study (in press) suffered the limitations of many others in the area of seasonal effects, which was the doubtful reliability of the diagnoses and the reliance on admissions rather than first contacts with services. In contrast, our study used the Operational Criteria Checklist for Psychotic Illness on all the first contacts between 1965 and
1984 with schizophrenia and related diagnoses living in a defined catchment area. The number of patients so identified was 566 and using the Edwards test for seasonality a statistically signiticant winter peak for first contact was found for males (p
FAMILIAL VS. NON-FAMILIAL SCHIZOPHRENIA Ann E. Pulver*, Paula Wolyniec, Beth Melton, Kung-Yee Liang The Johns Hopkins University. Department of Psychiatry and Behavioral Sciences, EpidemiologylGenetics Program, 1615 Thames St., Baltimore, MD 21231, Suite 205, USA Given the probable heterogeneity of schizophrenia, we were interested in determining whether or not there were observable differences in schizophrenic patients who had relatives affected with schizophrenia (familial) vs. schizophrenic patients who did not (non-familial). A latent class approach (Melton and Liang, 1992) was used to classify 383 schizophrenic patients identified in the Maryland Epidemiology Sample, a systematic sample of patients obtained from 15 hospitals in the Baltimore area. The DSM-III diagnosis of schizophrenia was formulated through a best estimate procedure based on multiple sources of information. The latent class method takes into consideration the fact that the classification of the patients into the familial or non-familial group could be influenced by the age and gender distribution of their family members. We found that 28% of the male patients and 33% of the female patients had at least one relative affected with schizophrenia and that the odds of having certain clinical characteristics (e.g. a history of manic symptoms) and other known risk factors for schizophrenia (e.g. winter-spring birth) was associated with familial schizophrenia.
LOW BIRTH WEIGHT AND POOR PREMORBID CHILDHOOD FUNCTION PREDICT COGNITIVE IMPAIRMENT IN SCHIZOPHRENIA Lamy R&in”,
Peter Jones, Robin Murray
Genetics Section, The Institute of Psychiatry, Denmark Hill, London SE5 8AF, UK
De Crespigny Park,
Schizophrenic patients with poor premorbid function have been reported to have earlier onset of illness, more negative symptoms, C.T. scan abnormalities and poor outcome. However while
AN ASSOCIATION BETWEEN SCHIZOPHRENIC BlRTHS AND INFLUENZA DEATHS IN IRELAND LN THE YEARS 1921-1971 Mary Morris*, David Cotter, Noriyoshi Takei, Dermot Walsh, Conall Larkin, John L. Waddington, Eadbhard O’Callaghan St. John of God Psychiatric Services, Blackrock, Dublin, Ireland There is much debate about whether an association exists between prenatal exposure to influenza and later schizophrenic births. Prompted by such controversy, we investigated this hypothesis in an Irish population. The birth dates of 2846 schizophrenics (ICD-9), born between 1921 and 1971 admitted to hospital (1988/1989) were used for the analysis. In Ireland, only quarterly figures for the population birth rates were available for the same years. We estimated the monthly birth rate from recent Census data. Data relating to influenza deaths were obtained from the Central Statistics Office. We applied a generalized linear model to our data, in which the fluctuations in the general population birth pattern, and the long term and seasonal variations in schizophrenic births were allowed for. An inclusion of influenza deaths in the month, and in the previous month, of birth into the model reduced the scaled deviance by 6.66 (p
by the Health Research
SCHIZOPHRENIA CLASS Fiona Mulvaney*,
Board.
AND PARENTAL
SOCIAL
HISTORY OF ARREST, PSYCHOTIC DISORDERS AND SOCIAL CLASS: A COMPARISON BETWEEN SCHIZOPHRENIA AND OTHER PSYCHOSES Carles Muntaner*, Paula Wolyniec,
Ann E. Pulver
Laboratory of Socio-environmental Studies, NIMH. Room BIA-12 Federal Building, 7550 Wisconsin Avenue, Bethesda, MD 20892, USA The present study investigates differences in history of arrest between patients with Schizophrenia and other psychotic disorders (Bipolar Disorder, Psychoactive-Substance Induced Psychosis, and other “functional” psychoses). All admissions with psychotic disorders to fifteen hospitals providing inpatient psychiatric services in the Baltimore-Washington area were surveyed between 1983-1989 (The Maryland Epidemiology Sample; Pulver and Bale, 1989). Study participants were interviewed using a modified version of the DIS. After adjusting for age, gender, number of admissions, and social class, we found that patients admitted for psychoactive substance-induced psychosis were more likely to report having been arrested than patients with schizophrenia. There were no substantial differences in arrest history between patients with schizophrenia and bipolar disorder. The relationship between psychotic diagnosis and history of arrest was modified by so&demographic factors. In particular, psychotic patients with substance-induced diagnoses who originated from a lower social class were more likely to report prior arrests than others. Future studies should investigate whether perceived dangerousness of schizophrenic patients in the community might be accounted for by psychoactive substance use and social class.
Majella Byrne, Eadbhard O’Callaghan
St John of God Psychiatric Services, Blackrock, Co Dublin, Ireland The over-representation of people with schizophrenia, in the lower social classes has been consistently reported. However, reports examining paternal social class at the time of their schizophrenic son’s birth have not demonstrated the same degree of consistency in their findings. This study examined the birth registration records of 145 male schizophrenic (ICD 9) first admission patients to a community psychiatric service between 1960 and 1990. Paternal occupation of the next registered male birth in the district was also recorded and used as a matched control. Occupations were classified according to the Irish Census based Social Class Scale. The social class distribution of fathers of schizophrenic males did not differ from controls. No excess was found in the lowest social class category (Patients 19.4% Controls 16.3% p=O.3). Age at first admission was examined to assess its contribution to the drift hypothesis. A strong trend towards social class differences in age at first presentation was identified with patients in Social Class I displaying the youngest age at first admission (X=21.13+4.41, 95% C.I.= 19.69 - 24.57: Kruskal-Wallis oneway analysis of variance: C.S.= 10.6, p=O.O6).
PRENATAL INFLUENZA, GENETIC SUSCEPTIBILITY AND SCHIZOPHRENIA R.M. Murray*, N. Takei, P. Sham, E. O’Callaghan,
P Wright
Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK We have completed 4 studies in England of the relationship between influenza and schizophrenic births; all have shown that exposure to epidemics in the 5th or 6th month of gestation increases the risk of later schizophrenia. This effect is more noticeable for females than males, and an examination of births of female affective psychotics has shown a decrease in their births 5 months following influenza epidemics. This suggests that some females predisposed to affective psychosis are diverted instead, by prenatal influenza, to developing a schizophrenia-like illness. Prenatal viral illness may explain the higher rates of schizophrenia we found in city-born individuals and in Afro-Caribbean immigrants in England. We hypothesise that the mechanism is an auto-immune impairment of neurodevelopment, and are therefore examining maternal HLA antigens. If the ‘schizophrenia gene’ is involved in the immune response to viral infections, then this
138
could explain the persistence gene in the population.
of such a seemingly
disadvantageous
SCHIZOPHRENIC BIRTHS IN ENGLAND AND WALES AND THEIR RELATIONSHIP TO INFECTIOUS DISEASES Eadbhard O’Callaghan, Pak C. Sham, Noriyoshi Takei, Graham Murray, Gyles Glover, Edward Hare, Robin M. Murray Department of Psychological Medicine, Kings College Hospital and Institute ofPsychiatry, London, UK Some recent epidemiological reports suggest an association between prenatal exposure to influenza and schizophrenic births. We investigated whether or not there was an association between deaths from 16 infections (measles, rubella, diphtheria, varicella zoster, mumps, herpes simplex, scarlet fever, whooping cough, typhoid, paratyphoid, encephalitis, meningitis, broncho-pneumonia, lobar pneumonia, rheumatoid fever and polio) between 1937 and 1965 and the births of schizophrenics. We examined schizophrenic birth dates from two large data sets (12 UK Regions, 19761986 and a National data set 1970-1975). Using the program GLIM (Numerical Algorithms Group 1985) a generalized linear model was employed to test for statistical association. Both data sets demonstrated an association between deaths from bronchopneumonia and later schizophrenic births. No other consistent associations across the data sets were found. Individual associations were found for: varicella-zoster and schizophrenic births three months later and a negative effect for encephalitis nine months before birth. These data provide little evidence for an association between infectious diseases other than influenza and later schizophrenia.
SEASONAL EFFECTS ON CLINICAL FEATURES OF SCHIZOPHRENIA R. Persaud*, G. Der, N. Takei, D. Castle, S. Wessley, R. Murray Department RAF, UK
of Psychiatry,
Institute of Psychiatry,
London SE5
A summer peak for admissions for manic-depression and schizophrenia has been widely reported. Another recent finding has been a statistically significant summer peak of admissions for female schizophrenics but no seasonal effect on male admissions. Based on routine hospital statistics the study (in press) suffered the limitations of many others in the area of seasonal effects, which was the doubtful reliability of the diagnoses and the reliance on admissions rather than first contacts with services. In contrast, our study used the Operational Criteria Checklist for Psychotic Illness on all the first contacts between 1965 and
1984 with schizophrenia and related diagnoses living in a defined catchment area. The number of patients so identified was 566 and using the Edwards test for seasonality a statistically signiticant winter peak for first contact was found for males (p
FAMILIAL VS. NON-FAMILIAL SCHIZOPHRENIA Ann E. Pulver*, Paula Wolyniec, Beth Melton, Kung-Yee Liang The Johns Hopkins University. Department of Psychiatry and Behavioral Sciences, EpidemiologylGenetics Program, 1615 Thames St., Baltimore, MD 21231, Suite 205, USA Given the probable heterogeneity of schizophrenia, we were interested in determining whether or not there were observable differences in schizophrenic patients who had relatives affected with schizophrenia (familial) vs. schizophrenic patients who did not (non-familial). A latent class approach (Melton and Liang, 1992) was used to classify 383 schizophrenic patients identified in the Maryland Epidemiology Sample, a systematic sample of patients obtained from 15 hospitals in the Baltimore area. The DSM-III diagnosis of schizophrenia was formulated through a best estimate procedure based on multiple sources of information. The latent class method takes into consideration the fact that the classification of the patients into the familial or non-familial group could be influenced by the age and gender distribution of their family members. We found that 28% of the male patients and 33% of the female patients had at least one relative affected with schizophrenia and that the odds of having certain clinical characteristics (e.g. a history of manic symptoms) and other known risk factors for schizophrenia (e.g. winter-spring birth) was associated with familial schizophrenia.
LOW BIRTH WEIGHT AND POOR PREMORBID CHILDHOOD FUNCTION PREDICT COGNITIVE IMPAIRMENT IN SCHIZOPHRENIA Lamy R&in”,
Peter Jones, Robin Murray
Genetics Section, The Institute of Psychiatry, Denmark Hill, London SE5 8AF, UK
De Crespigny Park,
Schizophrenic patients with poor premorbid function have been reported to have earlier onset of illness, more negative symptoms, C.T. scan abnormalities and poor outcome. However while