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Evidence of a Dose-Response Relationship Between Urbanicity During Upbringing and Schizophrenia Risk
Carsten Bøcker Pedersen, MSc;
Preben Bo Mortensen, DMSc
Arch Gen Psychiatry. 2001;58:1039-1046.
ABSTRACT
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Background Many studies have demonstrated that an urban birth or upbringing increases
schizophrenia risk, but no studies have been able to distinguish between these
effects. The objectives of this study were to discriminate the effect of urbanicity
at birth from an effect of urbanicity during upbringing, and to identify particularly
vulnerable age periods and a possible dose-response relationship between urbanicity
during upbringing and schizophrenia risk.
Methods Using data from the Danish Civil Registration System, we established
a population-based cohort of 1.89 million people, which included information
on place of birth, place of residence during upbringing, and the accumulated
number of years lived in each category of the 5-level degree of urbanization
during upbringing. Schizophrenia in cohort members and mental illness in a
parent or sibling were identified by linkage with the Danish Psychiatric Central
Register.
Results Individuals living in a higher degree of urbanization than 5 years earlier
had a 1.40-fold (95% confidence interval, 1.28-1.51) increased risk, while
individuals living in a lower degree of urbanization than 5 years earlier
had a 0.82-fold (95% confidence interval, 0.77-0.88) decreased risk of schizophrenia.
For fixed urbanicity at the 15th birthday, risk increased with increasing
degree of urbanization at birth. Furthermore, the more years lived in the
higher the degree of urbanization, the greater the risk. Individuals who lived
their first 15 years in the highest category of the 5-level urbanicity had
a 2.75-fold (95% confidence interval, 2.31-3.28) increased risk of schizophrenia.
Conclusion Continuous, or repeated, exposures during upbringing that occur more
frequently in urbanized areas may be responsible for the association between
urbanization and schizophrenia risk.
INTRODUCTION
ALTHOUGH A family history of schizophrenia is the best established risk
factor for the disease,1 it may account for
only a small proportion of the population occurrence of schizophrenia.2, 3 Other factors, such as urbanicity at
birth and upbringing, are associated with an increased risk also,2, 3, 4 and causal factors underlying
this association may account for a much higher proportion of the population
occurrence of the disease. Although the causes of these urban-rural differences
are unknown, they have been hypothesized to include, eg, obstetric complications,
infections, diet, toxic exposures, household crowding, breastfeeding, social
class, and an artifact due to migration.5, 6
To reduce the number of possible candidates responsible for this association,
the objective of this study was to investigate at what age during upbringing
(including birth) children were most vulnerable to urbanicity. However, since
urbanicity at birth and urbanicity during upbringing are strongly associated,
a large study population, including information on place of birth and upbringing,
is needed to discriminate the effect of urbanicity at birth from an effect
of urbanicity during upbringing, and vice versa.7
To our knowledge, studies based on such data have not been published previously.
This study uses a large population-based sample of the Danish population,
including complete information on all permanent addresses at which cohort
members had lived since 1971, to investigate the relative impact of urbanicity
at birth and during upbringing. Furthermore, the hypothesis that there is
a dose-response relationship between urbanicity during upbringing and schizophrenia
risk is investigated.
PARTICIPANTS AND METHODS
STUDY POPULATION
We used data from the Danish Civil Registration System8
to obtain a large and representative set of data on Danish persons, which
for all persons included current and historical information on address in
Denmark and Greenland and emigrations and immigrations to and from other countries,
together with exact dates for changes of residence. All citizens in Denmark
are obliged to inform the authorities about any change of permanent address
within 5 days. Failure to supply this information will result in the inability
to receive a supplementary benefit (eg, unemployment, sickness or disablement
benefits, and educational aid from public funds), to go to a day nursery,
to go to nursery school, to attend primary and lower secondary school, to
obtain free national health care, and to obtain a tax deduction card (required
to have paid work). Therefore, it is unlikely that this mandatory information
is not reported. This information is complete from January 1, 1971. Our study
cohort consists of all persons with known maternal identity who were born
in Denmark between January 1, 1956, and December 31, 1983, and who were alive
at the 15th birthday (1.89 million persons).
ASSESSMENT OF SCHIZOPHRENIA AND MENTAL ILLNESS IN A PARENT OR SIBLING
The study population and their mothers, fathers, and siblings were linked
with the Danish Psychiatric Central Register,9
which has been computerized since April 1, 1969. The Danish Psychiatric Central
Register contains data on all admissions to Danish psychiatric inpatient facilities
and includes data on approximately 450 000 persons and 1.6 million admissions.
From 1995 onward, information on outpatient visits to psychiatric departments
was included in the register. There are no private psychiatric departments
in Denmark. From April 1, 1969, to December 31, 1993, the diagnostic system
used was the International Classification of Diseases, 8th
Revision (ICD-8),10 and from January
1, 1994, the diagnostic system used was the International
Classification of Diseases, 10th Revision (ICD-10).11
Cohort members were classified as having schizophrenia if they had been admitted
to a psychiatric hospital or had been in outpatient care with a diagnosis
of the disorder (ICD-8 code 295 or ICD-10 code F20). The date of onset was defined as the first day of
the first contact (inpatient or outpatient) with a diagnosis of schizophrenia.
Parents and siblings were categorized hierarchically with a history of schizophrenia
(ICD-8 code 295 or ICD-10
code F20), schizophrenialike psychoses (ICD-8 code
297, 298.39, or 301.83 or ICD-10 codes F21-F29),
or other mental disorders (any ICD-8 or ICD-10 diagnosis) if they had been admitted to a psychiatric hospital
or had been in outpatient care with one of these diagnoses.
ASSESSMENT OF DEGREE OF URBANIZATION
The 276 municipalities in Denmark were classified according to the degree
of urbanization12: capital, capital suburb,
provincial city with more than 100 000 inhabitants, provincial town with
more than 10 000 inhabitants, or rural areas. Denmark is a small homogeneous
country with a population of 5.3 million people and a total area of 43 000
km2. The capital, capital suburb, provincial city, provincial town,
and rural area hold 5220, 845, 470, 180, and 55 people per square kilometer,
respectively.13 Distances are small in Denmark;
most people live within 25 km of a city with more than 30 000 inhabitants,
and are even closer to a psychiatric hospital.
STUDY DESIGN
Using data from the Danish Civil Registration System, for each person
in the cohort we obtained information on (1) the degree of urbanization in
1-year age points from birth to the 15th birthday; (2) the number of changes
of the address, the municipality, and the degree of urbanization in 1-year
age bands from birth to the 15th birthday; and (3) the accumulated number
of years each person born in 1971 or later had been living in each degree
of urbanization from birth to the 5th birthday, from the 5th to the 10th birthday,
and from the 10th to the 15th birthday. The reason we considered change of
residence was that initial analyses suggested that to investigate the association
between schizophrenia and urbanization we had to control for an increased
risk associated with change of residence. Furthermore, to avoid the potential
impact of selective migration to cities in the prodromal phase of schizophrenia,
only residence during upbringing was considered. By upbringing, we are referring
to the period from birth to the 15th birthday. Information on urbanicity at
birth, urbanicity during upbringing, and change of residence is independent
of the disease status. A total of 1.89 million persons were followed up from
their 15th birthday or from April 1, 1970, whichever came later, until the
date of onset of schizophrenia, the date of death, the date of emigration,
or December 31, 1998, whichever came first.
STATISTICAL ANALYSES
The relative risk of schizophrenia was estimated by log-linear Poisson
regression14 with the GENMOD procedure, using
SAS statistical software, version 6.12.15 All
relative risks were adjusted for age and its interaction with sex, calendar
year, and history of mental illness in a parent or sibling. Age, calendar
year, and history of mental illness in siblings were treated as time-dependent
variables,16 whereas history of mental illness
in a parent was treated as a variable that was independent of time. Age was
categorized using the following cut points: 15, 16, 17, 18, 19, 20, 22, 24,
26, 28, 30, 35, and 40 years. Calendar year was categorized using the following
cut points: 1971, 1976, 1979, 1982, 1985, 1988, 1991, 1993, 1994, 1995, 1996,
1997, and 1998. P values were based on findings from
the likelihood ratio tests, and 95% confidence limits were calculated by the
Wald test.16 The adjusted-score test17 suggested that the regression models were not subject
to overdispersion. Apart from the reduction in the size of the study population,
omission of adjustment for seasonality, maternal and paternal age, and the
inclusion of information on permanent address for all cohort members since
1971, the material described is identical to that used in our previous study,3 where we found that the effects of urbanicity at birth
and mental illness in a family member were invariant to the diagnostic system
and the inclusion of outpatient information.
To evaluate the hypothesis that there is a dose-response relationship
between urbanicity during upbringing and schizophrenia risk, we used a statistical
model for the accumulated number of years each person had been living in the
capital, the capital suburb, the provincial city, and the provincial town.
It implies that those who always lived in the rural area during upbringing
were chosen as the reference category, and that the effect of these 4 variables
measures the effect of exchanging upbringing in the rural area with upbringing
in the corresponding degree of urbanization.
By urbanicity at some age point, we refer only to the degree of urbanization
at the given age point, whereas by urbanicity during upbringing, we refer
to the full sequence of degrees of urbanization of places of residence from
birth to the 15th birthday. Furthermore, by a model for urbanicity during
upbringing, we refer to a model for the accumulated number of years each person
has lived in the capital, the capital suburb, the provincial city, and the
provincial town during upbringing.
RESULTS
A total of 8235 persons developed schizophrenia during the 27.1 million
person-years of follow-up (Table 1).
Urbanicity at birth is known for all persons, whereas information on urbanicity
at a given age depends on the year of birth, as information on place of residence
was accessible only from 1971 onward.
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Table 1. Distribution of 8235 Cases of Schizophrenia and 27.1 Million
Person-years at Risk in a Population-Based Cohort of 1.89 Million Danish People
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CHANGE OF RESIDENCE
The relative risk of schizophrenia increases with increasing age at
change of the address or the municipality (Figure 1). However, change of address within the same municipality
had no influence on schizophrenia risk. Furthermore, the effect of changes
of the municipality within the same degree of urbanization increased with
increasing age (data not shown). Therefore, the confounding effect of change
of residence can be described by changes of the municipality.
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Figure 1. Relative risk of schizophrenia
associated with age and change of the municipality (A), the address within
the same municipality (B), and the address (C). Those without change of the
municipality, the address within the same municipality, or the address are
used as the baseline category (relative risk = 1.00). Vertical lines indicate
95% confidence intervals. Age 0 indicates the age period from birth to the
first birthday, etc. Estimates of relative risks were adjusted for age and
its interaction with sex, calendar year, and mental illness in a parent or
sibling.
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We classified change of municipality by 4 variables, counting the number
of changes of the municipality from birth to the 5th birthday, from the 5th
to the 10th birthday, from the 10th to the 13th birthday, and from the 13th
to the 15th birthday (Table 2).
Compared with persons with no changes of the municipality from the 5th to
the 10th birthday, those with one change of the municipality had a relative
risk of 1.18. The effect of the number of changes of municipality increased
with increasing age and increasing number of changes. Overall, these 4 variables
had a significant effect (P<.001), and the model
with these 4 variables had a significantly better fit than the model in which
the change of municipality was described in 1-year bands (Figure 1).
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Table 2. Adjusted Relative Risks According to Number of Changes of
Municipality in a Population-Based Cohort of 1.89 Million Danish People*
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URBANICITY IN 1-YEAR AGE POINTS
Individuals who at birth lived in the capital, the capital suburb, the
provincial city, or the provincial town had a relative risk of schizophrenia
of 2.24 (95% confidence interval [CI], 1.92-2.61), 1.71 (95% CI, 1.46-2.00),
1.62 (95% CI, 1.36-1.92), and 1.27 (95% CI, 1.10-1.47), respectively, compared
with individuals who lived in the rural area (Figure 2). This difference remained almost constant for ages from
birth to the 15th birthday.
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Figure 2. Relative risk of schizophrenia
according to urbanicity and age at residence. Urbanicity from birth to the
15th birthday enters separately in these 16 models. Age 0 indicates the time
at birth, etc. Vertical lines indicate 95% confidence intervals. To avoid
the confidence intervals from overlapping graphically, the age scale for the
capital suburb was moved slightly to the left and the age scale for the provincial
city was moved slightly to the right. Estimates of relative risks were adjusted
for age and its interaction with sex, calendar year of diagnosis, and mental
illness in a parent or sibling. Further adjustment for change of the municipality
would reduce the effect of urbanicity only slightly.
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RELATIVE URBANICITY AT SUCCESSIVE AGES
Among those who were born in the capital suburb, those who at the 5th
birthday lived in a higher, the same, or a lower degree of urbanization than
at birth had a relative risk of schizophrenia of 2.01, 1.82, or 1.55, respectively
(Table 3, first adjustment), compared
with those who at birth and at the 5th birthday lived in the rural area. In
general, living in a higher degree of urbanization at the 5th birthday than
at birth increased risk, while living in a lower degree of urbanization at
the 5th birthday than at birth decreased risk. This tendency was not modified
by adjustment for change of the municipality (Table 3, second adjustment).
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Table 3. Adjusted Relative Risk of Schizophrenia According to Urbanicity
in a Population-Based Cohort of 1.89 Million Danish People
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Living in a higher or lower degree of urbanization at the 10th birthday
than at the 5th birthday increased risk, but risk was increased more if living
in a higher than in a lower degree of urbanization (Table 3, first adjustment). When these estimates were adjusted for
the number of changes of the municipality, living in a higher degree of urbanization
at the 10th birthday than at the 5th birthday increased risk, while living
in a lower degree of urbanization at the 10th birthday than at the 5th birthday
decreased risk (Table 3, second
adjustment). The same tendency was found when comparing place of residence
at the 10th birthday with place of residence at the 15th birthday. Overall,
living in a higher degree of urbanization than 5 years earlier increased risk
1.40-fold (95% CI, 1.28-1.51), while living in a lower degree of urbanization
than 5 years earlier decreased risk 0.82-fold (95% CI, 0.77-0.88). Furthermore,
for fixed urbanicity at birth, risk increases with increasing degree of urbanization
at place of residence at the 15th birthday, and for fixed urbanicity at the
15th birthday, risk increases with increasing degree of urbanization at place
of birth (data not shown).
URBANICITY DURING UPBRINGING
A total of 807 000 people in the cohort were born in 1971 or later
and, therefore, these people had accessible information on urbanicity during
upbringing. Among them, 1553 persons developed schizophrenia during the 5.6
million person-years at risk (Table 4). Compared with those who had always been living in the rural area, those who
had always been living in the capital had a relative risk of 2.62. In general,
the more years lived in the higher the degree of urbanization, the greater
the risk of schizophrenia.
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Table 4. Distribution of the Number of Cases, the Person-years at Risk,
and the Adjusted Relative Risk According to a Categorical Model for the Accumulated
Number of Years Lived in Each Degree of Urbanization During Upbringing*
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Estimates in the second column of Table 5 measure the risk per year associated with exchanging residence
in the rural area with residence in each degree of urbanization, and estimates
in the third column measure the risk associated with exchanging all residence
(15 years) in the rural area with residence in each degree of urbanization.
The relative risk per 15 years is calculated by raising the relative risk
per year to the 15th power, eg, 1.069715 = 2.75. Compared with
those who had always been living in the rural area during upbringing, those
who had always been living in the capital during upbringing had a relative
risk of 2.75. According to this model, a person who had been living 7 years
in the capital and 8 years in the capital suburb during upbringing had a relative
risk of 2.12 (1.06977 x 1.03558) compared with a person who had always been living in the rural area
(not accounting for the increased risk associated with change of residence).
In general, risk increases with increasing degree of urbanization, and inherent
in the log-linear model is that risk increases with increasing number of years
lived in each degree of urbanization. The categorical model (Table 4) could be simplified to the log-linear model (Table 5) for urbanicity during upbringing (P
= .63). In the rest of this article, we use the log-linear model to describe
the association between schizophrenia and urbanization. Furthermore, this
model had a significantly better fit than any of the models for the modifying
effects of urbanicity between the successive age points of birth, 5th, 10th,
and 15th birthday (Table 3).
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Table 5. Adjusted Relative Risk According to a Log-Linear Model for
the Accumulated Number of Years Lived in Each Degree of Urbanization During
Upbringing
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When urbanicity at birth and urbanicity during upbringing were adjusted
mutually, the effect of urbanicity at birth vanished (P = .80), while the effect of urbanicity during upbringing was not modified
and remained strongly significant (P<.001). This
means that urbanicity during upbringing explains the effect of urbanicity
at birth, ie, urbanicity at birth is a proxy for urbanicity during upbringing.
The effect of urbanicity during upbringing did not differ significantly by
age at residence (P = .08) or sex (P = .79) (data not shown), meaning that there was no evidence of age
at residence or sex differences in the vulnerability to upbringing in urbanized
areas. Furthermore, there were no urban-rural differences in age of onset
(P = .21).
In any of the models presented herein, the effect of change of municipality
remained constant.
COMMENT
Places of residence at nearby ages are strongly associated, meaning
that for most people, place of residence at the fifth birthday was identical
to place of residence at the fourth and sixth birthday. This correlation impedes
the interpretation of the finding of the constant effect of urbanicity according
to age (Figure 2). However, suppose
children were only vulnerable to urbanicity at the fifth birthday and not
to urbanicity at birth or urbanicity at any other age, then the reason many
studies (eg, Mortensen and others2, 3, 6)
have found an association between urbanicity at birth and schizophrenia risk
is that urbanicity at birth is a proxy for urbanicity at the fifth birthday.
Furthermore, because of attenuation caused by misclassification,18
the effect of this proxy variable would be lower than the effect of urbanicity
at the fifth birthday. Therefore, if children were most fragile to urbanicity
at some single age point during upbringing, then urbanicity would have a higher
effect for this age point than for the nearby age points. However, since the
effect of urbanicity (Figure 2)
does not depend on age at residence, these data show no indication of any
ages particularly vulnerable to residence in urbanized areas during upbringing.
The risk associated with 15 years of residence in any urbanicity was
greater than the risk associated with living in the same urbanicity as 5 years
earlier (Table 3, second adjustment,
and Table 5), which in turn was
greater than the effect of urbanicity at birth or at some age point (Figure 2). This indicates that the greater
the refinement of the modeling of urbanicity, the greater the risk, and that
not only urbanicity at birth or at some age point but also the effect of living
in the same urbanicity as 5 years earlier are proxies for urbanicity during
upbringing. In conclusion, the log-linear model for the accumulated number
of years lived in each degree of urbanization during upbringing is the best
model describing the association between urbanization and schizophrenia risk.
Furthermore, it provides evidence of a dose-response relationship between
urbanicity during upbringing and schizophrenia risk.
The possible etiological factors that might explain our findings remain
unknown. However, the finding of a dose-response relationship between schizophrenia
risk and urbanicity during upbringing lends support to a causal association.
Our findings may suggest that constant, cumulative, or repeated exposures
during upbringing occurring more frequently in urbanized areas are responsible
for the association between urbanization and schizophrenia risk. The potential
explanations for the urban-rural differences shift from factors influencing
children at or around birth to factors influencing children continuously,
or repeatedly, throughout upbringing. Factors such as obstetric complications,
prenatal infections, and breastfeeding are, therefore, less likely explanations
for these urban-rural differences, although they may well affect risk independently
of urbanicity. Also, studies have suggested that household crowding,19 obstetric complications,20
parental social class,21 and prenatal exposure
to influenza22 do not explain the urban-rural
differences in schizophrenia risk.
When Danish children move from one municipality to another, they usually
change school. Therefore, it is interesting that change of municipality had
a greater effect on schizophrenia risk than change of address, while change
of address within the same municipality had no effect (Figure 1). We can only speculate regarding the underlying causes
of these findings; however, they may be related to social maladjustment in
preschizophrenic children, the stress of making new friends, and the fact
that preschizophrenic children are more anxious in new environments.23, 24 Life events, such as parental death,
parental divorce, or change in social class, are possible but less likely
explanations as they are not related to change of the municipality only.
It is extremely unlikely that selective migration or urban-rural differences
in the availability of psychiatric services explain the effect of urbanicity
at birth; for fixed urbanicity at the 15th birthday, risk increases with increasing
degree of urbanization at place of birth, and there was no evidence that age
at onset was modified by urbanicity during upbringing, ie, there were no urban-rural
differences in the threshold for a psychiatric admission with schizophrenia.
Furthermore, services are free and distances are small in Denmark.
The results of the study are based on patients with schizophrenia admitted
to a psychiatric hospital or those in outpatient care diagnosed as having
schizophrenia. Although not all patients with schizophrenia are admitted to
a psychiatric hospital or are in outpatient care during the first episode,
many will eventually be admitted or come in for outpatient care and, thus,
subsequently will become registered. Furthermore, the classification of degree
of urbanization is based on the number of inhabitants in the largest city
in the municipality, and is almost certainly a crude proxy variable for the
unidentified underlying risk factors and mechanism. If the underlying risk-increasing
mechanisms explaining the urban-rural difference can be identified, it is
likely that their effects will be much larger than the association with urbanicity
during upbringing we demonstrated.
To our knowledge, this is the first study to directly assess the relative
importance of urbanicity at birth and during upbringing. Lewis et al4 have shown an association between being brought up
in urban areas and having schizophrenia later in life, but they did not distinguish
this effect from an effect of urban birth. Marcelis et al25
showed that urban residence at onset did not affect schizophrenia risk when
controlling for urban birth. However, their results may be biased by the migration
of preschizophrenic people before their first hospitalization with schizophrenia.
Although our findings must be replicated, they warrant direct tests of the
hypothesis that continuous, or repeated, exposures during upbringing that
occur more frequently in urbanized areas are responsible for the association
between urbanization and schizophrenia risk. Candidate risk factors would
include infections, diet, and exposure to pollution.
AUTHOR INFORMATION
Accepted for publication May 1, 2001.
This study was supported by the Theodore and Vada Stanley Foundation,
Bethesda, Md. The National Centre for Register-Based Research is funded by
the Danish National Research Foundation, Copenhagen.
From the Department of Psychiatric Demography, Institute for Basic
Psychiatric Research, Aarhus University Hospital, Risskov, and the National
Centre for Register-Based Research, Aarhus University, Aarhus C, Denmark.
Corresponding author and reprints: Carsten Bøcker Pedersen,
MSc, National Centre for Register-Based Research, Aarhus University, Taasingegade
1, 8000 Aarhus C, Denmark (e-mail: cbp{at}ncrr.au.dk).
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Are the Cause(s) Responsible for Urban-Rural Differences in Schizophrenia Risk Rooted in Families or in Individuals?
Pedersen and Mortensen
Am J Epidemiol 2006;163:971-978.
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Invited Commentary: Taking the Search for Causes of Schizophrenia to a Different Level
March and Susser
Am J Epidemiol 2006;163:979-981.
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Heterogeneity in Incidence Rates of Schizophrenia and Other Psychotic Syndromes: Findings From the 3-Center AeSOP Study.
Kirkbride et al.
Arch Gen Psychiatry 2006;63:250-258.
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Variations in the Incidence of Schizophrenia: Data Versus Dogma
McGrath
Schizophr Bull 2006;32:195-197.
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Schizophrenia and Urbanicity: A Major Environmental Influence--Conditional on Genetic Risk
Krabbendam and van Os
Schizophr Bull 2005;31:795-799.
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Social defeat: risk factor for schizophrenia?
SELTEN and CANTOR-GRAAE
Br. J. Psychiatry 2005;187:101-102.
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Schizophrenia and Migration: A Meta-Analysis and Review
Cantor-Graae and Selten
Am. J. Psychiatry 2005;162:12-24.
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First-contact incidence of schizophrenia in Surinam
Selten et al.
Br. J. Psychiatry 2005;186:74-75.
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Confirmation of Synergy Between Urbanicity and Familial Liability in the Causation of Psychosis
van Os et al.
Am. J. Psychiatry 2004;161:2312-2314.
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Phenomenology, science and the anthropology of the self: a new model for the aetiology of psychosis
Harland et al.
Br. J. Psychiatry 2004;185:361-362.
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Sibship Characteristics during Upbringing and Schizophrenia Risk
Pedersen and Mortensen
Am J Epidemiol 2004;160:652-660.
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Postnatal Development of Prefrontal Inhibitory Circuits and the Pathophysiology of Cognitive Dysfunction in Schizophrenia
LEWIS et al.
Ann. N. Y. Acad. Sci. 2004;1021:64-76.
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Risk for Cancer in Parents of Patients With Schizophrenia
Dalton et al.
Am. J. Psychiatry 2004;161:903-908.
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Does the urban environment cause psychosis?
VAN OS
Br. J. Psychiatry 2004;184:287-288.
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Urbanisation and incidence of psychosis and depression: Follow-up study of 4.4 million women and men in Sweden
SUNDQUIST et al.
Br. J. Psychiatry 2004;184:293-298.
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Individual and Familial Risk Factors for Bipolar Affective Disorders in Denmark
Mortensen et al.
Arch Gen Psychiatry 2003;60:1209-1215.
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Genetic Epidemiology of Schizophrenia: Phenotypes, Risk Factors, and Reproductive Behavior
Jablensky and Kalaydjieva
Am. J. Psychiatry 2003;160:425-429.
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Do Urbanicity and Familial Liability Coparticipate in Causing Psychosis?
van Os et al.
Am. J. Psychiatry 2003;160:477-482.
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Migration as a risk factor for schizophrenia: a Danish population-based cohort study
CANTOR-GRAAE et al.
Br. J. Psychiatry 2003;182:117-122.
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