Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland
Correspondence: Dr Laura Niemi, Department of Mental Health and Alcohol Research, KTL, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland. Tel: +358 9 4744 8894; fax: +358 9 4744 8478; e-mail: laura.niemi{at}ktl.fi
Declaration of interest None. Funding detailed in Acknowledgements.
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ABSTRACT |
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Aims To determine the cumulative incidence of adulthood Axis I disorders among offspring.
Method Using all hospital and out-patient treatment records we rediagnosed parents and offspring according to DSMIVTR criteria. Offspring were grouped by mothers diagnosis (schizophrenia n=104, schizoaffective disorder n=20, other schizophrenia-spectrum disorder n=30, and affective disorder n=25) and compared with a control group (n=176). The cumulative incidences of Axis I disorders among offspring were calculated.
Results The cumulative incidences of any psychotic disorder were 13.5%, 10.0%, 10.0%, 4.0% and 1.1% among offspring of mothers with schizophrenia, schizo-affective disorder, other schizophrenia-spectrum disorders, affective disorders and controls, respectively. The corresponding figures for schizophrenia were 6.7%, 5.0%, 6.7%, 0% and 0.6%, and for any mental disorder 23.1%, 20.0%, 20.0%, 12.0% and 6.9%.
Conclusions Offspring of mothers with a psychotic disorder have heightened risk of developing a wide range of severe mental disorders.
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INTRODUCTION |
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METHOD |
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For the adulthood follow-up we collected developmental, social, occupational and psychiatric outcome information. Information on mental disorders was obtained from two sources. Data on hospital treatments from 1969 to 1999 (age of offspring 3539 years, age of mothers 5381 years), and after 1995 on all in-patient detoxification treatments in social welfare institutions, were derived from the Finnish Hospital Discharge Register; Statistics Finland provided data on causes of death and death certificates up to 2000.
Diagnostic assessment
From the register information, all case records from hospital and
out-patient treatments were collected and assessed separately by two
psychiatrists (L.T.N. and J.M.S.), followed by a consensus diagnosis based on
the DSMIVTR criteria. Diagnostic assessment was similar for the
high-risk and control mothers, fathers and offspring, and consisted of
assigning a DSMIVTR diagnosis, and completing the Operational
Criteria Checklist for Psychotic Illness (OPCRIT;
McGuffin et al,
1991), the Major Symptoms of Schizophrenia Scale (MSSS; Kendler,
1993a), the global ratings of anhedoniaasociality and of
avolitionapathy on the Scale for the Assessment of Negative Symptoms
(SANS; Andreasen, 1982) and the
global rating of bizarre behaviour on the Scale for the Assessment of Positive
Symptoms (SAPS; Andreasen,
1984). For all case notes, L.T.N. completed the whole assessment
procedure; J.M.S. assigned DSMIVTR diagnoses for all case notes,
but completed the whole procedure only for the first 20 cases and thereafter
for every fifth case note. In cases of disagreement, the case records were
reassessed by both authors, and consensus ratings made. The values for
schizophrenia, schizophrenia-spectrum disorder, schizoaffective disorder,
bipolar disorder and major depressive disorder were 0.69 (95% CI
0.610.79), 0.42 (95% CI 0.250.60), 0.47 (95% CI
0.290.65), 0.57 (95% CI 0.360.79) and 0.48 (95% CI
0.230.73), respectively. Offspring were grouped according to the most
severe maternal diagnosis, the four groups being schizophrenia,
schizoaffective disorder, other schizophrenia-spectrum disorders and affective
disorders.
High-risk group
The original case selection was made according to ICD8 diagnoses
(Wrede et al, 1980).
Our revision on the basis of DSMIVTR identified 92 of the 183
women as having schizophrenia, 18 with schizoaffective disorder, 20 with
psychotic disorder not otherwise specified (NOS), 1 with brief psychotic
disorder, 6 with schizophreniform disorder, 1 with schizotypal personality
disorder, 16 with bipolar I disorder, 4 with major depressive disorder with
psychotic features, 1 with major depressive disorder without psychotic
features and 2 with mood disorder NOS. Because the sample sizes of separate
affective disorders were small, we formed one group by combining bipolar I
disorder with or without psychotic features, major depressive disorder with or
without psychotic features, and mood disorder NOS (n=23). Similarly,
cases of psychotic disorder NOS, schizophreniform disorder, schizotypal
personality disorder and brief psychotic disorder were combined to form the
group of other schizophrenia-spectrum disorders (n=28). Mostly
because the case notes had been destroyed, we were unable to assign a
diagnosis for 22 women (with 24 offspring).
The final sample consisted of 161 mothers with 179 offspring. For 149 offspring, the father was identified (altogether 132 fathers); for the remainder the father was unknown to the population register. The final control group consisted of 176 offspring, 176 mothers and 176 fathers. Three controls were missing because of identification problems. One of the control group mothers had developed schizophrenia, and two had a psychotic disorder NOS, but their children had no history of psychiatric hospitalisation.
Statistical assessment
Age at onset of illness was recorded using the OPCRIT definition, as the
earliest age (nearest year) at which medical advice was sought for psychiatric
reasons. The duration of treatment contact was calculated from the earliest to
the latest date of medical contact for psychiatric reasons. For most
individuals, our information about their treatment contacts spanned several
years and was quite detailed. All statistical analyses were performed using
S-PLUS statistical software (MathSoft,
1996). Differences in the background demographic variables between
groups were tested with likelihood ratio statistics using the
2 distribution. For comparing the means between groups we used
the F-test. Differences in the proportions were modelled using
logistic regression, tested with likelihood ratio statistics using the
2 distribution, and reported as odds ratios (ORs). Incidences
were modelled using the Poisson regression and tested with likelihood ratio
statistics using the
2 distribution, and their differences
were reported as relative risks (RRs). All tests were two-tailed, with
set at 0.05.
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RESULTS |
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The odds of the father having any psychiatric disorder were higher in the
high-risk groups than in the control group (OR=2.57, 95% CI 1.325.00,
2(1)=8.04; P=0.0046), and their odds of having
alcohol or other substance abuse or dependence were more than three times
greater (OR 3.36, 95% CI 1.269.00,
2(1)=6.42;
P=0.011). Other Axis I disorders were not more common among fathers
in the high-risk group (Table
3). In one family, both parents had schizophrenia.
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Cumulative incidences of Axis I disorders among offspring
The cumulative incidences of schizophrenia were 6.7% (RR v.
controls=12.3, 95% CI 1.52>100), 5.0% (RR=9.26, 95% CI
0.58148.12), 6.7% (RR=12.5, 95% CI 1.14138.1) and 0.57% among
offspring of mothers with schizophrenia, schizo-affective disorder, other
schizophrenia-spectrum disorder and controls, respectively
(Table 4). None of the
offspring of mothers with affective disorder developed schizophrenia. The
cumulative survival probability from schizophrenia is presented in
Fig. 1.
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The cumulative incidences of any psychotic disorder were 13.5% (RR=12.6, 95% CI 2.8755.5), 10.0% (RR=9.42, 95% CI 1.3566.9), 10.0% (RR=9.57, 95% CI 1.6057.3), 4.0% (RR=3.60, 95% CI 0.3339.70) and 1.14% among offspring of mothers with schizophrenia, schizoaffective disorder, other schizophrenia-spectrum disorders, affective disorders and controls, respectively (Table 4). After combining the groups of women with schizophrenia and those with schizophrenia-spectrum disorders, the cumulative incidence of any psychotic disorder among their offspring was 12.3% (RR=11.61, 95% CI 2.7149.86). The cumulative survival probability from all psychoses is presented in Fig. 2. Two of the control group offspring had developed a psychotic disorder, but none of their parents had any psychiatric diagnoses.
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Non-psychotic mood disorders (OR=3.40, 95% CI 1.229.49) and hospital-treated alcohol or other substance abuse and dependence (OR=4.27, 95% CI 1.4013.05) were more common among the high-risk offspring than among controls (see Table 4). In logistic regression analysis, mothers substance abuse was not related to her offsprings risk of substance abuse (OR=0.86, 95% CI 0.184.16), but paternal substance abuse increased the offsprings risk of hospital-treated alcohol or other substance abuse or dependence (OR=6.31, 95% CI 1.6324.5). There was no interaction between maternal and paternal alcohol or other substance abuse or dependence.
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DISCUSSION |
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Several factors might have caused the lower incidence in our study. We had only one family in which both parents had schizophrenia, whereas in the New York and Copenhagen studies this especially high-risk group was considerably larger (Erlenmeyer-Kimling et al, 1984; Parnas, 1985). However, it is also possible that the high prevalences observed in the New York and Copenhagen studies were partly due to their case selection methods. Since the follow-up period in the Copenhagen study was also slightly longer than ours (up to 3448 years of age), the late-onset schizophrenia cases would have raised our cumulative incidences only slightly. In addition, the incidence of schizophrenia in Finland, as well as in Denmark, was higher for the cohorts in the 1950s than in the 1960s, when the offspring in our cohort were born (Munk-Jorgensen & Mortensen, 1992; Suvisaari et al, 1999). Thus, the offspring in the Copenhagen study were born during a period (19421952) when the incidence of schizophrenia in the general population was higher than it was in the 1960s. Finally, we were able to diagnose only hospital-treated cases and could not interview the individuals.
Our findings are similar to those from family and adoption studies. Numerous family studies have found a morbid risk of schizophrenia among first-degree relatives ranging from 1.4% to 6.5% (Kendler & Diehl, 1993). The prevalence of schizophrenia among adoptees having a biological mother with schizophrenia was 5.1% in the Finnish Adoptive Family Study and 5.7% in the Danish Adoption Study (Kendler & Gruenberg, 1984; Tienari et al, 2003). A large, Danish population-based study found that having a mother with schizophrenia was associated with a seven-fold increase in risk of developing schizophrenia (Pedersen & Mortensen, 2001); however, that study, like ours, was based on a hospital discharge register that, until recently, recorded only those treated as in-patients.
In our study, the risk of developing schizophrenia or schizophrenia-spectrum disorder was approximately equal in the high-risk groups with maternal schizophrenia, schizoaffective disorder or schizophrenia-spectrum disorders. This finding is in accordance with the Irish Ros-common Family Study, in which the risks of schizophrenia and of schizophrenia-spectrum disorders were approximately equal among the relatives of probands with schizophrenia, schizotypal personality disorder, schizoaffective disorder or other non-affective psychotic disorders (Kendler et al, 1993b).
Other Axis I disorders
Apart from bipolar disorder, the cumulative incidences of hospital-treated
mental disorders among the offspring of mothers with affective disorders were
low and similar to those in the control group, whereas in the New York study,
cumulative incidences of schizophrenia-related psychotic disorders,
schizoaffective disorders and non-psychotic and psychotic affective disorders
were all increased among the offspring in the high-risk group compared with
controls (Erlenmeyer-Kimling et
al, 1997). It is likely that the cumulative incidences of
less severe disorders in our study would have been higher if we had
interviewed the offspring.
The cumulative incidence of hospital-treated non-psychotic mood disorders was increased among high-risk offspring, consistent with the findings from the Swedish (Schubert & McNeil, 2003) and Israeli (Ingraham et al, 1995) high-risk studies. We also found increased rates of hospital-treated alcohol and other substance abuse or dependence among high-risk mothers, fathers and offspring, compared with controls. In the Copenhagen and Swedish high-risk studies, alcohol or other substance abuse was more common among the high-risk than control offspring (Parnas et al, 1993; Schubert & McNeil, 2003), whereas there was no significant difference between the high-risk and control groups in the New York study (Erlenmeyer-Kimling et al, 1997). In our study, the cumulative incidences of substance use disorders are based on hospital records only and reflect severe, hospital-treated forms of the disorders. Interestingly, we found that paternal, but not maternal, substance abuse increased the offsprings risk of substance abuse. This might have been partly caused by the fact that paternal substance use disorders were severe and had usually been the cause of hospitalisation, whereas maternal substance use disorders were rarely severe enough to be the primary cause of hospitalisation. Consistent with our study, the occurrence of alcoholism and/or anti-social personality disorder in the Copenhagen Study was higher among fathers in the high-risk group compared with the control group (27% v. 17%; Parnas, 1985).
Limitations
We were not able to interview the study participants, which was clearly a
limitation. However, the average duration of treatment contact was long: 23.0
years for the mothers, 9.0 years for the fathers and 11.4 years for the
offspring. Thus, the case records usually spanned several years and were quite
detailed. We also assessed all available information, for example the notes
made by nurses and psychologists, not just the notes made by the treating
psychiatrist. It is reasonable to assume that the prevalence of psychotic
disorders is accurate: in a Finnish health survey of 8000 persons, 99% of
those with a psychotic disorder had received psychiatric treatment
(Lehtinen et al,
1991). Of the 73 individuals who had developed schizophrenia by
1994 in the North Finland 1996 Birth Cohort, only two had been treated as
out-patients only (Isohanni et al,
1997). In contrast, in the Copenhagen Study, only two-thirds of
the high-risk offspring who developed schizophrenia had had hospital treatment
(Parnas et al, 1993).
Because case notes included data on family history, the raters could not
always remain masked to whether the child belonged to the high-risk or control
group. However, they were masked to the actual parentchild pairs, and
thus the parental diagnoses did not affect the diagnostic assignment of
offspring.
The accuracy of data on psychiatric diagnoses in the Finnish Hospital Discharge Register is excellent: in 1986, the diagnoses in the register and in the hospital case notes were identical in 99% of cases of schizophrenia and in 98% of all mental disorders. The reliability of schizophrenia diagnoses in the Hospital Discharge Register has been assessed in several studies, which showed that Finnish psychiatrists tend to apply a narrow definition of schizophrenia in clinical practice and that the register diagnosis of schizophrenia is reasonably reliable (Suvisaari et al, 1999).
We excluded mothers for whom we could not assign a diagnosis because of inadequate information. This group included both women with severe psychotic disorders who had died before 1976 and whose case notes had therefore been destroyed, and women with less severe forms of the disorder who had had short hospital treatments only and thereby insufficient case-note information to assign diagnoses. Among the offspring of mothers with diagnoses deferred, one had psychotic disorder NOS and another had a hospital diagnosis of schizophreniform disorder, but the case notes were missing. Thus, the cumulative incidence of any psychotic disorder among the offspring of mothers with diagnoses deferred was 8.3%, and the exclusion of these cases from the high-risk group did not have a major effect on the cumulative incidences of psychotic disorders in the group.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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Received for publication June 18, 2003. Revision received January 23, 2004. Accepted for publication February 1, 2004.
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