Journal of Affective Disorders 72 (2002) 243–247

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Research report

Is there a familial overlap between schizophrenia and bipolar

disorder?

C.P. Somnath, Y.C. Janardhan Reddy*, S. Jain

Department of Psychiatry, National Institute of Mental Health and Neurosciences ( NIMHANS), Bangalore 560 029, India

Received 5 January 2001; received in revised form 13 June 2001; accepted 22 November 2001

Abstract

Background: Most investigators accept that schizophrenia and bipolar disorders are distinct entities. The proponents of
continuum model have challenged this dichotomy model. Methods: Information about the first-degree relatives of probands
with DSM-IV diagnosis of schizophrenia (n 5 90), bipolar disorder (n 5 90), and epilepsy (n 5 60) was collected by using
the Family Interview for Genetic Studies (FIGS). A trained psychiatrist blind to the status of index probands obtained the
information. Morbid risk in relatives was calculated using abridged Weinberg’s method of age correction. Results: Rates of
schizophrenia and bipolar disorder were elevated in the relatives of schizophrenia and bipolar probands, but there was no
evidence of coaggregation. The risk for major depression was significantly elevated in the relatives of schizophrenia
probands and was comparable to the risk in the relatives of bipolar probands. Limitations: Family history method was used
to obtain information about relatives. Schizoaffective disorder patients were not included in the study and this may have
amplified the distinction between schizophrenia and bipolar disorder. Conclusions: The findings suggest that schizophrenia
and bipolar disorders are familially independent, but there could be a familial relationship between the predisposition to
schizophrenia and to major depression.
 2002 Elsevier Science B.V. All rights reserved.

Keywords: Bipolar disorder; Schizophrenia; Family study

1. Introduction clinical entities. Kraepelin (cited in Crow, 1990),

Most investigators and clinicians believe that
schizophrenia and affective disorders are distinct
*Corresponding author. Tel.: 1 91-80-699-5278; fax: 1 91-80-
656-4822.
E-mail address: jreddy@nimhans.kar.nic.in (Y.C. Janardhan
Reddy).
based on follow-up data, was the first to propose that
manic-depressive illness was etiologically distinct
from the dementia praecox. The most compelling
evidence in support of this dichotomous model of
psychoses is derived from the family and twin data
(Gottesman et al., 1982; Kendler et al., 1985, 1993a;
Tsuang et al., 1980). However, those who propose a
‘continuum’ model of psychosis challenge the

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PII: S0165-0327( 01 )00466-9
244 C.P. Somnath et al. / Journal of Affective Disorders 72 (2002) 243–247
Kraepelinian view (Crow, 1990). The most persua-
sive argument in favour of a possible overlap
between schizophrenia and affective disorders is
presented in a selective review of the family, twin,
and adoption data (Taylor, 1992). Family studies are
powerful tools for clarifying the nosological relation-
ships between psychiatric syndromes if they are
known to show familial transmission (aggregation)
(Kendler, 1990). If two disorders have distinct
genetic etiologies, then they are transmitted indepen-
dently in families. That is, the cross-prevalence in
relatives of probands would be similar to the preval-
ence in the general population. If the disorders are
related, coaggregation would be higher than in the
general population. The present study based on
family history method was designed to test the
hypothesis of independent familial transmission of
schizophrenia and bipolar disorders in an Indian
sample recruited from a large psychiatric hospital.
2. Method
Subjects with DSM-IV diagnosis of schizophrenia
(n 5 90; males 5 66.7%; mean age 5 31.1610.5
years) and bipolar disorder (n 5 90; males 5 65.6%;
mean age 5 29.6610.5 years) were recruited from
the adult inpatient services of the National Institute
of Mental Health and NeuroSciences (NIMHANS),
Bangalore, India. All the subjects were consecutively
admitted inpatients. The proband diagnosis was
ascertained by a consultant psychiatrist by using the
information obtained from several sources: direct
unstructured clinical interview of the proband, cor-
roboration of the clinical history with relatives living
with the proband, clinical charts and the data ob-
tained by administering the Operational Criteria
Checklist for Psychotic Disorders (OPCRIT)
(McGuffin et al., 1991). The control group included
60 consecutive patients with a diagnosis of general-
ized epilepsy (males 5 66.7%; mean age 5
30.2610.7 years) attending the neurological outpati-
ent services of the same hospital. The three proband
groups were comparable in terms of age and sex
distribution.
Family history data was obtained from a total of
1486 first-degree relatives of 240 probands. They
included 529 relatives of schizophrenic probands
(parents 5 180; siblings 5 273; offspring 5 76;
males 5 49.3%), 574 relatives of bipolar probands
(parents 5 180; siblings 5 324; offspring 5 70;
males 5 49.7%), and 383 relatives of control prob-
ands (parents 5 120; siblings 5 217; offspring 5 46;
males 5 49.3%).The relatives of all the three groups
were comparable with regard to age and sex dis-
tribution. The details regarding affective illnesses
(bipolar disorder and major depression) and schizo-
phrenia in the relatives of probands was collected by
a trained psychiatrist blind to the proband status of
the index probands by using the Family Interview for
Genetic Studies (FIGS) (Maxwell, 1992). The FIGS
was administered to the first-degree relatives of the
probands who could provide adequate information
about their families. In most instances, a first-degree
relative stayed with the patient in the hospital during
the period of hospitalization, as it is a necessary
requirement for inpatient care.
Diagnosis of bipolar disorder, major depressive
disorder and schizophrenia in relatives was made
using the DSM-IV criteria. The morbid risk in
relatives was calculated using the abridged Wein-
berg’s method of age correction (McGuffin et al.,
1994) which adjusts the risk according to the number
of years of risk period that each relative has com-
pleted. The period of risk employed for affective
illnesses was 15–60 years and 15–45 years for
schizophrenia.
3. Results
Morbid risks for affective illnesses and schizo-
phrenia in relatives of probands are given in Table 1.
The findings of this study showed that the morbid
risk for schizophrenia was elevated in the relatives of
schizophrenic probands, compared to the risk in
relatives of bipolar probands and controls. Similarly,
the risk for bipolar disorder was increased in the
relatives of bipolar probands, compared to the risk in
relatives of schizophrenic probands and controls.
Tests of significance were not applied in both the
instances because of very small cell sizes. The risk
for major depression was comparable in the relatives
of both schizophrenic and bipolar probands (Chi-
square 5 0.42; P 5 NS). The risk for major depres-
sion, however, was found to be significantly elevated
 C.P. Somnath et al. / Journal of Affective Disorders 72 (2002) 243–247
Table 1
Morbid risks for affective disorders and schizophrenia in relatives of bipolar, schizophrenic and control probands
Relatives Age corrected number
of relatives (BZ)
Relatives of bipolar
probands (n 5 574) 318
Relatives of schizophrenic
probands (n 5 529) 281.5
Relatives of controls
(n 5 383) 211.5
in the relatives of both schizophrenic (Chi-square 5
3.93; P 5 , 0.05) and bipolar probands (Chi-
square 5 7.02; P 5 , 0.01) compared to those of
controls.
4. Discussion
The findings of our study support the Kraepelin’s
nosological dichotomy between schizophrenia and
affective illnesses partially. The findings are clear-
cut for bipolar disorder and schizophrenia, as each
disorder was familial but with no coaggregation.
This was, however, not the case with major depres-
sion, which was found to aggregate in the families of
both schizophrenic and bipolar probands.
The increased familial risk for schizophrenia in
relatives of schizophrenic probands is consistent with
the findings of previous studies (Gershon et al.,
1988; Tsuang et al., 1980; Kendler et al., 1985,
1993b). Similarly, the familiality of bipolar disorder
is in accordance with the findings of previous studies
(Gershon et al., 1982; Tsuang et al., 1980; Baron et
al., 1982; Andreasen et al., 1987). However, there
was no evidence of coaggregation of schizophrenia
and bipolar disorder suggesting that the disorders
breed true in families. The finding confirms the
observations of controlled family studies (Maier et
al., 1993; Kendler et al., 1993a) that schizophrenia
and bipolar disorder are transmitted independently
and challenges the doubts expressed about the dich-
otomy model (Taylor, 1992). However, schizophre-
nic probands had an increased familial risk for major
depression corroborating the findings of some previ-
ous reports (Gershon et al., 1988; Maier et al., 1993)
suggesting a possible familial relationship between
245
Major depression Bipolar disorder Schizophrenia
n Morbid risk n Morbid risk n morbid risk
46 14.5 26 8.2 2 0.6
35 12.4 2 0.7 26 7.8
14 6.6 1 0.5 1 0.4
schizophrenia and major depression. Such a result is
at variance with unitary model of psychosis (Crow,
1990). Several possible explanations other than the
familial relationship have been offered to account for
the increased risk for depression in relatives of
schizophrenic probands (Maier et al., 1993). One of
them is the possible underestimation of depression in
the families of controls. This is an unlikely possi-
bility in our study since our controls were not
screened for psychiatric disorder. Moreover, the rate
of depression is comparable to the general population
rate (Nandi et al., 2000). Another explanation is the
possibility of misdiagnosis of some schizoaffective
probands as schizophrenia probands because of the
hierarchic diagnostic approach resulting in a spurious
relationship between schizophrenia and major de-
pression. This is also an unlikely possibility as the
DSM-IV criteria were rigorously applied to include
only probands with schizophrenia and bipolar disor-
der. The elevated rate of depression in relatives of
schizophrenia probands could be attributed to as-
sortative mating. However, it is an unlikely possi-
bility in the Indian context because the spouse
selection is largely not by individual choice. Relig-
ion, community, language and other parameters such
as families’ direct role in arranging marriages largely
influence spouse selection. Moreover, a previous
study (Heun and Maier, 1993) concluded that as-
sortative mating was of minor relevance in family
studies. Lastly, it could be argued that the increased
familial risk for major depression in relatives of
schizophrenic probands might be the result of in-
creased psychosocial burden associated with a close
relative having schizophrenia. Our study design does
not allow us to exclude this possibility as the control
group in our study included those with epilepsy and
246 C.P. Somnath et al. / Journal of Affective Disorders 72 (2002) 243–247
the psychosocial burden on the families of epileptics
cannot be assumed to be similar to those in the
families of probands with severe psychotic disorders.
However, in the study by Maier et al. (1993),
relatives of alcoholic probands did not have an
increased familial risk for unipolar depression.
It is possible that a familial factor predisposes both
to schizophrenia and major depression in some
families. This interpretation, however, must be con-
sidered tentative because of three important factors.
Firstly, many studies have failed to find a familial
relationship between schizophrenia and depression.
Secondly, an increased risk for schizophrenia has not
been observed in studies of relatives of affectively ill
probands (Tsuang et al., 1980; Gershon et al., 1982;
Weissman et al., 1984). Thirdly, depression is a
heterogenous diagnosis. It has been hypothesized
that there could be subgroups of individuals with
shared familial liability for schizophrenia and depres-
sive disorder, while in others the liabilities are
independent (Maier et al., 1993). This hypothesis
might explain the lack of increased risk for schizo-
phrenia in relatives of those with major depressive
disorder. Depression is a common disorder with most
depressed probands probably having genetic liability
unrelated to schizophrenia. Whereas, schizophrenia is
a rare disorder with the liability to depression being
possibly present in sufficient number of families of
schizophrenic probands to produce an excess of
depression in some samples of relatives.
To conclude, our findings support dichotomy
between bipolar disorder and schizophrenia, but not
between major depression and schizophrenia. Limita-
tions of our study need to kept in mind. We have
used family history method, that is known to be less
sensitive than the family study method. As a result
we could not subtype depression in the relatives of
probands. It is important to examine the subtypes of
depression in the relatives of schizophrenic probands
in view of the heterogenous nature of major depres-
sion. Similarly, we have not diagnosed schizoaffec-
tive disorders in relatives. Previous studies have
found elevated rates of schizoaffective disorders in
relatives of both bipolar (Baron et al., 1982; Gershon
et al., 1982; Maier et al., 1993) and schizophrenic
probands (Gershon et al., 1988; Kendler et al.,
1993b; Maier et al., 1993). It is possible that we
could not diagnose schizoaffective disorders because
of the family history method employed. Secondly,
we have not studied families of schizoaffective
disorder patients. Studying only families of schizo-
phrenia and bipolar probands and excluding those of
schizoaffective probands may have resulted in am-
plifying the distinction between schizophrenia and
bipolar disorder. Schizoaffective disorder represents
the intermediate form with overlapping clinical
profile and studies have shown that schizoaffective
disorder shares familial etiological factors with both
schizophrenia and bipolar disorder (Bertelsen and
Gottesman, 1995). Lastly, there is a possibility of the
clinician’s diagnosis of the index probands being
influenced by a knowledge of the family history
resulting in a bias towards true breeding.
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