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Acta Psychiatr Scand 2002: 105: 317±319 Copyright ã Munksgaard 2002

Printed in UK. All rights reserved ACTA PSYCHIATRICA

ISSN 0001-690X

Short communication
Age-at-onset and schizophrenia:
reversed gender e€ect
B. N. Gangadhar, C. Panner Selvan, D. K. Subbakrishna, B. N. Gangadhar1, C. Panner
N. Janakiramaiah. Age-at-onset and schizophrenia: Selvan1, D. K. Subbakrishna2,
reversed gender e€ect N. Janakiramaiah1
Acta Psychiatr Scand 2002: 105: 317±319. ã Munksgaard 2002. 1
Department of Psychiatry and 2Department of
Biostatistics, NIMHANS, Bangalore 560 029, India
Objective: This study seeks an explanation for reversed gender e€ect
on age-at-onset (AAO) in schizophrenia. The hypothesis is older AAO
in males would be detected in a sample where higher infant mortality
(IMR) prevailed.
Method: Case records of International Classi®cation of Diseases-10
(ICD-10) schizophrenia patients from two states (n ˆ 70 each) with an
IMR of 13 and 67 per thousand were reviewed and AAO was obtained
by using the recorded age and duration of illness.
Results: In the sample from the state with lower IMR, AAO did not
di€er between the two sexes. However, men had older AAO than
women in the state with ®vefold higher IMR.
Conclusion: Gender di€erences in AAO may be a function of perinatal B. N. Gangadhar, Additional Professor, Department of
complications. In places where infants with perinatal complications are Psychiatry, NIMHANS, Bangalore 560 029, India.
less likely to survive, hence high IMR, a small group of potentially E-mail:
youngest AAO schizophrenic males may be eliminated thus changing
the gender e€ect on AAO. Accepted for publication 12 November, 2001

subpopulation at risk for very young AAO schi-

zophrenia. We hence hypothesized that older AAO
The tenth edition of International Classi®cation of in males would be associated with higher infant
Diseases (1) notes that schizophrenia has an earlier mortality rates (IMR) (assuming that infants with
onset in males. Several studies, mainly from the perinatal trauma would succumb).
West, support this (2). Nonetheless, some studies
failed to replicate earlier age-at-onset (AAO) in
Material and methods
males. Indeed, one Indian group has reported
earlier onset in females (3), a ®nding con®rmed in The study was record-based. NIMHANS although
another sample recently (4). Some of the explana- located in Karnataka, being a premier national
tions for earlier onset of schizophrenia in males institute, attracts some patients from neighboring
are, lack of protective e€ects of estrogens (2), states. Kerala is one of such states and has lowest
perinatal brain trauma (5, 6) and familial loading IMR in the country ± 13 of 1000, as against
(2, 7). Familial loading and perinatal insult can Karnataka that has IMR of 67 of 1000 (8). We
antagonize the protection o€ered by estrogen (2). looked for the case records under the diagnosis of
Perinatal complication and hence, mortality occurs schizophrenia (1). Seventy patients from Kerala
more often in male than female infants (8). Preti had registered during one calendar year. For each
et al. (9) found nearly threefold higher frequency of these patients the next consecutive patient
of severe obstetric/perinatal complications in males from Karnataka formed the control (n ˆ 70).
than female schizophrenics. It is, therefore, a likely Two psychiatrists (BNG, CPS) jointly reviewed
explanation for earlier AAO in males. Murthy the ®les, veri®ed the illness duration and then
et al. (3) argued that in some countries with less arrived at AAO thereof. Yet another measure
than adequate perinatal care facilities (perhaps so retrieved was age at ®rst consultation. Independent
about two decades ago), infants with such trauma sample t-test was used for comparing AAO
may not survive, thus reducing the size of this between the sexes.

Gangadhar et al.

Table 1. Patient characteristics and AAO of the two samples in the lower IMR state's sample and needs
Samples from
explanation. The IMR in Germany is only one-
third (3.5/1000) (11), as that of Kerala. This may
Variables Kerala (n ˆ 70) Karnataka (n ˆ 70) explain why the younger AAO for males in
Age (years) 29.8  9.0 29.6  8.9
Germany (2) is not seen in the Kerala sample of
Male : Female1 37 : 33 38 : 32 this study. The limitations of record-based data
AAO (years)2 23.5  8.3 25.4  8.5 have to be considered in accepting these results.
Age (years) at first Consultation3 24.8  7.8 27.9  8.8 For example, it is dicult to relate AAO from the
AAO (years)**
Male 23.5  8.5 27.4  8.6 case ®les to onset of psychosis reliably. The role of
Female 23.5  8.2 23.2  8.0 familial loading was not examined in this record-
Age (years) at first Consultation*** based study. This is yet another limitation consid-
Male 25.1  7.9 29.5  8.5
ering that females have higher incidence of familial
Female 24.4  7.8 25.9  9.0
morbidity (12).
Figures in cells are mean  SD in all except one cell that has number of subjects. Kerala being the most literate state in the
Kerala±Karnataka difference: 2P ˆ 0.181; 3P ˆ 0.028. country, the patients may have sought medical
Sex difference: Kerala; **P ˆ 0.99, ***P ˆ 0.68; Karnataka; **P ˆ 0.045,
***P ˆ 0.091. help earlier. While the AAO was only 2 years
younger in Kerala sample, the mean age at ®rst
consultation was 3 years earlier than in Karnataka
sample (Table 1). However, the sex di€erence was
Results absent in the Kerala sample. The social status of
Samples from Kerala and Karnataka were not women in the two states is not di€erent. Social
di€erent with respect to age and sex distribution. factors may have a less likely role a€ecting AAO.
The mean AAO and age at ®rst consultation of In summary, perinatal complications may in¯uence
Kerala sample were lesser than Karnataka; the the sex di€erence in AAO. Future studies on sex
di€erence being signi®cant only for the latter di€erences in AAO of schizophrenia may have to
measure. Sex di€erence was absent in the Kerala control for perinatal complications and perhaps
sample, whereas in the Karnataka sample the mean familial loading.
AAO and age at ®rst consultation were older in
males (Table 1). References
1. WORLD HEALTH ORGANIZATION. International classi®ca-
Discussion tion of diseases, 10th edn. Geneva: WHO, 1992.
The mean AAO in this (record-based) sample was HEIDEN W. Main risk factors for schizophrenia. increase
similar to an earlier prospective sample from the familial loading and pre- and peri-natal complications
same center (3) or from another Indian sample antagonize the protective e€ect of estrogen in women.
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(10). This validates partially the AAO information 3. MURTHY GVS, JANAKIRAMAIAH N, GANGADHAR BN,
obtained from the records. Sex and age distribu- SUBBAKRISHNA DK. Sex di€erence in age at onset: a dis-
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