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No season-of-birth effect in schizophrenic patients from a tropical island in the Southern Hemisphere
PSYCHIATRY RESEARCH ELSEVIER
Psychiatry Research 60 (1996) 205-210
No season-of-birth effect in schizophrenic patients from a tropical island in the Southern Hemisphere Thierry d ' A m a t o *a, Jean-Michel Guillaud-Bataille a, Thierry Rochet a, M a u r i c e Jay b, Catherine Mercier c, Jean-Louis Terra a, Jean Dal~ry a aHdpital du Vinatier, 95 Boulevard Pinel, F-69677 Lyon-Bron, France bCentre Hospitalier Spdcialisd, Saint Paul, 97460 Saint Paul, La R6~nion, France ©Laboratoire de Pharmacologie Clinique (Pr. J-P. Boissei), 162 Avenue Lacassagne, B.P. 3041, F-69394 Lyon, France
Received 27 February 1995; revision received 25 October 1995; accepted 27 February 1996
Abstract The distribution of birth rates was examined in 668 schizophrenic patients born in R~vnion, a tropical French island in the Southern Hemisphere, and compared with that in the general local population. We failed to observe a significant season-of-birth effect, either in the total sample of schizophrenic patients or in subgroups categorized by gender, age, or family history of schizophrenia. Seasonal factors do not appear to affect the yearly distributiot~ of births among schizophrenic patients on R~union Island. It is nevertheless possible that environmental factors which are seasonal in countries with more contrasting climates bare a continuous effect, throughout the whole year, in subtropical areas. Conversely, these findings provide some evidence against the hypothesis that there is an age-incidence artifact in seasonal studies from countries in the Northern Hemisphere. Keywords: Epidemiology; Psychosis; Geographical study; Age incidence, cohort effect; R~union Island
1. Introduction
Several studies (for review, see Bradbury and Miller, 1985; Boyd et al., 1986; Kendell and Adams, 1991) have emphasized a link between schizophrenia and birth in winter or early spring for most of h~ t~mper~tp count_ri_es in the Northern Hemisphere. Climatically related factors t .ll.a~,
~va
~
~ ,.~ ~
* Corresponding author, Tel: +33 72 358696; Fax: +33 72 358545.
have therefore been hypothesized to play a role in the pathogenesis of the disease. However, this seasonal birth imbalance has been the subject of a methodological controversy: the so-called seasonal effect may actually be an artifact based on the incidence of the disease, which increases with age (Lewis, 1989, 1990). Studies from Southern Hemisphere or tropicoequatorial countries may support the existence of a true seasonal effect by showing either (a) a pattern of schizophrenic births opposite to that of
0165.1781/96/$15.00 © 1996 Elsevier Science Ireland Ltd. All rights reserved PII: SO165-1781(96)02794-1
206
T. d'Amato et ai. / Psychiatry Research 60 (1996) 205-210
Northern Hemisphere countries: i.e., an excess number of births during winter in the Southern Hemisphere (July to September); or (b) no specific pattern compared with the local general population. Unfortunately, few Southern Hemisphere or tropico-equatorial surveys have been carried out to date. A tendency for a greater number of schizophrenic births in winter in the Southern Hemisphere was found in New Zealand (Parker, 1978), Australia (Victoria: Parker and Neilson, 1976; New South Wales: Jones and Frei, 1979), and South Africa (Dal6n, 1975). Similar findings were significant in Western Australia (Syme and lllingworth, 1978). On the other hand, a northernequatorial survey, carried out in the Philippines, revealed the same January-March effect reported in temperate countries in the Northern Hemisphere (Parker and Baiza, 1977). To our knowledge, no southern equatorial or south-tropical study has been carried out to date. We therefore decided to investigate whether a winter excess of births could be found in schizophrenic patients born in a southern tropical area. This hypothesis was also examined in various st,bgroups categorized by gender, age, and family history. 2. Methods 2.1. Geographical area R6union Island is located in the southwest Indian Ocean, 250 km north of the tropic of Capricorn (55° 29' E, 21° 05' S). This small island (2512 km 2) is a French territory. The average annual temperatures range from 20.3°C to 28.0°C in the principal city, Saint-Denis, with little seasonal variation. 2.2. Case identification The Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety Version (Fyer et al., 1985) was used to make a diagnosis according to DSM-III criteria (American Psychiatric Association, 1980). Month and year of birth were checked for all living DSM-III schizophrenic patients who were born on the island between January 1, 1910, and December 31, 1969. The whole group (N=668) was subdivided by gender (males,
n = 362; females, n = 306), age (old cohort, patients born between 1910 and 1949, n = 354; young cohort, patients born between 1950 and 1969, n = 314), and family history of schizophrenia (negative family history, n = 516; positive family history, n = 152). Positive family history was defined as the presence of one or more cases of schizophrenia in the first- or second-degree biological relatives of a schizophrenic proband. 2.3. Data collection An exhaustive census of living schizophrenic patients was carried out in the so-called geographical psychiatric 'secteur 1' of the island, corresponding to the territory of Saint-l~nis and its adjacent rural countryside. In this area, the prevalence of DSM.III schizophrenia reached 5.20%0 in 1990, with higher rates for males (5.79°/'00) than for females (4.66°/'00) (Jay, unpublished data). The purpose of this epidemiological survey was to estimate the incidence of psychosis on the island and to recruit 'multiplex families' of schizophrenic patients for molecular genetic research. Patients were derived from four sources: (a) all admissions to the psychiatric hospital of Saint-Paul, with its associated outpatient departments, were obtained from medical registers from January 1, 1955, to December 31, 1989. (b) Patients treated by private psychiatrists (the private practice of psychiatry dates only from 1955 on the island) up to December 31, 1989, were identified; all private psychiatrists had agreed to collaborate in the data collection. (c) Other patients were included from registers of disability benefits lists of the long-term ill. (d) Finally, a few cases, not recorded on any register, were identified in family investigations. Most of them had not been previously identified. 2. 4. Statistical analyses The observed rate of calendar winter-born cases of schizophrenia (from January to March) was compared with the theoretical rate of the general population. The sample was then subdivided by gender, age, and family history. The observed distribution of births was compared by quarters with the expected rates for each subsample, by means of
T. d'Amato et al./ Psychiatry Research 60 (1996) 205-210
X2 calculations. The possibility that schizophrenic births were distributed on a yearly cycle was analyzed using Roger's (1977) ~est for the patient sample only. The expected rates were established from unpublished census data (the French 'Minist6re des DOM-TOM' civil status registers from January 1, 1910, to December 31, 1969). For the years 1910-1949, we considered only the data from the city of Saint-Denis, corresponding exactly to the targeted psychiatric geographic area. To take into account an increase in intra-insular migration toward Saint-Denis (the main town of the island) since the beginning of the second half of the 20th century (Morville, 1990), the general population birth-rate data for the whole island were considered for the years 1950-1969. On the basis of the rate of surviving patients at the time of the study (1990), classed according to age in 5-year
207
bands, general population data were consequently adjusted t o take into account secular variations in monthly birth rates (Morville, 1990). 3. Results
No significant difference was found between the observed winter birth rate in the patient sample (95% confidence interval = 0.196-0.260) and the general population rate (P = 0.230). In the hypothesis of an artifactual age-incidence effect, only the possibility of a winter-excess is relevant, and, consequently, the statistical test was one-tailed. A calculation of statistical power indicated that if the study sample were too small to show a relative excess of winter births of 10% (at the P = 0.05 level, one-tailed), it would be large enough to show a difference of 12%. Indeed, most of the Northern Hemisphere studies have shown a winter excess of
Table 1 Quarter of birth for the total group of schizophrenic patients, for schizophrenic subgroups categorized by sex and family history of schizophrenia, and for the adjusted general population census data Quarter of birth
Total births
P
(df = 3) First
Second
Third
Fourth
152 ! 52.7
163 165.6
189 ! 79.8
164 169.8
668 668
NS
74 82.7
9! 89.8
106 97.5
91 92
362 362
NS
78 69.9
72 75.8
83 82.3
73 77.8
306 306
NS
121 127.8
140 ! 38.8
i 37 13 !. !
5!6 5 !6
NS
42 37.8
49 41
27 38.7
! 52 ! 52
NS
72 74. !
81 83.4
85 82.2
314 314
NS
108 96.2
79 86
354 354
NS
Schizophrenic patients (total sample) Observed births Expected births
Males Observed births Expected births a
Females Observed births Expected births a
Negative family history of schizophrenia Observed births Expected births
i !8 ! i 7.9
Positive family history of schizophrenia Observed births Expected births
34 34.8
Young cohort (born between 19.50 and 1969) Observed births Expected births ¢
76 74.3
Old cohort (born between 1910 and 1949) Obser;ed b.irths Expected births b
76 79.8
91 92
abased on data for both sexes. bbased on general births in Saint Denis from 1910 to 1949; Cba~d on general births on R6union Island from 1950 to 1969.
208
T. d'Amato et al./ Psychia:ry Research 60 (1996) 205-210
schizophrenic births from 10% to 15%. Similarly, the quarterly analysis beginning in December did not provide statistical confirmation of an imbalanced distribution. As a consequence, it can be concluded that the probability of an absence of a genuine calendar winter excess on R~union Island is strong. A moderate 5% excess of summer schizophrenic births did not reach significance but merits further study. Table 1 shows the numbers of observed and expected births per quarter for the whole group of schizophrenic patients and samples subdivided by gender, family history of schizophrenia, and age at the time of evaluation. None of these evaluations indicated a seasonal effect on schizophrenic births in R6union Island; this could reflect the absence of a genuine effect or could result from insufficient statistical power. The application of Roger's test to the seasonal birth distribution of patients also did not reveal a significant result for a yearly cyclical distribution of schizophrenic births (r = 1.856, NS). 4. Discussion
Season of birth in humans appears to be meteorologically controlled - - although variations of cultura~ origin are also apparent - - with a reverse periodicity in the Southern Hemisphere compared with the Northern Hemisphere (Cowgill, 1966). Genera~ ~population data from R6union Island, before i950, show a peak of births in the Southern Hemisphere winter and early spring (July to October) with a corresponding decrease in summer (Morville, 1990; this report). The pattern has been progressively modified, leading to a decrease in yearly variation, since 1950, probably because of the introduction of modern contraceptive methods and the progressive decline of rural life (Morville, 1990). However, this trend became more pronounced after 1970, i.e., after the end of our study period (Morville, 1990). Accordingly, the yearly general population pattern of births between the years 1950 and 1969 did not differ from that between 19!0 and 1949 (data from the present report), even if the seasonal contrast was less marked. Both the patients and the controls were born on R~union Island. Ethnic criteria were not taken
into account, but each ethnic group living on the island was represented in similar proportions in both the patient sample and the general population. The sample size may seem small (N = 668) when compared with studies based solely on register data. However, our sample corresponds to the total screening of a defined geographical area of more than 120 000 inhabitants. The exhaustive nature of the recruitmen~ process can be regarded with confidence because the hospital of Saint-Paul is both the only psychiatric inpatient facility in the area and situated far from other hospitals. Furthermore, all private psychiatrists agreed to collaborate in ~he survey. When there was a doubt about a first- or second-degree schizophrenic patient related to a proband, a family investigation was carried out. A positive family history of schizophrenia characterized 23% of cases. An age-incidence effect has been reported to occur in schizophrenia (Dal6n, 1975; Lewis and Griffin, 1981), but most investigators do not consider it strong enough to explain the season-ofbirth effect entirely (Dal6n, 1990; Pulver et al., 1990; Torrey and Bowler, 1990; Watson, 1990). Lewis (1989, 1990), however, has presented a variety of arguments to suggest that the age-incidence effect may indeed be a sufficient explanation of the winter excess of births found in many samples of schizophrenic patients (Lewis, 1989, i990). Southern Hemisphere countries provide one of the most convincing arguments in support of a genuine seasonal effect in schizophrenia by showing a calendar summer excess of schizophrenic births. Indeed, whatever region of the world is considered, if the age-incidence effect were strong enough to create an artifactual season-of-birth effect, the first months of the calendar year would be expected to have the highest schizophrenic birth rate while the latter months would be expected to have the lowest. Our results clearly failed to show such a pattern of birth in schizophrenic patients from R~union Island. Moreover, no cohort effect was observed; this does not support the thesis of a maximum effect among younger patients in whom incidence of the disease is increasing. On the contrary, in the whole sample, the yearly variations in the birth rate of schizophrenic patients appear to be moderate and similar to those of the general population, suggesting that a seasonal factor does
T. d'Amato et al./ Psychiatry Research 60 (1996) 205-210
not account for the disease in this area. It is nevertheless possible that the environmental factors that are strongly seasonal in countries with more contrasfing climates have a nonseasonal and more continuous effect in south-tropical areas. Unfortunately, no data are available on the yearly variation of the prevalence of viral infections on R~union Island. The relationship between family history of schizophrenia and season of birth has been examined in a number of studies, with disparate results (Kinney and Jacobsen, 1978; Shensky and Shur, 1982; Shur, 1982; Machon et al., 1983; Lo, 1985; McNeil, 1987; Zipursky and Schulz, 1987; Baron and Gruen, 1988; Owen et al., 1989; Sacchetti et al., 1989; O'Callaghan et al., 1991). This discrepancy led us to examine our data with patients subdivided by family history of schizophrenia; no difference was observed, however, between patients with positive vs. negative family histories in relation to season of birth. Therefore, the hypothesis that an environmental factor related to climatic condition could be of greater etiological significance in one of the two groups of schizophrenic patients is not supported here. As was to be expected in view of the hypothesis of a genuine seasonal effect in Northern Hemisphere countries - - dependent on environmental conditions related to yearly climatic changes m the present study, based on exhaustive data from a warm, climatically stable south-tropical region, failed to reveal any season-of-birth birth effect among schizophrenic patients. Aelmowledgments We are grateful to Dr. J. Mallet and his collaborators (CNRS, Paris) who kindly allowed us to analyze data from their group; and to M.B. Ribagnac and K. Snaith for their help with translation. This study was carried out with technical assistance from the Association Rh6ne-Aipes de Recherche en Psychiatrie and a grant from 'Jeune Equipe' JE 1943, Universit~ Claude Belaard. References American Psychiatric Association. (I 980) DSM-III: Diagnostic and Statistical Manual of Mental Disorders. 3rd edn. APA, Washington, DC.
209
Baron, M. and Gruen, R. (1988) Risk factors ia schizophrenia: season of birth and family history. Br J Psychiatry 152, 460-465. Boyd, J.H., Pulver, A.E. and Stewart, W. (1986) Season of birth: schizophrenia and bipolar disorder. Schizophr Bull 12, 173-186. Bradbury, T.N. and Miller, G.A. (1985) Season of birth in schizophrenia: a review of evidence, methodology and etiology. Psychol Bull 98, 569-594. Cowgili, U.M. (1966) Season of birth in man: contemporary situation with special reference to Europe and Southern Hemisphere. Ecology 47, 614-623. Dal~n, P. (1975) Season of Birth: A Study of Schizophrenia and Other Mental Disorders. Elsevier/North-Holland, Amsterdam. Dal6n, P. (19~) Does age incidence explain all season of birth effects in the literature? Schizophr Bull 16, 11-12. Fyer, A., Endicott, J., Mannuzza, S. and Klein, D.F. (1985) Schedulefor Affective Disorders and Schizophrenia, Lifetime Anxiety Version. New York State Psychiatric Institute, New York. Jones, I.H. and Frei, D. (1979) Seasonal births in schizophrenia: a Southern Hemisphere study using matched pairs. Aeta Psychiatr Scand 59, 164-172. Kendell, R.E. and Adams, W. (1991) Unexplained fluctuations in the risk for schizophrenia by month and year of birth. Br J Psychiatry 158, 758-763. Kinney, D.K. and Jacobsen, B. (1978) Environmental factors in schizophrenia: new adoption study evidence. In: Wynne, L.C., Cromwell, R.L. and Matthysse, S. (Eds.), The Nature of Schizophrenia. John Wiley & Sons, New York. Lewis, M.S. (1989) Age incidence and schizophrenia: I. The season of birth controversy. Schizop~r Bull 15, 59-73. l~wis, M.S. (1990) Res Ipsa Loquitor: The author replies. Schizophr Bull 16, 17-28. Lewis, M.S. and Griffin, P.A. (1981) An explanation for the season of birth effect in schizophrenia and certain other diseases. Psychol Bull 89, 589-596. Lo, C.W. (1985) Season of birth of schizophrenics in Hong Kong. Br J Psychiatry 147, 212-213. Machon, R.A., Mednick, S.A. and Sehulsinger, F. (1983) The interaction of seasonality, place of birth, genetic risk and subsequent schizophrenia in a high risk sample. Br J Ps.vchgatry 143, 383-388. McNeil, T.F. (1987) Perinatal influences in the development of schizophrenia. In: Helmchen, H. and Henn, F.A. (Eds.), Biological Perspective of Schizophrenia. John Wiley & Sons, New York. Morville, Y. (1990) Les d ~ s et !es conceptions/t la R6union. Une saisonnalit6 en ~voluti(m significative de 1950/t nos jours. La Note d'lnformation de i'Observatoire D~partementa! de !a R~,ur.ion9, !-!4. O'Cailaghan, E., Gibson, T. and Colohan, H.A. (1991) Season of birth in ~hizophrenia: evidence for confinement of an excess of winter births to patients without a family history of mental disorder. Br J Psychiatry 158, 764-769. Owen, M., Jones, P. and Lewis, S.W. (1989) The relationship between season of birth and biological variables in schizophrenia. Schizophr Res 2, 17.
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T. d'Amato et al. /Psychiatry Research 60 (1996) 20.5-210
Parker, G. (1978) Schizophrenia and season of birth: further Southern Hemisphere studies. Aust N Z J Psychiatry 12, 65-67. Parker, G. and Baiza, B. (1977) Season of birth and schizophrenia: an equatorial study. Acta Psychiatr Scand 56, 143-146. Parker, G. and lqeilson, M. (1976) Mental disorder and season of bi~h: a Southern Hemisphere study. Br J Psychiatry 129, 355-361. Pulver, A.E., Moorman, C.C., Brown, C.H., McGrath, J.A. and Wolyniec, P.S. (1990) Age incidence artifacts do not account for the season of birth effect in schizophrenia. $ch'gophr Bull 16, ! 3-15. Roller, J.H. (1977) A sisnificance test for cyclic trends in incidence data. Biometrika 64, 152-155. Sa~hetti, E., Vita, A. and Battaglia, A. (1989) Season of birth and cerebral ventricnlar enlargement in schizophrenia, in: CazzeUo, C.L., lnvernizzi, G., Sac~hetti, E., et al. (Eds.),
Etiopathogenic Hypotheses of Schizophrenia: The Impact of Epidemiological, Biochemical and Neuromorphological Stud/es. MTP Press, Lancaster. Shensky, T. and Shur, E. (1982) Season of birth of schizophreni~: cyclic trends and their analysis. Br J Psychiatry 141,316-317. Shut, E. (1982) Season of birth in high and low genetic risk schizophrenics. Br J Psychiatry 140, 410-415. Syme, G.J. and lUingworth, D.J. (1978) Sex differences in birth patterns of schizophrenics. J Clin Psychol 34, 633-635. Torrey, E.F. and Bowler, A.E. (1990) The seasonality of schizophrenic births: a reply to Mare S. Lewis. Schizophr Bull 16, 1-3. Watson, C.G. (1990) Schizophrenic birth seasonality and the age incidence artifact. $chizophr Bull 16, 5-10. Zipursky, R.B. and Sehulz, S.C. (1987) Seasonality of birth and CT findings in schizophrenia. Biol Psychiatry 22, 12881292.
Psychiatry Research 60 (1996) 205-210
No season-of-birth effect in schizophrenic patients from a tropical island in the Southern Hemisphere Thierry d ' A m a t o *a, Jean-Michel Guillaud-Bataille a, Thierry Rochet a, M a u r i c e Jay b, Catherine Mercier c, Jean-Louis Terra a, Jean Dal~ry a aHdpital du Vinatier, 95 Boulevard Pinel, F-69677 Lyon-Bron, France bCentre Hospitalier Spdcialisd, Saint Paul, 97460 Saint Paul, La R6~nion, France ©Laboratoire de Pharmacologie Clinique (Pr. J-P. Boissei), 162 Avenue Lacassagne, B.P. 3041, F-69394 Lyon, France
Received 27 February 1995; revision received 25 October 1995; accepted 27 February 1996
Abstract The distribution of birth rates was examined in 668 schizophrenic patients born in R~vnion, a tropical French island in the Southern Hemisphere, and compared with that in the general local population. We failed to observe a significant season-of-birth effect, either in the total sample of schizophrenic patients or in subgroups categorized by gender, age, or family history of schizophrenia. Seasonal factors do not appear to affect the yearly distributiot~ of births among schizophrenic patients on R~union Island. It is nevertheless possible that environmental factors which are seasonal in countries with more contrasting climates bare a continuous effect, throughout the whole year, in subtropical areas. Conversely, these findings provide some evidence against the hypothesis that there is an age-incidence artifact in seasonal studies from countries in the Northern Hemisphere. Keywords: Epidemiology; Psychosis; Geographical study; Age incidence, cohort effect; R~union Island
1. Introduction
Several studies (for review, see Bradbury and Miller, 1985; Boyd et al., 1986; Kendell and Adams, 1991) have emphasized a link between schizophrenia and birth in winter or early spring for most of h~ t~mper~tp count_ri_es in the Northern Hemisphere. Climatically related factors t .ll.a~,
~va
~
~ ,.~ ~
* Corresponding author, Tel: +33 72 358696; Fax: +33 72 358545.
have therefore been hypothesized to play a role in the pathogenesis of the disease. However, this seasonal birth imbalance has been the subject of a methodological controversy: the so-called seasonal effect may actually be an artifact based on the incidence of the disease, which increases with age (Lewis, 1989, 1990). Studies from Southern Hemisphere or tropicoequatorial countries may support the existence of a true seasonal effect by showing either (a) a pattern of schizophrenic births opposite to that of
0165.1781/96/$15.00 © 1996 Elsevier Science Ireland Ltd. All rights reserved PII: SO165-1781(96)02794-1
206
T. d'Amato et ai. / Psychiatry Research 60 (1996) 205-210
Northern Hemisphere countries: i.e., an excess number of births during winter in the Southern Hemisphere (July to September); or (b) no specific pattern compared with the local general population. Unfortunately, few Southern Hemisphere or tropico-equatorial surveys have been carried out to date. A tendency for a greater number of schizophrenic births in winter in the Southern Hemisphere was found in New Zealand (Parker, 1978), Australia (Victoria: Parker and Neilson, 1976; New South Wales: Jones and Frei, 1979), and South Africa (Dal6n, 1975). Similar findings were significant in Western Australia (Syme and lllingworth, 1978). On the other hand, a northernequatorial survey, carried out in the Philippines, revealed the same January-March effect reported in temperate countries in the Northern Hemisphere (Parker and Baiza, 1977). To our knowledge, no southern equatorial or south-tropical study has been carried out to date. We therefore decided to investigate whether a winter excess of births could be found in schizophrenic patients born in a southern tropical area. This hypothesis was also examined in various st,bgroups categorized by gender, age, and family history. 2. Methods 2.1. Geographical area R6union Island is located in the southwest Indian Ocean, 250 km north of the tropic of Capricorn (55° 29' E, 21° 05' S). This small island (2512 km 2) is a French territory. The average annual temperatures range from 20.3°C to 28.0°C in the principal city, Saint-Denis, with little seasonal variation. 2.2. Case identification The Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety Version (Fyer et al., 1985) was used to make a diagnosis according to DSM-III criteria (American Psychiatric Association, 1980). Month and year of birth were checked for all living DSM-III schizophrenic patients who were born on the island between January 1, 1910, and December 31, 1969. The whole group (N=668) was subdivided by gender (males,
n = 362; females, n = 306), age (old cohort, patients born between 1910 and 1949, n = 354; young cohort, patients born between 1950 and 1969, n = 314), and family history of schizophrenia (negative family history, n = 516; positive family history, n = 152). Positive family history was defined as the presence of one or more cases of schizophrenia in the first- or second-degree biological relatives of a schizophrenic proband. 2.3. Data collection An exhaustive census of living schizophrenic patients was carried out in the so-called geographical psychiatric 'secteur 1' of the island, corresponding to the territory of Saint-l~nis and its adjacent rural countryside. In this area, the prevalence of DSM.III schizophrenia reached 5.20%0 in 1990, with higher rates for males (5.79°/'00) than for females (4.66°/'00) (Jay, unpublished data). The purpose of this epidemiological survey was to estimate the incidence of psychosis on the island and to recruit 'multiplex families' of schizophrenic patients for molecular genetic research. Patients were derived from four sources: (a) all admissions to the psychiatric hospital of Saint-Paul, with its associated outpatient departments, were obtained from medical registers from January 1, 1955, to December 31, 1989. (b) Patients treated by private psychiatrists (the private practice of psychiatry dates only from 1955 on the island) up to December 31, 1989, were identified; all private psychiatrists had agreed to collaborate in the data collection. (c) Other patients were included from registers of disability benefits lists of the long-term ill. (d) Finally, a few cases, not recorded on any register, were identified in family investigations. Most of them had not been previously identified. 2. 4. Statistical analyses The observed rate of calendar winter-born cases of schizophrenia (from January to March) was compared with the theoretical rate of the general population. The sample was then subdivided by gender, age, and family history. The observed distribution of births was compared by quarters with the expected rates for each subsample, by means of
T. d'Amato et al./ Psychiatry Research 60 (1996) 205-210
X2 calculations. The possibility that schizophrenic births were distributed on a yearly cycle was analyzed using Roger's (1977) ~est for the patient sample only. The expected rates were established from unpublished census data (the French 'Minist6re des DOM-TOM' civil status registers from January 1, 1910, to December 31, 1969). For the years 1910-1949, we considered only the data from the city of Saint-Denis, corresponding exactly to the targeted psychiatric geographic area. To take into account an increase in intra-insular migration toward Saint-Denis (the main town of the island) since the beginning of the second half of the 20th century (Morville, 1990), the general population birth-rate data for the whole island were considered for the years 1950-1969. On the basis of the rate of surviving patients at the time of the study (1990), classed according to age in 5-year
207
bands, general population data were consequently adjusted t o take into account secular variations in monthly birth rates (Morville, 1990). 3. Results
No significant difference was found between the observed winter birth rate in the patient sample (95% confidence interval = 0.196-0.260) and the general population rate (P = 0.230). In the hypothesis of an artifactual age-incidence effect, only the possibility of a winter-excess is relevant, and, consequently, the statistical test was one-tailed. A calculation of statistical power indicated that if the study sample were too small to show a relative excess of winter births of 10% (at the P = 0.05 level, one-tailed), it would be large enough to show a difference of 12%. Indeed, most of the Northern Hemisphere studies have shown a winter excess of
Table 1 Quarter of birth for the total group of schizophrenic patients, for schizophrenic subgroups categorized by sex and family history of schizophrenia, and for the adjusted general population census data Quarter of birth
Total births
P
(df = 3) First
Second
Third
Fourth
152 ! 52.7
163 165.6
189 ! 79.8
164 169.8
668 668
NS
74 82.7
9! 89.8
106 97.5
91 92
362 362
NS
78 69.9
72 75.8
83 82.3
73 77.8
306 306
NS
121 127.8
140 ! 38.8
i 37 13 !. !
5!6 5 !6
NS
42 37.8
49 41
27 38.7
! 52 ! 52
NS
72 74. !
81 83.4
85 82.2
314 314
NS
108 96.2
79 86
354 354
NS
Schizophrenic patients (total sample) Observed births Expected births
Males Observed births Expected births a
Females Observed births Expected births a
Negative family history of schizophrenia Observed births Expected births
i !8 ! i 7.9
Positive family history of schizophrenia Observed births Expected births
34 34.8
Young cohort (born between 19.50 and 1969) Observed births Expected births ¢
76 74.3
Old cohort (born between 1910 and 1949) Obser;ed b.irths Expected births b
76 79.8
91 92
abased on data for both sexes. bbased on general births in Saint Denis from 1910 to 1949; Cba~d on general births on R6union Island from 1950 to 1969.
208
T. d'Amato et al./ Psychia:ry Research 60 (1996) 205-210
schizophrenic births from 10% to 15%. Similarly, the quarterly analysis beginning in December did not provide statistical confirmation of an imbalanced distribution. As a consequence, it can be concluded that the probability of an absence of a genuine calendar winter excess on R~union Island is strong. A moderate 5% excess of summer schizophrenic births did not reach significance but merits further study. Table 1 shows the numbers of observed and expected births per quarter for the whole group of schizophrenic patients and samples subdivided by gender, family history of schizophrenia, and age at the time of evaluation. None of these evaluations indicated a seasonal effect on schizophrenic births in R6union Island; this could reflect the absence of a genuine effect or could result from insufficient statistical power. The application of Roger's test to the seasonal birth distribution of patients also did not reveal a significant result for a yearly cyclical distribution of schizophrenic births (r = 1.856, NS). 4. Discussion
Season of birth in humans appears to be meteorologically controlled - - although variations of cultura~ origin are also apparent - - with a reverse periodicity in the Southern Hemisphere compared with the Northern Hemisphere (Cowgill, 1966). Genera~ ~population data from R6union Island, before i950, show a peak of births in the Southern Hemisphere winter and early spring (July to October) with a corresponding decrease in summer (Morville, 1990; this report). The pattern has been progressively modified, leading to a decrease in yearly variation, since 1950, probably because of the introduction of modern contraceptive methods and the progressive decline of rural life (Morville, 1990). However, this trend became more pronounced after 1970, i.e., after the end of our study period (Morville, 1990). Accordingly, the yearly general population pattern of births between the years 1950 and 1969 did not differ from that between 19!0 and 1949 (data from the present report), even if the seasonal contrast was less marked. Both the patients and the controls were born on R~union Island. Ethnic criteria were not taken
into account, but each ethnic group living on the island was represented in similar proportions in both the patient sample and the general population. The sample size may seem small (N = 668) when compared with studies based solely on register data. However, our sample corresponds to the total screening of a defined geographical area of more than 120 000 inhabitants. The exhaustive nature of the recruitmen~ process can be regarded with confidence because the hospital of Saint-Paul is both the only psychiatric inpatient facility in the area and situated far from other hospitals. Furthermore, all private psychiatrists agreed to collaborate in ~he survey. When there was a doubt about a first- or second-degree schizophrenic patient related to a proband, a family investigation was carried out. A positive family history of schizophrenia characterized 23% of cases. An age-incidence effect has been reported to occur in schizophrenia (Dal6n, 1975; Lewis and Griffin, 1981), but most investigators do not consider it strong enough to explain the season-ofbirth effect entirely (Dal6n, 1990; Pulver et al., 1990; Torrey and Bowler, 1990; Watson, 1990). Lewis (1989, 1990), however, has presented a variety of arguments to suggest that the age-incidence effect may indeed be a sufficient explanation of the winter excess of births found in many samples of schizophrenic patients (Lewis, 1989, i990). Southern Hemisphere countries provide one of the most convincing arguments in support of a genuine seasonal effect in schizophrenia by showing a calendar summer excess of schizophrenic births. Indeed, whatever region of the world is considered, if the age-incidence effect were strong enough to create an artifactual season-of-birth effect, the first months of the calendar year would be expected to have the highest schizophrenic birth rate while the latter months would be expected to have the lowest. Our results clearly failed to show such a pattern of birth in schizophrenic patients from R~union Island. Moreover, no cohort effect was observed; this does not support the thesis of a maximum effect among younger patients in whom incidence of the disease is increasing. On the contrary, in the whole sample, the yearly variations in the birth rate of schizophrenic patients appear to be moderate and similar to those of the general population, suggesting that a seasonal factor does
T. d'Amato et al./ Psychiatry Research 60 (1996) 205-210
not account for the disease in this area. It is nevertheless possible that the environmental factors that are strongly seasonal in countries with more contrasfing climates have a nonseasonal and more continuous effect in south-tropical areas. Unfortunately, no data are available on the yearly variation of the prevalence of viral infections on R~union Island. The relationship between family history of schizophrenia and season of birth has been examined in a number of studies, with disparate results (Kinney and Jacobsen, 1978; Shensky and Shur, 1982; Shur, 1982; Machon et al., 1983; Lo, 1985; McNeil, 1987; Zipursky and Schulz, 1987; Baron and Gruen, 1988; Owen et al., 1989; Sacchetti et al., 1989; O'Callaghan et al., 1991). This discrepancy led us to examine our data with patients subdivided by family history of schizophrenia; no difference was observed, however, between patients with positive vs. negative family histories in relation to season of birth. Therefore, the hypothesis that an environmental factor related to climatic condition could be of greater etiological significance in one of the two groups of schizophrenic patients is not supported here. As was to be expected in view of the hypothesis of a genuine seasonal effect in Northern Hemisphere countries - - dependent on environmental conditions related to yearly climatic changes m the present study, based on exhaustive data from a warm, climatically stable south-tropical region, failed to reveal any season-of-birth birth effect among schizophrenic patients. Aelmowledgments We are grateful to Dr. J. Mallet and his collaborators (CNRS, Paris) who kindly allowed us to analyze data from their group; and to M.B. Ribagnac and K. Snaith for their help with translation. This study was carried out with technical assistance from the Association Rh6ne-Aipes de Recherche en Psychiatrie and a grant from 'Jeune Equipe' JE 1943, Universit~ Claude Belaard. References American Psychiatric Association. (I 980) DSM-III: Diagnostic and Statistical Manual of Mental Disorders. 3rd edn. APA, Washington, DC.
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Baron, M. and Gruen, R. (1988) Risk factors ia schizophrenia: season of birth and family history. Br J Psychiatry 152, 460-465. Boyd, J.H., Pulver, A.E. and Stewart, W. (1986) Season of birth: schizophrenia and bipolar disorder. Schizophr Bull 12, 173-186. Bradbury, T.N. and Miller, G.A. (1985) Season of birth in schizophrenia: a review of evidence, methodology and etiology. Psychol Bull 98, 569-594. Cowgili, U.M. (1966) Season of birth in man: contemporary situation with special reference to Europe and Southern Hemisphere. Ecology 47, 614-623. Dal~n, P. (1975) Season of Birth: A Study of Schizophrenia and Other Mental Disorders. Elsevier/North-Holland, Amsterdam. Dal6n, P. (19~) Does age incidence explain all season of birth effects in the literature? Schizophr Bull 16, 11-12. Fyer, A., Endicott, J., Mannuzza, S. and Klein, D.F. (1985) Schedulefor Affective Disorders and Schizophrenia, Lifetime Anxiety Version. New York State Psychiatric Institute, New York. Jones, I.H. and Frei, D. (1979) Seasonal births in schizophrenia: a Southern Hemisphere study using matched pairs. Aeta Psychiatr Scand 59, 164-172. Kendell, R.E. and Adams, W. (1991) Unexplained fluctuations in the risk for schizophrenia by month and year of birth. Br J Psychiatry 158, 758-763. Kinney, D.K. and Jacobsen, B. (1978) Environmental factors in schizophrenia: new adoption study evidence. In: Wynne, L.C., Cromwell, R.L. and Matthysse, S. (Eds.), The Nature of Schizophrenia. John Wiley & Sons, New York. Lewis, M.S. (1989) Age incidence and schizophrenia: I. The season of birth controversy. Schizop~r Bull 15, 59-73. l~wis, M.S. (1990) Res Ipsa Loquitor: The author replies. Schizophr Bull 16, 17-28. Lewis, M.S. and Griffin, P.A. (1981) An explanation for the season of birth effect in schizophrenia and certain other diseases. Psychol Bull 89, 589-596. Lo, C.W. (1985) Season of birth of schizophrenics in Hong Kong. Br J Psychiatry 147, 212-213. Machon, R.A., Mednick, S.A. and Sehulsinger, F. (1983) The interaction of seasonality, place of birth, genetic risk and subsequent schizophrenia in a high risk sample. Br J Ps.vchgatry 143, 383-388. McNeil, T.F. (1987) Perinatal influences in the development of schizophrenia. In: Helmchen, H. and Henn, F.A. (Eds.), Biological Perspective of Schizophrenia. John Wiley & Sons, New York. Morville, Y. (1990) Les d ~ s et !es conceptions/t la R6union. Une saisonnalit6 en ~voluti(m significative de 1950/t nos jours. La Note d'lnformation de i'Observatoire D~partementa! de !a R~,ur.ion9, !-!4. O'Cailaghan, E., Gibson, T. and Colohan, H.A. (1991) Season of birth in ~hizophrenia: evidence for confinement of an excess of winter births to patients without a family history of mental disorder. Br J Psychiatry 158, 764-769. Owen, M., Jones, P. and Lewis, S.W. (1989) The relationship between season of birth and biological variables in schizophrenia. Schizophr Res 2, 17.
210
T. d'Amato et al. /Psychiatry Research 60 (1996) 20.5-210
Parker, G. (1978) Schizophrenia and season of birth: further Southern Hemisphere studies. Aust N Z J Psychiatry 12, 65-67. Parker, G. and Baiza, B. (1977) Season of birth and schizophrenia: an equatorial study. Acta Psychiatr Scand 56, 143-146. Parker, G. and lqeilson, M. (1976) Mental disorder and season of bi~h: a Southern Hemisphere study. Br J Psychiatry 129, 355-361. Pulver, A.E., Moorman, C.C., Brown, C.H., McGrath, J.A. and Wolyniec, P.S. (1990) Age incidence artifacts do not account for the season of birth effect in schizophrenia. $ch'gophr Bull 16, ! 3-15. Roller, J.H. (1977) A sisnificance test for cyclic trends in incidence data. Biometrika 64, 152-155. Sa~hetti, E., Vita, A. and Battaglia, A. (1989) Season of birth and cerebral ventricnlar enlargement in schizophrenia, in: CazzeUo, C.L., lnvernizzi, G., Sac~hetti, E., et al. (Eds.),
Etiopathogenic Hypotheses of Schizophrenia: The Impact of Epidemiological, Biochemical and Neuromorphological Stud/es. MTP Press, Lancaster. Shensky, T. and Shur, E. (1982) Season of birth of schizophreni~: cyclic trends and their analysis. Br J Psychiatry 141,316-317. Shut, E. (1982) Season of birth in high and low genetic risk schizophrenics. Br J Psychiatry 140, 410-415. Syme, G.J. and lUingworth, D.J. (1978) Sex differences in birth patterns of schizophrenics. J Clin Psychol 34, 633-635. Torrey, E.F. and Bowler, A.E. (1990) The seasonality of schizophrenic births: a reply to Mare S. Lewis. Schizophr Bull 16, 1-3. Watson, C.G. (1990) Schizophrenic birth seasonality and the age incidence artifact. $chizophr Bull 16, 5-10. Zipursky, R.B. and Sehulz, S.C. (1987) Seasonality of birth and CT findings in schizophrenia. Biol Psychiatry 22, 12881292.