There is general consensus that season of birth influences the risk of developing psychiatric conditions later in life. We aimed to investigate whether the risk of schizophrenia (SC), bipolar affective disorder (BAD) and recurrent depressive disorder (RDD) is influenced by month of birth in England to a similar extent as other countries using the largest cohort of English patients collected to date (n=57,971). When cases were compared to the general English population (n=29,183,034) all diseases showed a seasonal distribution of births (SC p=2.48E-05; BAD p=0.019; RDD p=0.015). This data has implications for future strategies of disease prevention.
Citation: Disanto G, Morahan JM, Lacey MV, DeLuca GC, Giovannoni G, Ebers GC, et al. (2012) Seasonal Distribution of Psychiatric Births in England. PLoS ONE 7(4): e34866. https://doi.org/10.1371/journal.pone.0034866
Editor: Mike B. Gravenor, University of Swansea, United Kingdom
Received: January 4, 2012; Accepted: March 6, 2012; Published: April 4, 2012
Copyright: © 2012 Disanto et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was funded by the Medical Research Council [GRANT NUMBER G0801976] and the Wellcome Trust [075491/Z/04]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. All authors state that this research was carried out independently of the influence of funding bodies.
Competing interests: The authors have declared that no competing interests exist.
Seasonality dominates many features of the global environment and that this will impact human health appears inevitable. Seasonal factors can potentially act even before birth, when according to the “fetal origin of adult disease hypothesis“ environmental influences leading to changes in embryonic/fetal tissue structure and function can influence the risk of adult physiological and pathological conditions –. As a consequence, being born in a certain time of the year may influence susceptibility to disease later in life. This is the case for several psychiatric diseases. Most studies performed to date have focused on schizophrenia and data collected on several thousands of patients across different countries suggest an excess of winter and early spring births –. Other psychiatric and psychological traits which have been associated with season of birth include bipolar disorder, major depression and suicidal behavior , –.
The concept of a season of birth study is simple and involves comparing the season or month of birth of individuals with a condition and comparing them to controls. However, performing the study with scientific rigour is more complicated. For example, since the size effect reported by such studies is often very small a large number of patients is required for statistical power. Furthermore, pooling data from different countries represents another potential source of bias since general population birth trends can substantially differ between countries.
We aimed to further confirm the association of psychiatric disease with season of birth using three new large and recently collected cohorts of schizophrenia (SC), bipolar affective disorder (BAD) and recurrent depression disorder (RDD) patients in a single country (England). To our knowledge this is the largest study performed to investigate this hypothesis within England.
Data on month of birth was collected for 57,971 patients from the English Hospital Episode Statistics (http://www.hesonline.nhs.uk/). In particular we gathered information on English resident outpatients seen by a doctor between 2003 and 2011 across England and suffering from SC (ICD-10=F20; n=26,676), BAD (ICD-10=F31; n= 14,569) and RDD (ICD-10=F33; n=16,726). As an additional non psychiatric control we also collected month of birth data from 3,545 Parkinson's disease (ICD-10=G20) patients. To avoid counting the same patient more than once with the same condition, counts were based on the unique patient identifier (HESID) which is based on date of birth, postcode, sex, local patient identifier and NHS number. Patients were compared to 29,183,034 English general population births between 1950 and 1990 from the Office for National Statistics (http://www.ons.gov.uk/). We used the Walter and Elwood seasonality test to estimate within year fluctuations with a 12 month periodicity (simple harmonic seasonal variation) . This test represents a standard technique in the analysis of seasonal trends and has been previously utilized in several month of birth studies –. Monthly odds ratios (OR) were calculated by comparing frequencies of patients and controls born in a certain month vs the rest of the year.
The birth distribution of controls, SC, BAD and RDD patients is presented in Table 1. In order to assess whether season of birth influences susceptibility to psychiatric conditions we initially compared the distribution of SC, BAD and RDD patients with that of the general population using the Walter and Elwood test. Strikingly the birth distribution of all these conditions was found to be significantly different from that of the general population (SC p=2.48E-05; BAD p=0.019; RDD p=0.015). No difference was observed between patients suffering from Parkinson's disease and the general population (p=0.48).
When monthly ORs were calculated, SC had a statistically significant peak in January (OR=1.13, 95%CI=1.09–1.18, p<0.0001) and a significant trough exactly six months later in July (OR=0.95, 95%CI=0.91–0.99, p=0.02). Peak to trough ratio showed a 17% increased risk for January vs July born individuals (OR=1.17, 95%CI=1.095–1.24, p<0.0001). Similarly to SC, BAD patients were more likely to be born than expected in January (OR=1.09, 95%CI=1.03–1.15, p=0.002) and less in August and September (OR=0.93, 95%CI=0.87–0.99, p=0.02; OR=0.91, 95%CI=0.86–0.93, p=0.005). The January vs September ratio also indicated a 17% increased risk (OR=1.17, 95%CI=1.08–1.26, p<0.0001). In RDD an almost significant May peak (OR=1.04, 95%CI=0.99–1.1, p=0.08) and a significant November deficit (OR=0.93, 95%CI=0.88–0.99, p=0.02) were observed. Odds ratios with 95% CI are presented in Figure 1.
We report here the largest study performed on month of birth and psychiatric conditions in England. In agreement with previous reports, seasonality of births was detected in SC, BAD and RDD patients. No significant difference was found between Parkinson's disease patients and the general population.
SC births showed the most striking seasonality. These results are also consistent with those of a previous study of English SC patients born between 1921 and 1960 indicating that the season of birth effect is a stable feature of SC . Furthermore, the OR values are surprisingly large and higher than those of a meta-analysis collecting data from more than 126,000 SC patients .
Similarly to SC, BAD also appeared to occur more frequently in January born individuals and to follow a seasonal distribution. This is in agreement with a large study of psychiatric patients from the United States in which the risk of both SC and BAD was significantly higher among winter born individuals . This is interesting given the well established overlap between these two conditions. Psychotic symptoms such as hallucinations and delusions are key manifestations of SC but also present in BAD. Furthermore, studies have confidently shown an increased risk of SC in relatives of patients suffering from bipolar disorder and vice versa –. Finally, genome wide association studies have shown the presence of overlap between genetic determinants of SC and bipolar disorder .
The risk of RDD was also seasonal but as compared to SC and BAD the effect appeared to be smaller and shifted to later in spring (peak) and autumn (trough). Not many studies have assessed the seasonality of births in patients with depression. However, our results are consistent with those of Torrey et al who reported a spring excess of births in a large cohort of American patients . Furthermore, Salib et al investigated the seasonality of birth of 26,915 British suicide cases and found excess and deficit of births in April–May and October–November respectively suggesting the presence of shared early life factors predisposing to both depression and suicidal behavior .
This study has limitations. Information on sex and ethnicity was not available and this represents a potential source of bias. However the large sample size (57,971 cases and 29,183,034 controls), and the strong a priori evidence for a season of birth effect in psychiatric conditions makes the data unlikely to be a chance finding. It could be that parents of psychiatric patients have an unusual pattern of conception and it would have been interesting to investigate whether the birth distribution of unaffected siblings of these psychiatric patients also follows a seasonal trend. Unfortunately data on siblings were not available to us, but other studies have tried to answer this question (in particular in SC) and overall the season of birth bias appears present in SC patients but not in their unaffected siblings –. This suggests that the role played by the season of birth in psychiatric conditions is truly causative.
Despite researchers' efforts, the causative factor/s behind this association remains unknown. A key factor which needs to be considered is that the risk is not only higher in certain months of the year vs others but also follows a seasonal distribution. This suggests a seasonal nature of the environmental causative factor. Seasonality dominates global environment, influencing effects of changing climate, sunlight, diet and infection. Interestingly, several lines of evidence now support a role for vitamin D deficiency in the pathogenesis of psychiatric conditions, in particular schizophrenia . Animal models of gestational vitamin D deficiency highlight the important role of vitamin D for correct neurodevelopment . Furthermore, neonatal vitamin D levels are significantly associated with risk of schizophrenia later in life . Finally, the size of the month of birth effect in SC increases with increasing latitude . Similar mechanisms may apply to BAD and RDD, but the evidence for vitamin D in these disorders is much less strong and other factors such as maternal infections and fluctuations in diet may also play an important role.
To conclude, season of birth influences the risk of SC, BAD and RDD in England to a similar extent as other countries and suggests that at least a proportion of psychiatric disease could be prevented by ameliorating the risk factor/s responsible for these intriguing epidemiological observations. It is now paramount to identify the seasonal factors that underlie the associations uncovered.
Conceived and designed the experiments: GD SVR. Performed the experiments: GD. Analyzed the data: GD. Contributed reagents/materials/analysis tools: GD JMM. Wrote the paper: GD. Critical revision of the manuscript for important intellectual content: JMM MVL GCD GG GE SVR. Study supervision: SVR.
- 1. Barker DJ (1995) The Wellcome Foundation Lecture, 1994. The fetal origins of adult disease. Proc Biol Sci 262: 37–43.DJ Barker1995The Wellcome Foundation Lecture, 1994. The fetal origins of adult disease.Proc Biol Sci2623743
- 2. Langley-Evans SC, McMullen S (2010) Developmental origins of adult disease. Med Princ Pract 19: 87–98.SC Langley-EvansS. McMullen2010Developmental origins of adult disease.Med Princ Pract198798
- 3. Davies G, Welham J, Chant D, Torrey EF, McGrath J (2003) A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia. Schizophr Bull 29: 587–593.G. DaviesJ. WelhamD. ChantEF TorreyJ. McGrath2003A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia.Schizophr Bull29587593
- 4. Torrey EF, Rawlings RR, Ennis JM, Merrill DD, Flores DS (1996) Birth seasonality in bipolar disorder, schizophrenia, schizoaffective disorder and stillbirths. Schizophr Res 21: 141–149.EF TorreyRR RawlingsJM EnnisDD MerrillDS Flores1996Birth seasonality in bipolar disorder, schizophrenia, schizoaffective disorder and stillbirths.Schizophr Res21141149
- 5. Adams W, Kendell RE, Hare EH, Munk-Jorgensen P (1993) Epidemiological evidence that maternal influenza contributes to the aetiology of schizophrenia. An analysis of Scottish, English, and Danish data. Br J Psychiatry 163: 522–534.W. AdamsRE KendellEH HareP. Munk-Jorgensen1993Epidemiological evidence that maternal influenza contributes to the aetiology of schizophrenia. An analysis of Scottish, English, and Danish data.Br J Psychiatry163522534
- 6. Cohen AS, Najolia GM (2011) Birth characteristics and schizotypy: evidence of a potential “second hit". J Psychiatr Res 45: 955–961.AS CohenGM Najolia2011Birth characteristics and schizotypy: evidence of a potential “second hit".J Psychiatr Res45955961
- 7. Schwartz PJ (2011) Season of birth in schizophrenia: a maternal-fetal chronobiological hypothesis. Med Hypotheses 76: 785–793.PJ Schwartz2011Season of birth in schizophrenia: a maternal-fetal chronobiological hypothesis.Med Hypotheses76785793
- 8. Tsuchiya KJ, Byrne M, Mortensen PB (2003) Risk factors in relation to an emergence of bipolar disorder: a systematic review. Bipolar Disord 5: 231–242.KJ TsuchiyaM. ByrnePB Mortensen2003Risk factors in relation to an emergence of bipolar disorder: a systematic review.Bipolar Disord5231242
- 9. Salib E, Cortina-Borja M (2006) Effect of month of birth on the risk of suicide. Br J Psychiatry 188: 416–422.E. SalibM. Cortina-Borja2006Effect of month of birth on the risk of suicide.Br J Psychiatry188416422
- 10. Joiner TE, Pfaff JJ, Acres JG, Johnson F (2002) Birth month and suicidal and depressive symptoms in Australians born in the Southern vs. the Northern hemisphere. Psychiatry Res 112: 89–92.TE JoinerJJ PfaffJG AcresF. Johnson2002Birth month and suicidal and depressive symptoms in Australians born in the Southern vs. the Northern hemisphere.Psychiatry Res1128992
- 11. Dome P, Kapitany B, Ignits G, Rihmer Z (2010) Season of birth is significantly associated with the risk of completed suicide. Biol Psychiatry 68: 148–155.P. DomeB. KapitanyG. IgnitsZ. Rihmer2010Season of birth is significantly associated with the risk of completed suicide.Biol Psychiatry68148155
- 12. Rihmer Z, Erdos P, Ormos M, Fountoulakis KN, Vazquez G, et al. (2011) Association between affective temperaments and season of birth in a general student population. J Affect Disord 132: 64–70.Z. RihmerP. ErdosM. OrmosKN FountoulakisG. Vazquez2011Association between affective temperaments and season of birth in a general student population.J Affect Disord1326470
- 13. Walter S, Elwood J (1975) A test for seasonality of events with a variable population at risk. Br J Prev Soc Med 29: 18–21.S. WalterJ. Elwood1975A test for seasonality of events with a variable population at risk.Br J Prev Soc Med291821
- 14. Rothwell PM, Gutnikov SA, McKinney PA, Schober E, Ionescu-Tirgoviste C, et al. (1999) Seasonality of birth in children with diabetes in Europe: multicentre cohort study. European Diabetes Study Group. BMJ 319: 887–888.PM RothwellSA GutnikovPA McKinneyE. SchoberC. Ionescu-Tirgoviste1999Seasonality of birth in children with diabetes in Europe: multicentre cohort study. European Diabetes Study Group.BMJ319887888
- 15. Hoffman S, Schellinger KA, Propp JM, McCarthy BJ, Campbell RT, et al. (2007) Seasonal variation in incidence of pediatric medulloblastoma in the United States, 1995–2001. Neuroepidemiology 29: 89–95.S. HoffmanKA SchellingerJM ProppBJ McCarthyRT Campbell2007Seasonal variation in incidence of pediatric medulloblastoma in the United States, 1995–2001.Neuroepidemiology298995
- 16. Disanto G, Handel AE, Para AE, Ramagopalan SV, Handunnetthi L (2011) Season of birth and anorexia nervosa. Br J Psychiatry 198: 404–405.G. DisantoAE HandelAE ParaSV RamagopalanL. Handunnetthi2011Season of birth and anorexia nervosa.Br J Psychiatry198404405
- 17. Potash JB, Bienvenu OJ (2009) Neuropsychiatric disorders: Shared genetics of bipolar disorder and schizophrenia. Nat Rev Neurol 5: 299–300.JB PotashOJ Bienvenu2009Neuropsychiatric disorders: Shared genetics of bipolar disorder and schizophrenia.Nat Rev Neurol5299300
- 18. Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, et al. (2009) Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373: 234–239.P. LichtensteinBH YipC. BjorkY. PawitanTD Cannon2009Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study.Lancet373234239
- 19. Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, et al. (2009) Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460: 748–752.SM PurcellNR WrayJL StonePM VisscherMC O'Donovan2009Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.Nature460748752
- 20. Torrey EF, Miller J, Rawlings R, Yolken RH (1997) Seasonality of births in schizophrenia and bipolar disorder: a review of the literature. Schizophr Res 28: 1–38.EF TorreyJ. MillerR. RawlingsRH Yolken1997Seasonality of births in schizophrenia and bipolar disorder: a review of the literature.Schizophr Res28138
- 21. Pulver AE, Liang KY, Wolyniec PS, McGrath J, Melton BA, et al. (1992) Season of birth of siblings of schizophrenic patients. Br J Psychiatry 160: 71–75.AE PulverKY LiangPS WolyniecJ. McGrathBA Melton1992Season of birth of siblings of schizophrenic patients.Br J Psychiatry1607175
- 22. Buck C, Simpson H (1978) Season of birth among the sibs of schizophrenics. Br J Psychiatry 133: 358–360.C. BuckH. Simpson1978Season of birth among the sibs of schizophrenics.Br J Psychiatry133358360
- 23. Hare EH (1976) The season of birth of siblings of psychiatric patients. Br J Psychiatry 129: 49–54.EH Hare1976The season of birth of siblings of psychiatric patients.Br J Psychiatry1294954
- 24. Suvisaari JM, Haukka JK, Lonnqvist JK (2001) Season of birth among patients with schizophrenia and their siblings: evidence for the procreational habits hypothesis. Am J Psychiatry 158: 754–757.JM SuvisaariJK HaukkaJK Lonnqvist2001Season of birth among patients with schizophrenia and their siblings: evidence for the procreational habits hypothesis.Am J Psychiatry158754757
- 25. McGrath JJ, Burne TH, Feron F, Mackay-Sim A, Eyles DW (2010) Developmental vitamin D deficiency and risk of schizophrenia: a 10-year update. Schizophr Bull 36: 1073–1078.JJ McGrathTH BurneF. FeronA. Mackay-SimDW Eyles2010Developmental vitamin D deficiency and risk of schizophrenia: a 10-year update.Schizophr Bull3610731078
- 26. McGrath JJ, Eyles DW, Pedersen CB, Anderson C, Ko P, et al. (2010) Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study. Arch Gen Psychiatry 67: 889–894.JJ McGrathDW EylesCB PedersenC. AndersonP. Ko2010Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study.Arch Gen Psychiatry67889894