Being Born in Winter-Spring and at Around the Time of an Influenza Pandemic Are Risk Factors for the Development of Schizophrenia: The Apna Study in Navarre, Spain

doi:10.3390/jcm10132859

. 2021 Jun 28;10(13):2859.

doi: 10.3390/jcm10132859.

Being Born in Winter-Spring and at Around the Time of an Influenza Pandemic Are Risk Factors for the Development of Schizophrenia: The Apna Study in Navarre, Spain

Miguel A Alvarez-Mon^{1

2}, Sara Guillen-Aguinaga^{3

4}, Victor Pereira-Sanchez^{1

5}, Luc Onambele⁶, Moad J Al-Rahamneh⁷, Antonio Brugos-Larumbe^{3

4}, Francisco Guillen-Grima^{4

8

9}, Felipe Ortuño^{1

9}

Affiliations

¹ Department of Psychiatry and Medical Psychology, University of Navarra Clinic, 31008 Pamplona, Spain.
² Department of Medicine and Medical Specialities, University of Alcala, 28805 Alcala de Henares, Spain.
³ Primary Health Care, Navarra Health Service, 31008 Pamplona, Spain.
⁴ Department of Health Sciences, Public University of Navarra (UPNA), 31008 Pamplona, Spain.
⁵ Department of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, New York, NY 10016, USA.
⁶ École des Sciences de la Santé, Université Catholique d'Afrique Centrale, Yaoundé, Cameroon.
⁷ The Eastern Mediterranean Public Health Network (EMPHNET), Global Health Development (GHD), Amman 11195, Jordan.
⁸ Department of Preventive Medicine, University of Navarra Clinic, 31008 Pamplona, Spain.
⁹ Healthcare Research Institute of Navarre (IdiSNA), 31008 Pamplona, Spain.

PMID: 34203208
PMCID: PMC8267856
DOI: 10.3390/jcm10132859

Being Born in Winter-Spring and at Around the Time of an Influenza Pandemic Are Risk Factors for the Development of Schizophrenia: The Apna Study in Navarre, Spain

Miguel A Alvarez-Mon et al. J Clin Med. 2021.

. 2021 Jun 28;10(13):2859.

doi: 10.3390/jcm10132859.

Authors

Affiliations

¹ Department of Psychiatry and Medical Psychology, University of Navarra Clinic, 31008 Pamplona, Spain.
² Department of Medicine and Medical Specialities, University of Alcala, 28805 Alcala de Henares, Spain.
³ Primary Health Care, Navarra Health Service, 31008 Pamplona, Spain.
⁴ Department of Health Sciences, Public University of Navarra (UPNA), 31008 Pamplona, Spain.
⁵ Department of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, New York, NY 10016, USA.
⁶ École des Sciences de la Santé, Université Catholique d'Afrique Centrale, Yaoundé, Cameroon.
⁷ The Eastern Mediterranean Public Health Network (EMPHNET), Global Health Development (GHD), Amman 11195, Jordan.
⁸ Department of Preventive Medicine, University of Navarra Clinic, 31008 Pamplona, Spain.
⁹ Healthcare Research Institute of Navarre (IdiSNA), 31008 Pamplona, Spain.

PMID: 34203208
PMCID: PMC8267856
DOI: 10.3390/jcm10132859

Abstract

Background: We analyzed the relationship between the prevalence of schizophrenia and the season of birth and gestation during a period of an influenza pandemic.

Methods: Cross-sectional analysis of a prospective population-based cohort of 470,942 adults. We fitted multivariant logistic regression models to determine whether the season of birth and birth in an influenza-pandemic year (1957, 1968, 1977) was associated with schizophrenia.

Results: 2077 subjects had been diagnosed with schizophrenia. Logistic regression identified a significantly greater prevalence of schizophrenia in men than in women (OR = 1.516, CI 95% = 1.388-1.665); in those born in the winter or spring than in those born in the summer or autumn (OR = 1.112, CI 95% = 1.020-1.212); and in those born in a period of an influenza pandemic (OR = 1.335, CI 95% = 1.199-1.486). The increase in risk was also significant when each influenza pandemic year was analyzed separately. However, neither month of birth nor season of birth, when each of the four were studied individually, were associated with a statistically significant increase in that risk.

Conclusions: The winter-spring period and the influenza pandemics are independent risk factors for developing schizophrenia. This study contradicts many previous studies and thus revitalizes a locked debate in understanding the neurodevelopmental hypothesis of this disorder.

Keywords: influenza pandemic; neurodevelopmental hypothesis; schizophrenia; season of birth.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Directed Acyclic Graph (DAG) of the relationship of the season of birth and birth during an Influenza Pandemic, in combination with a viral infection during pregnancy (exposure), with schizophrenia (outcome). Adjusted variables (white circle). Based on DAGitty version 3.0 [32].

**Figure 2**
Age structure of the population.

See this image and copyright information in PMC

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Guillen-Aguinaga S, Brugos-Larumbe A, Guillen-Aguinaga L, Ortuño F, Guillen-Grima F, Forga L, Aguinaga-Ontoso I. Guillen-Aguinaga S, et al. J Cardiovasc Dev Dis. 2022 Jan 13;9(1):25. doi: 10.3390/jcdd9010025. J Cardiovasc Dev Dis. 2022. PMID: 35050235 Free PMC article.

References

1. Fatemi S.H., Folsom T.D. The Neurodevelopmental Hypothesis of Schizophrenia, Revisited. Schizophr. Bull. 2009;35:528–548. doi: 10.1093/schbul/sbn187. - DOI - PMC - PubMed
1. Brown A.S. Exposure to Prenatal Infection and Risk of Schizophrenia. Front. Psychiatry. 2011;2:63. doi: 10.3389/fpsyt.2011.00063. - DOI - PMC - PubMed
1. Radua J., Ramella-Cravaro V., Ioannidis J.P.A., Reichenberg A., Phiphopthatsanee N., Amir T., Yenn Thoo H., Oliver D., Davies C., Morgan C., et al. What Causes Psychosis? An Umbrella Review of Risk and Protective Factors. World Psychiatry Off. J. World Psychiatr. Assoc. (WPA) 2018;17:49–66. doi: 10.1002/wps.20490. - DOI - PMC - PubMed
1. Mortensen P.B., Pedersen C.B., Westergaard T., Wohlfahrt J., Ewald H., Mors O., Andersen P.K., Melbye M. Effects of Family History and Place and Season of Birth on the Risk of Schizophrenia. N. Engl. J. Med. 1999;340:603–608. doi: 10.1056/NEJM199902253400803. - DOI - PubMed
1. Boyd J.H., Pulver A.E., Stewart W. Season of Birth: Schizophrenia and Bipolar Disorder. Schizophr. Bull. 1986;12:173–186. doi: 10.1093/schbul/12.2.173. - DOI - PubMed

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[1] Fatemi S.H., Folsom T.D. The Neurodevelopmental Hypothesis of Schizophrenia, Revisited. Schizophr. Bull. 2009;35:528–548. doi: 10.1093/schbul/sbn187. - DOI - PMC - PubMed

[2] Fatemi S.H., Folsom T.D. The Neurodevelopmental Hypothesis of Schizophrenia, Revisited. Schizophr. Bull. 2009;35:528–548. doi: 10.1093/schbul/sbn187. - DOI - PMC - PubMed

[3] Brown A.S. Exposure to Prenatal Infection and Risk of Schizophrenia. Front. Psychiatry. 2011;2:63. doi: 10.3389/fpsyt.2011.00063. - DOI - PMC - PubMed

[4] Brown A.S. Exposure to Prenatal Infection and Risk of Schizophrenia. Front. Psychiatry. 2011;2:63. doi: 10.3389/fpsyt.2011.00063. - DOI - PMC - PubMed

[5] Radua J., Ramella-Cravaro V., Ioannidis J.P.A., Reichenberg A., Phiphopthatsanee N., Amir T., Yenn Thoo H., Oliver D., Davies C., Morgan C., et al. What Causes Psychosis? An Umbrella Review of Risk and Protective Factors. World Psychiatry Off. J. World Psychiatr. Assoc. (WPA) 2018;17:49–66. doi: 10.1002/wps.20490. - DOI - PMC - PubMed

[6] Radua J., Ramella-Cravaro V., Ioannidis J.P.A., Reichenberg A., Phiphopthatsanee N., Amir T., Yenn Thoo H., Oliver D., Davies C., Morgan C., et al. What Causes Psychosis? An Umbrella Review of Risk and Protective Factors. World Psychiatry Off. J. World Psychiatr. Assoc. (WPA) 2018;17:49–66. doi: 10.1002/wps.20490. - DOI - PMC - PubMed

[7] Mortensen P.B., Pedersen C.B., Westergaard T., Wohlfahrt J., Ewald H., Mors O., Andersen P.K., Melbye M. Effects of Family History and Place and Season of Birth on the Risk of Schizophrenia. N. Engl. J. Med. 1999;340:603–608. doi: 10.1056/NEJM199902253400803. - DOI - PubMed

[8] Mortensen P.B., Pedersen C.B., Westergaard T., Wohlfahrt J., Ewald H., Mors O., Andersen P.K., Melbye M. Effects of Family History and Place and Season of Birth on the Risk of Schizophrenia. N. Engl. J. Med. 1999;340:603–608. doi: 10.1056/NEJM199902253400803. - DOI - PubMed

[9] Boyd J.H., Pulver A.E., Stewart W. Season of Birth: Schizophrenia and Bipolar Disorder. Schizophr. Bull. 1986;12:173–186. doi: 10.1093/schbul/12.2.173. - DOI - PubMed

[10] Boyd J.H., Pulver A.E., Stewart W. Season of Birth: Schizophrenia and Bipolar Disorder. Schizophr. Bull. 1986;12:173–186. doi: 10.1093/schbul/12.2.173. - DOI - PubMed

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Being Born in Winter-Spring and at Around the Time of an Influenza Pandemic Are Risk Factors for the Development of Schizophrenia: The Apna Study in Navarre, Spain

Affiliations

Being Born in Winter-Spring and at Around the Time of an Influenza Pandemic Are Risk Factors for the Development of Schizophrenia: The Apna Study in Navarre, Spain

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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Abstract

Conflict of interest statement

Figures

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References

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