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Exposure to Influenza Epidemics During Gestation and Adult Schizophrenia: Title and subTitle BreakA 40-Year Study

Christopher E. Barr, MA; Sarnoff A. Mednick, PhD, DM; Poul Munk-Jorgensen, MD
[+] Author Affiliations

Accepted for publication January 26, 1990.

Read in part before the National Institute of Mental Health Second International Conference on Schizophrenia, San Diego, Calif, April 3, 1989.

Reprint requests to Social Science Research Institute, University of Southern California, Denney Research Bldg, Room 128, Los Angeles, CA 90089-1111 (Mr Barr).


Arch Gen Psychiatry. 1990;47(9):869-874. doi:10.1001/archpsyc.1990.01810210077012
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• We attempted to replicate earlier findings of an association between exposure to influenza in the second trimester of gestation and adult schizophrenia. The number of live births, of births of future schizophrenics, and of cases of influenza reported to the Ministry of Health in Denmark was ascertained by month from 1911 to 1950. The relationship between fetal exposure to influenza and adult schizophrenia was examined. It is possible that unknown factors produce excesses of both influenza and schizophrenia in the winter, creating an artifactual association. To control for this coincidence, the effects of season were removed from the monthly influenza and schizophrenic birthrates by several methods. Using the residual scores, it was found that influenza rates higher than seasonally expected, occurring in the sixth month of gestation, were associated with rates of births of schizophrenics greater than seasonally expected. This association was not attributable to some winter-related, third factor or to climatic variables.

REFERENCES

Mednick SA, Machon RA, Huttunen MD, Bonett D.  Adult schizophrenia following prenatal exposure to an influenza epidemic . Arch Gen Psychiatry . 1988;;45:189-192.
Torrey EF, Rawlings R, Waldman IN.  Schizophrenic births and viral diseases in two states . Schizophr Res . 1988;;1:73-77.
Kendell RE, Kemp IW.  Maternal influenza in the etiology of schizophrenia . Arch Gen Psychiatry . 1989;;46:878-882.
McNeil TF.  Obstetric factors and perinatal injuries . In: Tsuang MT, Simpson JC, eds. Handbook of Schizophrenia. Amsterdam , the Netherlands: Elsevier Science Publishers; 1988;;3:319-344.
Hakosalo JK, Saxen L.  Influenza epidemic and congenital defects . Lancet . 1971;;2:1346-1347.
Berkow R, Fletcher AJ. The Merck Manual of Diagnosis and Therapy . Rahway, NJ: Merck & Co Inc; 1987;:172.
Smith H, Sweet C.  Lessons for human influenza from pathogenicity studies with ferrets . Rev Infect Dis . 1988;;10:56-75.
Hardy JB.  Fetal consequences of maternal viral infections in pregnancy . Arch Otolaryngol Head Neck Surg . 1973;;98:218-227.
Coffey VP, Jessop WSE.  Maternal influenza and congenital deformities . Lancet . 1963;;1:748-751.
Yawn DH, Pyeatte JC, Joseph JM, Eichler SL, Garcia-Bunuel R.  Transplacental transfer of influenza virus . JAMA . 1971;;216:1022-1023.
Edwards MJ.  Hyperthermia as a teratogen: a review of experimental studies and their clinical significance . Teratogenesis Carcinog Mutagen . 1986;;6:563-582.
Laing P, Knight JG, Hill JM, Harris AG, Oxford JS, Webster RG, Markwell MAK, Paul SM, Pert CB. Influenza viruses induce autoantibodies to brain in rabbit and mouse: possible implications for schizophrenia. Abstract presented at the International Congress on Schizophrenia Research; April 3, 1989; San Diego, Calif.
Kovelman JA, Scheibel AB.  A neurohistological correlate of schizophrenia . Biol Psychiatry . 1984;;19:1601-1621.
Jakob H, Beckmann H.  Prenatal developmental disturbances in the limbic allocortex in schizophrenics . J Neural Transm . 1986;;65:303-326.
Benes M, Davidson J, Bird ED.  Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics . Arch Gen Psychiatry . 1986;;43:31-35.
Falkai P, Bogerts B.  Cell loss in the hippocampus of schizophrenics . Eur Arch Psychiatry Neurol Sci . 1986;;236:154-161.
Rakic P, Sidman RL.  Histogenesis of cortical layers in human cerebellum, particularly the lamina dissecans . J Comp Neurol . 1970;;139:473-500.
Weinberger DR, Torrey EF, Wyatt RJ.  Cerebellar atrophy in chronic schizophrenia . Lancet . 1979;;1:718-719.
Weinberger DR, Wyatt RJ.  Structural pathology of the cerebellum in schizophrenia: CT and postmortem studies . In: Perris C, Jansson B, eds. Biological Psychiatry . Amsterdam, the Netherlands: North-Holland Publishing Co; 1981;:272-275.
Lippman S, Manshadi M, Baldwin H, Drasin G, Rice J, Alrajeh S.  Cerebellar vermis dimensions on computerized tomographic scans of schizophrenic and bipolar patients . Am J Psychiatry . 1982;;135:667-668.

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Mednick SA, Machon RA, Huttunen MD, Bonett D.  Adult schizophrenia following prenatal exposure to an influenza epidemic . Arch Gen Psychiatry . 1988;;45:189-192.
Torrey EF, Rawlings R, Waldman IN.  Schizophrenic births and viral diseases in two states . Schizophr Res . 1988;;1:73-77.
Kendell RE, Kemp IW.  Maternal influenza in the etiology of schizophrenia . Arch Gen Psychiatry . 1989;;46:878-882.
McNeil TF.  Obstetric factors and perinatal injuries . In: Tsuang MT, Simpson JC, eds. Handbook of Schizophrenia. Amsterdam , the Netherlands: Elsevier Science Publishers; 1988;;3:319-344.
Hakosalo JK, Saxen L.  Influenza epidemic and congenital defects . Lancet . 1971;;2:1346-1347.
Berkow R, Fletcher AJ. The Merck Manual of Diagnosis and Therapy . Rahway, NJ: Merck & Co Inc; 1987;:172.
Smith H, Sweet C.  Lessons for human influenza from pathogenicity studies with ferrets . Rev Infect Dis . 1988;;10:56-75.
Hardy JB.  Fetal consequences of maternal viral infections in pregnancy . Arch Otolaryngol Head Neck Surg . 1973;;98:218-227.
Coffey VP, Jessop WSE.  Maternal influenza and congenital deformities . Lancet . 1963;;1:748-751.
Yawn DH, Pyeatte JC, Joseph JM, Eichler SL, Garcia-Bunuel R.  Transplacental transfer of influenza virus . JAMA . 1971;;216:1022-1023.
Edwards MJ.  Hyperthermia as a teratogen: a review of experimental studies and their clinical significance . Teratogenesis Carcinog Mutagen . 1986;;6:563-582.
Laing P, Knight JG, Hill JM, Harris AG, Oxford JS, Webster RG, Markwell MAK, Paul SM, Pert CB. Influenza viruses induce autoantibodies to brain in rabbit and mouse: possible implications for schizophrenia. Abstract presented at the International Congress on Schizophrenia Research; April 3, 1989; San Diego, Calif.
Kovelman JA, Scheibel AB.  A neurohistological correlate of schizophrenia . Biol Psychiatry . 1984;;19:1601-1621.
Jakob H, Beckmann H.  Prenatal developmental disturbances in the limbic allocortex in schizophrenics . J Neural Transm . 1986;;65:303-326.
Benes M, Davidson J, Bird ED.  Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics . Arch Gen Psychiatry . 1986;;43:31-35.
Falkai P, Bogerts B.  Cell loss in the hippocampus of schizophrenics . Eur Arch Psychiatry Neurol Sci . 1986;;236:154-161.
Rakic P, Sidman RL.  Histogenesis of cortical layers in human cerebellum, particularly the lamina dissecans . J Comp Neurol . 1970;;139:473-500.
Weinberger DR, Torrey EF, Wyatt RJ.  Cerebellar atrophy in chronic schizophrenia . Lancet . 1979;;1:718-719.
Weinberger DR, Wyatt RJ.  Structural pathology of the cerebellum in schizophrenia: CT and postmortem studies . In: Perris C, Jansson B, eds. Biological Psychiatry . Amsterdam, the Netherlands: North-Holland Publishing Co; 1981;:272-275.
Lippman S, Manshadi M, Baldwin H, Drasin G, Rice J, Alrajeh S.  Cerebellar vermis dimensions on computerized tomographic scans of schizophrenic and bipolar patients . Am J Psychiatry . 1982;;135:667-668.

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