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Investigating whether adverse prenatal and perinatal events are associated with non-clinical psychotic symptoms at age 12 years in the ALSPAC birth cohort

  • S. Zammit (a1), D. Odd (a1), J. Horwood (a1), A. Thompson (a1), K. Thomas (a1), P. Menezes (a1), D. Gunnell (a1), C. Hollis (a1), D. Wolke (a1), G. Lewis (a1) and G. Harrison (a1)...



Non-clinical psychosis-like symptoms (PLIKS) occur in about 15% of the population. It is not clear whether adverse events during early development alter the risk of developing PLIKS. We aimed to examine whether maternal infection, diabetes or pre-eclampsia during pregnancy, gestational age, perinatal cardiopulmonary resuscitation or 5-min Apgar score were associated with development of psychotic symptoms during early adolescence.


A longitudinal study of 6356 12-year-old adolescents who completed a semi-structured interview for psychotic symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Prenatal and perinatal data were obtained from obstetric records and maternal questionnaires completed during pregnancy.


The presence of definite psychotic symptoms was associated with maternal infection during pregnancy [adjusted odds ratio (OR) 1.44, 95% confidence interval (CI) 1.11–1.86, p=0.006], maternal diabetes (adjusted OR 3.43, 95% CI 1.14–10.36, p=0.029), need for resuscitation (adjusted OR 1.50, 95% CI 0.97–2.31, p=0.065) and 5-min Apgar score (adjusted OR per unit decrease 1.30, 95% CI 1.12–1.50, p<0.001). None of these associations were mediated by childhood IQ score. Most associations persisted, but were less strong, when including suspected symptoms as part of the outcome. There was no association between PLIKS and gestational age or pre-eclampsia.


Adverse events during early development may lead to an increased risk of developing PLIKS. Although the status of PLIKS in relation to clinical disorders such as schizophrenia is not clear, the similarity between these results and findings reported for schizophrenia indicates that future studies of PLIKS may help us to understand how psychotic experiences and clinical disorders develop throughout the life-course.


Corresponding author

*Address for correspondence: Dr S. Zammit, Department of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, Wales, UK. (Email:


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ACOG (2006). ACOG Committee Opinion: the Apgar score. Obstetrics and Gynecology 107, 12091212.
Bowen, E, Heron, J, Waylen, A, Wolke, D (2005). Domestic violence risk during and after pregnancy: findings from a British longitudinal study. British Journal of Obstetrics and Gynaecology 112, 10831089.
Brown, AS, Begg, MD, Gravenstein, S, Schaefer, CA, Wyatt, RJ, Bresnahan, M, Babulas, VP, Susser, ES (2004). Serologic evidence of prenatal influenza in the etiology of schizophrenia. Archives of General Psychiatry 61, 774780.
Byrne, M, Agerbo, E, Bennedsen, B, Eaton, WW, Mortensen, PB (2007). Obstetric conditions and risk of first admission with schizophrenia: a Danish national register based study. Schizophrenia Research 97, 5159.
Callaway, LK, McIntyre, HD, O'Callaghan, M, Williams, GM, Najman, JM, Lawlor, DA (2007). The association of hypertensive disorders of pregnancy with weight gain over the subsequent 21 years: findings from a prospective cohort study. American Journal of Epidemiology 166, 421428.
Cannon, M, Jones, PB, Murray, RM (2002). Obstetric complications and schizophrenia: historical and meta-analytic review. American Journal of Psychiatry 159, 10801092.
Cannon, M, Kendell, R, Susser, E, Jones, P (2003). Prenatal and perinatal risk factors for schizophrenia. In The Epidemiology of Schizophrenia (ed. Murray, R., Jones, P. B., Susser, E., van Os, J. and Cannon, M.), pp. 7499. Cambridge University Press: Cambridge.
Cox, JL, Holden, JM, Sagovsky, R (1987). Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. British Journal of Psychiatry 150, 782786.
Eaton, WW, Romanoski, A, Anthony, JC, Nestadt, G (1991). Screening for psychosis in the general population with a self-report interview. Journal of Nervous and Mental Disorders 179, 689693.
Fatemi, SH, Reutiman, TJ, Folsom, TD, Huang, H, Oishi, K, Mori, S, Smee, DF, Pearce, DA, Winter, C, Sohr, R, Juckel, G (2008). Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: implications for genesis of neurodevelopmental disorders. Schizophrenia Research 99, 5670.
Fawke, J (2007). Neurological outcomes following preterm birth. Seminars in Fetal and Neonatal Medicine 12, 374382.
Golding, J, Pembrey, M, Jones, R (2001). ALSPAC – the Avon Longitudinal Study of Parents and Children. I. Study methodology. Paediatric and Perinatal Epidemiology 15, 7487.
Hanssen, M, Bak, M, Bijl, R, Vollebergh, W, van Os, J (2005). The incidence and outcome of subclinical psychotic experiences in the general population. British Journal of Clinical Psychology 44, 181191.
Horwood, J, Salvi, G, Thomas, K, Duffy, L, Gunnell, D, Hollis, C, Lewis, G, Menezes, P, Thompson, A, Wolke, D, Zammit, S, Harrison, G (2008). IQ and non-clinical psychotic symptoms in 12-year-olds: results from the ALSPAC birth cohort. British Journal of Psychiatry 193, 185191.
Inder, T, Neil, J, Yoder, B, Rees, S (2004). Non-human primate models of neonatal brain injury. Seminars in Perinatology 28, 396404.
Johns, LC, Cannon, M, Singleton, N, Murray, RM, Farrell, M, Brugha, T, Bebbington, P, Jenkins, R, Meltzer, H (2004). Prevalence and correlates of self-reported psychotic symptoms in the British population. British Journal of Psychiatry 185, 298305.
Kendler, KS, Gallagher, TJ, Abelson, JM, Kessler, RC (1996). Lifetime prevalence, demographic risk factors, and diagnostic validity of nonaffective psychosis as assessed in a US community sample. The National Comorbidity Survey. Archives of General Psychiatry 53, 10221031.
Ornoy, A (2005). Growth and neurodevelopmental outcome of children born to mothers with pregestational and gestational diabetes. Pediatric Endocrinology Reviews 3, 104113.
Pasamanick, B, Rogers, ME, Lilienfeld, AM (1956). Pregnancy experience and the development of behavior disorders in children. American Journal of Psychiatry 112, 613618.
Perala, J, Suvisaari, J, Saarni, SI, Kuoppasalmi, K, Isometsa, E, Pirkola, S, Partonen, T, Tuulio-Henriksson, A, Hintikka, J, Kieseppa, T, Harkanen, T, Koskinen, S, Lonnqvist, J (2007). Lifetime prevalence of psychotic and bipolar I disorders in a general population. Archives of General Psychiatry 64, 1928.
Plewis, I, Calderwoof, L, Hawkes, D, Nathan, G (2004). National Child Development Study and 1970 British Cohort Study Technical Report: changes in the NCDS and BCS70 populations and samples over time. Centre for Longitudinal Studies, Institute of Education: London.
Poulton, R, Caspi, A, Moffitt, TE, Cannon, M, Murray, R, Harrington, H (2000). Children's self-reported psychotic symptoms and adult schizophreniform disorder: a 15-year longitudinal study. Archives of General Psychiatry 57, 10531058.
Raghunathan, TE, Lepkowski, JM, Van Hoewyk, J, Solenberger, P (2001). A multivariate technique for multiply imputing missing values using a sequence of regression models. Survey Methodology 27, 8595.
Rossler, W, Riecher-Rossler, A, Angst, J, Murray, R, Gamma, A, Eich, D, van Os, J, Gross, VA (2007). Psychotic experiences in the general population: a twenty-year prospective community study. Schizophrenia Research 92, 114.
Royston, P (2004). Multiple imputation of missing values. Stata Journal 3, 227241.
Shaffer, D, Fisher, P, Lucas, CP, Dulcan, MK, Schwab-Stone, ME (2000). NIMH Diagnostic Interview Schedule for Children Version IV (NIMH DISC-IV): description, differences from previous versions, and reliability of some common diagnoses. Journal of the American Academy of Child and Adolescent Psychiatry 39, 2838.
Sorensen, HJ, Mortensen, EL, Reinisch, JM, Mednick, SA (2004). Association between prenatal exposure to analgesics and risk of schizophrenia. British Journal of Psychiatry 185, 366371.
Spauwen, J, Krabbendam, L, Lieb, R, Wittchen, HU, van Os, J (2004). Early maternal stress and health behaviours and offspring expression of psychosis in adolescence. Acta Psychiatrica Scandinavica 110, 356364.
St Clair, D, Xu, M, Wang, P, Yu, Y, Fang, Y, Zhang, F, Zheng, X, Gu, N, Feng, G, Sham, P, He, L (2005). Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959–1961. Journal of the American Medical Association 294, 557562.
Susser, E, Neugebauer, R, Hoek, HW, Brown, AS, Lin, S, Labovitz, D, Gorman, JM (1996). Schizophrenia after prenatal famine. Further evidence. Archives of General Psychiatry 53, 2531.
Thomas, K, Harrison, G, Zammit, S, Lewis, G, Horwood, J, Heron, J, Hollis, C, Wolke, D, Thompson, A, Gunnell, D (in press). The association of measures of fetal and childhood growth with non-clinical psychotic symptoms in 12 year olds: the ALSPAC cohort. British Journal of Psychiatry.
van Os, J, Hanssen, M, Bijl, RV, Vollebergh, W (2001). Prevalence of psychotic disorder and community level of psychotic symptoms: an urban–rural comparison. Archives of General Psychiatry 58, 663668.
Wechsler, D (1991). Manual for the Wechsler Intelligence Scale for Children – Third Edition (WISC-III). Psychological Corporation: San Antonio, TX.
WHO (1994). Schedules for Clinical Assessment in Neuropsychiatry. American Psychiatric Research: Washington, DC.
Wiles, NJ, Zammit, S, Bebbington, P, Singleton, N, Meltzer, H, Lewis, G (2006). Self-reported psychotic symptoms in the general population: results from the longitudinal study of the British National Psychiatric Morbidity Survey. British Journal of Psychiatry 188, 519526.
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Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
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