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Maternal tobacco, cannabis and alcohol use during pregnancy and risk of adolescent psychotic symptoms in offspring

  • Stanley Zammit (a1), Kate Thomas (a2), Andrew Thompson (a3), Jeremy Horwood (a2), Paulo Menezes (a3), David Gunnell (a2), Chris Hollis (a4), Dieter Wolke (a5), Glyn Lewis (a6) and Glynn Harrison (a6)...

Adverse effects of maternal substance use during pregnancy on fetal development may increase risk of psychopathology.


To examine whether maternal use of tobacco, cannabis or alcohol during pregnancy increases risk of offspring psychotic symptoms.


A longitudinal study of 6356 adolescents, age 12, who completed a semi-structured interview for psychotic symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.


Frequency of maternal tobacco use during pregnancy was associated with increased risk of suspected or definite psychotic symptoms (adjusted odds ratio 1.20, 95% CI 1.05–1.37, P = 0.007). Maternal alcohol use showed a non-linear association with psychotic symptoms, with this effect almost exclusively in the offspring of women drinking >21 units weekly. Maternal cannabis use was not associated with psychotic symptoms. Results for paternal smoking during pregnancy and maternal smoking post-pregnancy lend some support for a causal effect of tobacco exposure in utero on development of psychotic experiences.


These findings indicate that risk factors for development of non-clinical psychotic experiences may operate during early development. Future studies of how in utero exposure to tobacco affects cerebral development and function may lead to increased understanding of the pathogenesis of psychotic phenomena.

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Corresponding author
Stanley Zammit, Department of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, Wales, UK. Email:
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This study was funded by the Wellcome Trust grant No. GR072043MA. S.Z. is funded through a Clinician Scientist Award funded by the National Assembly for Wales. The UK Medical Research Council, the Wellcome Trust and the University of Bristol provide core support for ALSPAC.

Declaration of interest


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Maternal tobacco, cannabis and alcohol use during pregnancy and risk of adolescent psychotic symptoms in offspring

  • Stanley Zammit (a1), Kate Thomas (a2), Andrew Thompson (a3), Jeremy Horwood (a2), Paulo Menezes (a3), David Gunnell (a2), Chris Hollis (a4), Dieter Wolke (a5), Glyn Lewis (a6) and Glynn Harrison (a6)...
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Antenatal tobacco exposure and risk for psychosis - a role for epigenetics?

Helge Frieling, MD
02 December 2009

Dear Sir,

Stanley Zammit and co-workers have reported that maternal tobacco consumption during pregnancy increases the risk for the development of non-clinical psychotic experiences and might be a risk factor for psychotic disorders like schizophrenia (1). The authors discuss some possible biological mechanisms, but we believe that the important aspect of epigenetic programming during pregnancy was omitted. Disturbances in epigenetic mechanisms like DNA methylation and histone modifications have been shown to be the biological substrate of long-term behavioural programming due to early events and aberrant DNA methylation of different genes has been described in schizophrenia (2-3). We have recently shown that tobacco consumption influences DNA methylation (4) and epigenetic disturbances are believed to be one important way of tobacco-associated carcinogenesis.

To us it seems plausible to assume that the reported effect of maternal tobacco consumption on psychosis-like symptoms in the offspring might be mediated by epigenetic means. This could also help understand whymaternal smoking during the third trimester of pregnancy was associated with the highest risk, as other ‘epigenetic’ risk factors like hyperhomocysteinemia are also most deleterious during this time period (5). Further studies should also address the effect of maternal tobacco consumption on epigenetic markers in the offspring, which might open a window to effective preventive measures even after exposure during pregnancy.

1Zammit S., Thomas K., Thompson A., Horwood J., Menezes P., Gunnell D., et al. Maternal tobacco, cannabis and alcohol use during pregnancy andrisk of adolescent psychotic symptoms in offspring. Br J Psychiatry 2009; 195: 294-300.

2Mill J., Tang T., Kaminsky Z., Khare T., Yazdanpanah S., Bouchard L., et al. Epigenomic Profiling Reveals DNA-Methylation Changes Associatedwith Major Psychosis. The American Journal of Human Genetics 2008; 82: 696-711.

3Krebs M. O., Bellon A., Mainguy G., Jay T. M.,Frieling H. One-carbon metabolism and schizophrenia: current challenges and future directions. Trends in Molecular Medicine In Press, Corrected Proof:

4Hillemacher T., Frieling H., Moskau S., Muschler M. A., Semmler A.,Kornhuber J., et al. Global DNA methylation is influenced by smoking behaviour. Eur Neuropsychopharmacol 2008; 18: 295-298.

5Brown A. S., Bottiglieri T., Schaefer C. A., Quesenberry C. P., Jr., Liu L., Bresnahan M., et al. Elevated Prenatal Homocysteine Levels asa Risk Factor for Schizophrenia. Arch Gen Psychiatry 2007; 64: 31-39.
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Conflict of interest: None Declared

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