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• Maternal tobacco, cannabis and alcohol use during pregnancy and risk of adolescent psychotic symptoms in offspring (Full Text) 

Results

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.

Conclusions

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. . . .

Possible biological mechanisms

Animal studies indicate that fetal nicotine exposure can result in long-term structural and functional changes,7 including decreased neuronal density and size in the hippocampus and cortex, altered regulation of neuronal apoptosis,7,15 and increased expression of receptors for acetylcholine, which plays a critical role in brain maturation through modulation of axonogenesis and synaptogenesis.15 However, difficulties exist, both conceptually and pragmatically, in the interpretation of results from animal models in relation to effects in humans.

We are not aware of animal studies to date that have examined the effects of nicotine exposure in utero on putative endophenotypes of schizophrenia. Although endophenotypes of schizophrenia that can be modelled in animals are yet to be clearly determined this could potentially become an informative area for future research.

We observed suggestive evidence that maternal smoking during the third trimester was most strongly associated with risk of PLIKS, although results from subgroup comparisons should be interpreted cautiously. This is rather inconsistent with results from studies of famine38,39 and influenza,40,41 where early pregnancy exposure is associated with greatest risk of schizophrenia, but may reflect different sensitive periods of risks in brain development for different types of exposure. Maternal smoking,5,42 particularly during late pregnancy,43 is thought to lead to lower birth weight.7 However, adjusting for birth weight, as well as for gestation and 5-minute Apgar score had no effect on the results, and although these measures are likely to be rather crude markers of pre- and perinatal adversity, it seems unlikely that such adversity mediates or confounds the relationship between maternal smoking and offspring psychotic experiences. . . .

Implications

Observational studies are limited in determining causality due to potential problems of residual confounding. We observed an association between maternal, but not paternal, smoking during pregnancy and risk of psychotic symptoms in the offspring, consistent with accumulating evidence from animal models of adverse effects on brain development from in utero nicotine exposure. These findings suggest 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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