Neurodevelopmental consequences of prenatal exposure: a population based brain MRI study

PhD project (3/4 yr research project leading to independent research at the doctorate level)

Dr Luisa Zuccolo, Dr Esther Walton, Prof Marcus Munafo


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Rationale

Evidence is emerging suggesting that even small amounts of alcohol during pregnancy could potentially affect neurodevelopment and result in lower cognitive and academic scores [1-3]. On the other hand, it is well understood that any level of tobacco use in pregnancy is detrimental to fetal neurodevelopment; yet the specific mechanisms involved in both alcohol and tobacco brain toxicity remain unconfirmed.
Differences in brain morphology (white and grey matter) provide one possible mechanism for the neurodevelopmental effects of alcohol and tobacco use before pregnancy. However, another line of research (animal studies mainly) has found evidence that differences in brain morphology could be caused by alcohol consumption by the main carer during their offspring’s early life, possibly through altered parental behaviour. Whether this is also true for smoking is unclear, and robust studies with human participants are currently awaited.

Aims & objectives

1. To study the effects of exposure to prenatal alcohol and tobacco use on structural brain morphology in adolescents.
2. To study the effects of exposure to parental alcohol and tobacco use during childhood on structural brain morphology in adolescents.
3. To explore the causal nature of the observed associations using causal analysis methods such as negative control and Mendelian randomization methods.

Methods

The studentship will involve a number of different methodologies and the use of data of various nature already collected as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) [4], including data to allow investigation of possible confounding and mediating effects (e.g. prenatal and postnatal environmental and neuropsychological assessments, genome-wide genetic scans and DNA methylation data). The student(s) will have the opportunity to familiarise with different research methodologies. These will include epigenomics and neuroimaging data processing and analyses (e.g. see http://www.godmc.org.uk/, http://www.ariesepigenomics.org.uk and [5]), and causal analysis methods such as negative control and Mendelian randomization methods [6], to help rule out major biases and confounding as explanation of the results. Where possible, cross-cohort comparisons will additionally be performed via collaboration with independent cohorts.

References

1- Valenzuela CF 2012;35(5):284-292
2- Zuccolo L Int J Epidemiol, 2013. 42(5):1358-70
3- Lewis SJ Plos One, 2012 2012;7(11):e49407
4- Boyd A Int J Epidemiol, 2013. 42(1): 111-27
5- White T Eur J Epidemiol, 2013. 28(1): 99-111
6- Gage SH Depress Anxiety, 2013 30(12): 1185–1193


Created on Nov. 17, 2016, 3:48 p.m.

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