Neurodevelopmental consequences of in utero exposure to psychotropic medications

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

Dr Dheeraj Rai, Professor George Davey Smith, Professor Stan Zammit, Professor Cecilia Magnusson at Karolinska Institute - will host student during visits to Sweden and act as external supervisor/collaborator.


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Rationale

Psychiatric disorders are common in women of childbearing age. There are considerable risks of untreated mental disorders to pregnant women and their babies, and although caution is advised, psychotropic drugs such as antidepressants, mood stabilizers, and antipsychotics are often necessary after weighing the risks and benefits. All psychotropic medications cross the placental barrier and are available to the developing fetus. Receptors and neural circuits of the neurotransmitters these medications act on emerge early in embryogenesis, and are critical for neurodevelopment. Recent evidence suggests that common psychotropic medications which were until recently considered ‘safe’ may be associated with longer-term developmental problems such as autism. However, understanding causal associations is challenging and confounding by indication a particular problem. Such difficulties disentangling the causal role of medication versus indication create a dilemma for clinical practice.

Aims & objectives

Aim: To study the long term neurodevelopmental risks associated with in-utero exposure to psychotropic medications

Objectives:
1) To study the relationship between maternal psychotropic drug use during pregnancy and offspring diagnosis or trait measures of autism spectrum disorder, attention deficit hyperactivity disorder, and intellectual disability.

2) To disentangle the effect of medication exposures from the underlying condition in the pathways to causation in any observed relationships.

Methods

This project will utilise the complementary strengths of large intergenerational sources of observational data. Examples include the ALSPAC birth cohort, the Swedish Birth Cohort and the Clinical Practice Research Datalink.

The doctoral student will learn the application of traditional and novel epidemiologic approaches; and understand the relative strengths and limitations of each in relation to ascribing causal inference using observational data. Examples of these methods include linear and/or logistic regression methods, negative control approaches such as maternal and paternal comparisons, sibling control design, propensity score matching, instrumental variable analysis and cross cohort comparisons.

There will be opportunities to work with a number of international collaborators and to spend time at centres of excellence such as the Karolinska Institute in Stockholm, Sweden.

References

Rai D et al. Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders. BMJ 2013;346:f2059

Lewis S et al. Approaches for strengthening causal inference regarding prenatal risk factors. J Child Psychol Psychiatry (2013);54,1095-108


Created on Oct. 1, 2015, 9 a.m.

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