The biology of fetal exposure to serotonin reuptake inhibitors: Implications for neurodevelopment
Galbally, M., Lewis, A.J., Gentile, S., Walker, S. and Buist, A. (2012) The biology of fetal exposure to serotonin reuptake inhibitors: Implications for neurodevelopment. In: Migne, L.J. and Post, J.W., (eds.) Antidepressants: Pharmacology, Health Effects and Controversy. Nova Science Publishers, New York, USA, pp. 1-26.
This chapter will discuss the biology of exposure to antidepressants during pregnancy as it interacts with fetal neurodevelopment. A systematic review of prevalence rates in pregnancy found 12% of women in third trimester meet criteria for depression and the Avon Longitudinal Study of Parents and Children (ALSPAC) found that more women were depressed at 32 weeks pregnant than 8 weeks postpartum. Untreated depression in pregnancy has been associated with increased pregnancy complications, poorer child development and increased risk of postnatal depression. While psychological treatments are indicated for many women with antenatal depression, pharmacological treatment may be indicated for those who either don‟t respond, have moderate to severe depressive symptoms, or don‟t have access to psychological treatments. Antidepressants may also be indicated for women with Anxiety Disorders. The most commonly prescribed antidepressants are the selective serotonin reuptake inhibitors (SSRIs). Rates of prescription in North America for antidepressants in pregnancy are rising yet the implications for exposure on the child‟s longer term neurodevelopment are still relatively unknown. Until now, the limited number of studies has not revealed any effects on global cognitive function. Yet there have been 5 studies published recently which suggest an effect of exposure on psychomotor development and a single, unreplicated study which suggested an increased risk of autism-spectrum disorders in children exposed to these antidepressants in pregnancy.
This chapter includes a brief review of the published research on neurodevelopmental outcomes for children following exposure to antidepressants in pregnancy and in particular, findings on psychomotor development. Methodological limitations in this body of literature including sample size, the measures of child development, the age of the children assessed and potential confounding variables will be discussed.
Several models can be used to understand these findings and the chapter will discuss models such as DOHaD’s fetal programming concept and neurodevelopmental teratology. While structural teratology is generally limited to the first trimester, neurodevelopmental teratology recognizes the long term effects of exposure to agents or events across pregnancy that can have effect on child development that are often not apparent until well beyond infancy.
In the second half of the chapter, the origins and principles of neurodevelopmental teratology are outlined and discussed in the context of the developing serotonin system. This includes an overview of the development and functioning of the serotonin system and the pharmacology of SSRIs in order to consider how these might interact. An overview will be presented of the key animal and human studies on the effects of SSRIs on the developing serotonin system. Finally, implications and suggestions for future research are discussed.
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