The effects of maternal antidepressant use on offspring behaviour and brain development: Implications for risk of neurodevelopmental disorders

Abstract

Approximately 10% of pregnant women are prescribed antidepressant drugs (ADDs), with selective serotonin reuptake inhibitors (SSRIs) the most widely prescribed. SSRIs bind to the serotonin transporter (SERT), blocking the reabsorption of serotonin by the presynaptic neuron and increasing serotonin levels in the synaptic cleft. The serotonergic system regulates a range of brain development processes including neuronal proliferation, migration, differentiation and synaptogenesis. Given the presence of SERT in early brain development, coupled with the ability of SSRIs to cross the placenta and also enter breast milk, concerns have been raised regarding the effects of SSRI exposure on the developing foetus and newborns. In this review, we evaluate preclinical and clinical studies that have examined the effects of maternal SSRI exposure and the risk for altered neurodevelopment and associated behaviours in offspring. While the current body of evidence suggests that maternal SSRI treatment may cause perturbations to the neurobiology, behaviour and ultimately risk for neurodevelopmental disorders in exposed offspring, conflicting findings do exist and the evidence is not conclusive. However, given the increasing incidence of depression and number of women prescribed ADDs during pregnancy, further investigation into this area is warranted.

Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes: a systematic review and meta-analyses of animal studies

“…The neurodevelopmental pattern of the serotonin system is remarkably conserved across species 29, 32, 33 . Therefore, rodent studies of early SSRI exposure can yield important insights and circumvent some of the difficulties of studying this phenomenon in humans.…”

“…A major challenge in human studies is to properly control for the confounding factor of maternal 33 psychiatric condition. Statistical methods aim to approximate this, illustrated by the finding that the association between in utero SSRI exposure and risk of ASD was not significant when controlled for maternal psychiatric diagnosis 156 .…”

“…In humans, SSRI use leads to more stable concentrations over the course of the day. In addition, dosing and route of administration varied widely 33 .…”

Antidepressant use during pregnancy and the risk of attention‐deficit/hyperactivity disorder in the children: a meta‐analysis of cohort studies

“…Thus, recognition of the risk factors for ADHD and implementation of appropriate interventions may help to prevent the disorder. Antidepressant use during pregnancy is a risk factor for ADHD, given that the long‐lasting effects of in utero exposure to antidepressants on brain function and behaviour are well established . Several epidemiological case‐control studies have investigated the association between prenatal exposure to antidepressants and the risk of ADHD, but the results have been inconsistent.…”

Early developmental exposure to Fluoxetine and Citalopram results in different neurodevelopmental outcomes

“…In a large meta-analysis of environmental risk factors for ASD, SSRI exposure was one of the associations that retained high level of significance (Kim et al, 2019). However, recent comprehensive reviews (Millard et al, 2017;Rotem-Kohavi and Oberlander, 2017), describe the lack of consensus among these clinical studies and meta-analyses. While some report an increased risk of ASD following prenatal SSRI exposure (Boukhris et al, 2016;Croen et al, 2011;Kim et al, 2019), others have countered such conclusions (Malm et al, 2016;Sorensen et al, 2013;Suri et al, 2011).…”