Central nervous system effects of prenatal selective serotonin reuptake inhibitors: sensing the signal through the noise

Abstract

Rationale Women are increasingly prescribed selective serotonin reuptake inhibitors (SSRIs) during pregnancy, with potential implications for neurodevelopment. Whether prenatal SSRI exposure has an effect on neurodevelopment and behavior in the offspring is an important area of investigation. Objectives The aim of this paper was to review the existing preclinical and clinical literature of prenatal SSRI exposure on serotonin-related behaviors and markers in the offspring. The goal is to determine if there is a signal in the literature that could guide clinical care and/or inform research. Results Preclinical studies (n = 4) showed SSRI exposure during development enhanced depression-like behavior. Half of rodent studies examining anxiety-like behavior (n = 13) noted adverse effects with SSRI exposure. A majority of studies of social behavior (n = 4) noted a decrease in sociability in SSRI exposed offspring. Human studies (n = 4) examining anxiety in the offspring showed no adverse effects of prenatal SSRI exposure. The outcome of one study suggested that children with autism were more likely to have a mother who was prescribed an SSRI during pregnancy. Conclusions Preclinical findings in rodents exposed to SSRIs during development point to an increase in depression- and anxiety-like behavior and alteration in social behaviors in the offspring, though both the methods used and the findings were not uniform. These data are not robust enough to discourage use of SSRIs during human pregnancy, particularly given the known adverse effects of maternal mental illness on pregnancy outcomes and infant neurodevelopment. Future research should focus on consistent animal models and prospective human studies with larger samples.

Maternal SSRI discontinuation, use, psychiatric disorder and the risk of autism in children: a meta‐analysis of cohort studies

“…The similar effect size of this group to that of SSRI exposure any time during pregnancy group with a largely overlapping confidence interval strengthens our previous suggestion that the maternal psychiatric disorder may be a strong confounder in studies assessing the connection between maternal SSRI use and ASD risk in children . Although sought by an increasing number of studies and considered as biologically plausible , the suggested association of SSRI exposure during pregnancy and risk of ASD in children still remains to be adequately substantiated.…”

Major depressive disorder during pregnancy: Psychiatric medications have minimal effects on the fetus and infant yet development is compromised

“…Psychosocial services that promote the mother-child relationship also may be needed to help optimize the postnatal environment and thereby positively affect child development (Forman et al, 2007). Gur et al (2013) have reasoned that since serotonin (5-HT) modulates neuroplasticity, the impact of SRI exposure on fetal brain development likely is significant, but may evolve over time and be context dependent. Similarly, Brummelte, Mc Glanaghy, Bonnin, and Oberlander, (2016) suggest that prenatal exposures that change 5-HT levels may act as plasticity rather than risk factor per se.…”

Are Attributes of Pregnancy and the Delivery Room Experience Related to Development of Autism? A Review of the Perinatal and Labor Risk Factors and Autism

“…Further, other studies using animal models show that preclinical findings in rodents exposed to SSRIs during development point to an increase in depression and anxiety, exhibiting alteration in social behaviors in the offspring. The data show adverse effects of maternal mental illness on pregnancy outcomes and infant neurodevelopment but are not robust enough to discourage the use of SSRIs during human pregnancy [ 66 ]. In a study by Gur et al [ 66 ], it was shown that the manipulation of serotonin during early development in both in vitro and in vivo models disturbs characteristic chemoarchitectural and electrophysiological brain features.…”

“…The data show adverse effects of maternal mental illness on pregnancy outcomes and infant neurodevelopment but are not robust enough to discourage the use of SSRIs during human pregnancy [ 66 ]. In a study by Gur et al [ 66 ], it was shown that the manipulation of serotonin during early development in both in vitro and in vivo models disturbs characteristic chemoarchitectural and electrophysiological brain features. This includes changes in raphe and callosal connections, sensory processing, myelin sheath formation, neophobia, and disrupted juvenile play behavior.…”

“…These findings indicate that serotonin homeostasis is necessary for proper brain maturation and fetal development. Although SSRIs are not contraindicated for use during pregnancy, the effects should be examined more carefully [ 66 ]. In a similar study done by Simpson et al [ 38 ], animal models were used to study the importance of serotonin homeostasis for the development of rat pups' brains.…”