Developmental effects of SSRIs: lessons learned from animal studies

Borue, Xenia; Chen, John; Condron, Barry

doi:10.1016/j.ijdevneu.2007.06.003

Cited by 56 publications

(38 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to evidence for gross birth defects, there has been evidence from animal studies for over a decade that SSRIs can lead to abnormalities in cerebral architecture [85][86][87]. We have not found any studies demonstrating normal brain architecture.…”

Section: Potential Mechanismscontrasting

confidence: 52%

Links between serotonin reuptake inhibition during pregnancy and neurodevelopmental delay/spectrum disorders: A systematic review of epidemiological and physiological evidence

Healy

Noury

Mangin

2016

JRS

View full text Add to dashboard Cite

Abstract. OBJECTIVE:To investigate possible linkages between neurodevelopmental delay and neurodevelopmental spectrum disorders and exposure to medication with effects on serotonin reuptake inhibition during pregnancy. METHODS: We systematically reviewed the epidemiological literature for studies bearing on this relationship in children born with neurodevelopmental spectrum disorder and related conditions, as well as animal studies giving serotonin reuptake inhibitors to pregnant animals and in addition reviewed the literature for proposals as to possible mechanisms that might link effects on serotonin reuptake with cognitive changes post-partum.The epidemiological studies were analysed to produce Forest plots to illustrate possible relations. RESULTS: The odds ratio of Autistic Spectrum or related Disorders in children born to women taking serotonin reuptake inhibiting antidepressants during pregnancy in case control studies was 1.95 (95% C.I. 1.63, 2.34) and in prospective cohort studies was 1.96 (95% C.I. 1.33, 2.90).CONCLUSIONS: There appears to be a link between serotonin reuptake inhibition in pregnancy and developmental delay and spectrum disorders in infancy leading to cognitive difficulties in childhood. More work needs to be done to establish more precisely the nature of the difficulties and possible mechanisms through which this link might be mediated.Keywords: Autism spectrum disorder, neurodevelopmental delay, neurodevelopmental spectrum disorders, antidepressants, serotonin reuptake inhibitors, pregnancy BackgroundThe clinical syndrome later called autism was first reported in 1943 [1]. The first studies of the prevalence of autism or autistic disorder (AD) in the 1960s pointed to a rate of 4 per 10,000 [2,3]. Later studies indicated the existence of a spectrum of disorders, and brought the term autistic spectrum disorder (ASD) into being in the mid-1990s 126 D. Healy et al. / Link between SSRIs in pregnancy and autistic spectrum disordersand ASD also now includes other syndromes such as Pervasive Developmental Disorder and Aspergers Disorder so that it is difficult to know how closely current clinical usage of an ASD diagnosis maps onto AD and ASD as first conceived. Current estimates are that ASD in research studies occurs at a rate of more than 1 in 70 children [5,6].Kanner autism was recognized before the emergence of modern psychotropic drugs, and given its submergence in ASD, it may not now be possible to establish whether it is linked to commonly used psychotropic medications. A number of clinical pictures linked to psychotropic drug use, fetal anticonvulsant syndrome (FACS), fetal valproate syndrome (FVS), and fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorder (FASD) have been described since 1970. Aside from the link to treatment, the clinical features of these disorders are consistent with a diagnosis of ASD but not Kanner autism. A growing number of epidemiological studies point to an increase in rates of ASD. This translates popularly into concerns about a change in the p...

show abstract

Section: Potential Mechanismscontrasting

confidence: 52%

Links between serotonin reuptake inhibition during pregnancy and neurodevelopmental delay/spectrum disorders: A systematic review of epidemiological and physiological evidence

Healy

Noury

Mangin

2016

JRS

View full text Add to dashboard Cite

show abstract

“…For instance, dysregulation of the finely tuned spatial and temporal balance between 5-HT production and breakdown may have fatal consequences for the developing embryo. Indeed, for several years it has been a matter of discussion of whether or not pharmacological intervention aimed at 5-HT homeostasis, such as selective serotonin reuptake inhibitors, during pregnancy has teratogenic effects (45,46).…”

Section: Discussionmentioning

confidence: 99%

Monoamine Oxidase A Expression Is Vital for Embryonic Brain Development by Modulating Developmental Apoptosis

Wang

Borchert

Ugun-Klusek

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Monoamine oxidases (MAO-A, MAO-B) metabolize biogenic amines and have been implicated in neuronal apoptosis. Although apoptosis is an important process in embryo development, the role of MAO isoenzymes has not been investigated in detail. We found that expression of MAO-A and MAO-B can be detected early on during embryo development. Expression levels remained constant until around midgestation but then dropped to almost undetectable levels toward birth. Similar expression kinetics were observed in the brain. Isoform-specific expression silencing of MAO-A mediated by siRNA during in vitro embryogenesis induced developmental defects, as indicated by a reduction of the crown rump length and impaired cerebral development. These alterations were paralleled by elevated serotonin levels. Similar abnormalities were observed when embryos were cultured in the presence of the MAO-A inhibitor clorgyline or when the transcriptional inhibitor of MAO-A expression R1 was overexpressed. In contrast, no such alterations were detected when expression of MAO-B was knocked down. To explore the underlying mechanisms for the developmental abnormalities in MAO-A knockdown embryos, we quantified the degree of developmental apoptosis in the developing brain. MAO-A knockdown reduced the number of apoptotic cells in the neuroepithelium, which coincided with impaired activation of caspases 3 and 9. Moreover, we observed reduced cyclin D1 levels as an indicator of impaired cell proliferation in MAO-A knockdown embryos. This data highlights MAO-A as a vital regulator of embryonic brain development.

show abstract

“…However, SSRIs cross the placenta and have been shown to accumulate in the fetal brain of sheep and rats [2,37]. In addition, perinatal exposures to SSRI and tricyclic antidepressants have a significant and long-term impact on the central serotonergic system [13,38,39,40]. These changes in serotonergic function likely influence many aspects of brain development and neural plasticity, both directly, such as through alterations in the serotonin transporter (SERT) [40], and indirectly, through alterations in other physiological systems such as the hypothalamic-pituitary-adrenal axis [41].…”

Section: Perinatal Exposure To Ssris and Neural Development: Preclinimentioning

confidence: 99%

“…It should also be noted that most preclinical research with regards to the effects of perinatal antidepressant medication exposure on neurobehavioral outcomes has investigated the effects of these antidepressant medications on offspring of healthy mothers [13,38,39,40,43]. However, because the primary action of antidepressant medications is to alleviate depressive symptoms, more preclinical research is needed on the impact of SSRIs on development in offspring subject to maternal adversity.…”

Section: Perinatal Exposure To Ssris and Neural Development: Preclinimentioning

confidence: 99%

Perinatal Selective Serotonin Reuptake Inhibitor Exposure: Impact on Brain Development and Neural Plasticity

Pawluski¹

2011

Neuroendocrinology

View full text Add to dashboard Cite

Selective serotonin reuptake inhibitor (SSRI) medications are the most common antidepressant treatment used during pregnancy and the postpartum period. Up to 10% of pregnant women are prescribed SSRIs. Serotonin plays an integral part in neurodevelopment, and questions have been raised about the placental transfer of SSRIs and the effects of preventing reuptake of presynaptic serotonin on fetal neurodevelopment. Preclinical data is beginning to document a role of early exposure to SSRIs in long-term developmental outcomes related to a number of brain regions, such as the hippocampus, cortex and cerebellum. To date, the majority of preclinical work has investigated the developmental effects of SSRIs in the offspring of healthy mothers; however, more research is needed on the effects of these medications in the face of maternal adversity. This minireview will highlight emerging evidence from clinical and preclinical studies investigating the impact of perinatal SSRI exposure on brain development and neural plasticity.

show abstract

Developmental effects of SSRIs: lessons learned from animal studies

Cited by 56 publications

References 65 publications

Links between serotonin reuptake inhibition during pregnancy and neurodevelopmental delay/spectrum disorders: A systematic review of epidemiological and physiological evidence

Links between serotonin reuptake inhibition during pregnancy and neurodevelopmental delay/spectrum disorders: A systematic review of epidemiological and physiological evidence

Monoamine Oxidase A Expression Is Vital for Embryonic Brain Development by Modulating Developmental Apoptosis

Perinatal Selective Serotonin Reuptake Inhibitor Exposure: Impact on Brain Development and Neural Plasticity

Contact Info

Product

Resources

About