Prenatal SSRI Exposure Increases the Risk of Autism in Rodents via Aggravated Oxidative Stress and Neurochemical Changes in the Brain

Abstract

The mechanisms underlying selective serotonin reuptake inhibitor (SSRI) use during pregnancy as a major autism risk factor are unclear. Here, brain neurochemical changes following fluoxetine exposure and in an autism model were compared to determine the effects on autism risk. The study was performed on neonatal male western albino rats which were divided into Groups one (control), two (propionic acid [PPA]-induced autism model), and three (prenatal SSRI-exposed newborn rats whose mothers were exposed to 5 mg/kg of fluoxetine over gestation days 10–20). SSRI (fluoxetine) induced significant neurochemical abnormalities in the rat brain by increasing lipid peroxide (MDA), Interferon-gamma (IFN-γ), and caspase-3 levels and by depleting Glutathione (GSH), Glutathione S-transferases (GST), Catalase, potassium (K+), and Creatine kinase (CK) levels, similarly to what has been discovered in the PPA model of autism when compared with control. Prenatal fluoxetine exposure plays a significant role in asset brain damage in newborns; further investigation of fluoxetine as an autism risk factor is thus warranted.

Does prenatal exposure to antidepressants cause autism? - literature review

“…This theory may be supported by studies showing impaired levels of serotonin and its metabolites, including 5-hydroxyindoleacetic acid (5-HIAA), in the blood and cerebrospinal fluid of children on the autism spectrum [27,28]. Bhat et al [10] published a paper examining the prenatal effects of fluoxetine on brain neurochemical changes in rats, confirming the link in several mechanisms suspected to be involved in the etiopathogenesis of autism such as oxidative stress, nervous system inflammation, altered neurochemistry, apoptosis and impaired energy metabolism.…”

“…A higher incidence of ASD has been observed in children with a psychiatrically burdened family history [7,8], and male gender, toxins, low socioeconomic status or obstetric complications, among other factors, have also been cited as contributors to autism spectrum disorders [9]. Researchers pose many theories about the pathogenesis of ASD, such as oxidative stress, damage to the nervous system during fetal development, and abnormalities in brain neurochemistry [10,11].…”

The Autism Spectrum Disorder and Its Possible Origins in Pregnancy

“…These drugs cross the placental barrier, representing a significant risk factor for ASD [ 86 , 87 ]. Using an animal model of prenatal SSRI exposure, Bhat and colleagues identified that this medication induces biochemical changes in the brains of rats [ 88 ]. This includes lipid peroxidation, an increase in inflammatory cytokines, and apoptotic proteins such as Interferon-gamma (IFN-γ) and caspase-3, respectively [ 88 ].…”

“…Using an animal model of prenatal SSRI exposure, Bhat and colleagues identified that this medication induces biochemical changes in the brains of rats [ 88 ]. This includes lipid peroxidation, an increase in inflammatory cytokines, and apoptotic proteins such as Interferon-gamma (IFN-γ) and caspase-3, respectively [ 88 ]. Additionally, the use of SSRI during pregnancy resulted in a reduction of antioxidant molecules in the brain, such as glutathione (GSH), glutathione S-transferases (GST), and catalase [ 88 ].…”

“…This includes lipid peroxidation, an increase in inflammatory cytokines, and apoptotic proteins such as Interferon-gamma (IFN-γ) and caspase-3, respectively [ 88 ]. Additionally, the use of SSRI during pregnancy resulted in a reduction of antioxidant molecules in the brain, such as glutathione (GSH), glutathione S-transferases (GST), and catalase [ 88 ]. These alterations may represent potential mechanisms through which SSRI use during pregnancy increases the risk of ASD.…”