Role of Serotoninergic Antidepressants in the Development of Autism Spectrum Disorders: A Systematic Review

Abstract

Autism spectrum disorders (ASDs) are one of the most common, highly heritable neurodevelopmental diseases affecting 1-2% of children under the age of 3. Although studies have implicated genetic predispositions, environmental risk factors, and maternal depression as the pathophysiology of ASD, it remains unclear. The association between antidepressant (AD) usage during pregnancy and the likelihood of ASD in children is still debatable. We carried out a systematic review to determine the relation of ASD with AD in offspring exposed to ADs in utero. We used the following terms of medical subject heading (MeSH) and keywords separately and in combination: "antidepressants," "maternal/pregnancy depression," "autism spectrum disorders/autism," and "selective serotonin reuptake inhibitors (SSRI)." Our data search was conducted on PubMed, PubMed Central, Google Scholar, and Cochrane, which resulted in 28,141 articles. We identified and eliminated duplicates and then screened 9,965 articles by title and abstract. We then applied eligibility criteria over 143 relevant articles; a quality assessment was performed, and finally we included 18 selected studies. Mothers who had taken ADs during pregnancy for at least two medication prescription cycles and children detected to have ASD from two years to 18 years of age were included. We excluded articles in languages other than English, grey literature, case reports, letters to the editor, books, documents, animal studies, and studies published before 2017. Out of 18 studies, 17 evaluated ASD as the primary outcome, and for one study, the outcome was child behavioral as well as neurodevelopmental changes. Other additional outcomes studied were attention deficit hyperactivity disorder (ADHD), preterm birth, spontaneous abortion, small for gestational age, maternal mental illness, and persistent pulmonary hypertension. After adjusting for confounding factors, in six studies, the higher correlations between ASD and ADs were eliminated. Also, paternal AD use, maternal pre-conceptional AD drug use, and maternal depression itself are additional factors that raise the incidence of ASD.

Keywords: antidepressants; autism specrum disorders; gestational age; maternal depression; pregnancy; selective serotonin reuptake inhibitors.

Figure 1. PRISMA diagram showing the study selection process

PRISMA: Preferred Reporting Items for Systematic Review and Meta-Analyses

Figure 2. Effects of perinatal SSRI exposure on the fetal brain

SSRI, selective serotonin reuptake inhibitor; 5HT, 5-hydroxy tryptamine Figure created by the authors