SSRIs in pregnancy could change the child's neurobiology in the long term

The placenta and endometrium react to maternal infections and antidepressants with immunological changes that can influence neurodevelopment.

SSRIs may increase inflammatory processes and thereby affect brain development

A recent study published in the journal Brain, Behavior, and Immunity reports that prenatal exposure to antidepressants increases the risk for neurodevelopmental changes, including those leading to autism.1,2

A team from the University of Virginia (UVA) used a murine autism model to explore how the all-important fetomaternal organ (mainly consisting of the decidua and placenta) responds to inflammatory states and altered serotonergic tone.

Previous research had already shown this: Infections, autoimmune diseases and other conditions that affect the immune status of the mother during pregnancy can affect neurodevelopment. Maternal immune activation leads to an acute inflammatory response at the decidua and placenta. The scientists found that this was strongly dominated by interferon signalling, to the detriment of normal developmental transcriptional programmes. 

Serotonin is a potent immune cell modulator that regulates almost all immune cells in response to inflammation.3 The researchers found that inflammation alone and in combination with SSRIs altered serotonin levels in the placenta, but in the opposite direction: dams exposed to immunological stress during pregnancy showed a completely different signature in the placenta when given SSRIs than mothers not given SSRIs.

Normally, the changes in the transcriptome were reversed when the inflammatory response subsided. However, under increased immune response, there was disturbed sex-specific gene expression and increased serotonin levels. Inflammation-prone offspring also exhibited sex-specific behavioural changes comparable to those seen in humans with autism, such as impaired communication and reduced interest in social interactions.

In mothers that faced an immunological challenge during pregnancy, the combination with pharmacological inhibition of serotonin reuptake led to a particularly strong inflammatory response at the placenta. This potentiated the changes in the neurobiology of the offspring, which equally affected the immune and serotonin signalling pathways.

The rise in autism over the last 20 years

"Our findings may help explain the rise in autism prevalence over the last 20 years, as this period coincides with the introduction of widespread SSRI use in developed countries," says research group leader John Lukens, Ph.D., of the UVA's Department of Neuroscience and its Center for Brain Immunology and Glia (BIG) and the UVA Brain Institute.2

SSRIs are prescribed to 80% of pregnant women for whom antidepressants are deemed necessary.2 Although there is evidence that SSRIs may increase the risk of preterm birth and neurological and other health problems in children, this association has not been extensively studied in the past and further studies would be urgently needed. The effects could be passed down through generations.

Autism rates have risen dramatically, according to a 2022 report in JAMA Pediatrics: about 1 in 30 children and adolescents aged 3 to 17 in the US (3.3%) received an autism spectrum disorder (ASD) diagnosis in 2020. Among young Americans, ASDs have increased by 53% since 2017. The causes for this remains poorly understood.4,5 Recent issues such as the dangers of clamping the umbilical cord immediately after birth (now a common procedure) are also important to investigate in this regard, added biochemist PhD Eileen Nicole Simon, in a commentary.6,7

  1. Zengeler, K. E. et al. SSRI treatment modifies the effects of maternal inflammation on in utero physiology and offspring neurobiology. Brain, Behavior, and Immunity 108, 80–97 (2023).
  2. Antidepressant Use and Infection During Pregnancy Linked to Neurodevelopmental Disorders. Neuroscience News (2022).
  3. Kanova, M. & Kohout, P. Serotonin—Its Synthesis and Roles in the Healthy and the Critically Ill. Int J Mol Sci 22, 4837 (2021).
  4. Li, Q. et al. Prevalence of Autism Spectrum Disorder Among Children and Adolescents in the United States From 2019 to 2020. JAMA Pediatrics 176, 943–945 (2022).
  5. 1 in 30 U.S. Kids Diagnosed With Autism in 2020 — What’s Behind the Surge? Children’s Health Defense.
  6. The Brain Disorder in Autism: Where and how does it happen?.
  7. Eileen Nicole Simon, RN, PhD (Biochemistry) [@HearingSpeech]. Twitter (2023).