A new study from Karolinska Institutet shows that different SSRI medications affect metabolic processes in developing nerve cells in distinct ways. Alterations in energy metabolism, oxidative stress and lipid profiles suggest that these drugs are not biologically equivalent. The findings provide new insights into biological mechanisms but do not show that SSRIs cause autism, ADHD or other neurodevelopmental disorders.
The study was conducted at the Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND) in collaboration with researchers in Australia and has been published in the scientific journal eBioMedicine.
SSRI use during pregnancy
SSRIs are widely used to treat depression and anxiety, including during pregnancy. Treating mental health conditions is important for both maternal and child health, and current clinical guidelines recommend continued SSRI treatment when medically indicated. At the same time, previous studies following children exposed to SSRIs have shown mixed results. One reason is the difficulty of separating potential drug effects from the effects of underlying maternal mental health, as well as shared genetic and environmental factors.
"Through our cell-based experiments, we can study how SSRIs affect human nerve cells at an early stage of brain development, without the influence of maternal depression or anxiety. At the same time, we are careful not to interpret findings from population data as causal. Mental health conditions themselves, as well as genetic and environmental factors shared between mother and child, are important parts of the overall picture," says Abishek Arora , first author of the study and postdoctoral researcher at Karolinska Institutet.
SSRIs studied in human nerve cells
In the study, stem cell-derived human nerve cells were exposed to four commonly used SSRIs-fluoxetine, citalopram, sertraline and paroxetine-during the early stages of neuronal development. The researchers then analysed cellular energy metabolism, oxidative stress and metabolic profiles.
"We observed that several of the drugs affected cellular processes linked to energy metabolism and oxidative stress, and that this was accompanied by reproducible changes in certain lipid metabolites," says Abishek Arora.
In particular, three lipids in the lysophosphatidylcholine (LPC) group showed consistent changes across multiple experiments and cell lines. These effects differed between the drugs. The strongest metabolic effects were observed after exposure to sertraline and paroxetine, while fluoxetine showed more limited changes. The effects of citalopram were the least pronounced. This suggests that different SSRIs may have distinct biological profiles, underscoring that they are not biologically equivalent and should be studied individually.
Similar lipid patterns in newborns
To explore possible clinical relevance, the researchers also analysed cord blood from a large population-based study in Australia. Elevated levels of the same LPC lipids were found in children whose mothers reported SSRI use.
"Identifying similar lipid patterns in both human nerve cells and cord blood strengthens the biological relevance of our findings and suggests that these changes are linked to SSRI exposure," says Abishek Arora.
Higher levels of certain LPC lipids were associated with early behaviours related to autism and ADHD, based on assessments at two years of age. However, these associations were not observed at later follow-up, indicating that the links were limited to early traits rather than diagnoses.
The researchers emphasise that the findings do not mean that SSRIs cause autism, ADHD or other neurodevelopmental disorders. Instead, the lipid changes should be seen as biological patterns that may be sensitive to exposure.
"Our findings do not change current clinical recommendations. Treating depression during pregnancy remains very important," says Kristiina Tammimies , senior author of the study and group leader at the Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND).
Next steps
The researchers highlight the need for further studies to better understand how these lipid-related changes interact with genetic factors, maternal mental health and other prenatal influences. Larger and more genetically informed studies will be important to determine how these biological patterns relate to variation in children's development.
Original article
Full reference:
Arora A, Vacy K, Marques C, Degeratu M‑O, Mastropasqua F, Humphrey J, Ye X, Oksanen M, the Barwon Infant Study Investigator Group, Vuillermin P, Ponsonby A‑L, Lanekoff I, Tammimies K. Metabolomic signatures of SSRI exposure during neural differentiation and correlation of lysophosphatidylcholines with early symptoms of neurodevelopmental disorders. eBioMedicine. 2026.
Link:
https://www.sciencedirect.com/science/article/pii/S2352396426001738
