Evidence map›Paper›PMID 42150307›Full record

ArticleEBioMedicine2026

Metabolomic signatures of SSRI exposure during neural differentiation and correlation of lysophosphatidylcholines with early symptoms of neurodevelopmental disorders.

Abishek Arora, Kristina Vacy, Cátia Marques, Mihai-Ovidiu Degeratu, Francesca Mastropasqua, Jenny Humphrey, Xuan Ye, Marika Oksanen, Peter Vuillermin, Anne-Louise Ponsonby and 3 more

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Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Abishek AroraCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet, and Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden; Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
Kristina VacyFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia; Melbourne School of Population and Global Health, University of Melbourne, Victoria, Australia.
Cátia MarquesDepartment of Chemistry for Life Sciences, Uppsala University, Uppsala, Sweden.
Mihai-Ovidiu DegeratuCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet, and Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden.
Francesca MastropasquaCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet, and Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden.
Jenny HumphreyCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet, and Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden.
Xuan YeCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet, and Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden.
Marika OksanenCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet, and Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden.
Peter VuillerminFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia; Murdoch Children's Research Institute, Royal Children's Hospital, and Department of Paediatrics, University of Melbourne, Victoria, Australia.
Anne-Louise PonsonbyFlorey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia; Murdoch Children's Research Institute, Royal Children's Hospital, and Department of Paediatrics, University of Melbourne, Victoria, Australia.
Ingela LanekoffDepartment of Chemistry for Life Sciences, Uppsala University, Uppsala, Sweden; Center of Excellence for the Chemical Mechanisms of Life, Uppsala University, Uppsala, Sweden.
Kristiina TammimiesCenter of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Department of Women's and Children's Health, Karolinska Institutet, and Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Region Stockholm, Stockholm, Sweden. Electronic address: kristiina.tammimies@ki.se.
Barwon Infant Study Investigator Group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSelective serotonin reuptake inhibitors (SSRIs) are often prescribed during pregnancy. Epidemiological studies examining in-utero SSRI exposure and neurodevelopmental outcomes such as autism and ADHD have produced mixed results, in part due to challenges in accounting for underlying maternal mental health conditions and other confounding factors. The molecular pathways through which SSRIs may affect early neurodevelopment remain poorly understood.

methodsWe exposed neuroepithelial stem cells derived from four human induced pluripotent stem cell (iPSC) lines to fluoxetine, citalopram, sertraline, and paroxetine. We then assessed cellular viability, reactive oxygen species (ROS) levels, mitochondrial function using adenosine triphosphate (ATP) assays, and performed high-throughput metabolomics at two timepoints: proliferation and neural differentiation stages. The key metabolic findings were validated in the in-vitro model and in a complementary population-based cohort, the Barwon Infant Study, consisting of 1074 mother-child pairs with analysed cord-blood metabolomes.

findingsSertraline and paroxetine significantly decreased ROS and ATP levels in-vitro, indicating mitochondrial alteration. Metabolomic profiling revealed consistent elevation of three lysophosphatidylcholines (LPCs 16:0, 18:0, 18:1) in cells exposed to all SSRIs except citalopram. We further observed elevated LPC levels in the cord blood of infants prenatally exposed to SSRIs compared to those who were not (LPC 16:0 sn1: β = 0.173, 95% CI = 0.011-0.334, p = 0.037; LPC 16:0 sn2: β = 0.175, 95% CI = 0.007-0.343, p = 0.042 and LPC 18:0 sn2 β = 0.174, 95% CI = 0.018-0.330, p = 0.029), with a dose-dependent correlation to autism (LPC 16:0 sn2: overall p = 0.01) and ADHD-related symptoms (LPC 16:0 sn1: overall p = 0.007; LPC 16:0 sn2: overall p = 0.002) at age two.

interpretationThese findings provide insights into SSRI-induced molecular changes in human iPSC derived neural cell cultures and highlight candidate metabolites that were validated in a clinical cohort. This may warrant their further investigation as indicators of SSRI exposure and emphasise the need for exploring prenatal SSRI exposure effects and neurodevelopmental outcomes in a wider context of other more well-established liability factors, including genetic background.

fundingVetenskapsrådet, Swedish Foundation for Strategic Research, Hjärnfonden, H.K.H. Kronprinsessan Lovisas förening för barnasjukvård, StratNeuro, Swedish Foundation for International Cooperation in Research and Higher Education, Karolinska Institutet and the European Research Council.

Indexed as

Cell DifferentiationLysophosphatidylcholinesMetabolomeMetabolomicsNeurodevelopmental DisordersNeuronsSelective Serotonin Reuptake InhibitorsBiomarkersCell LineFemaleHumansInduced Pluripotent Stem CellsMitochondriaPregnancyReactive Oxygen SpeciesBiomarkersLysophosphatidylcholinesReactive Oxygen SpeciesSelective Serotonin Reuptake InhibitorsCellular assaysClinical cohortInduced pluripotent stem cellsMetabolomicsNeurodevelopmental disordersSelective serotonin reuptake inhibitors

Identifiers

PMID42150307
PMCPMC13213235

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