Maternal stress, cord blood zinc and attention deficit hyperactivity disorder
Abstract Zinc regulates dopaminergic signaling, and reduced serum zinc levels have been reported in individuals with ADHD. However, genetic associations between zinc and ADHD remain unclear. We examined this link using large-scale GWAS and molecular analyses across three cohorts: iPSYCH (14,584 ADHD...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | npj Mental Health Research |
| Online Access: | https://doi.org/10.1038/s44184-025-00149-3 |
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| author | Nagahide Takahashi Tomoko Nishimura Akemi Okumura Toshiki Iwabuchi Taeko Harada Md Shafiur Rahman Yoko Nomura Jeffrey H. Newcorn Kenji J. Tsuchiya |
| author_facet | Nagahide Takahashi Tomoko Nishimura Akemi Okumura Toshiki Iwabuchi Taeko Harada Md Shafiur Rahman Yoko Nomura Jeffrey H. Newcorn Kenji J. Tsuchiya |
| author_sort | Nagahide Takahashi |
| collection | DOAJ |
| description | Abstract Zinc regulates dopaminergic signaling, and reduced serum zinc levels have been reported in individuals with ADHD. However, genetic associations between zinc and ADHD remain unclear. We examined this link using large-scale GWAS and molecular analyses across three cohorts: iPSYCH (14,584 ADHD cases and 22,492 controls), FAMHES (n = 1798), and the Hamamatsu Birth Cohort (n = 726). Two-sample Mendelian randomization revealed bidirectional associations between low serum zinc levels and ADHD diagnosis. Genetic correlation and polygenic risk score analyses supported this association. In the birth cohort, lower cord blood zinc were associated with higher ADHD symptom scores at ages 8–9. Zinc levels negatively correlated with IL-6 and maternal depressive symptoms. Directed acyclic graph analysis indicated that maternal stress increased IL-6, which reduced fetal zinc levels, linking to ADHD symptoms. These findings suggest low prenatal zinc may contribute to ADHD pathophysiology in genetically vulnerable children, potentially mediated by maternal stress and inflammation. |
| format | Article |
| id | doaj-art-a8aa8c372f674d628efd55efdb8c61de |
| institution | Kabale University |
| issn | 2731-4251 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Mental Health Research |
| spelling | doaj-art-a8aa8c372f674d628efd55efdb8c61de2025-08-20T03:46:25ZengNature Portfolionpj Mental Health Research2731-42512025-08-01411410.1038/s44184-025-00149-3Maternal stress, cord blood zinc and attention deficit hyperactivity disorderNagahide Takahashi0Tomoko Nishimura1Akemi Okumura2Toshiki Iwabuchi3Taeko Harada4Md Shafiur Rahman5Yoko Nomura6Jeffrey H. Newcorn7Kenji J. Tsuchiya8Department of Developmental Disorders, National Center of Neurology and PsychiatryResearch Center for Child Mental Development, Hamamatsu University School of MedicineResearch Center for Child Mental Development, Hamamatsu University School of MedicineResearch Center for Child Mental Development, Hamamatsu University School of MedicineResearch Center for Child Mental Development, Hamamatsu University School of MedicineResearch Center for Child Mental Development, Hamamatsu University School of MedicineQueens College and Graduate Center, City University of New YorkDepartment of Child and Adolescent Psychiatry, Ichan School of Medicine at Mount SinaiResearch Center for Child Mental Development, Hamamatsu University School of MedicineAbstract Zinc regulates dopaminergic signaling, and reduced serum zinc levels have been reported in individuals with ADHD. However, genetic associations between zinc and ADHD remain unclear. We examined this link using large-scale GWAS and molecular analyses across three cohorts: iPSYCH (14,584 ADHD cases and 22,492 controls), FAMHES (n = 1798), and the Hamamatsu Birth Cohort (n = 726). Two-sample Mendelian randomization revealed bidirectional associations between low serum zinc levels and ADHD diagnosis. Genetic correlation and polygenic risk score analyses supported this association. In the birth cohort, lower cord blood zinc were associated with higher ADHD symptom scores at ages 8–9. Zinc levels negatively correlated with IL-6 and maternal depressive symptoms. Directed acyclic graph analysis indicated that maternal stress increased IL-6, which reduced fetal zinc levels, linking to ADHD symptoms. These findings suggest low prenatal zinc may contribute to ADHD pathophysiology in genetically vulnerable children, potentially mediated by maternal stress and inflammation.https://doi.org/10.1038/s44184-025-00149-3 |
| spellingShingle | Nagahide Takahashi Tomoko Nishimura Akemi Okumura Toshiki Iwabuchi Taeko Harada Md Shafiur Rahman Yoko Nomura Jeffrey H. Newcorn Kenji J. Tsuchiya Maternal stress, cord blood zinc and attention deficit hyperactivity disorder npj Mental Health Research |
| title | Maternal stress, cord blood zinc and attention deficit hyperactivity disorder |
| title_full | Maternal stress, cord blood zinc and attention deficit hyperactivity disorder |
| title_fullStr | Maternal stress, cord blood zinc and attention deficit hyperactivity disorder |
| title_full_unstemmed | Maternal stress, cord blood zinc and attention deficit hyperactivity disorder |
| title_short | Maternal stress, cord blood zinc and attention deficit hyperactivity disorder |
| title_sort | maternal stress cord blood zinc and attention deficit hyperactivity disorder |
| url | https://doi.org/10.1038/s44184-025-00149-3 |
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