Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population
Background: Hippocampal volume increases throughout early development and is an important indicator of cognitive abilities and mental health. However, hippocampal development is highly vulnerable to exposures during development, as seen by smaller hippocampal volume and differential epigenetic progr...
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Elsevier
2025-03-01
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| Series: | Biological Psychiatry Global Open Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667174324001344 |
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| author | Taena Hanson Sophia Spencer Samantha A. Harker Fatoumata Barry Phoebe Burton Jennifer Beauchemin Sarah E. Mennenga B. Blair Braden Viren D'Sa Daphne Koinis-Mitchell Sean C.L. Deoni Candace R. Lewis |
| author_facet | Taena Hanson Sophia Spencer Samantha A. Harker Fatoumata Barry Phoebe Burton Jennifer Beauchemin Sarah E. Mennenga B. Blair Braden Viren D'Sa Daphne Koinis-Mitchell Sean C.L. Deoni Candace R. Lewis |
| author_sort | Taena Hanson |
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| description | Background: Hippocampal volume increases throughout early development and is an important indicator of cognitive abilities and mental health. However, hippocampal development is highly vulnerable to exposures during development, as seen by smaller hippocampal volume and differential epigenetic programming in genes implicated in mental health. However, few studies have investigated hippocampal volume in relation to the peripheral epigenome across development, and even less is known about potential genetic moderators. Therefore, in this study, we explored relationships between hippocampal volume and peripheral DNA methylation of mental health–related genes, specifically NR3C1, FKBP5, and SLC6A4, throughout early development and whether these associations were moderated by age or genotype. Methods: Bilateral hippocampal volume was computed from T2-weighted images through FreeSurfer, and DNA methylation was measured from saliva using the Illumina MethylationEPIC microarray in a pediatric population (N = 248, females = 112, meanage = 5.13 years, SDage = 3.60 years). Results: Multiple linear regression and bootstrapping analyses revealed that DNA methylation of NR3C1, FKBP5, and SLC6A4 was associated with hippocampal volume and that these relationships were moderated by age and gene-specific variants. Conclusions: These findings support the validity of peripheral DNA methylation profiles for indirectly assessing hippocampal volume and development and underscore the importance of genotype and age considerations in research. Therefore, peripheral epigenetic profiles may be a promising avenue for investigating the impacts of early-life stress on brain structure and subsequent mental health outcomes. |
| format | Article |
| id | doaj-art-ed1b39cac26244978e2f5046ca8421a3 |
| institution | Kabale University |
| issn | 2667-1743 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biological Psychiatry Global Open Science |
| spelling | doaj-art-ed1b39cac26244978e2f5046ca8421a32025-01-08T04:53:48ZengElsevierBiological Psychiatry Global Open Science2667-17432025-03-0152100421Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric PopulationTaena Hanson0Sophia Spencer1Samantha A. Harker2Fatoumata Barry3Phoebe Burton4Jennifer Beauchemin5Sarah E. Mennenga6B. Blair Braden7Viren D'Sa8Daphne Koinis-Mitchell9Sean C.L. Deoni10Candace R. Lewis11Department of Psychology, Arizona State University, Tempe, ArizonaDepartment of Psychology, Arizona State University, Tempe, ArizonaSchool of Life Sciences, Arizona State University, Tempe, ArizonaWarren Alpert Medical School of Brown University, Providence, Rhode IslandWarren Alpert Medical School of Brown University, Providence, Rhode IslandWarren Alpert Medical School of Brown University, Providence, Rhode IslandSchool of Life Sciences, Arizona State University, Tempe, ArizonaCollege of Health Solutions, Arizona State University, Tempe, ArizonaMaternal, Newborn, and Child Health Discovery & Tools, Bill & Melinda Gates Foundation; Seattle, Washington; Providence, Rhode IslandMaternal, Newborn, and Child Health Discovery & Tools, Bill & Melinda Gates Foundation; Seattle, Washington; Providence, Rhode IslandMaternal, Newborn, and Child Health Discovery & Tools, Bill & Melinda Gates Foundation; Seattle, Washington; Providence, Rhode Island; Advanced Baby Imaging Laboratory, Rhode Island Hospital, Providence, Rhode IslandDepartment of Psychology, Arizona State University, Tempe, Arizona; School of Life Sciences, Arizona State University, Tempe, Arizona; Neurogenomics, Translational Genomics Research Institute, Phoenix, Arizona; Address correspondence to Candace R. Lewis, Ph.D.Background: Hippocampal volume increases throughout early development and is an important indicator of cognitive abilities and mental health. However, hippocampal development is highly vulnerable to exposures during development, as seen by smaller hippocampal volume and differential epigenetic programming in genes implicated in mental health. However, few studies have investigated hippocampal volume in relation to the peripheral epigenome across development, and even less is known about potential genetic moderators. Therefore, in this study, we explored relationships between hippocampal volume and peripheral DNA methylation of mental health–related genes, specifically NR3C1, FKBP5, and SLC6A4, throughout early development and whether these associations were moderated by age or genotype. Methods: Bilateral hippocampal volume was computed from T2-weighted images through FreeSurfer, and DNA methylation was measured from saliva using the Illumina MethylationEPIC microarray in a pediatric population (N = 248, females = 112, meanage = 5.13 years, SDage = 3.60 years). Results: Multiple linear regression and bootstrapping analyses revealed that DNA methylation of NR3C1, FKBP5, and SLC6A4 was associated with hippocampal volume and that these relationships were moderated by age and gene-specific variants. Conclusions: These findings support the validity of peripheral DNA methylation profiles for indirectly assessing hippocampal volume and development and underscore the importance of genotype and age considerations in research. Therefore, peripheral epigenetic profiles may be a promising avenue for investigating the impacts of early-life stress on brain structure and subsequent mental health outcomes.http://www.sciencedirect.com/science/article/pii/S2667174324001344DNA methylationEpigeneticsHippocampusNeuroimagingPediatrics |
| spellingShingle | Taena Hanson Sophia Spencer Samantha A. Harker Fatoumata Barry Phoebe Burton Jennifer Beauchemin Sarah E. Mennenga B. Blair Braden Viren D'Sa Daphne Koinis-Mitchell Sean C.L. Deoni Candace R. Lewis Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population Biological Psychiatry Global Open Science DNA methylation Epigenetics Hippocampus Neuroimaging Pediatrics |
| title | Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population |
| title_full | Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population |
| title_fullStr | Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population |
| title_full_unstemmed | Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population |
| title_short | Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population |
| title_sort | peripheral dna methylation of cortisol and serotonin related genes predicts hippocampal volume in a pediatric population |
| topic | DNA methylation Epigenetics Hippocampus Neuroimaging Pediatrics |
| url | http://www.sciencedirect.com/science/article/pii/S2667174324001344 |
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