Adolescent depression, childhood maltreatment, and the immune system; a role for epigenetic aging?
Background: Childhood maltreatment is a major risk factor for the development of depression, as well as for imbalances in the immune system, including chronic low-grade inflammation. Less is known about potential immune imbalances in adolescent depression and the role of childhood maltreatment. Furt...
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Elsevier
2025-10-01
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| Series: | Brain, Behavior, & Immunity - Health |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666354625001383 |
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| author | Marieke S. Tollenaar Nicole Creasey Mirjam C.M. Wever Karen Knipping Johan Garssen Lisanne E.A.M. van Houtum Wilma G.M. Wentholt Loes Janssen Elad Lax Bernet M. Elzinga |
| author_facet | Marieke S. Tollenaar Nicole Creasey Mirjam C.M. Wever Karen Knipping Johan Garssen Lisanne E.A.M. van Houtum Wilma G.M. Wentholt Loes Janssen Elad Lax Bernet M. Elzinga |
| author_sort | Marieke S. Tollenaar |
| collection | DOAJ |
| description | Background: Childhood maltreatment is a major risk factor for the development of depression, as well as for imbalances in the immune system, including chronic low-grade inflammation. Less is known about potential immune imbalances in adolescent depression and the role of childhood maltreatment. Furthermore, accelerated epigenetic aging may contribute to the development of inflammation, but has never been examined in the context of adolescent depression. Methods: We investigated childhood maltreatment, inflammation, and epigenetic aging in 78 healthy adolescents and 33 adolescents with a clinically diagnosed depressive disorder. Childhood maltreatment was assessed via self-report, and inflammatory markers (CRP, IL-1β, IL-6, IL-8, sIgA, and TNF-α) were analyzed in saliva. DNA methylation was analyzed in a subsample (n = 48) of both healthy and unmedicated, depressed adolescents to estimate epigenetic age (Horvath and PedBE clocks). Results: The MANOVA showed that depression was significantly associated with the immune markers, but not with epigenetic aging. Post-hoc tests suggested however that IL-8 levels were reduced, while none of the other markers were affected. Unexpectedly, childhood (emotional) maltreatment was significantly associated with epigenetic age deceleration on the PedBE clock (p = .01), and not with inflammation. The inflammatory markers were not associated with either of the epigenetic age clocks. Conclusions: Our results contrast with previous literature in adults, indicating that epigenetic age acceleration and inflammation are not unequivocal indicators of depression and childhood trauma in adolescents. Future studies with larger, more heterogeneous samples should investigate under which circumstances increased or decreased levels of these biological markers indicate vulnerability for health-related outcomes. Better understanding of these mechanisms in adolescence may help to develop appropriate interventions supporting a healthy development of children who experienced maltreatment or depression. |
| format | Article |
| id | doaj-art-53d3554c42d74334a0e57d49da7d6550 |
| institution | Matheson Library |
| issn | 2666-3546 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain, Behavior, & Immunity - Health |
| spelling | doaj-art-53d3554c42d74334a0e57d49da7d65502025-07-31T04:53:56ZengElsevierBrain, Behavior, & Immunity - Health2666-35462025-10-0148101080Adolescent depression, childhood maltreatment, and the immune system; a role for epigenetic aging?Marieke S. Tollenaar0Nicole Creasey1Mirjam C.M. Wever2Karen Knipping3Johan Garssen4Lisanne E.A.M. van Houtum5Wilma G.M. Wentholt6Loes Janssen7Elad Lax8Bernet M. Elzinga9Leiden University, Institute of Psychology and Leiden Institute for Brain and Cognition, the Netherlands; Corresponding author. Institute of Psychology, Leiden University, the Netherlands P.O. Box 9555, 2300 RB Leiden, the Netherlands.Faculty of Education, PEDAL Research Centre, University of Cambridge, Cambridge, UKLeiden University, Institute of Psychology and Leiden Institute for Brain and Cognition, the NetherlandsUtrecht Institute for Pharmaceutical Sciences, Division Pharmacology, Utrecht University, the NetherlandsUtrecht Institute for Pharmaceutical Sciences, Division Pharmacology, Utrecht University, the Netherlands; Danone Nutricia Research, Utrecht, the NetherlandsDepartment of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Centre–Sophia, Rotterdam, the NetherlandsLeiden University, Institute of Psychology and Leiden Institute for Brain and Cognition, the NetherlandsLeiden University, Institute of Psychology and Leiden Institute for Brain and Cognition, the NetherlandsAriel University, Department of Molecular Biology, IsraelLeiden University, Institute of Psychology and Leiden Institute for Brain and Cognition, the NetherlandsBackground: Childhood maltreatment is a major risk factor for the development of depression, as well as for imbalances in the immune system, including chronic low-grade inflammation. Less is known about potential immune imbalances in adolescent depression and the role of childhood maltreatment. Furthermore, accelerated epigenetic aging may contribute to the development of inflammation, but has never been examined in the context of adolescent depression. Methods: We investigated childhood maltreatment, inflammation, and epigenetic aging in 78 healthy adolescents and 33 adolescents with a clinically diagnosed depressive disorder. Childhood maltreatment was assessed via self-report, and inflammatory markers (CRP, IL-1β, IL-6, IL-8, sIgA, and TNF-α) were analyzed in saliva. DNA methylation was analyzed in a subsample (n = 48) of both healthy and unmedicated, depressed adolescents to estimate epigenetic age (Horvath and PedBE clocks). Results: The MANOVA showed that depression was significantly associated with the immune markers, but not with epigenetic aging. Post-hoc tests suggested however that IL-8 levels were reduced, while none of the other markers were affected. Unexpectedly, childhood (emotional) maltreatment was significantly associated with epigenetic age deceleration on the PedBE clock (p = .01), and not with inflammation. The inflammatory markers were not associated with either of the epigenetic age clocks. Conclusions: Our results contrast with previous literature in adults, indicating that epigenetic age acceleration and inflammation are not unequivocal indicators of depression and childhood trauma in adolescents. Future studies with larger, more heterogeneous samples should investigate under which circumstances increased or decreased levels of these biological markers indicate vulnerability for health-related outcomes. Better understanding of these mechanisms in adolescence may help to develop appropriate interventions supporting a healthy development of children who experienced maltreatment or depression.http://www.sciencedirect.com/science/article/pii/S2666354625001383DepressionInflammationEpigenetic agingChildhood maltreatmentImmune system |
| spellingShingle | Marieke S. Tollenaar Nicole Creasey Mirjam C.M. Wever Karen Knipping Johan Garssen Lisanne E.A.M. van Houtum Wilma G.M. Wentholt Loes Janssen Elad Lax Bernet M. Elzinga Adolescent depression, childhood maltreatment, and the immune system; a role for epigenetic aging? Brain, Behavior, & Immunity - Health Depression Inflammation Epigenetic aging Childhood maltreatment Immune system |
| title | Adolescent depression, childhood maltreatment, and the immune system; a role for epigenetic aging? |
| title_full | Adolescent depression, childhood maltreatment, and the immune system; a role for epigenetic aging? |
| title_fullStr | Adolescent depression, childhood maltreatment, and the immune system; a role for epigenetic aging? |
| title_full_unstemmed | Adolescent depression, childhood maltreatment, and the immune system; a role for epigenetic aging? |
| title_short | Adolescent depression, childhood maltreatment, and the immune system; a role for epigenetic aging? |
| title_sort | adolescent depression childhood maltreatment and the immune system a role for epigenetic aging |
| topic | Depression Inflammation Epigenetic aging Childhood maltreatment Immune system |
| url | http://www.sciencedirect.com/science/article/pii/S2666354625001383 |
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