DNA methylation age acceleration, depression and anxiety: evidence from a longitudinal adolescent cohort…

Abstract

BackgroundDNA methylation (DNAm) based age acceleration is an indicator of biological ageing. However, it is unclear how age acceleration is linked to mental health in adolescents. We examined the longitudinal associations between DNAm age acceleration and depression and anxiety in adolescents. We also triangulated the evidence using Mendelian Randomisation (MR).

MethodsWe analysed a subsample of adolescents (n=261) from a London-based adolescent cohort study. DNAm profile was generated from saliva samples collected at ages 11-12 years. DNAm age acceleration measures were derived from Horvath, PhenoAge, and PedBE clocks. Depressive and anxiety symptoms were measured at ages 13-15 years, using the Patient Health Questionnaire and Generalised Anxiety Disorder scale, respectively. The associations between DNAm age acceleration and depressive and anxiety symptoms were assessed using logistic regression. We also conducted a two-sample MR to investigate the potential causal relationship between Horvath and PhenoAge acceleration and depression and anxiety.

ResultsWe found that PhenoAge age acceleration was associated with higher severity levels of depressive symptoms (OR=1.04, 95% CI 1.01, 1.08) and clinically significant depressive symptoms (OR=1.05, 95% CI 1.01, 1.10). None of these three clocks was associated with anxiety outcomes. MR suggested a potential causal relationship between PhenoAge age acceleration and depression (Inverse variance weighted OR = 1.01, 95% CI 1.00, 1.02).

ConclusionsPhenoAge acceleration at ages 11-12 years was associated with depressive symptoms at ages 13-15 years. The association patterns are consistent between longitudinal and MR analyses. PhenoAge acceleration may represent a potential early biomarker for subsequent depressive symptoms in adolescents.

Sleep and the Daytime Course of Anhedonia in Adolescent Depression: An Ecological Momentary Assessment Study
Hannah E. Marshall, Linda Nduka, Tahjanee Givens +6
PsyArXiv6 Nov 2026PreprintAll rights reservedFull textPsychiatry & mental healthOSF
Association of low parental mental health literacy with adolescent depression and anxiety: a large-scale cross-sectional study in Guangdong, China
Xing Wang, Qing Wan, Yanbin Liu +8
Scientific Reports17 Oct 2026Peer-reviewedCC BY-NC-ND 4.0Full textPsychiatry & mental healthCrossref
Adolescent idiopathic scoliosis and comorbid anxiety and depression: advances in psychophysiological interaction mechanisms and integrated interventions
Zhaomeng Hou, Jiaojiao Wu, Hua Lu +3
Frontiers in Psychiatry28 Oct 2026Peer-reviewedCC BY 4.0Surgery & anaesthesiaCrossref
Adolescent depression in Chinese schools and families: a case study of 20 adolescents
Xuelian Wang, Chokchai Suttawet
Frontiers in Psychiatry5 Nov 2026Peer-reviewedCC BY 4.0Psychiatry & mental healthCrossref
Laboratory methods and quality assurance in the National Longitudinal Study of Adolescent to Adult Health Waves V and VI
Timothy B. Plante, Eric A. Whitsel, Allison E. Aiello +7
The journals of gerontology. Series B, Psychological sciences and social sciences1 Oct 2026Peer-reviewedLicence not statedFull text2 citedPhysiologyPMC

Cite

BibTeX RIS

BibTeX

@misc{shen2026methylation,
  title = {{DNA methylation age acceleration, depression and anxiety: evidence from a longitudinal adolescent cohort study (SCAMP) and Mendelian Randomisation}},
  author = {C. Shen and O. Robinson and P. Vineis and D. S. Hargreaves and D. Nicholls and A. Dehghan and M. B. Toledano},
  howpublished = {medRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.15.26362972},
  url = {https://www.medrxiv.org/content/10.64898/2026.09.15.26362972v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - DNA methylation age acceleration, depression and anxiety: evidence from a longitudinal adolescent cohort study (SCAMP) and Mendelian Randomisation
AU  - C. Shen
AU  - O. Robinson
AU  - P. Vineis
AU  - D. S. Hargreaves
AU  - D. Nicholls
AU  - A. Dehghan
AU  - M. B. Toledano
PY  - 2026
DA  - 2026/09/15
PB  - medRxiv
DO  - 10.64898/2026.09.15.26362972
UR  - https://www.medrxiv.org/content/10.64898/2026.09.15.26362972v1
AB  - BackgroundDNA methylation (DNAm) based age acceleration is an indicator of biological ageing. However, it is unclear how age acceleration is linked to mental health in adolescents. We examined the longitudinal associations between DNAm age acceleration and depression and anxiety in adolescents. We also triangulated the evidence using Mendelian Randomisation (MR).  MethodsWe analysed a subsample of adolescents (n=261) from a London-based adolescent cohort study. DNAm profile was generated from saliva samples collected at ages 11-12 years. DNAm age acceleration measures were derived from Horvath, PhenoAge, and PedBE clocks. Depressive and anxiety symptoms were measured at ages 13-15 years, using the Patient Health Questionnaire and Generalised Anxiety Disorder scale, respectively. The associations between DNAm age acceleration and depressive and anxiety symptoms were assessed using logistic regression. We also conducted a two-sample MR to investigate the potential causal relationship between Horvath and PhenoAge acceleration and depression and anxiety.  ResultsWe found that PhenoAge age acceleration was associated with higher severity levels of depressive symptoms (OR=1.04, 95% CI 1.01, 1.08) and clinically significant depressive symptoms (OR=1.05, 95% CI 1.01, 1.10). None of these three clocks was associated with anxiety outcomes. MR suggested a potential causal relationship between PhenoAge age acceleration and depression (Inverse variance weighted OR = 1.01, 95% CI 1.00, 1.02).  ConclusionsPhenoAge acceleration at ages 11-12 years was associated with depressive symptoms at ages 13-15 years. The association patterns are consistent between longitudinal and MR analyses. PhenoAge acceleration may represent a potential early biomarker for subsequent depressive symptoms in adolescents.
ER  -

Abstract

Related

Cite