In light of the rising mental health crisis among European adolescents, researchers are adopting a cautious optimism towards the integration of DNA methylation-based diagnostics in mental health settings. New evidence underscores that stress during adolescence triggers epigenetic changes that can inform robust biomarker development, supporting potential early interventions. Pilot studies are set to advance, with a focus on ethical oversight and longitudinal monitoring to validate these promising methylation signatures while mitigating risks.
“Nine million adolescents in Europe are affected by mental health disorders, with anxiety and depression accounting for more than half of these cases.”
“It is indeed well established that SLE induce changes in stable epigenetic states that regulate gene expression and ultimately complex neural functions, including the regulation of the hypothalamus-pituitary-adrenal (HPA) axis.”
“Moreover, this emerging body of research provides strong evidence that stress exposure during adolescence can lead to short- and long-term changes in limbic and cortical structure and function, with important behavioral repercussions.”
“The study selection process is shown in Fig. 1. A total of 30 studies were included in our systematic review.”
“Two researchers (GP and NC) independently screened the articles and performed data extraction of the retrieved articles.”
“For the risk of bias assessment in preclinical studies, the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE)’s RoB tool was used.”
“The screening yielded 9 preclinical studies in mice and 11 in rats, mostly run on males.”
“The search of three databases retrieved a relatively limited number of original articles published until May 2025 (n = 327).”
“With respect to FST, aversive experiences during adolescence increased immobility in adult rats and mice. This was observed when all the studies were combined in the analysis (Hedges’ g = 0.81, [95%CI 0.43 to 1.19; PI 0.16 to 2.18], standard error = 0.16)...”
“With respect to SPT, aversive experiences during adolescence reduced the preference for sucrose in adult rats and mice. This was observed when all the studies were combined in the analysis (Hedges’ g = -1.43, [95%CI -2.16 to -0.69; PI -3.39 to 0.55], standard error = 0.33)...”
“About 26% of adolescents were at high risk for depression as assessed by the DAWBA.”
“Specifically, Ran and collaborators conducted a genome-wide miRNA sequencing of serum extracellular vesicles (EVs) from 9 untreated depressed adolescents and 8 matched controls. The depressed group scored significantly higher than the control group on depression, anxiety and total childhood trauma, assessed through the childhood trauma questionnaire (CTQ), including higher scores in emotional and physical abuse and in emotional and physical neglect.”
