DNA methylation in adolescents with anxiety disorder: a longitudinal study

Abstract

Anxiety disorders (AD) typically manifest in children and adolescents and might persist into adulthood. However, there are still few data concerning epigenetic mechanisms associated with onset, persistence or remission of AD over time. We investigated a cohort of adolescents and young adults at baseline (age; 13.19 ± 2.38) and after 5 years and classified them according to the AD diagnosis and their longitudinal trajectories into 4 groups: (1) Typically Developing Comparisons (TDC; control group, n = 14); (2) Incident (AD in the second evaluation only, n = 11); (3) Persistent (AD in both evaluations, n = 14) and (4) Remittent (AD in the first evaluation only, n = 8). DNA methylation was evaluated with the Infinium HumanMethylation450 BeadChip from saliva samples collected at both evaluations. Gene set enrichment analysis was applied to consider biological pathways. We found decreased DNA methylation in TDC group while the chronic cases of AD presented hypermethylation in central nervous system development pathways. Moreover, we showed that this persistent group also presented hypermethylation while the other three groups were associated with hypomethylation in nervous system development pathway. Incidence and remission groups were associated with increased and decreased methylation in neuron development pathways, respectively. Larger studies are likely to detect specific genes relevant to AD.

Telomere length and epigenetic age acceleration in adolescents with anxiety disorders

“…The sample re-evaluated after 5 years (n = 76) was representative of the whole 234 non-medicated children and adolescents recruited from public schools at baseline as described elsewhere 38 . Similarly, the sub-sample we used to evaluate the epigenetic data did not differ from the whole sample according to Bortoluzzi et al 39 . Descriptive data about the baseline sample and the 5-year follow-up one is depicted in Table 1 .…”

“…DNA methylation status was performed using the Infinium HumanMethylation450 (IHM450) BeadChip 72 which covers 99% of Ref Seq genes regions and 96% of CpG islands/CpG island regions to explore the genome-wide DNA methylome 72 – 74 . Data regarding pre-processing of raw data of IHM450 BeadChip and differential methylation analysis can be found elsewhere 39 . All data of DNA methylation including methylated vs. unmethylated probes are deposited in GEO (GSE78975).…”

We Know Even More Things: A Decade Review of Parenting Research

“…Environmental influences (e.g., social interactions and stress) can initiate epigenetic changes, such as DNA methylation, that alter the extent to which various genes are expressed (Turecki & Meaney, 2016). Research suggests certain epigenetic changes, specifically DNA methylation, are associated with adolescent depression and anxiety (Bortoluzzi et al., 2018; Dempster et al., 2014). Using a longitudinal study design, Bortoluzzi et al., (2018) found that adolescents with a persistent anxiety disorder had higher levels of genome‐wide DNA methylation compared to healthy control adolescents.…”

“…Research suggests certain epigenetic changes, specifically DNA methylation, are associated with adolescent depression and anxiety (Bortoluzzi et al., 2018; Dempster et al., 2014). Using a longitudinal study design, Bortoluzzi et al., (2018) found that adolescents with a persistent anxiety disorder had higher levels of genome‐wide DNA methylation compared to healthy control adolescents. Dempster et al., (2014) found differences in the variability of genome‐wide DNA methylation in adolescent twins discordant for depression, such that levels of DNA methylation were more variable for the twin with depression compared to the unaffected twin.…”

Perinatal protein malnutrition results in genome-wide disruptions of 5-hydroxymethylcytosine at regions that can be restored to control levels by an enriched environment

“…Epigenetic mechanisms such as DNA methylation have emerged as environmentally sensitive biochemical modifications that modulate gene expression [6]. Alterations in DNA methylation levels are linked to a number of neurodevelopmental disorders, including learning disabilities, attention-deficit/hyperactivity disorder, autism, as well as anxiety and depressive disorders [7][8][9][10][11]. Studies in rodents have shown that DNA methylation is nutrition-sensitive, resulting in altered DNA methylation levels on neuropsychiatric-related genes, which suggests epigenetic regulatory mechanisms have a key role in the development of early life adversity-related behaviours [12,13].…”