Stress exposure and psychopathology alter methylation of the serotonin receptor 2A (HTR2A) gene in preschoolers

Abstract

Serotonin signaling pathways play a key role in brain development, stress reactivity, and mental health. Epigenetic alterations in the serotonin system may underlie the effect of early life stress on psychopathology. The current study examined methylation of the serotonin receptor gene HTR2A in a sample of 228 children including 119 with child welfare documentation of moderate to severe maltreatment within the last 6 months. Child protection records, semi-structured interviews in the home, and parent reports were used to assess child stress exposure, psychiatric symptoms, and behavior. HTR2A genotype and methylation of HTR2A was measured at two CpG sites (−1420 and −1224) from saliva DNA. HTR2A genotype was associated with HTR2A methylation at both CpG sites. HTR2A genotype also moderated associations of contextual stress exposure and HTR2A methylation at site −1420. Contextual stress was positively associated with −1420 methylation among A homozygotes, but negatively associated with −1420 methylation among G homozygotes. PTSD and MDD symptoms were negatively associated with methylation at −1420, but positively associated with methylation at −1224. Results support the view that the serotonin system is sensitive to stress exposure and psychopathology, and HTR2A methylation may be a mechanism by which early adversity is biologically encoded.

Early Life Stress and the Onset of Obesity: Proof of MicroRNAs’ Involvement Through Modulation of Serotonin and Dopamine Systems’ Homeostasis

“…Interestingly, 5HT1A is also the target of miR-16, which has its expression modulated by ELS (Bai et al, 2012). The receptor 5HT2A is, as well, modulated by ELS in animals and humans (Rentesi et al, 2013;Parade et al, 2017) and involved with the pathophysiology of obesity (Rosmond et al, 2002;Huang et al, 2004). Interestingly, the 5HT2A is also targeted by the miR-16 (Yang et al, 2017).…”

An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci

“…Hypothesis and mechanism-focused candidate gene studies have identified PTSD-related differences in DNAm levels in genes associated with the hypothalamicpituitary-adrenal (HPA) axis (e.g., ADCYAP1 [9], FKBP5 [10], and NR3C1 [11]), inflammation (e.g., BDNF [4], HTR2A [12] and IL-18 [13]), and neurotransmission (e.g., BDNF [4], HTR2A [14], and HTR3A [15]). Epigenome-wide association studies (EWASs), on the other hand, take a hypothesis-free approach to identifying DNAm loci from across the genome that are statistically associated with the phenotype of interest.…”

DNA methylation analysis from saliva samples for epidemiological studies

“…Another study investigating temporal changes of DNA methylation in adult blood found dynamic changes of DNA methylation of stress-associated genes within 30 minutes of acute psychosocial stress [47]. More recently, there has been growing interest in identifying dynamic changes in DNA methylation that occur early in life [11][12][13]48].…”

“…It is non-invasive, does not require specialized equipment or training and can be stored at room temperature for more than a year, making it feasible to sample outside of a laboratory. When compared to a blood draw, saliva is also more easily collected from young children [11][12][13][14]. Finally, it is convenient for repetitive collection from the same participant, making saliva a useful proxy tissue for epidemiological studies such as birth cohorts [15,16].…”