title: Adverse life events and allele-specific methylation of the serotonin transporter gene (SLC6A4) in adolescents: the TRAILS study.
abstract: OBJECTIVE
  Adverse life events increase vulnerability to affective disorders later in life, possibly mediated by methylation of the serotonin transporter gene (SLC6A4). We investigated the relationship of SLC6A4 methylation with various types of adversity (perinatal adversity, traumatic youth experiences and stressful life events [SLEs]), as well as with the timing of SLEs (during childhood [0-11 years] or during adolescence [12-15 years]). In addition, we investigated whether different serotonin-transporter-linked polymorphic region genotypes were equally sensitive to SLE-related methylation.
  
  
  METHODS
  In a population sample of 939 adolescents (mean age = 16.2 years), we assessed SLC6A4 methylation, SLC6A4 functionality (serotonin-transporter-linked polymorphic region "long" and "short" alleles, and rs25531), and adverse life events.
  
  
  RESULTS
  Only a higher number of SLEs was positively associated with higher SLC6A4 methylation (B = 0.11, p = .011). Adolescent SLEs were associated with higher SLC6A4 methylation (B = 0.13, p = .004) independently of childhood SLEs (B = 0.02, p = .57). L-allele homozygotes showed a greater impact of SLEs on methylation (B = 0.37, p < .001) than did s-allele carriers (B = 0.04, p = .66), resulting in higher levels of SLC6A4 methylation for l-allele homozygotes among those experiencing high levels of SLEs.
  
  
  CONCLUSIONS
  Our findings demonstrate a higher level of SLC6A4 methylation after SLEs in adolescents, with a more pronounced association for SLEs during adolescence than during childhood. Considering the allele-specific sensitivity of SLC6A4 methylation to SLEs, this study may help clarify the role of SLC6A4 in the development of affective disorders.
authors: From the Department of Child and Adolescent Psychiatry/Psychology (van der Knaap, Hudziak, Verhulst, van Oort), Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, the Netherlands; Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE) (Riese, Oldehinkel), Department of Psychiatry, University of Groningen, University Medical Center Groningen, the Netherlands; Vermont Center for Children, Youth, and Families (Hudziak), The University of Vermont, Burlington, Vermont; and Department of Internal Medicine (Verbiest), Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Lisette J
authors: LJ
authors: van der Knaap
authors: Harriëtte
authors: H
authors: Riese
authors: James J
authors: JJ
authors: Hudziak
authors: Michael M P J
authors: MM
authors: Verbiest
authors: Frank C
authors: FC
authors: Verhulst
authors: Albertine J
authors: AJ
authors: Oldehinkel
authors: Floor V A
authors: FV
authors: van Oort
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D002649:Child Abuse; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008016:Life Change Events; D008297:Male; D009426:Netherlands; D011446:Prospective Studies; D000067073:Psychological Trauma / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics*; D013997:Time Factors; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins