title: Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder.
abstract: Childhood maltreatment is likely to influence fundamental biological processes and engrave long-lasting epigenetic marks, leading to adverse health outcomes in adulthood. We aimed to elucidate the impact of different early environment on disease-related genome-wide gene expression and DNA methylation in peripheral blood cells in patients with posttraumatic stress disorder (PTSD). Compared with the same trauma-exposed controls (n = 108), gene-expression profiles of PTSD patients with similar clinical symptoms and matched adult trauma exposure but different childhood adverse events (n = 32 and 29) were almost completely nonoverlapping (98%). These differences on the level of individual transcripts were paralleled by the enrichment of several distinct biological networks between the groups. Moreover, these gene-expression changes were accompanied and likely mediated by changes in DNA methylation in the same loci to a much larger proportion in the childhood abuse (69%) vs. the non-child abuse-only group (34%). This study is unique in providing genome-wide evidence of distinct biological modifications in PTSD in the presence or absence of exposure to childhood abuse. The findings that nonoverlapping biological pathways seem to be affected in the two PTSD groups and that changes in DNA methylation appear to have a much greater impact in the childhood-abuse group might reflect differences in the pathophysiology of PTSD, in dependence of exposure to childhood maltreatment. These results contribute to a better understanding of the extent of influence of differences in trauma exposure on pathophysiological processes in stress-related psychiatric disorders and may have implications for personalized medicine.
authors: Max Planck Institute of Psychiatry, 80804 Munich, Germany. mehta@mpipsykl.mpg.de
authors: Divya
authors: D
authors: Mehta
authors: Torsten
authors: T
authors: Klengel
authors: Karen N
authors: KN
authors: Conneely
authors: Alicia K
authors: AK
authors: Smith
authors: André
authors: A
authors: Altmann
authors: Thaddeus W
authors: TW
authors: Pace
authors: Monika
authors: M
authors: Rex-Haffner
authors: Anne
authors: A
authors: Loeschner
authors: Mariya
authors: M
authors: Gonik
authors: Kristina B
authors: KB
authors: Mercer
authors: Bekh
authors: B
authors: Bradley
authors: Bertram
authors: B
authors: Müller-Myhsok
authors: Kerry J
authors: KJ
authors: Ressler
authors: Elisabeth B
authors: EB
authors: Binder
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002649:Child Abuse / Q000175:diagnosis* / Q000523:psychology*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis* / Q000235:genetics*; D014947:Wounds and Injuries
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger
keywords: biomarkers; development; epigenome; psychiatry
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