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Monoamine Oxidase A Gene Methylation and Its Role in Posttraumatic Stress Disorder: First Evidence from the South Eastern Europe (SEE)- PTSD Study

BACKGROUND: Posttraumatic Stress Disorder (PTSD) is characterized by an overactive noradrenergic system conferring core PTSD symptoms such as hyperarousal and re-experiencing. Monoamine oxidase A (MAO-A) is one of the key enzymes mediating the turnover of noradrenaline. Here, DNA methylation of the MAOA gene exonI/intronI region was investigated for the first time in regards to its role in PTSD risk and severity. METHODS: MAOA methylation was analyzed via direct sequencing of sodium bisulfite treated DNA extracted from blood cells in a total sample of N=652 (m=441) patients with current PTSD, patients with remitted PTSD and healthy probands (comparison group) recruited at five centres in Bosnia-Herzegovina, Croatia, and the Republic of Kosovo. PTSD severity was measured by means of the Clinician-Administered PTSD Scale (CAPS) and its respective subscores representing distinct symptom clusters. RESULTS: In the male, but not the female sample, patients with current PTSD displayed hypermethylation of three CpGs (CpG3=43, 656, 362 ; CpG12=43, 656, 514 ; CpG13=43, 656, 553, GRCh38.p2 Assembly) as compared to remitted PTSD patients and healthy probands. Symptom severity (CAPS scores) in male patients with current PTSD significantly correlated with MAOA methylation. This applied particularly to symptom clusters related to re- experiencing of trauma (cluster 'B') and hyperarousal (cluster 'D'). CONCLUSIONS: The present findings suggest MAOA gene hypermethylation - potentially resulting in enhanced noradrenergic signalling - as a disease status and severity marker of current PTSD in males. If replicated, MAOA hypermethylation might serve as a surrogate marker of a hyperadrenergic subtype of PTSD guiding personalized treatment decisions on the use of anti-adrenergic agents.

CAPS ; DNA methylation ; MAOA ; PTSD ; epigenetics

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