Abstract
Changes in epigenetic modifications present a mechanism how environmental factors, such as the experience of stress, can alter gene regulation. While stress-related disorders have consistently been associated with differential DNA methylation, little is known about the time scale in which these alterations emerge. We investigated dynamic DNA methylation changes in whole blood of 42 healthy male individuals in response to a stressful cognitive task, its association with concentration changes in cortisol, and its modulation by transcranial direct current stimulation (tDCS). We observed a continuous increase in COMT promotor DNA methylation which correlated with higher saliva cortisol levels and was still detectable one week later. However, this lasting effect was suppressed by concurrent activity-enhancing anodal tDCS to the dorsolateral prefrontal cortex. Our findings support the significance of gene-specific DNA methylation in whole blood as potential biomarkers for stress-related effects. Moreover, they suggest alternative molecular mechanisms possibly involved in lasting behavioral effects of tDCS.
Highlights
Tübingen Center for Mental Health, Department of Psychiatry and Psychotherapy, Molecular Psychiatry, International Max Planck Research School for Cognitive and Systems Neuroscience, University of Tübingen, 72076 Tübingen, Germany
The key findings of the present study are (i) a continuous increase of COMT gene promotor methylation in blood after a challenging, stressful, and frustrating cognitive task which correlates with an increase in salivary cortisol, (ii) increased COMT DNA methylation (DNAm) detectable one week later, and (iii) a suppression of this lasting effect by concurrent activityenhancing anodal transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex
These data support the notion of dynamic DNAm in response to mental stress that is associated with changes in cortisol levels and can be modulated by tDCS
Summary
22 healthy participants (mean age: 23.6 years, SD = 3.0; mean years of formal education: 16.9, SD = 3.3) took part in the experiment. To increase reliability of our findings, we replicated the same experiment with another 20 healthy participants (mean age: 23.3 years, SD = 3.5; mean years of formal education: 14.4, SD = 6.2). Participants completed the PANAS three times throughout each session: before starting the PASAT (pre), immediately after they completed the PASAT (post), and 90 min after task completion (follow-up). During the anodal stimulation session, a continuous current of 1 mA was delivered for 20 min until task completion and faded out for another 5 s. Participants were asked for tDCS adverse effects at the end of each session (see Supplementary Table S1)
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