SA52 - EFFECTS OF TRANSCRANIAL DIRECT CURRENT STIMULATION ON COGNITIVE CONTROL AND DNA METHYLATION

Abstract

Background Coping with the complexity of our daily life requires cognitive flexibility and control over emotions and behavior. Deficits in cognitive control are often involved in the psychopathology of psychiatric diseases, e.g. Major Depressive Disorder (MDD), a severe mental illness characterized by increased receptiveness for negative stimuli and unbalanced emotion processing. On a neural basis, MDD as well as deficient cognitive control are associated with hypoactivity of the Dorsolateral Prefrontal Cortex (dlPFC). Transcranial Direct Current Stimulation (tDCS) is a well-established brain stimulation technique inducing targeted modulation of cortical activity. It is discussed as promising approach to support conventional psychiatric therapies but so far little is known about the underlying molecular mechanisms. Epigenetic changes might be a potential mechanism how tDCS effects manifest as long-lasting cognitive improvements and amelioration of psychiatric symptoms. In two previous stimulation genetics studies, we demonstrated an influence of the COMT genotype, which renders this gene an interesting candidate for a stimulation epigenetics study. Methods For the present study, healthy male participants performed a potentially frustrating and challenging task, a 2-back version of the Paced Auditory Serial Addition Task (PASAT), once under sham stimulation and once under anodal tDCS over the left dlPFC. Participants’ affective states were assessed several times throughout the experiment. To investigate epigenetic effects of the stimulation protocol, one blood sample was collected before the PASAT and five blood samples were collected after task completion. DNA methylation status of the COMT gene promoter region was assessed by pyrosequencing. Results Our results provide further evidence that anodal tDCS applied to the left dlPFC improves task performance. In addition, tDCS seems to prevent task-induced decline in positive affect, whereas task-related negative affect was suppressed. Furthermore, our data suggest a dynamic increase in DNA methylation of the COMT gene promoter region in response to the task. Depending on the type of stimulation (anodal or sham) participants received during their first session, they showed different methylation levels in their second session. Discussion Together, our data extend previous findings showing improved cognitive performance under anodal stimulation, which correlates with enhanced control over emotions. In response to stimulation, we observed increased positive affect and reduced negative affect, which supports the idea of tDCS as a potential treatment approach for MDD targeting the negativity bias. In addition, we observed dynamic methylation changes in the COMT gene promoter region in response to a challenging cognitive task, which might be differentially modulated by tDCS. COMT is an enzyme involved in the degradation of dopamine and dopamine levels are critical in executive functioning. Therefore, the observed changes in COMT promoter methylation might indicate an adaptive process to the task and they might indicate an underlying mechanism to induce long-lasting tDCS effects.