Genetic Polymorphisms Do Not Predict Interindividual Variability to Cathodal Transcranial Direct Current Stimulation...

High variability between individuals (i.e., interindividual variability) in response to transcranial direct current stimulation (tDCS) has become a commonly reported issue in the tDCS literature in recent years. Inherent genetic differences between individuals have been proposed as a contributing factor to observed response variability. This study investigated whether tDCS interindividual variability was genetically mediated. A large sample size of 61 healthy males received cathodal tDCS (c-tDCS) and sham-tDCS of the primary motor cortex at 1 mA and 10 min via 6 × 4 cm active and 7 × 5 cm return electrodes. Corticospinal excitability (CSE) was assessed via 25 single-pulse transcranial magnetic stimulation motor-evoked potentials (MEPs). Intracortical inhibition was assessed via twenty-five 3 msec interstimulus interval (ISI) paired-pulse MEPs, known as short-interval intracortical inhibition (SICI). Intracortical facilitation (ICF) was assessed via twenty-five 10 msec ISI paired-pulse MEPs. Gene variants encoding for excitatory and inhibitory neuroreceptors were determined via saliva samples. Predetermined thresholds and statistical cluster analyses were used to subgroup individuals. Two distinct subgroups were identified, "responders" reducing CSE following c-tDCS and "nonresponders" showing no reduction or even increase in CSE. Differences in CSE between responders and nonresponders following c-tDCS were not explained by changes in SICI or ICF. No significant relationships were reported between gene variants and interindividual variability to c-tDCS, suggesting that the chosen gene variants did not influence the activity of the neuroreceptors involved in eliciting changes in CSE in responders following c-tDCS. In this largest c-tDCS study of its kind, novel insights were reported into the contribution genetic factors may play in observed interindividual variability to c-tDCS. Impact statement This study adds insight into the issue of interindividual variability to c-tDCS. It highlights not all individuals respond to c-tDCS similarly when exposed to the same stimulus parameters. This disparity in response to c-tDCS between individuals does not appear to be genetically mediated. For c-tDCS to progress to large-scale clinical application, reliability, predictability and reproducibility are essential. Systematically investigating factors contributing to interindividual variability take steps towards this progress the c-tDCS field towards the potential development of screening tools to determine clinical suitability to c-tDCS to ensure its application in those who may benefit the most.