Limitations and future directions
depressed
This study has several limitations. First, mood scores were not measured beyond the post-treatment timepoint, such that it was not possible to evaluate antidepressant effects (which recent studies indicate may improve for up to 6 weeks after tDCS) and their relationship with the observed treatment-induced neurostructural changes. A second limitation of our study is the relatively small sample size of each individual treatment group (n ≤ 20), which limits the sensitivity of the analyses performed. Although widespread gray matter increases were observed within the active HD treatment group in the follow-up analyses (due to its more powerful within-subjects design), these could not be dissociated from placebo effects except within the left DLPFC brain region. Even so, the latter results provide a rational means for future studies to restrict an otherwise whole-brain voxelwise analysis to specific regions, to conserve statistical power and improve the sensitivity of analyses. For example, we plan to use the brain regions identified in this study to investigate structural changes in our follow up study arm that involves data acquisition in N = 100 depressed participants receiving active or sham HD tDCS (NCT03556124