Study’s strengths, limitations, and future directions
treatment-derived
DISORDER
Notably, and to the best of the researchers’ knowledge, this study is the first to evaluate the effects of lithium on ER in healthy participants. This is considered to aid the understanding of the mechanisms behind lithium treatment due to the lack of interactions between treatment and disorder-related factors (i.e. disorder severity, duration, state, and/or history of medication).The lack of treatment-derived differential effects in self-reported negative affect, however, limits the establishment of whether lithium’s neural effects were beneficial or detrimental to the overall ER process. Importantly, the absence of treatment-derived self-reported effects does not necessarily imply that differences do not exist, but perhaps that the measurement was not sensitive enough to detect them. Establishing the directionality of these effects is of importance to further understand lithium’s mood-stabilising properties. Another important limitation when interpreting the connectivity results is that the PPI analysis employed does not specify whether the seed region is the driver or the driven area, or if the connection is direct or mediated by other areas. Therefore, interpreting the causality or directionality of these results is not possible and they should be considered with caution. Respective to the study sample, and although a healthy volunteer sample poses some benefits mentioned above, these individuals may have an already near-optimal ability to regulate their emotions and so the effects of lithium may not accurately represent what would be seen with treatment in BD. Additionally, we had a relatively small sample size (Considering the study’s limitations and the potential implications of these results for research in BD treatment, future work should validate the present evidence in a larger sample size, with a longer treatment administration, and including the assessment of physiological measurements (i.e. heart rate and/or arousal) that could inform if the implementation of reappraisal in any group is more successful. Moreover, prospective work should consider the inclusion of a condition involving the downregulation of positive stimuli. Altogether, these future recommendations could broaden the understanding of how lithium achieves mood-stabilisation in BD through ER. Lastly, and of general clinical implication, is the AG’s role in ER. Given lithium’s downregulating effect in the left AG during reappraisal and considering similar downregulation patterns observed in clinical populations (Picó-Pérez et al. 