We appreciate the opportunity to comment on the issues raised by Drs. Li and Su. First, as noted in the article, this is a case-control study and we cannot offer any certain explanation as to why we observed an increase in NOTCH4 expression in patients with bipolar disorder. Although we controlled for a range of potential environmental factors, other environmental factors or even epigenetic mechanisms that we have not taken into account might be influencing NOTCH4 expression. As stated in the article, we call for longitudinal studies investigating NOTCH4 activity in relation to disease state and trait.