A recent investigation elucidates a novel molecular mechanism underlying its antidepressant efficacy: Geniposide upregulates the expression of transcription factors CREB1 and lncRNA Six3os1, thereby enhancing synaptic protein synthesis (e.g., Htr3a and Htr2a), which ultimately modulates neuronal function and ameliorates MDD-related behaviors (Li et al., 2023a). This evidence concerns the gene CREB1 and major depressive disorder.