In a significant study including animal and patient samples, it has been revealed that experimental overexpression of S1PR3 in the medial prefrontal cortex (mPFC) led to a resilient phenotype, whereas knock-down of S1PR3 resulted in vulnerability with higher anxiety- and depressive-like behaviors, effects mediated, once again, by TNF-α [230]. This evidence concerns the gene S1PR3 and Anxiety.