EGF and EGFR can be detected in nerve cells of manic patients.[41] Studies have shown that in the plasma of adolescent patients with MDD, EGF and EGFR are elevated, while BDNF is significantly decreased, suggesting that EGF and EGFR may promote the occurrence of MDD.[42] PTGS2, also known as cyclooxygenases 2, is the first key rate-limiting enzyme that catalyzes AA and prostaglandin synthesis. This evidence concerns the gene PTGS2 and major depressive disorder.