Among these studies, one of the earliest reported that the free 5HT pool detected in human plasma can be found reduced in drug-free melancholic patients without TRP decrease and without responding to the tricyclic antidepressant clomipramine (88), suggesting that low 5-HT in plasma found in this work would rather be a trait marker of depression more specifically belonging to 5-HT system. The gene discussed is HTR5A; the disease is major depressive disorder.