Serotonergic and noradrenergic markers of post-traumatic stress disorder with and without major depression

Some studies have suggested that disorders ill the peripheral and central m etabolism of serotonin (5-HT) and noradrenaline (NE) may play roles in the pathophysiology of post-traumatic stress disorder (PTSD). This study examin es (1) the availability of plasma total tryptophan, the precursor of 5-HT, and tyrosine, the precursor of NE; and (2) the platelet 5-HT transporter an d alpha 2-adrenoceptor (alpha 2-AR) binding sites ill patients with PTSD an d healthy volunteers. High-performance liquid chromatography (HPLC) was emp loyed to measure plasma tryptophan and tyrosine as well as amino acids know n to compete with the same cerebral transport system; that is, valine, leuc ine, phenylalanine, and isoleucine. The maximum number of binding sites (B- max) and their affinity (Kd) for binding to [H-3]-paroxetine and [H-3]-rauw olscine, a selective alpha 2-AR antagonist, were determined. [H-3]-paroxeti ne and [H-3]-rauwolscine binding Kd values were significantly higher in pat ients with PTSD than in healthy volunteers. [H-3]-rauwolscine binding Kd va lues were significantly higher in patients with PTSD and concurrent major d epression (MD) than in PTSD patients without MD and healthy volunteers. Pla sma tyrosine concentrations and the ratio of tyrosine/valine + leucine + is oleucine phenylalanine + tryptophan were significantly higher in PTSD patie nts with MD than in those without MD and healthy volunteers. The results sh ow that PTSD is accompanied by lower affinity of paroxetine binding sites a nd that PTSD with concurrent MD is accompanied by lower affinity of alpha 2 -ARs and increased plasma tyrosine availability to the brain. The results s uggest that (1) serotonergic mechanisms, such as defects in the 5-HT transp orter system, may play a role in the pathophysiology of PTSD; and (2) that catecholaminergic mechanisms, such as increased precursor availability and lowered affinity of alpha 2-ARs, may play a role ill the pathophysiology of PTSD with concurrent MD. [Neuropsychopharmacology 20: 188-197, 1999] (C) 1 998 American College of Neuropsychopharmacology.. Published by Elsevier Sci ence Inc.