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| Original Article | |
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| Neuropsychopharmacology (1999) 20 188-197.10.1038/sj.npp.1395241 Serotonergic and Noradrenergic Markers of Post-Traumatic Stress Disorder with and without Major Depression Michael Maes1,2,3 MD, Ph.D, Ai-hua Lin1 MD, MSci, Robert Verkerk4 Ing, Laure Delmeire1 MD, An Van Gastel MD, Marc Van der Planken5 MD, Ph.D and Simon Scharpé4 Ph.D | |
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| 1Clinical Research Center for Mental Health [CRC-MH], Antwerp, Belgium 2Department of Psychiatry, Vanderbilt University, Nashville, Tennessee, USA 3IRCSS, Fatebenefratelli, Brescia, Italy 4Department of Medical Biochemistry, University of Antwerp, Wilrijk USA 5Department of Hematology, University Hospital of Antwerp, Antwerp, Belgium Correspondence: Dr Michael Maes, Director Clinical Research Center for Mental Health (CRC-MH), University Department of Psychiatry, AZ Stuivenberg,Lange Beeldekensstraat 267, 2060 Antwerpen, Belgium | |
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| ABSTRACT | |
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Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline (NE) may play roles in the pathophysiology of post-traumatic stress disorder (PTSD). This study examines (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 and  2-adrenoceptor (2-AR) binding sites in patients with PTSD and healthy volunteers. High-performance liquid chromatography (HPLC) was employed to measure plasma tryptophan and tyrosine as well as amino acids known to compete with the same cerebral transport system; that is, valine, leucine, phenylalanine, and isoleucine. The maximum number of binding sites (Bmax) and their affinity (Kd) for binding to [3H]-paroxetine and [3H]-rauwolscine, a selective 2-AR antagonist, were determined. [3H]-paroxetine and [3H]-rauwolscine binding Kd values were significantly higher in patients with PTSD than in healthy volunteers. [3H]-rauwolscine binding Kd values were significantly higher in patients with PTSD and concurrent major depression (MD) than in PTSD patients without MD and healthy volunteers. Plasma tyrosine concentrations and the ratio of tyrosine/valine + leucine + isoleucine + phenylalanine + tryptophan were significantly higher in PTSD patients with MD than in those without MD and healthy volunteers. The results show that PTSD is accompanied by lower affinity of paroxetine binding sites and that PTSD with concurrent MD is accompanied by lower affinity of 2-ARs and increased plasma tyrosine availability to the brain. The results suggest that (1) serotonergic mechanisms, such as defects in the 5-HT transporter system, may play a role in the pathophysiology of PTSD; and (2) that catecholaminergic mechanisms, such as increased precursor availability and lowered affinity of 2-ARs, may play a role in the pathophysiology of PTSD with concurrent MD.Keywords: Post-traumatic stress disorder; Depression; Serotonin; Norepinephrine; Tryptophan; Tyrosine | |
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