Abstract
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 α2-adrenoceptor (α2-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 α2-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 α2-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 α2-ARs, may play a role in the pathophysiology of PTSD with concurrent MD.
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Acknowledgements
This research was supported in part by the Fund for Scientific Research, Vlaanderen (FWO); the Clinical Research Center for Mental Health (CRC-MH), Antwerp; and Pfizer, Belgium. The assistance of T. Creten, E. DeBoel, G. Belis, CRC-MH, Antwerp; Prof. J. Mylle, Royal Military School, Brussels; Prof. B. VanHoudenhove, M.D., KUL, Leuven; Prof. Dr. J. Leysen and W. Gommeren, the Janssen Research Foundation, Beerse, Belgium; and Assoc. Prof. C. S. North, M.D., Washington University, St. Louis, USA is greatly appreciated. The authors thank Slachtofferhulp Vlaanderen; the “Stad Antwerpen” (L. Detiege); the O.C.M.W. Antwerpen; Politie van Antwerpen and Slachtofferzorg (B. Engelen, R. VanLooveren); Slachtofferhulp, Antwerpen; the Red Cross, Vlaanderen; and the “Dienst Dringende Spoed Interventie” (D. DeBeukelaer, H. Van Gastel). The secretarial assistance of Ms M. Maes is greatly appreciated.
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Maes, M., Lin, Ah., Verkerk, R. et al. Serotonergic and Noradrenergic Markers of Post-Traumatic Stress Disorder with and without Major Depression. Neuropsychopharmacol 20, 188–197 (1999). https://doi.org/10.1016/S0893-133X(98)00058-X
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DOI: https://doi.org/10.1016/S0893-133X(98)00058-X
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