Platelet [alpha]2-adrenoceptor density in humans: relationships to stress-induced anxiety, psychasthenic constitution, gender and stress-induced changes in the inflammatory response system
Background. This study examined the effects of psychological stress on platelet [alpha]2-adrenergic receptor ([alpha]2-AR) binding sites in relation to stress-induced anxiety and changes in the inflammatory response system (IRS).
Methods. The maximum number of binding sites (Bmax) and their affinity (Kd) for [3H]-rauwolscine, a selective [alpha]2-AR antagonist, and the stimulated production of tumor necrosis factor-[alpha] (TNF[alpha]), the Th1-like cytokine, interferon-[gamma] (IFN[gamma]), and the Th2-like cytokines, interleukin-10 (IL-10) and IL-5, were measured in 35 university students a few weeks before (baseline) as well as on the day before a difficult, oral examination (stress condition). The State-Trait-Anxiety Inventory (STAI)- was recorded during both conditions. The Minnesota Multiphase Personality Inventory (MMPI-2TM) was used to assess psychasthenia (Scale 7).
Results. Academic examination stress induced a significant increase in [alpha]2-AR density in students whose STAI scores increased in the stress period, in female students and in students who scored higher on psychasthenia. There were significant and positive correlations between stress-induced anxiety and changes in [alpha]2-AR density. Stress-induced anxiety was accompanied by a pro-inflammatory and Th1-like response, i.e. increased IFN[gamma] and TNF[alpha] production. The stress-induced changes in platelet [alpha]2-AR density were significantly and positively related to the production of TNF[alpha], IL-10 and IL-5 and negatively to that of IFN[gamma].
Conclusions. Subchronic psychological stress in humans induces increased [alpha]2-AR density, which is related to stress-induced anxiety, an anxiety-prone constitution and female sex. Increased [alpha]2-AR density is accompanied by a Th2-like response and increased TNF[alpha] production. The results suggest that: (i) [alpha]2-AR density is sensitive to graded differences in stress-induced anxiety; and (ii) psychological stress is accompanied by intertwined responses in the catecholaminergic system, such as [alpha]2-ARs, and the IRS, such as Th1/Th2-like functions and the production of TNF[alpha].
c1 Address for correspondence: Professor Michael Maes, Department of Psychiatry and Neuropsychology, University Hospital of Maastricht, Postbus 5800, 6202 AZ Maastricht, The Netherlands.