Evaluation of Monoamine Receptor Sensitivity in the Central Nervous System of Depressive Patients : Ites application to psychosomatic disease(An Overview of Psychosomatic Medicine for 21 st Cebtury-On Research)

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  • 中枢モノアミンレセプターの機能評価法と心身症への応用 : うつ病による検討から(21世紀に向けての心身医学の展望-研究について)(第28回日本心身医学会総会)
  • 中枢モノアミンレセプターの機能評価法と心身症への応用--うつ病例による検討から
  • チュウスウ モノアミン レセプター ノ キノウ ヒョウカホウ ト シンシンショ

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Abstract

Monoamine receptor sensitivity in the central nervous system (CNS) of depressive patients was evaluated by making two drugloading tests and measuring 5HT-induced shape change of blood platelet(5HT-SC. The application of these loading tests and measurement of 5HT-SC to psychosomatic disease was discussed. l) Clonidine is a specific α-2 adrenergic receptor (α-2 receptor) agonist. The presynaptic and postsynaptic a2 receptor sensitivity can be assessed by determining the plasma level of noradrenaline (NA) and human growth hormone (HGH) after an oral loading of clonidine ( 3 μg/kg). Results obtained in depressive patients were as follows : Significantly low decrease rate of plasma NA was found in the depressive patients before treatment and it returned to normal on recovery. The depressive patients with severe symptoms showed a low decrease rate of plasma NA, which elevated within normal level on recovery. The HGH response was blunted in 61.5% of depressive patients before treatment, whose ratio of the blunted response reduced to 23.1% on recovery. These results suggest that the sensitivity of both presynaptic and postsynaptic a2 receptor decreased in depression. 2) In order to know the serotonin (5HT) receptor sensitivity, a precursor loading study with L5hydroxytryptophan (5HTP) was made. Depressive patients were given an intravenous loading dose of 5HTP ester ( 2 mg/kg) after premedication with the peripheral decarboxylase inhibitor, benserazide (60 mg) and were investigated for the subsequent change in mental state and blood parameter (free tryptophan, 5HT, cyclic AMP and GMP, prolactin and HGH). According to the change after 5HTP ester, the depressive patients were devided into two groups, the one of which showed a normal blood level of free tryptophan and 5HT but relatively slight mood elation and psychomotor activity. The results suggest that there may be a blunted sensitivity of 5HT receptor in the CNS of this group. 3) 5HT-SC, the degree of which is thought to refiect the sensitivity of 5HT2 receptor in the CNS, was measured in depressive patients. 5HT-SC in depressive patients was unchanged in untreated depressive state, however, significantly increased in recovery state. The results suggest that antidepressants may increase the functional sensitivity of 5HT-2 receptor in the CNS. 4) As to the application to psychosomatic disease, all of the above-mentioned methods are practical to patients with psychosomatic disease. However, the aggravation of disease by loading test should be avoided unconditionally. The results obtained in depressive patients strongly suggest that these methods are useful for evaluating the monoamine receptor sensitivity in the CNS and for elucidating the cause of psychosomatic disease.

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