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自闭症谱系障碍患儿高血清素血症亲属的血小板5-羟色胺研究

Platelet serotonin studies in hyperserotonemic relatives of children with autistic disorder.

作者信息

Cook E H, Arora R C, Anderson G M, Berry-Kravis E M, Yan S Y, Yeoh H C, Sklena P J, Charak D A, Leventhal B L

机构信息

Department of Psychiatry, University of Chicago, IL 60637.

出版信息

Life Sci. 1993;52(25):2005-15. doi: 10.1016/0024-3205(93)90685-v.

DOI:10.1016/0024-3205(93)90685-v
PMID:7684805
Abstract

Platelet serotonin (5-HT) studies were conducted with 12 hyperserotonemic and 12 normoserotonemic age-, sex-, and relationship-matched relatives of autistic probands. Each group consisted of 7 mothers, 4 fathers, and 1 sister of autistic children and adolescents. The density (Bmax) of platelet 5-HT2 receptor binding sites, labelled with [3H]-lysergic acid diethylamide (LSD), was significantly lower in 11 hyperserotonemic subjects compared to 12 normoserotonemic subjects (40.9 +/- 13.5 fmol/mg protein, 59.6 +/- 13.2; p < 0.004). The affinity (Kd) for [3H]-LSD binding did not differ. Although the density (Bmax) of [3H]-paroxetine binding did not differ between groups, there was a small difference in the affinity (Kd) for [3H]-paroxetine binding (hyperserotonemic 47.6 +/- 9.0 pM, normoserotonemic 54.8 +/- 12.1; p < 0.05). There were no significant differences in platelet 5-HT uptake, or in thrombin-stimulated 5-HT release. Basal, 5-HT-stimulated, and arginine-vasopressin (AVP)-stimulated inositol phosphate production, as well as basal, prostaglandin E1 (PGE1)-, and forskolin-stimulated cAMP production did not differ. There were significant correlations between whole blood 5-HT levels and LSD Bmax (rs = -0.63, N = 23, p < 0.002) and whole blood 5-HT levels and 5-HT uptake Vmax (rs = 0.56, N = 18, p < 0.02). However, [3H]-LSD labelled 5-HT2 binding and 5-HT uptake were not correlated with each other. Hyperserotonemia of autism may be heterogeneous with one subgroup of subjects with increased 5-HT uptake and another subgroup with decreased 5-HT2 binding.

摘要

对12名血清素水平过高和12名血清素水平正常的自闭症先证者的亲属进行了血小板5-羟色胺(5-HT)研究,这些亲属在年龄、性别和亲属关系上相匹配。每组包括7名母亲、4名父亲和1名自闭症儿童及青少年的姐妹。与12名血清素水平正常的受试者相比,11名血清素水平过高的受试者中,用[3H] - 麦角酸二乙酰胺(LSD)标记的血小板5-HT2受体结合位点的密度(Bmax)显著降低(40.9±13.5 fmol/mg蛋白质,59.6±13.2;p<0.004)。[3H] - LSD结合的亲和力(Kd)没有差异。虽然两组之间[3H] - 帕罗西汀结合的密度(Bmax)没有差异,但[3H] - 帕罗西汀结合的亲和力(Kd)存在微小差异(血清素水平过高组为47.6±9.0 pM,血清素水平正常组为54.8±12.1;p<0.05)。血小板5-HT摄取或凝血酶刺激的5-HT释放没有显著差异。基础状态下、5-HT刺激下以及精氨酸加压素(AVP)刺激下的肌醇磷酸生成,以及基础状态下、前列腺素E1(PGE1)和福斯高林刺激下的环磷酸腺苷(cAMP)生成没有差异。全血5-HT水平与LSD Bmax之间存在显著相关性(rs = -0.63,N = 23,p<0.002),全血5-HT水平与5-HT摄取Vmax之间也存在显著相关性(rs = 0.56,N = 18,p<0.02)。然而,[3H] - LSD标记的5-HT2结合与5-HT摄取之间没有相关性。自闭症的高血清素血症可能具有异质性,一部分受试者的5-HT摄取增加,另一部分受试者的5-HT2结合减少。

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