Garver D L, Zemlan F, Hirschowitz J, Hitzemann R, Mavroidis M L
Psychopharmacology (Berl). 1984;84(1):138-40. doi: 10.1007/BF00432044.
The time course of antipsychotic response following the initiation of an antipsychotic drug and functional dopamine receptor sensitivity were explored in a cohort of recently admitted psychotic (mood-incongruent) patients. The distribution of the latencies of antipsychotic response suggested at least two populations. Rapid responders (RRs) had 60% reduction of baseline psychotic symptoms by a mean of 5.5 days of drug treatment. Delayed/nonresponders required 2-7 weeks for a similar reduction of psychotic symptoms. The sensitivity of postsynaptic dopamine receptors was explored using a neuroendocrine probe: growth hormone response to the dopamine agonist, apomorphine (AP). RRs had an exaggerated growth hormone response to AP in comparison to delayed/nonresponders (P less than 0.05). Exaggerated sensitivity of postsynaptic dopamine receptors and rapid antipsychotic response following dopamine receptor blockade in RRs suggest a true functional dopamine hypersensitivity disorder in the RR group. In contrast, lower postsynaptic receptor sensitivity (as reflected by lower growth hormone response to AP) and failure of early response following dopamine receptor blockade focus attention away from dopamine hyperactivity as a relevant etiologic mechanism in delayed/nonresponders. Response rates to neuroleptic drugs and neuroendocrine probes of receptor sensitivity may separate two or more etiologically distinct diseases with schizophrenic-like symptoms.
在一组近期入院的精神病性（心境不相符）患者中，研究了抗精神病药物起始治疗后抗精神病反应的时间进程以及功能性多巴胺受体敏感性。抗精神病反应潜伏期的分布表明至少存在两个群体。快速反应者（RRs）在平均5.5天的药物治疗后，基线精神病性症状减少了60%。延迟/无反应者则需要2至7周才能有类似程度的精神病性症状减轻。使用一种神经内分泌探针（生长激素对多巴胺激动剂阿扑吗啡（AP）的反应）来探究突触后多巴胺受体的敏感性。与延迟/无反应者相比，RRs对AP的生长激素反应更为强烈（P小于0.05）。RRs中突触后多巴胺受体的过度敏感性以及多巴胺受体阻断后快速的抗精神病反应表明RR组存在真正的功能性多巴胺超敏障碍。相比之下，较低的突触后受体敏感性（以对AP较低的生长激素反应为反映）以及多巴胺受体阻断后早期无反应，使得多巴胺活动亢进作为延迟/无反应者的相关病因机制的关注度降低。抗精神病药物的反应率以及受体敏感性的神经内分泌探针可能会区分出两种或更多具有精神分裂症样症状的病因上不同的疾病。
