Effects of Dopamine D2/D3 Blockade on Human Sensory and Sensorimotor Gating in Initially Antipsychotic-Naive, First-Episode Schizophrenia Patients
Effects of Dopamine D2/D3 Blockade on Human Sensory and Sensorimotor Gating in Initially Antipsychotic-Naive, First-Episode Schizophrenia Patients
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DOI：
10.1038/npp.2014.152
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发表时间：
2014-12-01
影响因子：
7.6
通讯作者：
Oranje, Bob
中科院分区：
文献类型：
--
作者：
During, Signe;Glenthoj, Birte Y.;Oranje, Bob
已经表明，感觉和感觉运动门控、P50门控和惊吓反射（PPI）的前脉冲抑制的心理生理学测量是精神分裂症的核心特征的基础，并且与纹状体和前额叶皮层中的多巴胺能通路有关。在本研究中，一种有效的D2/D3受体拮抗剂，氨磺必利，PPI和P50门控在一个大样本的抗精神病药初治，首发精神分裂症患者的影响进行了研究。共有52名最初未接受过抗精神病药物治疗的首发精神分裂症患者在基线时以及接受灵活剂量的氨磺必利治疗2周和6周后评估了他们的P50门控、PPI和习惯化/致敏能力。此外，在基线和6周后评估了47名匹配的健康对照。在基线时，患者显示PPI显著降低，但P50门控、习惯化和致敏水平正常。在2周或6周的随访中，氨磺必利治疗对这些指标均无影响。这是第一项研究，调查单一治疗的影响，相对选择性多巴胺D2/D3受体拮抗剂（氨磺必利）的感觉和感觉运动门控缺陷的纵向研究的一大组最初抗精神病药初治，首发精神分裂症患者。我们发现氨磺必利有效地降低了我们患者的症状严重程度，而没有降低他们的PPI缺陷，表明多巴胺D2受体活性的增加可能与精神分裂症患者的精神病学有关，但与他们的感觉运动门控缺陷无关。
It has been suggested that psychophysiological measures of sensory and sensorimotor gating, P50 gating and prepulse inhibition of the startle reflex (PPI), underlie core features of schizophrenia and are linked to dopaminergic pathways in the striatum and prefrontal cortex. In the present study, the effects of a potent D2/D3 receptor antagonist, amisulpride, were investigated on PPI and P50 gating in a large sample of antipsychotic-naive, first-episode patients with schizophrenia. A total of 52 initially antipsychotic-naive, first-episode schizophrenia patients were assessed for their P50 gating, PPI, and habituation/sensitization abilities at baseline and after 2 and 6 weeks of treatment with flexible doses of amisulpride. In addition, 47 matched healthy controls were assessed at baseline and after 6 weeks. At baseline, the patients showed significantly reduced PPI, yet normal levels of P50 gating, habituation, and sensitization. Treatment with amisulpride showed no effects on these measures, either at 2 or 6 weeks of follow-up. This is the first study investigating the effects of monotherapy with a relatively selective dopamine D2/D3 receptor antagonist (amisulpride) on sensory and sensorimotor gating deficits in a longitudinal study of a large group of initially antipsychotic-naive, first-episode patients with schizophrenia. Our finding that amisulpride effectively reduced symptom severity in our patients without reducing their PPI deficits indicates that increased activity of dopamine D2 receptors may be involved in symptomatology of patients with schizophrenia, but not in their sensorimotor gating deficits.