Effects of Amphetamine on Sensorimotor Gating and Neurocognition in Antipsychotic-Medicated Schizophrenia Patients.
Effects of Amphetamine on Sensorimotor Gating and Neurocognition in Antipsychotic-Medicated Schizophrenia Patients.
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安非他明对抗精神病药物精神分裂症患者感觉运动门控和神经认知的影响。
DOI：
10.1038/npp.2017.285
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Light,GregoryA
中科院分区：
文献类型：
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作者：
Swerdlow,NealR;Bhakta,SavitaG;Talledo,JoA;Franz,DanielM;Hughes,EricaL;Rana,BrindaK;Light,GregoryA
Prepulse inhibition (PPI) of startle is being explored both as an indicator of target engagement for, and a biomarker predicting the sensitivity to, procognitive effects of drugs. We now report the effects of the pro-attentional drug, d-amphetamine, on PPI and neurocognition in antipsychotic-medicated schizophrenia patients and healthy subjects (HS) who were also tested in a targeted cognitive training (TCT) module. 44 HS and 38 schizophrenia patients completed a double-blind, placebo-controlled crossover study of the effects of a single dose of amphetamine (10 mg po) on PPI and MATRICS Consensus Cognitive Battery (MCCB) performance; TCT results were previously reported from 60 of these subjects. Moderators predicting AMPH sensitivity were assessed, including the rs4680 single-nucleotide polymorphism for catechol-O-methyltransferase (COMT). After placebo, patients exhibited PPI deficits with 60 ms prepulse intervals; these deficits were ‘rescued’by amphetamine. The magnitude of amphetamine-enhanced PPI was greater in patients than in HS (p< 0.032), and was associated with positive symptoms (p< 0.007), antipsychotic load (p< 0.015), hedonic effects of AMPH (p< 0.003), and with the presence of at least one methionine allele in rs4680 (p< 0.008). No significant effects of amphetamine on MCCB performance were detected in either group, though pro-attentional effects of amphetamine in patients were associated with greater amphetamine-enhanced TCT learning. Amphetamine acutely ‘normalized’PPI in antipsychotic-medicated schizophrenia patients; no concurrent acute neurocognitive changes were detected by the MCCB. Findings suggest that in the context of appropriate antipsychotic medication, a low dose of amphetamine enhances brain processes associated with higher function in schizophrenia patients, without accompanying changes in MCCB performance.
