Abstract：
OBJECTIVE: The dopamine theory of schizophrenia suggests that antipsychotics alleviate symptoms by blocking dopamine D2/3 receptors, yet a significant subset of patients does not respond adequately to treatment. To investigate potential predictors, we evaluated d-amphetamine-induced dopamine release and 1-year clinical outcomes in 21 antipsychotic-naive patients with first-episode schizophrenia.
METHODS: Twenty-one antipsychotic-naive patients (6 female) underwent dopamine D2/3 receptor radioligand [11C]-(+)-PHNO positron emission tomography. For estimating dopamine release, scans were performed with and without d-amphetamine pretreatment. The Positive and Negative Syndrome Scale was performed at regular intervals over 1 year while receiving treatment in a naturalistic setting (Clinical Trial Registry: EUDRACT 2010-019586-29).
RESULTS: A group analysis revealed no significant differences in d-amphetamine-induced dopamine release between patients with or without clinically significant improvement. However, d-amphetamine-induced dopamine release in ventral striatum was significantly associated with reductions in positive symptoms (r = 0.54, P = .04; uncorrected P-values); release in globus pallidus correlated with a decrease in PANSS negative (r = 0.58, P = .02), general (r = 0.53, P = .04), and total symptom scores (r = 0.063, P = .01). Higher dopamine release in substantia nigra/ventral tegmental area predicted larger reductions in general symptoms (r = 0.51, P = .05). Post-amphetamine binding in putamen correlated positively with negative symptom scores at baseline (r = 0.66, P = .005) and throughout all follow-up visits.
CONCLUSIONS: These exploratory results support a relationship between d-amphetamine-induced dopamine release and the severity and persistence of symptoms during the first year of psychosis.
METHODS: Twenty-one antipsychotic-naive patients (6 female) underwent dopamine D2/3 receptor radioligand [11C]-(+)-PHNO positron emission tomography. For estimating dopamine release, scans were performed with and without d-amphetamine pretreatment. The Positive and Negative Syndrome Scale was performed at regular intervals over 1 year while receiving treatment in a naturalistic setting (Clinical Trial Registry: EUDRACT 2010-019586-29).
RESULTS: A group analysis revealed no significant differences in d-amphetamine-induced dopamine release between patients with or without clinically significant improvement. However, d-amphetamine-induced dopamine release in ventral striatum was significantly associated with reductions in positive symptoms (r = 0.54, P = .04; uncorrected P-values); release in globus pallidus correlated with a decrease in PANSS negative (r = 0.58, P = .02), general (r = 0.53, P = .04), and total symptom scores (r = 0.063, P = .01). Higher dopamine release in substantia nigra/ventral tegmental area predicted larger reductions in general symptoms (r = 0.51, P = .05). Post-amphetamine binding in putamen correlated positively with negative symptom scores at baseline (r = 0.66, P = .005) and throughout all follow-up visits.
CONCLUSIONS: These exploratory results support a relationship between d-amphetamine-induced dopamine release and the severity and persistence of symptoms during the first year of psychosis.
摘要：
目的：精神分裂症的多巴胺理论表明，抗精神病药通过阻断多巴胺D2/3受体来缓解症状，然而,相当一部分患者对治疗没有充分反应.为了调查潜在的预测因素，我们评估了21例未接受抗精神病药物治疗的首发精神分裂症患者中d-苯丙胺诱导的多巴胺释放和1年临床结局.
方法：21例未服用抗精神病药物的患者（6例女性）接受了多巴胺D2/3受体放射性配体[11C]-（+）-PHNO正电子发射断层扫描。为了估计多巴胺的释放，扫描在有和没有d-苯丙胺预处理的情况下进行。阳性和阴性综合征量表在1年内定期进行，同时在自然环境中接受治疗（临床试验注册：EUDRACT2010-019586-29）。
结果：组分析显示，在有或没有临床上显著改善的患者之间，d-苯丙胺诱导的多巴胺释放没有显着差异。然而,d-苯丙胺诱导的腹侧纹状体多巴胺释放与阳性症状的减少显着相关（r=0.54，P=.04；未校正的P值）；苍白球的释放与PANSS阴性的减少相关（r=0.58，P=.02），一般(r=0.53，P=.04)，和总症状评分（r=0.063，P=0.01）。黑质/腹侧被盖区多巴胺释放增加，一般症状减少幅度更大（r=0.51，P=0.05）。在基线（r=0.66，P=0.005）和所有随访期间，壳核中苯丙胺的结合与阴性症状评分呈正相关。
结论：这些探索性结果支持d-苯丙胺诱导的多巴胺释放与精神病第一年症状的严重程度和持久性之间的关系。
方法：21例未服用抗精神病药物的患者（6例女性）接受了多巴胺D2/3受体放射性配体[11C]-（+）-PHNO正电子发射断层扫描。为了估计多巴胺的释放，扫描在有和没有d-苯丙胺预处理的情况下进行。阳性和阴性综合征量表在1年内定期进行，同时在自然环境中接受治疗（临床试验注册：EUDRACT2010-019586-29）。
结果：组分析显示，在有或没有临床上显著改善的患者之间，d-苯丙胺诱导的多巴胺释放没有显着差异。然而,d-苯丙胺诱导的腹侧纹状体多巴胺释放与阳性症状的减少显着相关（r=0.54，P=.04；未校正的P值）；苍白球的释放与PANSS阴性的减少相关（r=0.58，P=.02），一般(r=0.53，P=.04)，和总症状评分（r=0.063，P=0.01）。黑质/腹侧被盖区多巴胺释放增加，一般症状减少幅度更大（r=0.51，P=0.05）。在基线（r=0.66，P=0.005）和所有随访期间，壳核中苯丙胺的结合与阴性症状评分呈正相关。
结论：这些探索性结果支持d-苯丙胺诱导的多巴胺释放与精神病第一年症状的严重程度和持久性之间的关系。
