Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Transl Psychiatry. 2012 May 22;2(5):e119. doi: 10.1038/tp.2012.48.
Phenylalanine is an essential amino acid required for the synthesis of catecholamines including dopamine. Altered levels of phenylalanine and its metabolites in blood and cerebrospinal fluid have been reported in schizophrenia patients. This study attempted to examine for the first time whether phenylalanine kinetics is altered in schizophrenia using L-[1-(13)C]phenylalanine breath test ((13)C-PBT). The subjects were 20 chronically medicated schizophrenia patients (DSM-IV) and the same number of age- and sex-matched controls. (13)C-phenylalanine (99 atom% (13)C; 100 mg) was administered orally and the breath (13)CO(2) /(12)CO(2) ratio was monitored for 120 min. The possible effect of antipsychotic medication (risperidone (RPD) or haloperidol (HPD) treatment for 21 days) on (13)C-PBT was examined in rats. Body weight (BW), age and diagnostic status were significant predictors of the area under the curve of the time course of Δ(13)CO(2) (‰) and the cumulative recovery rate (CRR) at 120 min. A repeated measures analysis of covariance controlled for age and BW revealed that the patterns of CRR change over time differed between the patients and controls and that Δ(13)CO(2) was lower in the patients than in the controls at all sampling time points during the 120 min test, with an overall significant difference between the two groups. Chronic administration of RPD or HPD had no significant effect on (13)C-PBT indices in rats. Our results suggest that (13)C-PBT is a novel laboratory test that can detect altered phenylalanine kinetics in chronic schizophrenia patients. Animal experiments suggest that the observed changes are unlikely to be attributable to antipsychotic medication.
苯丙氨酸是合成儿茶酚胺（包括多巴胺）所必需的必需氨基酸。有报道称，精神分裂症患者的血液和脑脊液中的苯丙氨酸及其代谢物水平发生了改变。本研究首次尝试使用 L-[1-(13)C]苯丙氨酸呼吸试验（(13)C-PBT）来检测精神分裂症患者苯丙氨酸动力学是否发生改变。研究对象为 20 名慢性服用药物的精神分裂症患者（DSM-IV）和相同数量的年龄和性别匹配的对照组。（13)C-苯丙氨酸（99 原子%（13)C；100mg）经口给予，监测 120 分钟的呼吸（13)CO(2)/(12)CO(2)比值。在大鼠中，还检测了抗精神病药物（利培酮（RPD）或氟哌啶醇（HPD）治疗 21 天）对（13)C-PBT 的可能影响。体重（BW）、年龄和诊断状态是时间曲线下 Δ(13)CO(2)（‰）和 120 分钟时累积恢复率（CRR）的面积的显著预测因子。在控制年龄和 BW 的重复测量协方差分析中，发现 CRR 随时间的变化模式在患者和对照组之间不同，并且在 120 分钟测试的所有采样时间点，患者的 Δ(13)CO(2)均低于对照组，两组之间存在总体显著差异。慢性给予 RPD 或 HPD 对大鼠（13)C-PBT 指标没有显著影响。我们的结果表明，（13)C-PBT 是一种新的实验室检测方法，可检测慢性精神分裂症患者的苯丙氨酸动力学改变。动物实验表明，观察到的变化不太可能归因于抗精神病药物。
