Abstract
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-[1-13C]phenylalanine breath test (13C-PBT). The subjects were 20 chronically medicated schizophrenia patients (DSM-IV) and the same number of age- and sex-matched controls. 13C-phenylalanine (99 atom% 13C; 100 mg) was administered orally and the breath 13CO2 /12CO2 ratio was monitored for 120 min. The possible effect of antipsychotic medication (risperidone (RPD) or haloperidol (HPD) treatment for 21 days) on 13C-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 Δ13CO2 (‰) 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 Δ13CO2 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 13C-PBT indices in rats. Our results suggest that 13C-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.
Highlights
IntroductionAltered levels of phenylalanine and its metabolites, including another precursor for dopamine biosynthesis, the downstream amino acid tyrosine, could be related to the dopamine hypothesis of schizophrenia.[1,2] serum phenylalanine levels were found to be significantly higher,[3] and tyrosine levels lower[4] in drug-free patients with schizophrenia than in healthy controls
L-Phenylalanine is an essential amino acid required for catecholamine biosynthesis
The majority (85%) of the schizophrenia patients were chronic inpatients, and the mean length of hospitalization was 2.7±4.3 years at the time of the 13C]phenylalanine breath test (13C-PBT); this duration would not be considered unusually long in Japan, where long-term hospitalization due to disability in daily living is common, so that psychiatric hospitalization does not necessarily mean that the patient is in the acute phase of illness
Summary
Altered levels of phenylalanine and its metabolites, including another precursor for dopamine biosynthesis, the downstream amino acid tyrosine, could be related to the dopamine hypothesis of schizophrenia.[1,2] serum phenylalanine levels were found to be significantly higher,[3] and tyrosine levels lower[4] in drug-free patients with schizophrenia than in healthy controls. Wei et al.[5] reported no significant difference between serum phenylalanine levels of drug-free schizophrenics and healthy controls, the ratio of tyrosine to phenylalanine was significantly lower in patients with early-onset disease than in controls. The phenylalanine level in cerebrospinal fluid was significantly higher in schizophrenia patients with or without neuroleptics than in controls.[6] Potkin et al.[7] found no significant difference in plasma phenylalanine or tyrosine levels between chronic schizophrenia patients with or without neuroleptics and controls. Phenylethylamine, a metabolite of phenylalanine that is considered an endogenous neuroamine, was significantly higher in plasma samples from medicated patients with schizophrenia than in those from controls.[8,9]
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