Regulation of cortical and peripheral GCH1 expression and biopterin levels in schizophrenia-spectrum disorders.
Regulation of cortical and peripheral GCH1 expression and biopterin levels in schizophrenia-spectrum disorders.
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精神分裂症谱系疾病中皮质和外周 GCH1 表达以及生物蝶呤水平的调节。
DOI：
10.1016/j.psychres.2018.02.020
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发表时间：
2018
影响因子：
11.3
通讯作者：
Clelland,CatherineL
中科院分区：
文献类型：
--
作者：
Clelland,JamesD;Read,LauraL;Smeed,Jennifer;Clelland,CatherineL
Tetrahydrobiopterin (BH4) is an essential cofactor for dopamine, serotonin and nitric oxide synthesis. Deficits of plasma total biopterin (a measure of BH4) have been described in schizophrenia and schizoaffective disorder.GCH1encodes the first and rate-limiting enzyme in BH4synthesis. PeripheralGCH1expression is lower in first episode psychosis patients versus controls, and we hypothesized that aGCH1promoter polymorphism associated with psychiatric illness, contributes to regulation of bothGCH1expression and BH4levels. We tested this hypothesis in 120 subjects (85 patients with schizophrenia or schizoaffective disorder and 35 controls): Patients with the rs10137071 A allele had significantly lower plasma biopterin than GG patients and controls. In additional samples we assessed the relationship between genotype and diagnosis (schizophrenia or control) onGCH1expression in the prefrontal cortex (n = 67) and peripheral leukocytes (n = 53). We found a significant linear relationship betweenGCH1and study group in the CNS and periphery, with A allele patients having lower expression. Finally, in antipsychotic naïve patients (n = 13) we tested for an effect of medication onGCH1: Expression rose significantly after the onset of medication, primarily in A allele patients. These data suggest the potential for personalized genetic approaches to ameliorating BH4deficits in schizophrenia-spectrum disorders.
