Dataset Information

Regulation of cortical and peripheral GCH1 expression and biopterin levels in schizophrenia-spectrum disorders.

ABSTRACT: 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. GCH1 encodes the first and rate-limiting enzyme in BH4 synthesis. Peripheral GCH1 expression is lower in first episode psychosis patients versus controls, and we hypothesized that a GCH1 promoter polymorphism associated with psychiatric illness, contributes to regulation of both GCH1 expression and BH4 levels. 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) on GCH1 expression in the prefrontal cortex (n?=?67) and peripheral leukocytes (n?=?53). We found a significant linear relationship between GCH1 and 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 on GCH1: Expression rose significantly after the onset of medication, primarily in A allele patients. These data suggest the potential for personalized genetic approaches to ameliorating BH4 deficits in schizophrenia-spectrum disorders.

SUBMITTER: Clelland JD

PROVIDER: S-EPMC5866784 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Regulation of cortical and peripheral GCH1 expression and biopterin levels in schizophrenia-spectrum disorders.

Clelland James D JD Read Laura L LL Smeed Jennifer J Clelland Catherine L CL

Psychiatry research 20180208

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. GCH1 encodes the first and rate-limiting enzyme in BH4 synthesis. Peripheral GCH1 expression is lower in first episode psychosis patients versus controls, and we hypothesized that a GCH1 promoter polymorphism associated with psychiatric illnes ...[more]

PMID: 29471261

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Project description:Studies of head size and brain volume in autism spectrum disorders have suggested that early cortical overgrowth may be followed by prematurely arrested growth. However, the few investigations quantifying cortical thickness have yielded inconsistent results, probably due to variable ages and/or small sample sizes. We assessed differences in cortical thickness between high-functioning adolescent and young adult males with autism spectrum disorders (n = 41) and matched typically developing males (n = 40). We hypothesized thinner cortex, particularly in frontal, parietal and temporal regions, for individuals with autism spectrum disorders in comparison with typically developing controls. Furthermore, we expected to find an age × diagnosis interaction: with increasing age, more pronounced cortical thinning would be observed in autism spectrum disorders than typically developing participants. T(1)-weighted magnetization prepared rapid gradient echo 3 T magnetic resonance imaging scans were acquired from high-functioning males with autism spectrum disorders and from typically developing males matched group-wise on age (range 12-24 years), intelligence quotient (? 85) and handedness. Both gyral-level and vertex-based analyses revealed significantly thinner cortex in the autism spectrum disorders group that was located predominantly in left temporal and parietal regions (i.e. the superior temporal sulcus, inferior temporal, postcentral/superior parietal and supramarginal gyri). These findings remained largely unchanged after controlling for intelligence quotient and after accounting for psychotropic medication usage and comorbid psychopathology. Furthermore, a significant age × diagnosis interaction was found in the left fusiform/inferior temporal cortex: participants with autism spectrum disorders had thinner cortex in this region with increasing age to a greater degree than did typically developing participants. Follow-up within group comparisons revealed significant age-related thinning in the autism spectrum disorders group but not in the typically developing group. Both thinner temporal and parietal cortices during adolescence and young adulthood and discrepantly accelerated age-related cortical thinning in autism spectrum disorders suggest that a second period of abnormal cortical growth (i.e. greater thinning) may be characteristic of these disorders.

Dataset Information

Regulation of cortical and peripheral GCH1 expression and biopterin levels in schizophrenia-spectrum disorders.

Publications

Regulation of cortical and peripheral GCH1 expression and biopterin levels in schizophrenia-spectrum disorders.

Similar Datasets

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