fundamental role of methylenetetrahydrofolate reductase 677 c->t genotype and flavin compounds in biochemical phenotypes for schizophrenia and schizoaffective psychosis.
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ID: 248303
2016
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Abstract
The Mental Health Biomarker Project (2010-2016) explored variables for psychosis in schizophrenia and schizoaffective disorder. Blood samples from 67, highly-characterized symptomatic cases and 67 gender and age matched control participants were analysed for methyl tetrahydrofolate reductase (MTHFR) 677C->T gene variants and for vitamin B6, B12 and D, folate, unbound copper, zinc cofactors for enzymes in the methylation cycle and related catecholamine pathways. Urine samples were analysed for indole-catecholamines, their metabolites and oxidative-stress marker, hydroxylpyrolline-2-one (HPL). Rating scales were Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, Global Assessment of Function scale, Clinical Global Impression score and Social and Occupational Functioning Scale. Analysis used Spearman’s correlates, Receiver Operating Characteristics and structural equation modelling (SEM). The correlative pattern of variables in the overall participant sample strongly implicated Monoamine Oxidase (MAO) enzyme inactivity so the significant role of MAO’s cofactor flavin adenine nucleotide (FAD) and its precursor flavin adenine mononucleotide (FMN) within the biochemical pathways was investigated and confirmed as 70% on SEM of the total sample. Splitting the data sets for MTHFR 677C->T polymorphism variants coding for the MTHFR enzyme, discovered that biochemistry variables relating to the wild-type enzyme differed markedly in pattern from those coded by the homozygous variant and that the hereozygous-variant pattern resembled the wild type-coded pattern. The MTHFR 677C->T -wild and -heterozygous gene variants have a pattern of depleted vitamin cofactors characteristic of flavin insufficiency with under-methylation and severe oxidative stress. The second homozygous MTHFR 677TT pattern related to elevated copper:zinc ratio and a vitamin pattern related to flavin sufficiency and risk of over-methylation. The two gene variants and their different biochemical phenotypes govern findings in relationship to case-identification, illness severity, duration of illness and functional disability in schizophrenia and schizoaffective psychosis and establish a basis for gene variation guided precision treatment for the management of psychosis.
| Reference Key |
fryar-williams2016frontiersfundamental
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|---|---|
| Authors | ;Stephanie Fryar-Williams |
| Journal | journal of experimental psychology general |
| Year | 2016 |
| DOI |
10.3389/fpsyt.2016.00172
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| URL | |
| Keywords | Keywords not found |
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