Abstract:
:Tetrahydrobiopterin (BH(4)) is a vital cofactor maintaining availability of the amine neurotransmitters [dopamine (DA), noradrenaline (NA), and serotonin (5-HT)], regulating the synthesis of nitric oxide (NO) by nitric oxide synthase (NOS), and stimulating and modulating the glutamatergic system (directly and indirectly). These BH(4) properties and their potential relevance to schizophrenia led us to investigate the hypothesis of a study group (healthy controls, n=37; schizophrenics, n=154) effect on fasting plasma total biopterin levels (a measure of BH(4)). Study analysis showed a highly significant deficit of total biopterins for the schizophrenic sample after partialling out the effects of potential confounds of gender, age, ethnicity, neuroleptic use history and dose of current use, 24-hour dietary phenylalanine/protein ratio (a dietary variable relevant to BH(4) synthesis), and plasma phenylalanine (which stimulates BH(4) synthesis). A mean decrement of 34% in plasma total biopterins for schizophrenics from control values supports clinical relevance for the finding. In a subsample (21 controls and 23 schizophrenics), sequence analysis was done of the GTP cyclohydrolase I feedback regulatory gene and no mutations were found in the coding region of the gene. A deficiency of BH(4) could lead to hypofunction of the systems of DA, NA, 5-HT, NOS/NO, and glutamate, all of which have been independently implicated in schizophrenia psychopathology. Further, evidence has been accumulating which implicates the critical interdependence of these neurotransmitter systems in schizophrenia; this concept, along with the present study finding of a biopterin deficit, suggests that further study of the BH(4) system in schizophrenia is warranted and desirable.
journal_name
Neuropsychobiologyjournal_title
Neuropsychobiologyauthors
Richardson MA,Read LL,Taylor Clelland CL,Reilly MA,Chao HM,Guynn RW,Suckow RF,Clelland JDdoi
10.1159/000089002keywords:
subject
Has Abstractpub_date
2005-01-01 00:00:00pages
190-201issue
4eissn
0302-282Xissn
1423-0224pii
89002journal_volume
52pub_type
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