Tetrahydrobiopterin (BH4) is a necessary cofactor for the synthesis by the body of neurotransmitters containing amines (catecholamines), such as dopamine and serotonin. BH4 is needed to convert phenylalanine to tyrosine and to convert tyrosine to L-DOPA. The conversion to L-DOPA is the “rate limiting step,” (the step that controls the speed of the reaction) in the production of catecholamines. BH4 is necessary for the conversion of 5-OH tryptophan to serotonin, it controls the glutaminergic system and regulates nitric oxide (NO) synthesis from arginine. All of these neurotransmitters are important to brain function.
Biopterin blood levels are a measure of BH4 in a person’s body and 80% of total biopterin appears in the blood as BH4. Plasma phenylalanine levels must be tested at the same time as blood tests are done for BH4 because phenylalanine increases BH4 levels.
There is believed to be a role for BH4 treatment in psychiatric disorders. The following psychiatric disorders have been studied in regard to BH4 levels: depressive disorders, schizophrenia, obsessive-compulsive disorder, bipolar disorder and schizoaffective disorder. The results of these studies are not clear-cut and previous studies of BH4 in mental disorders have given inconsistent results. A markedly reduced level of BH4 has been noted in schizophrenia.
“DOPA responsive dystonia” is a genetic disorder caused by a mutation in the pathway of BH4 production. People with this disorder often are shown to be 50% deficit in plasma BH4. These patients have a higher risk of getting major depression and obsessive-compulsive disorder than the rest of the population.
The present study was done to compare BH4 levels in normal patients with patients with schizoaffective disorder, bipolar disorder and schizophrenia. The study included 277 subjects who were normal or diagnosed with schizoaffective disorder, schizophrenia or bipolar disorder.
The results showed that plasma BH4 levels were statistically at a significantly lower level in schizoaffective disorder and in schizophrenia. Schizophrenics show around a 34% deficit of BH4, while schizoaffective patients show a 25% deficit of BH4 levels. The results appeared lower than normal in bipolar patients, but the results were not statistically significant.
The authors theorize that some of the more severe symptoms seen in schizophrenia and schizoaffective disorder, but not seen in bipolar disorder, may be caused by the BH4 deficit.
CONCLUSION: Tetrahydrobiopterin deficits were found in patients with schizophrenia and schizoaffective disorder. Perhaps, reduced BH4 may be part of the etiology of the disorders in some patients because of abnormal neurotransmitter production in the brain.
NOTE: Phenylalanine supplementation is known to increase BH4 levels by stimulating BH4 production. It has been suggested that supplementation with phenylalanine can be of benefit in the above psychiatric disorders. Read about biopterin and aging.
Amines are nitrogen containing organic compounds. Neurotransmitters are chemicals necessary for the conduction of electrical impulses in the nervous system.
Schizophrenia is a severe psychiatric disorder that may manifest as poor contact with reality, delusions, hallucinations and difficulty functioning independently. Schizoaffective is a less severe form of schizophrenia.
PMID: 17160504.
Summary #180.
