Analysis of Plasma Biopterin Levels in Psychiatric Disorders Suggests a Common BH4 Deficit in Schizophrenia and Schizoaffective Disorder

Abstract

Tetrahydrobiopterin (BH4) is an essential cofactor for amine neurotransmitter synthesis. BH4 also stimulates and modulates the glutamatergic system, and regulates the synthesis of nitric oxide by nitric oxide synthases. A connection between BH4 deficiencies and psychiatric disorders has been previously reported; major depression and obsessive-compulsive disorder have been found in subjects with a BH4 deficiency disorder and more recently we have observed a robust plasma deficit of biopterin (a measure of BH4), in a large group of schizophrenic patients compared to control subjects. To extend our previous finding in schizophrenia, we analyzed plasma biopterin levels from patients with schizoaffective and bipolar disorders. A significant difference in biopterin was seen among the diagnostic groups (P < 0.0001). Post hoc analyses indicated significant biopterin deficits relative to the normal control group for the schizoaffective group, who had biopterin levels comparable to the schizophrenic group. Bipolar disorder subjects had plasma biopterin levels that were higher that the schizoaffective disorder group and significantly higher than the schizophrenic group. The demonstrated significant biopterin deficit in both schizophrenia and schizoaffective disorder, may suggest an etiological role of a BH4 deficit in these two disorders, via dysregulation of neurotransmitter systems.

Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder

“…This assumption may be justified when the molecular mechanisms of psychosis are of prime interest. Molecular abnormalities common for schizophrenia and schizoaffective disorder have been documented (Richardson et al, 2007). Genetic linkage studies suggest that functional psychosis is a spectrum of clinical phenotypes controlled by overlapping sets of susceptibility genes (Craddock et al, 2006; Craddock et al, 2005; Craddock and Owen, 2005; Hamshere et al, 2005).…”

Alterations in dopamine and glutamate neurotransmission in tetrahydrobiopterin deficient spr-/- mice: relevance to schizophrenia

“…Another study reported that total biopterin levels were only low in plasma and but not in urine of patients diagnosed with schizophrenia (59). In contrast, more recent studies found profound reductions in plasma total biopterin levels in schizophrenia and schizoaffective patients (by 34% and 25%, respectively) compared to normal controls (60,61). Meta-analysis studies for the International Database of BH4 Deficiencies found significant correlation between biopterin levels in plasma and CSF but failed to establish such a correlation between biopterin levels in urine and CSF of schizophrenia patients (60).…”

Elevated Levels of Plasma Phenylalanine in Schizophrenia: A Guanosine Triphosphate Cyclohydrolase-1 Metabolic Pathway Abnormality?

“…BH4 is ubiquitous and is likely present in all cells and tissues but current knowledge of the regulatory mechanism of BH4 in the brain is far from complete [14]. BH4 also modulates glutamatergic system function and regulates nitric oxide production [15]. BH4 deficit has previously been reported in schizophrenia patients relative to healthy controls [16].…”