thromboxane-b2 and Psychotic-Disorders

The methylenetetrahydrofolate reductase (MTHFR) 677 C→T polymorphism may be associated with elevated total homocysteine (tHcy) levels, an independent risk factor for cardiovascular disease. It was the study objective to evaluate in vivo lipid peroxidation and platelet activation in carriers of the MTHFR 677 C→T polymorphism and in non-carriers, in relation to tHcy and folate levels. A cross-sectional comparison of urinary 8-iso-prostaglandin (PG)F(2α) and 11-dehydro-thromboxane (TX)B(2) (markers of in vivo lipid peroxidation and platelet activation, respectively) was performed in 100 carriers and 100 non-carriers of the polymorphism. A methionine-loading test and folic acid supplementation were performed to investigate the causal relationship of the observed associations. Urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2) were higher in carriers with hyperhomocysteinaemia than in those without hyperhomocysteinaemia (p<0.0001). Hyperhomocysteinaemic carriers had lower folate levels (p=0.0006), higher urinary 8-iso-PGF(2α) (p<0.0001) and 11-dehydro-TXB(2) (p<0.0001) than hyperhomocysteinaemic non-carriers. On multiple regression analysis, high tHcy (p<0.0001), low folate (p<0.04) and MTHFR 677 C→T polymorphism (p<0.001) independently predicted high rates of 8-iso-PGF(2α) excretion. Methionine loading increased plasma tHcy (p=0.002), and both urinary prostanoid metabolites (p=0.002). Folic acid supplementation was associated with decreased urinary 8-iso-PGF(2α) and 11-dehydro-TXB2 excretion (p<0.0003) in the hyperhomocysteinaemic group, but not in the control group, with substantial inter-individual variability related to baseline tHcy level and the extent of its reduction. In conclusion, hyperhomocysteinaemia due to the MTHFR 677 C→T polymorphism is associated with enhanced in vivo lipid peroxidation and platelet activation that are reversible, at least in part, following folic acid supplementation. An integrated biomarker approach may help identifying appropriate candidates for effective folate supplementation.

Topics: Biomarkers; Cardiovascular Diseases; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus; Dinoprost; Dyslipidemias; Folic Acid; Homocystinuria; Humans; Hyperhomocysteinemia; Lipid Peroxidation; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Muscle Spasticity; Oxidative Stress; Platelet Activation; Polymorphism, Single Nucleotide; Psychotic Disorders; Smoking; Thromboxane B2

It has been hypothesized that a disturbance of glutathione (GSH) metabolism might be a common factor in many psychiatric disorders. The aim of the present study was to test this hypothesis in transient acute psychotic patients with distorted perceptions. Since the metabolism of GSH is related to that of thromboxane B2 (TXB2), prostaglandin E (PGE) and some amino acids, we determined these substances in the plasma of 15 patients and 17 normal controls. Plasma concentrations of TXB2 were significantly higher and concentrations of serine and tryptophan were significantly lower in patients than in controls. Large variation was observed in plasma PGE levels in patients, although mean values did not differ significantly from controls. These results are consistent with the hypothesis that the metabolism of GSH is impaired in transient psychotic states.

Topics: Adult; Female; Glutathione; Humans; Male; Methionine; Prostaglandins E; Psychotic Disorders; Serine; Taurine; Thromboxane B2