Tetrahydrobiopterin metabolism in depression and senile dementia of Alzheimer type
Excretion of biopterin and the related pteridines neo-pterin and pterin was measured in urine samples from a group of 25 male and 51 female depressed outpatients receiving lithium therapy, and compared to 61 male and female control subjects. The ratio of neopterin to biopterin excreted (N/B) was significantly higher in the patients than controls (p< 0.01), and the significant (p< 0.01) positive correlation between urinary neopterin and biopterin shown by the controls was absent in the patients, indicating disrupted biosynthesis of BH4. Urinary cortisol excretion was similar in all groups, but creatinine excretion was diminished in the patients, suggesting a nephrogenic effect of lithium. Serum folate was shown to correlate with urinary biopterin in female unipolar patients. Two groups of elderly females with senile dementia of Alzheimer type (SDAT) were examined for urinary pteridine excretion. In group I (n= 10), N/B was significantly higher than in 24 controls (p< 0.05) and the ratio B/B+ N significantly lower, indicating diminished tetrahydrobiopterin biosynthesis. A second study on 30 patients and 24 age-matched controls confirmed these findings. However, as N correlated with B in both patients and controls, the alteration in BH4 metabolism in SDAT is possibly different to that shown in depression. Lithium had no effect in vivo or in vitro on wistar rat brain or liver BH4 biosynthesis or salvage enzyme dihydropteridine reductase at a range of concentrations and duration of dosing period. In general, no significant effects were shown by the tricyclic antidepressant imipramine, the anticonvulsant sodium valproate, the vitamin folic acid or the anticholinergic agent methylparatyrosine, indicating that BH_4 may differ in man and rat. The synthetic corticosteroid dexamethasone had no effect on rat brain metabolism, nor did stimulation of natural cortisol by stress-immobilisation, although hypothalamic-pituitary-adrenal axis disturbances are know in depression.