Uric-Acid Metabolism in Manic-Depressive Illness and During Lithium Therapy

The effect of lithium salts on the urinary excretion of α‐oxoglutarate in man

“…During the periods studied in these experiments, there was no correlation between uric acid excretion and a-oxoglutarate excretion, and no clear increase of uric acid excretion. However, Anumonye et al (1968) observed the changes over longer periods of time and hence their findings are not necessarily in conflict with our results.…”

“…Hence the increased a-oxoglutarate excretion due to lithium is not a simple analogue of that due to alkalosis. Anumonye, Reading, Knight & Ashcroft (1968) found a marked uricosuric effect of lithium and, because of this, suggested possible effects on the transport of organic acids. During the periods studied in these experiments, there was no correlation between uric acid excretion and a-oxoglutarate excretion, and no clear increase of uric acid excretion.…”

Increased uric acid levels in bipolar disorder subjects during different phases of illness

“…Second, the choice of a control group of patients with mainly OCD or MDD in remission was made for practical reasons, and limits our ability to examine the specificity of the purinergic dysfunction with regard to other psychiatric conditions. A third limitation is that we could not completely control for the exposure to mood stabilizers or antipsychotics in the bipolar group; however, we identified a large subgroup of subjects (N ¼84) who had never been exposed before to lithium, carbamazepine (both drugs seem to decrease uric levels - Anumonye et al, 1968), or valproate (which does not reduce uric levels but might increase them - Ring et al, 1991) and this subgroup also showed increased uric acid levels as compared to controls. It is important to note that the effect of mood stabilizers (and mostly of antipsychotics used for the treatment of bipolar disorder) on uric acid levels in relationship to clinical improvement has not been systematically evaluated.…”

“…Particular attention was devoted to lifetime exposure to lithium, valproate and carbamazepine because of the known potential effects of mood stabilizers on serum uric acid levels; in particular, lithium was found to lower uric acid plasma levels and to have uricosuric effects in mania (Anumonye et al, 1968); carbamazepine similarly decreased uric acid levels; in contrast, valproate appeared to have the opposite effect (Ring et al, 1991).…”

Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics

“…Early studies conducted in the 1960s and 1970s implicated purinergic system dysfunction in BD (Anumonye et al, 1968; Brown et al, 1972; Jenner et al, 1972; Hansen and Dimitrakoudi, 1974). Subsequently, CSF levels of the purine metabolites hypoxanthine and xanthine were linked with depressive symptoms in MDD.…”