Reduced urinary excretion of homocysteine could be the reason of elevated plasma homocysteine in patients with psychiatric illnesses.

Objectives: Although increased plasma total homocysteine (tHcy) concentrations were reported in psychiatric diseases, currently the reasons of elevated tHcy levels were not clearly understood. In this study we aimed to investigate the contribution of renal clearance of homocysteine on plasma tHcy load in patients with depression and first episode psychosis.
Design and Methods: Thirty depression, 14 first episode psychosis patients and 34 healthy individuals (control group) were involved in the study. In patients and control groups, plasma and urine tHcy levels, urine methylmalonic acid (uMMA), serum vitamin B12 and folate concentrations were measured.
Results: Although there was not any difference between depression, psychosis and control groups with respect to mean (SD) values of vitamin B12 (289(131), 230 (72) and 249(79) pg/mL, respectively) and folate (6.4(4.0), 5.3(2.3) and 5.7(2.3) ng/mL, respectively), plasma tHcy levels of depression and psychosis group were higher than the control values (16.3(6.2), 15.5(4.3) and 9.9(2.1) micromol/L, respectively). Urine tHcy values of patient groups were significantly lower than those in the control group (14.5(7.6), 15.8(6.8) and 29.6(16.9) micromol/g creatinine, respectively). There were elevated uMMA levels in depression and psychosis groups compared with control group (4.9(2.4), 6.6(3.2) and 2.8(1.2) mmol/mol creatinine, respectively). There were a significant and negative correlation between urinary tHcy and plasma tHcy levels (r=-0.258 and p=0.011).
Conclusion: In conclusion, reduced urinary tHcy levels in psychiatric patients could be one of the reasons of plasma tHcy elevations with normal folate and vitamin B12 levels. Altered renal handling mechanisms of homocysteine may lead to elevated plasma tHcy levels by reduced clearance of homocysteine via glomerular filtration.