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Strong association between homocysteine (Hcy) and metabolic syndrome (MetS) is documented in individuals with schizophrenia and it is suggested that alterations in Hcy levels might be secondary to metabolic changes induced by atypical antipsychotics (AA). Serum paraoxonase (PON-1) activity, which is negatively affected by increased Hcy concentrations are lower in schizophrenia, and this may impact the development of metabolic side effects. Forty-five subjects with schizophrenia and 43 healthy volunteers, matched according to age, gender, smoking habits, and MetS predictors, were enrolled in this study to examine how Hcy level, PON-1 activity, and MetS indicators influence each other in schizophrenic individuals on AA treatment. Serum Hcy concentrations were significantly higher (15 ± 8 μmol/L vs 12 ± 3 μmol/L), and PON activity tended to be impaired (182±82 U/L vs 216 ± 110 U/L) in schizophrenia. Serum Hcy concentrations were not different between subjects with and without metabolic syndrome in study (14±4 μmol/L and 16±9 μmol/L) and control groups (12±3 μmol/L and 13±7 μmol/L), respectively. Similarly, PON and aryl esterase (AE) activities were not different between subjects with and without metabolic syndrome in study (PON: 185±100 U/L and 181±76 U/L; AE: 84±34 kU/L and 89±20 kU/L) and control (PON: 215±111 U/L and 216±113 U/L; AE: 83±27 kU/L and 88±33 kU/L) groups, respectively. . Hcy levels and MetS predictors were not statistically correlated. Results indicate that schizophrenic subjects on AA treatment have increased levels of Hcy compared to healthy controls and this is not influenced by the presence of MetS. [ABSTRACT FROM AUTHOR]