Alterations in methionine to homocysteine ratio in individuals with first-episode psychosis and those with at-risk mental state.

Background: Disturbance of the methionine (Met) cycle, which produces Met from homocysteine (Hcy), is suggested to be involved in several diseases, including psychiatric disorders. This study was aimed to investigate both levels of Met and Hcy in serum from individuals with first-episode psychosis (FEP) and individuals with at-risk mental state (ARMS).

Method: We measured serum Met and Hcy levels in individuals with FEP (n = 13) and ARMS (n = 30) using HPLC with fluorescence detection and LC-ESI-MS/MS. Met and Hcy levels in healthy controls (n = 41) were also measured. Differences between the 3 groups were analyzed by one-way analysis of variance (ANOVA) with Bonferroni correction.

Results: Serum Met levels were decreased (p = 0.038) and Hcy levels were increased (p = 0.017) in the FEP group. Hcy levels were also significantly increased compared to the ARMS group (p = 0.016), while Met levels were not significantly different between the FEP and ARMS groups. A significant decrease in the Met to Hcy ratio (Met/Hcy) was observed in the FEP group compared to both the control (p = 4.58 × 10) and ARMS (p = 8.07 × 10) groups. Furthermore, Met/Hcy ratio was correlated with Positive and Negative Syndrome Scale, especially positive scores (p = 5.90 × 10).

Conclusion: Taken together, these data indicate that a decrease in the serum Met/Hcy ratio may be a risk factor for developing psychosis during the transition from ARMS to FEP, and may prove to be a useful marker of the phase between ARMS and FEP.