Abstract
BACKGROUND: Schizophrenia is a debilitating mental disorder affecting about 1% of the global population, characterized by significant cognitive impairments and a strong hereditary component. Carnitine, particularly Levo-carnitine and its derivatives, plays a crucial role in cellular metabolism and mitochondrial function, with evidence suggesting a link between levo-carnitine deficiency and schizophrenia pathology. This study aims to investigate the causal relationship between different subtypes of levo-carnitine and the susceptibility to schizophrenia using Mendelian randomization analysis. METHODS: Forward Mendelian randomization analysis was conducted using levo-carnitine and its derivatives as exposure and schizophrenia as the outcome. Candidate data were obtained from the Open-GWAS database. Instrumental variables were identified as single nucleotide polymorphisms closely associated with exposure and harmonized with the outcome data after removing confounders and outliers. Mendelian randomization analysis was performed using inverse variance weighting as the primary approach, and sensitivity analysis was conducted to assess the reliability and robustness of the results. Finally, a reverse Mendelian randomization analysis was carried out using the same analytical procedures. RESULTS: The Mendelian randomization results indicate a significant negative causal relationship between isovaleryl-levo-carnitine and schizophrenia (P < 0.05), but no significant associations in other groups (P > 0.05). Additionally, the reverse Mendelian randomization analysis did not identify any causal relationship between schizophrenia and levo-carnitine related exposures (P > 0.05). Sensitivity analyses, including pleiotropy and heterogeneity analysis, did not reveal any potential bias in the Mendelian randomization results (P > 0.05). CONCLUSION: The results suggest that elevated levels of isovaleryl-levo-carnitine may potentially mitigate the risk of developing schizophrenia, highlighting the prospective therapeutic and preventive implications of isovaleryl-levo-carnitine in the clinical management of schizophrenia.