Ceramides: Shared Lipid Biomarkers of Cardiovascular Disease and Schizophrenia

INTRODUCTION: Schizophrenia, although a debilitating mental illness, greatly affects individuals physical health as well. One of the leading somatic comorbidities associated with schizophrenia is cardiovascular disease, which has been estimated to be one of the leading causes of excess mortality in patients diagnosed with schizophrenia. Although the shared susceptibility to schizophrenia and cardiovascular disease is well established, the mechanisms linking these two disorders are not well understood. Genetic studies have hinted toward shared lipid metabolism abnormalities co-occurring in the two disorders, while lipid compounds have emerged as prognostic markers for cardiovascular disease. In particular, three ceramide species in the blood plasma, Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1), have been robustly linked to the latter disorder. AIM: We aimed to assess the differences in abundances of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) in the blood plasma of schizophrenia patients compared to healthy controls. METHODS: We measured the abundances of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) in a cohort of 82 patients with schizophrenia and 138 controls without a psychiatric diagnosis and validated the results using an independent cohort of 26 patients with schizophrenia, 55 control individuals, and 19 patients experiencing a first psychotic episode. RESULTS: We found significant alterations for all three ceramide species Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) and a particularly strong difference in concentrations between psychiatric patients and controls for the ceramide species Cer(d18:1/18:0). CONCLUSIONS: The alteration of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) levels in the blood plasma might be a manifestation of metabolic abnormalities common to both schizophrenia and cardiovascular disease.