Abstract: Background Cardiometabolic disorders are largely responsible for excess mortality in schizophrenia. Non-alcoholic fatty liver disease (NAFLD) is increasingly relevant in the development of metabolic risk factors that have been associated with antipsychotic treatment. We aimed to assess the incidence of NAFLD and metabolic disturbances during the first 3 years of antipsychotic treatment in patients with first episode of psychosis (FEP), and compare it with the incidence in a control group. Methods Data were obtained from patients with psychosis (n = 160) and healthy controls (n = 66) included in the Cantabria's clinical and research program on FEP (PAFIP) from 2012 to 2018. Fatty Liver Index (FLI) was used to estimate the amount of fat in the liver. FLI has been validated for the diagnosis of NAFLD against different standards such as liver ultrasound and biopsy. FLI and metabolic parameters were registered at baseline, 3 months and then yearly for 3 years. Results At the end of the follow-up (3-years), 21.9 % of patients with psychosis developed a FLI ? 60, suggestive of liver steatosis, compared to only a 3 % of subjects within the control group (X2 = 12.120; p < 0.001). In the FEP patients group, developing a FLI ? 60 was statistically associated with significant increments in metabolic parameters, and with Metabolic Syndrome (MetS) (X2 = 16.151; p < 0.001) and high blood pressure (X2 = 10.654; p = 0.001). Conclusions Having a first episode of non-affective psychosis was significantly associated with developing liver steatosis (FLI ? 60) in the first three years after initiating antipsychotic treatment. The results highlight the importance of early screening the emergence of NAFLD in schizophrenia patients.

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