Incidence of non-alcoholic fatty liver disease and metabolic dysfunction in first episode schizophrenia and related psychotic disorders: a 3-year prospective randomized interventional study.
Patients with schizophrenia spectrum disorders have increased morbidity and mortality, largely due to cardiovascular disease, which is associated with antipsychotic treatment.



Because of the link between cardiometabolic risk, non-alcoholic fatty liver disease (NAFLD), and antipsychotics, we aimed to investigate the development of NAFLD during the first 3 years of antipsychotic treatment in first episode non-affective psychosis patients.



A sample of 191 subjects was included in final analyses, randomly assigned to aripiprazole (N = 83), risperidone (N = 12), quetiapine (N = 46), and ziprasidone (N = 50). At intake, 180 patients were antipsychotic naïve. The NAFLD fibrosis score, FIB-4 score, and the fatty liver index (FLI) were calculated at baseline, at 3 months, and then yearly for 3 years. None of the patients showed significant liver fibrosis according to the mentioned scores at baseline, prior to randomization. At 3 years follow-up, 25.1 % individuals showed a FLI score ≥60, which is a predictor of steatosis. Of the individuals considered indeterminate at baseline, 64.7 % developed a FLI score ≥60 and only 16.6 % who had a FLI score <30 at baseline, showed a FLI score predictor of steatosis at endpoint. The FLI score ≥60 at endpoint was associated with an increase of more than 7 % of the body mass index (FLI score ≥ 60, 91.7 %; FLI < 60, 55.9 %; p < 0.001), increased triglyceride levels (FLI score ≥ 60, 54.2 %; FLI < 60, 5.6 %; p < 0.001), decreased HDL levels (FLI score ≥ 60, 41.7 %; FLI < 60, 17.5 %; p = 0.001), hypertension (FLI score ≥ 60, 19.5 %; FLI < 60, 4.5 %; p = 0.002), and waist circumference increase (steatosis 68.8 %; FLI < 60, 14.0 %; p < 0.001).



Our results support the importance of assessing the potential development of NAFLD in schizophrenia spectrum patients receiving antipsychotic medication.
Department of Medicine and Psychiatry. Psychiatry Unit. IDIVAL, Instituto de Investigación Valdecilla, Hospital Universitario Marques de Valdecilla, 39008, Santander, Spain. josetamc@hotmail.com.
María José
MJ
Morlán-Coarasa
Gastroenterology and Hepatology Department. Infection, Immunity and Digestive Pathology Group. IDIVAL, Instituto de Investigación Valdecilla, Hospital Universitario Marques de Valdecilla, 39008, Santander, Spain.
María Teresa
MT
Arias-Loste
Department of Medicine and Psychiatry. Psychiatry Unit. IDIVAL, Instituto de Investigación Valdecilla; Instituto de Salud Carlos III, 3-CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Hospital Universitario Marques de Valdecilla, 39008, Santander, Spain.
Víctor
V
Ortiz-García de la Foz
Department of Medicine and Psychiatry. Psychiatry Unit. IDIVAL, Instituto de Investigación Valdecilla; Instituto de Salud Carlos III, 3-CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Hospital Universitario Marques de Valdecilla, 39008, Santander, Spain.
Obdulia
O
Martínez-García
Gastroenterology and Hepatology Department. Infection, Immunity and Digestive Pathology Group. IDIVAL, Instituto de Investigación Valdecilla, Hospital Universitario Marques de Valdecilla, 39008, Santander, Spain.
Carmen
C
Alonso-Martín
Gastroenterology and Hepatology Department. Infection, Immunity and Digestive Pathology Group. IDIVAL, Instituto de Investigación Valdecilla, Hospital Universitario Marques de Valdecilla, 39008, Santander, Spain.
Javier
J
Crespo
UCM Digestive Diseases and Ciberehd, University of Seville, Hospital Universitario de Valme, 41004, Sevilla, Spain.
Manuel
M
Romero-Gómez
Gastroenterology and Hepatology Department. Infection, Immunity and Digestive Pathology Group. IDIVAL, Instituto de Investigación Valdecilla, Hospital Universitario Marques de Valdecilla, 39008, Santander, Spain.
Emilio
E
Fábrega
Department of Medicine and Psychiatry. Psychiatry Unit. IDIVAL, Instituto de Investigación Valdecilla; Instituto de Salud Carlos III, 3-CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Hospital Universitario Marques de Valdecilla, 39008, Santander, Spain. benedicto.crespo@unican.es.
Benedicto
B
Crespo-Facorro
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008659:Metabolic Diseases / Q000453:epidemiology*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology*; D010879:Piperazines / Q000627:therapeutic use; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000150:complications* / Q000188:drug therapy; D000069348:Quetiapine Fumarate / Q000627:therapeutic use; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy*; D013844:Thiazoles / Q000627:therapeutic use; D055815:Young Adult
D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; D000069348:Quetiapine Fumarate; C092292:ziprasidone; D000068180:Aripiprazole; D018967:Risperidone
Antipsychotics; Cardiometabolic risk; Hepatic steatosis; Lipids; Metabolic syndrome; Psychosis