Patients Initiating Treatment for First Episode Psychosis May Be at Increased Risk for Liver Steatosis

The Cantabria Early Intervention in Psychosis Program (PAFIP) was conducted between 2012 and 2018 in Spain.

Initiating treatment for a first episode of nonaffective psychosis was potentially associated with developing liver steatosis, according to results of a study published in Schizophrenia Research.

The Cantabria Early Intervention in Psychosis Program (PAFIP) was conducted between 2012 and 2018 in Spain. Patients (n=160) with a first psychosis episode were randomized to receive 5-30 mg/day aripiprazole or 1-6 mg/day risperidone. Patients were followed-up with at 12 weeks and 1, 2, and 3 years using the Scale and evaluated using the Assessment of Negative Symptoms and safety was evaluated using the Udvalg for Kliniske Undersøgelser (Task force for Clinical Investigations) (UKU) side effect rating scale. Liver health was measured using the fatty liver index (FLI), triglycerides, and gamma-glutamyl transpeptidase (GGT) and compared with a group of 66 healthy individuals. Liver steatosis was defined as FLI ≥60.

The patients and controls were aged mean 33.1 (SD, 11.1) and 30.4 (SD, 8.3) years (P =.043), 46.9% and 59.1% were men, 86.3% and 100.0% were White (P =.002), and 85.0% and 74.2% had baseline FLI <30, respectively.

Among the patient cohort, 44.0% had schizophrenia, 28.3% schizoaffective disorder, 14.5% brief psychotic disorder, 11.3% psychotic disorder not otherwise defined, 1.3% schizoaffective disorder, and 0.6% delusional disorder. A quarter of patients (28.0%) had a family history of a psychiatric disorder.

Stratified by baseline FLI, 136 had FLI <30 and 24 had FLI ≥30 to <60. The patients with higher FLI were older at psychosis onset (P =.001) and fewer were students (P =.028).

At the follow-up, fewer patients had FLI <60 (78.1% vs 97.0%; P <.001), more had gained >7% of their body weight (70.0% vs 19.7%; P <.001), high-density lipoprotein ≤40 mg/dl for men or ≤50 mg/dl for women (27.5% vs 0.0%; P <.001), metabolic syndrome (16.4% vs 0.0%; P =.001), insulin >17 μg/ml (12.3%.vs 0.0%; P =.003), glucose ≥100 mg/dl (18.8% vs 4.5%; P =.006), waist ≥102 cm for men or ≥88 cm for women (31.3% vs 13.6%; P =.006), systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg (31.6% vs 15.6%; P =.015), and triglycerides ≥150 mg/dl (16.3% vs 6.1%; P =.040).

The patients were associated with significantly decreased overall survival probability (P <.001).

At the final follow-up, 35 patients had FLI ≥60. More patients with high FLI gained >7% of body weight, had GGT >50 UI/L, metabolic syndrome, high triglyceride levels, systolic or diastolic blood pressures, and increased waist circumference (all P ≤.001).

No significant group differences were observed on the basis of medication.

The major limitation of this study was the baseline differences between patients and controls.

The study authors concluded, “Patients with an antipsychotic-treated first episode psychosis are at greater risk of developing a FLI score ≥60, suggestive of liver steatosis, when compared to a control group.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Rus SG, de la Foz VOG, Arias-Loste MT, et al. Elevated risk of liver steatosis in first-episode psychosis patients: Results from a 3-year prospective study. Schizophr Res. 2022;246:30-38. doi:10.1016/j.schres.2022.06.001