Determinants of Real-World Functioning in Schizophrenia

Blood samples in a test tube rack.
Researchers found data that showed the predictors of poor real-world functioning in patients with early stage schizophrenia were negative symptoms and IL-2.

Negative symptoms, levels of the inflammatory biomarker interleukin-2 (IL-2), and baseline cognitive performance and functioning predict real-world functioning at 1-year follow-up in outpatients with schizophrenia, according to a study published in Psychiatry Research.

Although several prior studies have indicated that cognitive and negative symptoms are determinants in the real-world functioning of patients with schizophrenia, these studies do not usually include biological factors, such as inflammatory markers. This prospective study was designed to identify biological and clinical factors that can predict the real-world functioning of outpatients in an early stage of schizophrenia. Of an initial sample of 73 patients, 57 completed the 1-year follow-up.

Related Articles

At baseline and 1 year, assessments of functioning, psychopathology, and cognitive performance were made using the Brief Negative Symptom Scale; the Positive and Negative Syndrome Scale; the Calgary Depression Scale; the MATRICS Consensus Cognitive Battery; and the Personal and Social Performance Scales (PSP). Biological biomarkers, including blood parameters and anthropometric data, were also collected. The PSP was also used at baseline and 1-year follow-up to assess the level of global personal and social functioning. Pearson correlation and multiple regression analyses were performed.

For PSP total scores at baseline, statistically significant correlations were found with every psychopathological score and subscore (r= -0.717 to -0.378) and every MATRICS Consensus Cognitive Battery cognitive domain (r= 0.420 to 0.347) except reasoning/problem solving and attention/vigilance. PSP scores negatively correlated with IL-1β levels (r= -0.392) and IL-2 levels (r= -0.448). In the regression model, PSP was mainly associated with the asociality subscore of the Brief Negative Symptom Scale, but also with the subscores for avolition and blunted affect. For PSP total scores at 1-year follow-up, statistically significant correlations were found with every baseline psychopathological score (r= -0.364 to -0.694) except for Calgary Depression Scale, and with every cognitive domain (r= 0.400-0.564) except for problem-solving and reasoning. A significant negative correlation was found between baseline IL-1β level (r= -0.352) and poor real-world functioning.

The study investigators concluded that despite the small sample size and the inability to clarify the involvement of IL-2 in schizophrenia because of a lack of data on biological markers at follow-up, the most important predictors of poor real-world functioning in patients with early stage schizophrenia were negative symptoms and IL-2, with baseline cognitive performance and previous functioning also determining functioning at 1-year follow-up. “A correct approach to and treatment of the potential causes of secondary negative symptoms, along with limited use of sedative treatments to reduce attention deficit, should be the targets of intervention of these patients in clinical practice. More evidence is needed regarding the effect of interventions to address inflammatory pathways.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Gonzalez-Blanco L, Garcia-Portilla MP, Santo FD, et al. Predicting real-world functioning in outpatients with schizophrenia: role of inflammation and psychopathology [published online August 16, 2019]. Psychiatry Res. doi: 10.1016/j.psychres.2019.112509