Low mood in individuals with schizophrenia: Integrating cognitive performance, structural brain alterations and interleukin-6 levels

Depressive symptoms in schizophrenia have been implicated in poor functional outcome, including treatment resistance. Cognitive deficits, reduced structural brain measures (reduced cortical thickness, lower surface area, and reduced volume), and elevated interleukin (IL)-6 may contribute to low mood and fatigue in schizophrenia. We applied structural equation modelling (SEM) to examine the unique and combined relationships between these measures in 44 individuals with established schizophrenia (SZ; 70.5% males, mean age = 44.1; standard deviation (SD) ± 10.8) and 161 healthy controls (HC; 94% males; mean age: 36.4; SD ± 12.5). We ran SEM in two groupings of (i) all participants across SZ and HC and (ii) HC only. SEM findings across all participants showed that higher IL-6 levels, but not reduced structural brain measures, predicted greater fatigue (Beta = 0.241, SE = 0.086, p=0.005) and lower mood (Beta = 0.217, SE = 0.086, p=0.012). General cognitive performance was positively related to structural brain changes (Beta = 0.403, SE = 0.062, p