Interaction of BDNF and cytokines in executive dysfunction in patients with chronic schizophrenia

Multiple lines of evidence indicate that patients with chronic schizophrenia (SCZ) display executive dysfunction across the illness course. However, the potential molecular pathophysiologic mechanisms remain poorly elucidated. Neurodevelopmental changes caused by alterations of inflammatory mediators and neurotrophins have been shown to occur in the earliest stages of SCZ, and be associated with executive dysfunction (ED) in SCZ. Therefore, the current study was to investigate whether the interplay between BDNF and inflammatory mediators was involved in the disruption of executive function of long-term hospitalized patients with chronic SCZ. Serum cytokines and BDNF levels were measured in 112 long-term hospitalized patients with chronic SCZ and 44 healthy normal controls. Executive functions were assessed by verbal fluency tests (VFT), the Stroop word-color test (Stroop), and the Wisconsin card sorting tests (WCST).The results showed that the patients had higher IL-2, IL-6, IL-8, but lower TNF-α and BDNF compared to control subjects. In the patient group, BDNF was positively associated with IL-2 and IL-8 levels, while lower BDNF levels were correlated with ED measured by VFT and WCST tests. Multiple stepwise regression analyses confirmed that BDNF × IL-8 and BDNF × TNF-α were factors influencing the total score of VFT, while BDNF × IL-8 and BDNF × TNF-α were recognized as influencing factors for WCST scores. Our results suggest complex interactions between BDNF and cytokines were involved in the pathophysiology of executive function impairments in patients with SCZ.