Interaction of oxidative stress and BDNF on executive dysfunction in patients with chronic schizophrenia

Executive dysfunction is increasingly recognized as one of the widely observed dimensions of cognitive impairments in the course of schizophrenia (SCZ). However, the potential molecular pathological mechanisms remain elusive. Previous studies have demonstrated that decreased brain-derived neurotrophic factor (BDNF) and oxidative damage may be associated with the psychopathology and cognitive impairment of SCZ. The present study aims to assess whether the interaction between BDNF and oxidative damage is involved in the disruption of executive function (EF) in patients with chronic SCZ. Serum BDNF and plasma oxidative stress markers were measured in 189 patients and 60 control subjects. EFs were evaluated by Wisconsin card sorting tests (WCST), Stroop word/color test (Stroop), and verbal fluency tests (VFT). The results showed that patients performed worse in the VFT, WCST and Stroop tests than healthy subjects. Moreover, patients had lower activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and lower BDNF levels, but higher malondialdehyde (MDA) levels than healthy controls. In patients, BDNF was negatively correlated with SOD (p < 0.01). For patients, catalase (CAT) activity was negatively associated with WCST error score (p = 0.02) and BDNF was positively correlated to VFT score (p = 0.02). However, all these correlations between biomarkers and EF domains did not pass Bonferroni corrections. Finally, multiple regression analyses identified BDNF × SOD activity and BDNF × MDA as influencing factors for VFT score in patients (both p < 0.05). Our results highlight the complex interplay between OS parameters and BDNF in the pathophysiology of EF impairment in SCZ, consistent with its neurodevelopmental hypothesis.