Exploratory Associations of Inflammatory Cytokines, Brain-Derived Neurotrophic Factor, and Vascular Endothelial Growth Factor with Clinical Outcomes in Patients with Bipolar Disorder

Background/Objectives: Bipolar disorder is characterized by psychosocial dysfunction, cognitive impairment, and incomplete recovery. Although inflammatory and neurotrophic mechanisms have been implicated, their relationships with multidimensional recovery outcomes remain unclear. We examined the relationships of inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) with depressive symptoms, psychosocial functioning, cognitive performance, personal recovery, and quality of life (QOL) in patients with bipolar disorder. Methods: This cross-sectional study of 24 patients with bipolar disorder assessed depressive symptoms, psychosocial functioning, cognitive functions, personal recovery, and QOL. Plasma tumor necrosis factor alpha, interleukin (IL)-6, IL-1β, IL-2, BDNF, and VEGF-A were measured by assay. Results: Subjective cognitive dysfunction was significantly associated with depressive symptom severity (rho = 0.53, p = 0.0083) and reduced QOL (rho = −0.56, p = 0.0042). Depressive symptoms were also associated with lower WHO-QOL-26 scores (rho = −0.43, p = 0.038). Significant interrelationships were observed among objective cognitive measures, and after false discovery rate (FDR) correction, the associations between FAST and PDQ-5-D, Symbol Check and Codebreaker, and Codebreaker and Trail remained statistically significant. High plasma IL-6 levels were associated with worse executive function (rho = 0.43, p = 0.0068). Higher VEGF levels were associated with better attentional performance (rho = −0.42, p = 0.042). Plasma IL-1β levels were positively associated with QOL (rho = 0.54, p = 0.02). After FDR correction, only the association between IL-1β and QOL remained statistically significant. Conclusions: This pilot study suggests that there may be associations between cognitive impairment and cytokines, as well as between quality of life and VEGF, in bipolar disorder. Further studies with larger sample sizes are needed.