The differential levels of inflammatory cytokines and BDNF among bipolar spectrum disorders

[[abstract]]OBJECTIVE: Emerging evidence suggests that inflammation and neurodegeneration underlies bipolar disorder. To investigate biological markers of cytokines and brain-derived neurotrophic factor between bipolar I, bipolar II, and other specified bipolar disorder with short duration hypomania may support the association with inflammatory dysregulation and bipolar disorder and, more specifically, provide evidence for specified bipolar disorder patients were similar to bipolar disorder-II patients from a biological marker perspective. METHODS: We enrolled patients with bipolar disorder-I (n=234), bipolar disorder-II (n=260), specified bipolar disorder (n=243), and healthy controls (n=140). Their clinical symptoms were rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale. Inflammatory cytokine (tumor necrosis factor-alpha, C-reactive protein, transforming growth factor-beta1, and interleukin-8) and brain-derived neurotrophic factor levels were measured in each group. Multivariate analysis of covariance and linear regression controlled for possible confounders were used to compare cytokine and brain-derived neurotrophic factor levels among the groups. RESULTS: Multivariate analysis of covariance adjusted for age and sex and a main effect of diagnosis was significant (P<.001). Three of the 5 measured biomarkers (tumor necrosis factor-alpha, transforming growth factor-beta1, and interleukin-8) were significantly (P=.006, .01, and <.001) higher in all bipolar disorder patients than in controls. Moreover, covarying for multiple associated confounders showed that bipolar disorder-I patients had significantly higher IL-8 levels than did bipolar disorder-II and specified bipolar disorder patients in Multivariate analysis of covariance (P=.03) and linear regression (P=.02) analyses. Biomarkers differences between bipolar disorder-II and specified bipolar disorder patients were nonsignificant. CONCLUSION: The immunological disturbance along the bipolar spectrum was most severe in bipolar disorder-I patients. Specified bipolar disorder patients and bipolar disorder-II patients did not differ in these biological markers