Relationship of serum neurofilament light chain, serum oligoclonal band and inflammatory marker levels with cognitive functions in different periods of bipolar disorder

Introduction: In our study, we aimed to investigate the levels of neuroinflammatory and neurodegenerative parameters (neurofilament light chain (NfL), serum oligoclonal band (OCB), intracellular cytokines (TNF-α, IL-1β, IL-6)) change in different stages of the disease in patients diagnosed with bipolar disorder and to evaluate the relationship between these neurobiological parameters and executive functions. Method: Our study was planned as a prospective paired case-control study. A total of 76 participants, 46 of whom were diagnosed with bipolar disorder according to DSM-5 criteria (16 in depression, 15 in hypomania, 15 in remission period) and admitted to the Psychiatry Outpatient Clinic of Bezmialem Vakıf University Medical Faculty Hospital between October 2019 and January 2021 and 30 healthy controls were included. Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scales (HDRS) were administered to all participants in the study. The clinical interviews, scales and neurocognitive tests were applied, and then blood was drawn to measure neuroinflammation-related parameters (NfL, OCB, intracellular cytokines (TNF-α, IL-1β, IL-6). Executive functions were examined via the Wisconsin card sorting test (WCST) and Stroop tests, and the relationship between these neurobiological parameters in different disease periods and executive functions were evaluated. Results: In our study, proinflammatory markers such as IL-1β, IL-6, TNF-α and NfL, OCB levels were found to be significantly higher in patients with bipolar disorder than in the control group (p<.001). No statistically significant difference was found in IL-1β, IL-6, TNF-α, NfL and OCB levels between patients in depression, hypomania and remission phase of bipolar disorder (p>0.05). In all these groups, there was a statistically significant prolongation of the total completion times in all sub-categories of the Stroop test with respect to healthy controls. The prolongation of stroop 2, stroop 3 and stroop 4 completion times correlated with increasing age (respectively; p=.029, p=.045, p=.011). It was determined that as the age of onset of the disease increased, the completion times of stroop 2 and stroop 5 lengthened. Apart from these findings, no statistically significant relationship was found between the duration of the disease, the number of mood episodes during the disease and the stroop test scores. When the WCMT total correct numbers analysed, it was determined that the patients in depression and the patients in remission performed significantly worse than the control group (p=.012, p=.015). Patients in depression period performed significantly worse than the control group in the number of completed categories of WCST (p=.001). When the number of depressive episodes increased, the patient's repetitive response level increased, but this was not statistically significant (p=.061). As IL-6 level decreased, it was determined that stroop 1, stroop 2 and stroop 5 completion times were impaired (p<0.05). No statistically significant relationship was observed between IL-1β, TNF-α, NfL and OCB levels and the stroop test scores. There was a negative correlation between IL-1β level and the completed first category on WCST. No statistically significant relationship was found between other biochemical parameters and WCST subcategories. A statistically significant difference was found in all subcategories, except for the stroop test and the total number of WCST errors in patients using only lithium, only valproic acid, and only antipsychotics (p<0.05). In post-hoc comparisons, a statistically significant prolongation was found in the total duration of stroop 1 and total time of stroop 3 in patients using only antipsychotics, and in the number of completed categories of WCST in patients using antipsychotics and valproic acid, compared to the control group. Conclusion: These findings from our study show that intracellular cytokines, NfL and OCB levels are higher in patients with bipolar disorder than in healthy controls. In addition, it was determined that patients with bipolar disorder have impaired executive functions compared to the healthy controls. IL-6 and IL-1β levels were associated with deterioration in cognitive functions. From this point of view, the level of these biochemical parameters can help us to evaluate the cognitive functions of patients diagnosed with bipolar disorder. We think that further studies are needed in larger samples on this subject. Keywords: Bipolar disorder, neuroinflamation, neurodegeneration, cognitive functions