Changes in olfactory function and serum interleukin-6 levels in the acute phase of bipolar I disorder: a longitudinal study.

Abstract

Objectives: In this study, we horizontally compared olfactory function and interleukin-6 levels in bipolar disorder (BD) patients with manic and depressive episodes with those in healthy controls. We also compared these variables longitudinally between patients in the acute versus euthymic phase, and assessed the correlation between olfactory function and interleukin-6 in BD patients overall. The purpose of this study was to search potential biomarkers for early diagnosis and efficacy evaluation of BD, and to provide more clinical evidence for exploring the hypothesis of neuroimmune pathways in BD.

Methods: The study included 50 manic BD patients, 31 depressive BD patients, and 59 healthy controls, and all patients were followed until they entered the euthymic phase. Olfactory sensitivity (OS) and olfactory identification (OI) were evaluated via the Sniffin' Sticks test. We collected blood samples and measured serum interleukin-6 levels.

Results: The results showed that the OS and OI in manic BD group and depressive BD group were significantly lower than those in healthy controls (P < 0.05, Cohen's d = 0.657, 0.446, η² = 0.744, 0.676, respectively), and the OI in euthymic manic BD group and euthymic depressive BD group were significantly lower than those in healthy controls (P < 0.0167, η² = 0.72, 0.653, respectively). OS returned to normal levels with remission of the disease (P < 0.0167, η² = 12.106), while OI was continuously impaired. Serum interleukin-6 decreased with remission in manic BD (P = 0.038, η² = 12.118), but did not return to normal levels (P = 0.006, η² = 0.719). OS was negatively correlated with serum interleukin-6 in manic BD patients (r = -0.386, P = 0.006).

Conclusion: The dynamic recovery of OS (impaired in acute phase, restored in euthymia) suggests its potential as a disease-activity biomarker in BD, while persistent OI deficits may reflect trait-related neurobiological features. However, their specificity and clinical utility require rigorous validation. There is a potential correlation between inflammatory activity and olfactory dysfunction in manic BD patients, but its causal relationship and specific mechanism need to be further verified.