Yang Chunhong, Zhou Zhuohui, Li Qiping, Zhao Ao, Chen Chao, Li Chunyang
Department of Psychiatry, The Fourth People's Hospital of Shunde District (Shunde WuZhongpei Memorial Hospital), Foshan City, Guangdong, 528300, China.
BMC Psychiatry. 2025 Jul 1;25(1):605. doi: 10.1186/s12888-025-07048-z.
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.
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.
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, η = 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, η = 0.72, 0.653, respectively). OS returned to normal levels with remission of the disease (P < 0.0167, η = 12.106), while OI was continuously impaired. Serum interleukin-6 decreased with remission in manic BD (P = 0.038, η = 12.118), but did not return to normal levels (P = 0.006, η = 0.719). OS was negatively correlated with serum interleukin-6 in manic BD patients (r = -0.386, P = 0.006).
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.
在本研究中，我们横向比较了双相情感障碍（BD）躁狂发作和抑郁发作患者与健康对照者的嗅觉功能和白细胞介素-6水平。我们还纵向比较了急性期与心境正常期患者的这些变量，并评估了BD患者总体嗅觉功能与白细胞介素-6之间的相关性。本研究的目的是寻找BD早期诊断和疗效评估的潜在生物标志物，并为探索BD神经免疫途径假说提供更多临床证据。
该研究纳入了50例躁狂发作的BD患者、31例抑郁发作的BD患者和59名健康对照者，所有患者均随访至进入心境正常期。通过嗅棒测试评估嗅觉敏感度（OS）和嗅觉识别能力（OI）。我们采集血样并测量血清白细胞介素-6水平。
结果显示，躁狂发作BD组和抑郁发作BD组的OS和OI均显著低于健康对照者（P < 0.05，Cohen's d分别为0.657、0.446，η分别为0.744、0.676），心境正常的躁狂发作BD组和心境正常的抑郁发作BD组的OI也显著低于健康对照者（P < 0.0167，η分别为0.72、0.653）。随着疾病缓解，OS恢复到正常水平（P < 0.0167，η = 12.106），而OI持续受损。躁狂发作BD患者血清白细胞介素-6随着缓解而下降（P = 0.038，η = 12.118），但未恢复到正常水平（P = 0.006，η = 0.719）。躁狂发作BD患者的OS与血清白细胞介素-6呈负相关（r = -0.386，P = 0.006）。
OS的动态恢复（急性期受损，心境正常期恢复）表明其在BD中作为疾病活动生物标志物的潜力，而持续的OI缺陷可能反映与特质相关的神经生物学特征。然而，它们的特异性和临床实用性需要严格验证。躁狂发作BD患者的炎症活动与嗅觉功能障碍之间存在潜在相关性，但其因果关系和具体机制需要进一步证实。
