Data_Sheet_1_The association between neuroendocrine/glucose metabolism and clinical outcomes and disease course in different clinical states of bipolar disorders.PDF

ObjectiveThe treatment of bipolar disorder (BD) remains challenging. The study evaluated the impact of the hypothalamic–pituitary–adrenal (HPA) axis/hypothalamic–pituitary-thyroid (HPT) axis and glucose metabolism on the clinical outcomes in patients with bipolar depression (BD-D) and manic bipolar (BD-M) disorders.
MethodsThe research design involved a longitudinal prospective study. A total of 500 BD patients aged between 18 and 65 years treated in 15 hospitals located in Western China were enrolled in the study. The Young Mania Rating Scale (YMRS) and Montgomery and Asberg Depression Rating Scale (MADRS) were used to assess the BD symptoms. An effective treatment response was defined as a reduction in the symptom score of more than 25% after 12 weeks of treatment. The score of symptoms was correlated with the homeostatic model assessment of insulin resistance (HOMA-IR) index, the HPA axis hormone levels (adrenocorticotropic hormone (ACTH) and cortisol), and the HPT axis hormone levels (thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (fT3), and free thyroxine (fT4)).
ResultsIn the BD-M group, the YMRS was positively correlated with baseline T4 (r = 0.349, p = 0.010) and fT4 (r = 0.335, p = 0.013) and negatively correlated with fasting insulin (r = −0.289, p = 0.013). The pre-treatment HOMA-IR was significantly correlated with adverse course (p = 0.045, OR = 0.728). In the BD-D group, the baseline MADRS was significantly positively correlated with baseline fT3 (r = 0.223, p = 0.032) and fT4 (r = 0.315, p = 0.002), while baseline T3 (p = 0.032, OR = 5.071) was significantly positively related to treatment response.
ConclusionThe HPT axis and glucose metabolism were closely associated with clinical outcomes at 12 weeks in both BD-D and BD-M groups. If confirmed in further longitudinal studies, monitoring T3 in BD-D patients and HOMA-IR for BD-M could be used as potential treatment response biomarkers.

研究目的 双相障碍（bipolar disorder, BD）的临床治疗仍颇具挑战。本研究旨在探讨下丘脑-垂体-肾上腺（hypothalamic–pituitary–adrenal, HPA）轴/下丘脑-垂体-甲状腺（hypothalamic–pituitary-thyroid, HPT）轴功能及糖代谢状态对双相抑郁（bipolar depression, BD-D）与躁狂相双相障碍（manic bipolar, BD-M）患者临床结局的影响。

研究方法 本研究采用纵向前瞻性研究设计。共纳入中国西部15家医院收治的500名年龄18~65岁的双相障碍患者。采用杨氏躁狂评定量表（Young Mania Rating Scale, YMRS）与蒙哥马利-艾斯伯格抑郁评定量表（Montgomery and Asberg Depression Rating Scale, MADRS）评估双相障碍症状。将治疗12周后症状评分较基线降低≥25%定义为有效治疗应答。对症状评分与胰岛素抵抗稳态模型评估（homeostatic model assessment of insulin resistance, HOMA-IR）指数、HPA轴激素水平（促肾上腺皮质激素（adrenocorticotropic hormone, ACTH）及皮质醇）以及HPT轴激素水平（促甲状腺激素（thyroid stimulating hormone, TSH）、三碘甲状腺原氨酸（triiodothyronine, T3）、甲状腺素（thyroxine, T4）、游离三碘甲状腺原氨酸（free triiodothyronine, fT3）、游离甲状腺素（free thyroxine, fT4））进行相关性分析。

研究结果 躁狂相双相障碍组中，YMRS评分与基线T4水平呈正相关（r=0.349，p=0.010），与基线fT4水平亦呈正相关（r=0.335，p=0.013），而与空腹胰岛素水平呈负相关（r=-0.289，p=0.013）；治疗前HOMA-IR指数与不良病程显著相关（p=0.045，OR=0.728）。双相抑郁组中，基线MADRS评分与基线fT3水平（r=0.223，p=0.032）及基线fT4水平（r=0.315，p=0.002）均呈显著正相关；而基线T3水平与治疗应答呈显著正相关（p=0.032，OR=5.071）。

研究结论 双相抑郁组与躁狂相双相障碍组患者的HPT轴功能及糖代谢状态均与12周临床结局密切相关。若后续纵向研究可进一步验证该结果，则双相抑郁患者的T3监测指标与躁狂相双相障碍患者的HOMA-IR指数可作为潜在的治疗应答生物标志物。