Kopczak Anna, Stalla Günter Karl, Uhr Manfred, Lucae Susanne, Hennings Johannes, Ising Marcus, Holsboer Florian, Kloiber Stefan
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
Eur Neuropsychopharmacol. 2015 Jun;25(6):864-72. doi: 10.1016/j.euroneuro.2014.12.013. Epub 2015 Jan 5.
We analyzed insulin-like growth factor I (IGF-I) in serum of 78 inpatients with depression and 92 healthy controls. Patients were selected according to remission status after 6 weeks of antidepressant treatment with remission defined by Hamilton depression rating scale (HAM-D) 21-item score <10 (39 remitters and 39 non-remitters). IGF-I was analyzed in patients at admission and after 6 weeks of psychopharmacological treatment. IGF-I levels were compared between patients and controls and between remitters and non-remitters with general linear model using age, gender, and body mass index as covariates. In patients, IGF-I levels were significantly higher at admission (p=3.29E-04) and in week 6 (p=0.002) compared to controls. Furthermore, non-remitters showed significantly higher IGF-I levels at admission (p=0.046) and a trend for higher IGF-I levels in week 6 (p=0.11) compared to remitters. In remitters change in IGF-I levels during treatment was significantly correlated with change in cortisol levels (p=0.019). A genetic association analysis of polymorphisms in 10 genes contributing to the IGF-I system (IGF1, IGF1R, IGFBP1 to IGFBP7, and IGFBPL1) in the currently largest genetic databases for major depression (Psychiatric Genomics Consortium) revealed nominal associations with susceptibility for depression and treatment response, although results did not remain significant after multiple testing correction. In our study, elevated IGF-I levels were significantly associated with depression and impaired treatment response. Based on these findings IGF-I signaling could play a role in the pathophysiology of depression and could possibly influence the response to antidepressant treatment.
我们分析了78例抑郁症住院患者和92例健康对照者血清中的胰岛素样生长因子I（IGF-I）。根据抗抑郁治疗6周后的缓解状态选择患者，缓解定义为汉密尔顿抑郁量表（HAM-D）21项评分<10（39例缓解者和39例未缓解者）。在患者入院时和接受6周心理药物治疗后分析IGF-I。使用年龄、性别和体重指数作为协变量，通过一般线性模型比较患者与对照者之间以及缓解者与未缓解者之间的IGF-I水平。与对照者相比，患者入院时（p=3.29E-04）和第6周时（p=0.002）的IGF-I水平显著更高。此外，与缓解者相比，未缓解者入院时的IGF-I水平显著更高（p=0.046），且在第6周时有IGF-I水平升高的趋势（p=0.11）。在缓解者中，治疗期间IGF-I水平的变化与皮质醇水平的变化显著相关（p=0.019）。在目前最大的重度抑郁症遗传数据库（精神基因组学联盟）中，对10个参与IGF-I系统的基因（IGF1、IGF1R、IGFBP1至IGFBP7以及IGFBPL1）的多态性进行遗传关联分析，结果显示与抑郁症易感性和治疗反应存在名义上的关联，尽管在多重检验校正后结果不再显著。在我们的研究中，IGF-I水平升高与抑郁症及治疗反应受损显著相关。基于这些发现，IGF-I信号传导可能在抑郁症的病理生理学中起作用，并可能影响对抗抑郁治疗的反应。
