Koch Jakob M, Hinze-Selch Dunja, Stingele Karoline, Huchzermeier Christian, Goder Robert, Seeck-Hirschner Mareen, Aldenhoff Josef B
Department of Psychiatry and Psychotherapy, Christian-Albrechts University Kiel, Niemannsweg 147, Kiel, Germany.
Psychother Psychosom. 2009;78(3):187-92. doi: 10.1159/000209350. Epub 2009 Mar 24.
The cyclic adenosine monophosphate response element-binding proteins (CREB) and their interaction with brain-derived neurotrophic factor (BDNF) are essential elements in signal transduction pathways important for cellular resilience and neuroplasticity. They play a decisive role in the concept of altered neuroplasticity in major depression. We have previously demonstrated that the increase in phosphorylated CREB (pCREB) in T lymphocytes is significantly associated with clinical improvement in patients treated with antidepressants. In the present study, we focused on patients treated only with psychotherapy to exclude direct pharmacological actions. In addition to pCREB, we also measured the BDNF plasma levels.
pCREB in T lymphocytes was determined by Western blot; the BDNF plasma levels with solid-phase ELISA. Psychopathology was evaluated with the Hamilton Rating Scale for Depression (HAMD). Thirty patients meeting DSM-IV criteria for major depressive episodes (MDE) were recruited into this 6-week study. They received interpersonal psychotherapy (IPT) twice weekly.
After 6 weeks of IPT, 17 patients responded (reduction of > or =50% of baseline HAMD); after 1 week of treatment pCREB increased significantly compared to the nonresponder group. Measurement of the BDNF plasma levels revealed no differences between the responder and nonresponder groups. Furthermore, the correlations between BDNF plasma levels and pCREB were not significant.
The early increase in pCREB is related to treatment response and does not depend on pharmacological interventions or BDNF plasma levels. For the first time, cellular biological markers could be associated with response to psychotherapy.
环磷酸腺苷反应元件结合蛋白（CREB）及其与脑源性神经营养因子（BDNF）的相互作用是信号转导通路中的关键要素，对细胞恢复力和神经可塑性至关重要。它们在重度抑郁症神经可塑性改变的概念中起决定性作用。我们之前已经证明，T淋巴细胞中磷酸化CREB（pCREB）的增加与接受抗抑郁药治疗患者的临床改善显著相关。在本研究中，我们聚焦于仅接受心理治疗的患者，以排除直接的药物作用。除了pCREB，我们还测量了血浆BDNF水平。
通过蛋白质免疫印迹法测定T淋巴细胞中的pCREB；采用固相酶联免疫吸附测定法测定血浆BDNF水平。用汉密尔顿抑郁评定量表（HAMD）评估精神病理学。30名符合DSM-IV重度抑郁发作（MDE）标准的患者被纳入这项为期6周的研究。他们每周接受两次人际心理治疗（IPT）。
经过6周的IPT治疗后，17名患者有反应（HAMD评分较基线降低≥50%）；与无反应组相比，治疗1周后pCREB显著增加。血浆BDNF水平的测定显示，有反应组和无反应组之间没有差异。此外，血浆BDNF水平与pCREB之间的相关性不显著。
pCREB的早期增加与治疗反应相关，且不依赖于药物干预或血浆BDNF水平。细胞生物学标志物首次可能与心理治疗反应相关。
