Background: 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. Methods: 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. Results: After 6 weeks of IPT, 17 patients responded (reduction of ≥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. Conclusions: 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.

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