European Journal of Psychotraumatology (Sep 2012)

Diurnal pattern of serum BDNF before partial sleep deprivation in stress-related mood disorders – an association with therapy response in major depression

  • Maria Giese,
  • J. Beck,
  • Serge Brand,
  • F. Muheim,
  • Martin Hatzinger,
  • Edith Holsboer-Trachsler,
  • Anne Eckert

DOI
https://doi.org/10.3402/ejpt.v3i0.19435
Journal volume & issue
Vol. 3, no. 0
pp. 1 – 1

Abstract

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Background : Depression is one of the most prevalent forms of mood disorders. Compelling evidence suggests that mood disorders are characterized by reduced neuronal plasticity, which can be brought about by exposure to stress. Furthermore, there is good agreement in considering key proteins such as the brain-derived neurotrophic factor (BDNF), as a central player for the effects of stress on brain function and plasticity and psychopathological implications. Still, there is a high non-responder rate in antidepressant therapy, which explains the need to find reliable predictors for adequate treatment. Previous studies revealed that plasma and serum BDNF levels in depressed patients were significantly lower than in healthy controls. Since the protein can cross the blood brain-barrier serum content correspondingly correlates with cortical BDNF concentrations suggesting BDNF levels as a promising candidate biomarker for depression and antidepressant treatment response. Methods : To investigate the association between serum BDNF levels and treatment outcome, blood was drawn from 28 patients with a major depressive episode (DMS-IV, ICD-10) that participated in a double-blind placebo controlled treatment study. All patients were treated with a stable mirtazapine monotherapy. Partial sleep deprivation (PSD) was performed after one week. Placebo controlled additional morning treatment with the stimulant modafinil to reduce microsleep throughout the day was started during PSD and maintained over two weeks. Serum concentrations of BDNF and cortisol were assessed by an enzyme-linked immunosorbent assay (ELISA) from day 1 (“before PSD”) at 8 am, 2 pm, 8 pm and day 2 (“after PSD”) at 8 am, 2 pm and 8 pm. Samples were appropriately diluted and detection of soluble BDNF or cortisol was carried out in an antibody sandwich format in duplicates and means were calculated for the corresponding group. Moreover, sleep EEG and microsleep episodes were recorded with a portable EEG. Depression severity using the Hamilton Depression Rating Scale and mood, tiredness and relaxation were assessed with visual analog scales (VASs) for psychological functioning at days 1, 2 and 3 (“after recovery night”) as well as after one and two weeks of ongoing treatment. Results : Notably, depressive patients who showed an acute HDRS-6 improvement after PSD exhibited a prominent diurnal pattern of serum BDNF levels during the day before PSD whereas acute non-responders did not show such a pattern and BDNF levels were rather constantly expressed. Serum BDNF levels were significantly elevated in acute responders compared to non-responders in the morning at 8.00 am before PSD corrected for Bonferroni (p>0.01). Also responders after two weeks (FU2) exhibited a prominent diurnal serum BDNF pattern before and after PSD on day one and two, while it was more pronounced after PSD. There was no diurnal pattern for non-responders after two weeks before; however, after PSD on day two an even modest diurnal change was visible in this group but less pronounced compared to FU2-responders. We found no association between treatment condition placebo vs. modafinil and response for acute neither response after two weeks. When we linked daily peak BDNF levels from day two at 2 pm with overall HDRS-6 improvement, responders were associated with elevated BDNF levels compared to non-responders on day three after recovery night already. Even after one (FU1) and two (FU2) weeks increased BDNF levels of day two at 2 pm were more prominent in the responder group. This difference between responders and non-responders of peak serum BDNF levels from 2 pm after PSD was statistically significant after two weeks. In addition, HDRS-6 improvement after two weeks of on-going treatment was significantly correlated with elevated serum BDNF levels in all patients. Moreover, peak levels of serum BDNF after PSD on day 2 at 2 pm were correlated with increased relaxation and improved mood in all depressive patients. In addition, placebo treated patients during PSD exhibited a significant increase of serum cortisol levels during PSD when compared to morning peak levels at 8 am between day one and two. There was no serum cortisol increase in the modafinil treated group during PSD intervention. Conclusions : Altogether, it seems that a diurnal pattern of serum BDNF during the day is necessarily associated with acute and response after two weeks in terms of partial sleep deprivation independently from additional treatment (modafinil vs. placebo). BDNF levels peaking in the morning and declining during the day seem to be favourable for an antidepressant response. Therefore, BDNF expression profile in serum at baseline could be used as possible predictor for therapy outcome.

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