Giese, Maria. The role of brain-derived neurotropic factor (BDNF) in stress-related brain disorders. 2013, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_10519
The purpose of the present study was to elucidate the role of BDNF in stress related-brain disorders regarding the interplay of stress with the human homeostasis connected to sleep and prediction of therapy outcome. Therefore, we assessed systemic serum BDNF levels from human subjects. We could reveal that (1) there is a connection between sleep and serum BDNF levels, (2) sleep mediates the relationship between stress and BDNF and (3) a diurnal variation of serum BDNF levels is linked to favourable antidepressant treatment response.
(1) Insomnia is very common among depressed patients. Although a majority of studies have concentrated on specifying the role of BDNF in depression, the relation between BDNF and insomnia has not been a focus of recent research. Therefore, we investigated serum BDNF levels of subjects with current symptoms of insomnia and non-sleep disturbed controls including patients. We found subjective sleep impairment to be associated with lower serum BDNF levels, whereas reported good sleep was related to higher serum BDNF levels, as shown for those suffering from current insomnia compared with sleep-healthy subjects. Furthermore, serum BDNF levels were correlated with severity of insomnia in all participants.
(2) However, the underlying mechanism in this relationship between sleep and BDNF has to be further elucidated. It might be possible that sleep impairment reflects a chronic stressor influencing the brain and in turn is accompanied by a deregulation of the HPA system, leading in the long term to decreased BDNF levels. Consequently, we wanted to reveal how stress and sleep could affect serum BDNF levels. Therefore we reanalysed the previous study were we could already demonstrate an association between decreased serum BDNF levels and insomnia severity (see ), by including further data. Remarkably, we could demonstrate an interaction between stress and insomnia with an impact on serum BDNF levels. With regard to insomnia severity, we divided all participants into three subgroups reflecting their score on the Insomnia severity Index. Insomnia severity groups and stress each
exhibited a significant main effect on serum BDNF levels. Furthermore, insomnia severity was associated with increased stress experience affecting serum BDNF levels. Notably, the association between stress and BDNF was only observed in subjects without insomnia. By using a mediation model we could show for the first time that the interplay between stress and sleep impacts BDNF levels suggesting an important role of this relationship in the pathology of stress-related brain disorders.
(3) Finally, we complemented our previous work by investigating serum BDNF levels within a therapeutic intervention setting focussing on the association between BDNF and depressive symptoms as well as prediction of treatment response. Patients suffering from major depressive disorder, naïve to sleep therapy experienced a partial sleep deprivation (PSD). We could show that serum BDNF levels followed a diurnal pattern during the day before therapy intervention at baseline with high levels peaking in the morning and decreasing throughout the day. This diurnal pattern on the day before PSD was associated with an acute antidepressant treatment response since diurnal variation in serum BDNF was absent in non-responders. Responders of the day after PSD revealed significantly increased serum BDNF levels in combination with a prominent diurnal variation of BDNF levels at baseline before PSD compared to non-responders. Notably, the same was also relevant for long-term responders, who showed an improvement of depressive symptoms after two weeks of on-going treatment. In addition, serum BDNF levels were increased for acute and long-term responders at the day after PSD when compared to non-responders. Hence, our results indicate that the elasticity in diurnal serum BDNF variation is associated with favourable treatment response to PSD in patients suffering from MDD. Therefore, a normalized BDNF serum profile which oscillates in a circadian fashion seemed to precede, rather than follow a favourable treatment outcome in depressed patients.
|Committee Members:||Krähenbühl, Stephan and Papassotiropoulos, Andreas|
|Faculties and Departments:||03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Brain Aging and Mental Health (Eckert)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||80 Bl.|
|Last Modified:||30 Jun 2016 10:53|
|Deposited On:||07 Oct 2013 14:25|
Repository Staff Only: item control page