Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker for affective disorders?

Abstract

After more than a decade of ‘a molecular and cellular theory of depression’ the neurotrophin brain-derived neurotrophic factor (BDNF) remains a central part of the concept for the pathophysiology of depression and antidepressant treatment (Altar, 1999; Duman et al. 1997). Stress, an important precipitant of depression, reduces the expression of BDNF, especially in the hippocampus, while a plethora of antidepressant measures, e.g. antidepressant drugs, electroconvulsive treatment and also environmental enrichment, increase BDNF expression (Krishnan & Nestler, 2008; Martinowich et al. 2007). Thus, BDNF could be a valuable biomarker for a depressive state and the recovery from it. Unfortunately, CSF levels of BDNF are already at the limit of detection in healthy individuals, despite sensitive methods of analysis (Burbach et al. 2004). Of course it is also not possible to easily determine BDNF brain tissue levels in the living patient. Therefore, there is great interest in peripheral measures of humoral BDNF, particularly in blood (Brunoni et al. 2008; Sen et al. 2008). The normally very high concentration of BDNF in blood could be derived not only from the brain, but also from peripheral sources, since most body tissues express this growth factor (Lommatzsch et al. 2005 a ; Nockher & Renz, 2005). Given that cerebral BDNF crosses the blood–brain barrier (Pan et al. 1998), it is reasonable to assume that serum BDNF concentrations are associated with BDNF levels in the brain. This assumption is substantiated by animal experiments showing that BDNF serum levels are correlated with BDNF expression in cortical brain regions (Karege et al. 2002 b ), and the recently demonstrated positive association between N -acetylaspartate – a well established marker …