S100B and major depressive disorder: The observed S100B and BDNF elevations may therefore reflect early neuroinflammatory and compensatory neurotrophic processes in acute depression, consistent with the proposed involvement of BDNF in the therapeutic mechanisms of antidepressants. The limited permeability of the blood-brain barrier to large peptides such as S100B and BDNF, together with evidence that this barrier may be disrupted in psychosis and depression, creates uncertainty over whether elevated blood levels reflect systemic inflammation or direct effects on the brain.