Serum S100B represents a new biomarker for mood disorders

Matthias L Schroeter, Julia Sacher, Johann Steiner, Peter Schoenknecht, Karsten Mueller, Matthias L Schroeter, Julia Sacher, Johann Steiner, Peter Schoenknecht, Karsten Mueller

Abstract

Recently, mood disorders have been discussed to be characterized by glial pathology. The protein S100B, a growth and differentiation factor, is located in, and may actively be released by astro- and oligodendrocytes. This protein is easily assessed in human serum and provides a useful parameter for glial activation or injury. Here, we review studies investigating the glial marker S100B in serum of patients with mood disorders. Studies consistently show that S100B is elevated in mood disorders; more strongly in major depressive than bipolar disorder. Consistent with the glial hypothesis of mood disorders, serum S100B levels interact with age with higher levels in elderly depressed subjects. Successful antidepressive treatment has been associated with serum S100B reduction in major depression, whereas there is no evidence of treatment effects in mania. In contrast to the glial marker S100B, the neuronal marker protein neuron-specific enolase is unaltered in mood disorders. Recently, serum S100B has been linked to specific imaging parameters in the human white matter suggesting a role for S100B as an oligodendrocytic marker protein. In sum, serum S100B can be regarded as a promising in vivo biomarker for mood disorders deepening the understanding of the pathogenesis and plasticity-changes in these disorders. Future longitudinal studies combining serum S100B with other cell-specific serum parameters and multimodal imaging are warranted to further explore this serum protein in the development, monitoring and treatment of mood disorders.

Figures

Fig. (1)
Fig. (1)
S100B serum concentrations in mood disorders as identified by systematic meta-analyses. Calculation of effect sizes according to Cohen [67]. A Values for mood disorders in comparison with schizophrenia [56]; median is shown for schizophrenia (solid), major depressive disorder MDD (dashed), and bipolar disorder BD (dashed and dotted line). B Serum S100B in relation to age, illness duration and age at onset in mood disorders [55]; results of linear regression analyses with 95% confidence intervals are shown. C Changes of serum S100B versus clinical improvement in major depression [54]; effect sizes were calculated for clinical (HAMD scores) and serological (serum S100B) treatment effects in major depression as changes between admission and discharge. HAMD Hamilton Depression Rating Scale.
Fig. (2)
Fig. (2)
Associations between S100B and the brain. For details see Streitbürger et al. [71]. A Diffusion tensor imaging parameters correlate with serum S100B in the corpus callosum, anterior forceps, and the right superior longitudinal fasciculus of the female brain (upper row) and in comparison with male brains (lower row). B-D Expression & localization of S100B in the human brain and in cultured oligodendrocytes. B Co-localization (yellow) of S100B (red) and myelin basic protein (MBP)-positive (green) myelinated fibres in the human corpus callosum. C Co-localization (yellow) between S100B (red) and the oligodendroglial marker p75 neurotrophin receptor (green) in the oligodendrocyte cell line OLN-93. D Individual normalized gene expression of S100B in heat map in z scores normalized to whole human brain expression, where green indicates relatively low and red relatively high expression. Highest expression was detected in the corpus callosum (CC), followed by globus pallidus (GP). Bar chart shows quantitative values in CC and external/internal (e/i) GP (mean+SD). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this paper).
Fig. (3)
Fig. (3)
Framework for S100B’s role in mood disorders and their treatment. The figure summarizes evidence from human, animal and cell culture studies for the involvement of S100B in the pathogenesis and treatment of mood disorders. hippoc. hippocampal.

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