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Reconceptualization of translocator protein as a biomarker of neuroinflammation in psychiatry

Molecular Psychiatry volume 23, pages 36–47 (2018)Cite this article

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Abstract

A great deal of interest in psychiatric research is currently centered upon the pathogenic role of inflammatory processes. Positron emission tomography (PET) using radiolabeled ligands selective for the 18 kDa translocator protein (TSPO) has become the most widely used technique to assess putative neuroimmune abnormalities in vivo. Originally used to detect discrete neurotoxic damages, TSPO has generally turned into a biomarker of ‘neuroinflammation’ or ‘microglial activation’. Psychiatric research has mostly accepted these denotations of TSPO, even if they may be inadequate and misleading under many pathological conditions. A reliable and neurobiologically meaningful diagnosis of ‘neuroinflammation’ or ‘microglial activation’ is unlikely to be achieved by the sole use of TSPO PET imaging. It is also very likely that the pathological meanings of altered TSPO binding or expression are disease-specific, and therefore, not easily generalizable across different neuropathologies or inflammatory conditions. This difficulty is intricately linked to the varying (and still ill-defined) physiological functions and cellular expression patterns of TSPO in health and disease. While altered TSPO binding or expression may indeed mirror ongoing neuroinflammatory processes in some cases, it may reflect other pathophysiological processes such as abnormalities in cell metabolism, energy production and oxidative stress in others. Hence, the increasing popularity of TSPO PET imaging has paradoxically introduced substantial uncertainty regarding the nature and meaning of neuroinflammatory processes and microglial activation in psychiatry, and likely in other neuropathological conditions as well. The ambiguity of conceiving TSPO simply as a biomarker of ‘neuroinflammation’ or ‘microglial activation’ calls for alternative interpretations and complimentary approaches. Without the latter, the ongoing scientific efforts and excitement surrounding the role of the neuroimmune system in psychiatry may not turn into therapeutic hope for affected individuals.

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Acknowledgements

TN receives financial support from a 2017 ‘Forschungskredit’ granted by the University of Zurich and by a Swiss National Science Foundation Early Postdoc.Mobility fellowship (P2ZHP3_174868); JMC receives financial support from the Johns Hopkins Doris Duke Early Clinician Investigator Award and the Alexander Wilson Schweizer Fellowship; AS receives financial support from the NIH (DA040127, MH092443, MH094268,and MH105660) and foundations of Stanley, BBRF and S-R/RUSK; and UM receives financial support from the Swiss National Science Foundation (310030_169544) and the Foundation for Research in Science and the Humanities at the University of Zurich.

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  1. Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland

    T Notter & U Meyer

  2. Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland

    T Notter & U Meyer

  3. Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    J M Coughlin & A Sawa

  4. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    J M Coughlin

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Notter, T., Coughlin, J., Sawa, A. et al. Reconceptualization of translocator protein as a biomarker of neuroinflammation in psychiatry. Mol Psychiatry 23, 36–47 (2018). https://doi.org/10.1038/mp.2017.232

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