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Lower levels of the glial cell marker TSPO in drug-naive first-episode psychosis patients as measured using PET and [11C]PBR28

Molecular Psychiatry volume 22, pages 850–856 (2017)Cite this article

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Abstract

Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn. Here, we examined 16 drug-naive, first-episode psychosis patients and 16 healthy controls using PET and the TSPO radioligand [11C]PBR28. Gray matter (GM) volume of distribution (VT) derived from a two-tissue compartmental analysis with arterial input function was the main outcome measure. Statistical analyses were performed controlling for both TSPO genotype, which is known to affect [11C]PBR28 binding, and gender. There was a significant reduction of [11C]PBR28 VT in patients compared with healthy controls in GM as well as in secondary regions of interest. No correlation was observed between GM VT and clinical or cognitive measures after correction for multiple comparisons. The observed decrease in TSPO binding suggests reduced numbers or altered function of immune cells in brain in early-stage schizophrenia.

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Acknowledgements

The Swedish Research Council (09114 (LFA); 523-2014-3467 (SC); 2009-7053; 2013-2838 (SE)), Stockholm County Council (ALF; LFA, LF, SC), Swedish Society of Medicine (SLS-332411(SC)), PRIMA Barn-och Vuxenpsykiatri AB (KC), Torsten Söderbergs Stiftelse, Söderström Königska fonden, the European Union’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. HEALTH-F2-2011-278850 (INMIND; CH), Centre for Psychiatry Research (HFB). We thank Joachim Eckerström, Martin Szabo and other personnel of KaSP for their help with recruitment of subjects, as well as all members of the PET group at the Karolinska Institutet for their close assistance during this study. We also express our gratitude toward the patients and the healthy volunteers for their participation.

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Author notes

  1. Members of Karolinska Schizophrenia Project (KaSP) are listed at the end of the article as collaborators.

Authors and Affiliations

  1. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden

    K Collste, P Plavén-Sigray, H Fatouros-Bergman, P Victorsson, M Schain, A Forsberg, N Amini, C Halldin, L Flyckt, L Farde & S Cervenka

  2. Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia University, New York, NY, USA

    M Schain

  3. Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    S Aeinehband

  4. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

    S Erhardt

  5. Personalised Healthcare and Biomarkers, AstraZeneca PET Science Centre, Karolinska Institutet, Stockholm, Sweden

    L Farde

  6. Department of Psychiatry, University of Cambridge, Cambridge, UK

    S Cervenka

  7. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden

    Farde L, Flyckt L, Fatouros-Bergman H, Cervenka S, Agartz I, Collste K & Victorsson P

  8. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

    Engberg G, Erhardt S, Schwieler L, Malmqvist A, Hedberg M & Orhan F

  9. Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden

    Piehl F

  10. Division of Mental Health and Addiction, NORMENT, KG Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway

    Agartz I

  11. Department of Psychiatry Research, Diakonhjemmet Hospital, Oslo, Norway

    Agartz I

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  1. K Collste
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Consortia

Karolinska Schizophrenia Project (KaSP) consortium

  • Farde L
  • , Flyckt L
  • , Engberg G
  • , Erhardt S
  • , Fatouros-Bergman H
  • , Cervenka S
  • , Schwieler L
  • , Piehl F
  • , Agartz I
  • , Collste K
  • , Victorsson P
  • , Malmqvist A
  • , Hedberg M
  •  & Orhan F

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Correspondence to S Cervenka.

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Competing interests

LFa is an employee of AstraZeneca and affiliated with KI. SC has received grant support from AstraZeneca as a co-investigator, and has served as a one-off speaker for Roche and Otsuka Pharmaceuticals. SE has received grant support from AstraZeneca as the principal investigator, has served as a one-off speaker for Roche pharmaceuticals and participated in workshops organized by Otsuka Pharmaceuticals. The remaining authors declare no conflict of interest.

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Collste, K., Plavén-Sigray, P., Fatouros-Bergman, H. et al. Lower levels of the glial cell marker TSPO in drug-naive first-episode psychosis patients as measured using PET and [11C]PBR28. Mol Psychiatry 22, 850–856 (2017). https://doi.org/10.1038/mp.2016.247

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