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. 2018 May:195:206-214.
doi: 10.1016/j.schres.2017.08.063. Epub 2017 Oct 12.

Brain TSPO imaging and gray matter volume in schizophrenia patients and in people at ultra high risk of psychosis: An [11C]PBR28 study

Sudhakar Selvaraj  1 , Peter S Bloomfield  2 , Bo Cao  3 , Mattia Veronese  4 , Federico Turkheimer  4 , Oliver D Howes  5
Affiliations

Brain TSPO imaging and gray matter volume in schizophrenia patients and in people at ultra high risk of psychosis: An [11C]PBR28 study

Sudhakar Selvaraj et al. Schizophr Res. 2018 May.

Abstract

Patients with schizophrenia show whole brain and cortical gray matter (GM) volume reductions which are progressive early in their illness. Microglia, the resident immune cells in the CNS, phagocytose neurons and synapses. Some post mortem and in vivo studies in schizophrenia show evidence for elevated microglial activation compared to matched controls. However, it is currently unclear how these results relate to changes in cortical structure.

Methods: Fourteen patients with schizophrenia and 14 ultra high risk for psychosis (UHR) subjects alongside two groups of age and genotype matched healthy controls received [11C]PBR28 PET scans to index TSPO expression, a marker of microglial activation and a 3T MRI scan. We investigated the relationship between the volume changes of cortical regions and microglial activation in cortical GM (as indexed by [11C]PBR28 distribution volume ratio (DVR).

Results: The total cortical GM volume was significantly lower in SCZ than the controls [mean (SD)/cm3: SCZ=448.83 (39.2) and controls=499.6 (59.2) (p=0.02) but not in UHR (mean (SD)=503.06 (57.9) and controls=524.46 (45.3) p=0.3). Regression model fitted the total cortical GM DVR values with the cortical regional volumes in SCZ (r=0.81; p<0.001) and in UHR (r=0.63; p=0.02). We found a significant negative correlation between the TSPO signal and total cortical GM volume in SCZ with the highest absolute correlation coefficient in the right superior-parietal cortex (r=-0.72; p=0.006).

Conclusions: These findings suggest that microglial activity is related to the altered cortical volume seen in schizophrenia. Longitudinal investigations are required to determine whether microglial activation leads to cortical gray matter loss.

Keywords: Brain volume; Gray matter; Microglia; PET; Psychosis; Schizophrenia.

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Conflict of interest statement

Conflicts of interest

Dr. Howes has received investigator-initiated research funding from and/or participated in advisory/ speaker meetings organised by Astra-Zeneca, Autifony, BMS, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Otsuka, Servier, Sunovion, Rand and Roche. Neither Dr. Howes or his family have been employed by or have holdings/ a financial stake in any biomedical company. Sudhakar Selvaraj, Peter S Bloomfield, Cao Bo, Mattia Veronese and Federico Turkheimer have no conflicts of interest for this work. The authors would like to thank all the clinical imaging staff at Imanova for their help with this study.

Figures

Figure 1
Figure 1. Negative correlation between normalized volume of right superior parietal cortex and [11C]PBR28 gray matter DVR (a) and the distribution of r and –logp for the 1000 regressions (b).
Figure 2
Figure 2. Negative correlation between normalized volume of left temporal pole and temporal [11C]PBR28 gray matter DVR (a) and the distribution of r and –logp for the 1000 regressions (b).
See this image and copyright information in PMC

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References

    1. Abourbeh G, Thézé B, Maroy R, Dubois A, Brulon V, Fontyn Y, Dollé F, Tavitian B, Boisgard R. Imaging microglial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by positron emission tomography using the mitochondrial 18 kDa translocator protein radioligand [18F]DPA-714. J Neurosci. 2012;32(17):5728–5736. - PMC - PubMed
    1. Albrecht DS, Granziera C, Hooker JM, Loggia ML. In Vivo Imaging of Human Neuroinflammation. ACS Chem Neurosci. 2016;7(4):470–483. - PMC - PubMed
    1. Andreasen NC, Nopoulos P, Magnotta V, Pierson R, Ziebell S, Ho BC. Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia. Biol Psychiatry. 2011;70(7):672–679. - PMC - PubMed
    1. Arlicot N, Petit E, Katsifis A, Toutain J, Divoux D, Bodard S, Roussel S, Guilloteau D, Bernaudin M, Chalon S. Detection and quantification of remote microglial activation in rodent models of focal ischaemia using the TSPO radioligand CLINDE. Eur J Nucl Med Mol Imaging. 2010;37(12):2371–2380. - PubMed
    1. Banati RB, Cagnin A, Brooks DJ, Gunn RN, Myers R, Jones T, Birch R, Anand P. Long-term trans-synaptic glial responses in the human thalamus after peripheral nerve injury. Neuroreport. 2001;12(16):3439–3442. - PubMed

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