Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Immediate Communication
  • Published:

In vivo imaging of brain microglial activity in antipsychotic-free and medicated schizophrenia: a [11C](R)-PK11195 positron emission tomography study

Molecular Psychiatry volume 21, pages 1672–1679 (2016)Cite this article

Subjects

Abstract

Positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO) has been used to investigate whether microglial activation, an indication of neuroinflammation, is evident in the brain of adults with schizophrenia. Interpretation of these studies is confounded by potential modulatory effects of antipsychotic medication on microglial activity. In the first such study in antipsychotic-free schizophrenia, we have used [11C](R)-PK11195 PET to compare TSPO availability in a predominantly antipsychotic-naive group of moderate-to-severely symptomatic unmedicated patients (n=8), similarly symptomatic medicated patients with schizophrenia taking risperidone or paliperidone by regular intramuscular injection (n=8), and healthy comparison subjects (n=16). We found no evidence for increased TSPO availability in antipsychotic-free patients compared with healthy controls (mean difference 4%, P=0.981). However, TSPO availability was significantly elevated in medicated patients (mean increase 88%, P=0.032) across prefrontal (dorsolateral, ventrolateral, orbital), anterior cingulate and parietal cortical regions. In the patients, TSPO availability was also strongly correlated with negative symptoms measured using the Positive and Negative Syndrome Scale across all the brain regions investigated (r=0.651–0.741). We conclude that the pathophysiology of schizophrenia is not associated with microglial activation in the 2–6 year period following diagnosis. The elevation in the medicated patients may be a direct effect of the antipsychotic, although this study cannot exclude treatment resistance and/or longer illness duration as potential explanations. It also remains to be determined whether it is present only in a subset of patients, represents a pro- or anti-inflammatory state, its association with primary negative symptoms, and whether there are significant differences between antipsychotics.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. McGrath J, Saha S, Welham J, El Saadi O, MacCauley C, Chant D . A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Med 2004; 2: 13.

    PubMed  PubMed Central  Google Scholar 

  2. Brown AS, Derkits EJ . Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry 2010; 167: 261–280.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Chaudhry IB, Hallak J, Husain N, Minhas F, Stirling J, Richardson P et al. Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment. J Psychopharmacol 2012; 26: 1185–1193.

    Article  PubMed  Google Scholar 

  4. Ghanizadeh A, Dehbozorgi S, OmraniSigaroodi M, Rezaei Z . Minocycline as add-on treatment decreases the negative symptoms of schizophrenia; a randomized placebo-controlled clinical trial. Recent Pat Inflamm Allergy Drug Discov 2014; 8: 211–215.

    Article  CAS  PubMed  Google Scholar 

  5. Levkovitz Y, Mendlovich S, Riwkes S, Braw Y, Levkovitch-Verbin H, Gal G et al. A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry 2010; 71: 138–149.

    Article  CAS  PubMed  Google Scholar 

  6. Eaton WW, Byrne M, Ewald H, Mors O, Chen CY, Agerbo E et al. Association of schizophrenia and autoimmune diseases: linkage of Danish national registers. Am J Psychiatry 2006; 163: 521–528.

    Article  PubMed  Google Scholar 

  7. Irani SR, Bera K, Waters P, Zuliani L, Maxwell S, Zandi MS et al. N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain 2010; 133: 1655–1667.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009; 460: 748–752.

    CAS  PubMed  Google Scholar 

  9. Shi J, Levinson DF, Duan J, Sanders AR, Zheng Y, Pe'er I et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature 2009; 460: 753–757.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D et al. Common variants conferring risk of schizophrenia. Nature 2009; 460: 744–747.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Potvin S, Stip E, Sepehry AA, Gendron A, Bah R, Kouassi E . Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry 2008; 63: 801–808.

    Article  CAS  PubMed  Google Scholar 

  12. Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B . Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry 2011; 70: 663–671.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Upthegrove R, Manzanares-Teson N, Barnes NM . Cytokine function in medication-naive first episode psychosis: a systematic review and meta-analysis. Schizophr Res 2014; 155: 101–108.

    Article  PubMed  Google Scholar 

  14. Radewicz K, Garey LJ, Gentleman SM, Reynolds R . Increase in HLA-DR immunoreactive microglia in frontal and temporal cortex of chronic schizophrenics. J Neuropathol Exp Neurol 2000; 59: 137–150.

    Article  CAS  PubMed  Google Scholar 

  15. Fillman SG, Cloonan N, Catts VS, Miller LC, Wong J, McCrossin T et al. Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry 2013; 18: 206–214.

    Article  CAS  PubMed  Google Scholar 

  16. Bayer TA, Buslei R, Havas L, Falkai P . Evidence for activation of microglia in patients with psychiatric illnesses. Neurosci Lett 1999; 271: 126–128.

    Article  CAS  PubMed  Google Scholar 

  17. van Berckel BN, Bossong MG, Boellaard R, Kloet R, Schuitemaker A, Caspers E et al. Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C]PK11195 positron emission tomography study. Biol Psychiatry 2008; 64: 820–822.

    Article  PubMed  Google Scholar 

  18. Doorduin J, de Vries EF, Willemsen AT, de Groot JC, Dierckx RA, Klein HC . Neuroinflammation in schizophrenia-related psychosis: a PET study. J Nucl Med 2009; 50: 1801–1807.

    PubMed  Google Scholar 

  19. Bloomfield PS, Selvaraj S, Veronese M, Rizzo G, Bertoldo A, Owen DR et al. Microglial activity in people at ultra high risk of psychosis and in schizophrenia: an [(11)C]PBR28 PET brain imaging study. Am J Psychiatry 2016; 173: 44–52.

    Article  PubMed  Google Scholar 

  20. Takano A, Arakawa R, Ito H, Tateno A, Takahashi H, Matsumoto R et al. Peripheral benzodiazepine receptors in patients with chronic schizophrenia: a PET study with [11C]DAA1106. Int J Neuropsychopharmacol 2010; 13: 943–950.

    Article  CAS  PubMed  Google Scholar 

  21. Kenk M, Selvanathan T, Rao N, Suridjan I, Rusjan P, Remington G et al. Imaging neuroinflammation in gray and white matter in schizophrenia: an in vivo PET study with [18F]-FEPPA. Schizophr Bull 2015; 41: 85–93.

    Article  PubMed  Google Scholar 

  22. Coughlin JM, Wang Y, Ambinder EB, Ward RE, Minn I, Vranesic M et al. In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [(11)C]DPA-713 PET and analysis of CSF and plasma. Transl Psychiatry 2016; 6: e777.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Monji A, Kato TA, Mizoguchi Y, Horikawa H, Seki Y, Kasai M et al. Neuroinflammation in schizophrenia especially focused on the role of microglia. Prog Neuropsychopharmacol Biol Psychiatry 2013; 42: 115–121.

    Article  CAS  PubMed  Google Scholar 

  24. Kluge M, Schuld A, Schacht A, Himmerich H, Dalal MA, Wehmeier PM et al. Effects of clozapine and olanzapine on cytokine systems are closely linked to weight gain and drug-induced fever. Psychoneuroendocrinology 2009; 34: 118–128.

    Article  CAS  PubMed  Google Scholar 

  25. Danovich L, Veenman L, Leschiner S, Lahav M, Shuster V, Weizman A et al. The influence of clozapine treatment and other antipsychotics on the 18 kDa translocator protein, formerly named the peripheral-type benzodiazepine receptor, and steroid production. Eur Neuropsychopharmacol 2008; 18: 24–33.

    Article  CAS  PubMed  Google Scholar 

  26. Cotel MC, Lenartowicz EM, Natesan S, Modo MM, Cooper JD, Williams SC et al. Microglial activation in the rat brain following chronic antipsychotic treatment at clinically relevant doses. Eur Neuropsychopharmacol 2015; 25: 2098–2107.

    Article  CAS  PubMed  Google Scholar 

  27. Perry VH, Nicoll JA, Holmes C . Microglia in neurodegenerative disease. Nat Rev Neurol 2010; 6: 193–201.

    Article  PubMed  Google Scholar 

  28. Knegtering R, Baselmans P, Castelein S, Bosker F, Bruggeman R, van den Bosch RJ . Predominant role of the 9-hydroxy metabolite of risperidone in elevating blood prolactin levels. Am J Psychiatry 2005; 162: 1010–1012.

    Article  PubMed  Google Scholar 

  29. Vita A, De Peri L, Deste G, Sacchetti E . Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies. Transl Psychiatry Psychiatry 2012; 2: e190.

    Article  CAS  Google Scholar 

  30. First MB, Spitzer RL, Gibbon M, Williams JBW . Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I/P). Biometrics Research, New York State Psychiatric Institute: New York, NY, USA, 2002.

    Google Scholar 

  31. Kay SR, Fiszbein A, Opler LA . The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261–276.

    Article  CAS  PubMed  Google Scholar 

  32. Talbot PS, Bradley S, Clarke CP, Babalola KO, Philipp AW, Brown G et al. Brain serotonin transporter occupancy by oral sibutramine dosed to steady state: a PET study using (11)C-DASB in healthy humans. Neuropsychopharmacology 2010; 35: 741–751.

    Article  CAS  PubMed  Google Scholar 

  33. Shah F, Hume SP, Pike VW, Ashworth S, McDermott J . Synthesis of the enantiomers of [N-methyl-11C]PK 11195 and comparison of their behaviours as radioligands for PK binding sites in rats. Nucl Med Biol 1994; 21: 573–581.

    Article  CAS  PubMed  Google Scholar 

  34. Su Z, Herholz K, Gerhard A, Roncaroli F, Du Plessis D, Jackson A et al. [11C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches. Eur J Nucl Med Mol Imaging 2013; 40: 1406–1419.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hudson HM, Larkin RS . Accelerated image reconstruction using ordered subsets of projection data. IEEE Trans Med Imaging 1994; 13: 601–609.

    Article  CAS  PubMed  Google Scholar 

  36. Hong IK, Chung ST, Kim HK, Kim YB, Son YD, Cho ZH . Ultra fast symmetry and SIMD-based projection-backprojection (SSP) algorithm for 3-D PET image reconstruction. IEEE Trans Med Imaging 2007; 26: 789–803.

    Article  CAS  PubMed  Google Scholar 

  37. Cizek J, Herholz K, Vollmar S, Schrader R, Klein J, Heiss WD . Fast and robust registration of PET and MR images of human brain. Neuroimage 2004; 22: 434–442.

    Article  PubMed  Google Scholar 

  38. Ashburner J, Friston KJ . Unified segmentation. Neuroimage 2005; 26: 839–851.

    Article  PubMed  Google Scholar 

  39. Hammers A, Allom R, Koepp MJ, Free SL, Myers R, Lemieux L et al. Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp 2003; 19: 224–247.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Gousias IS, Rueckert D, Heckemann RA, Dyet LE, Boardman JP, Edwards AD et al. Automatic segmentation of brain MRIs of 2-year-olds into 83 regions of interest. Neuroimage 2008; 40: 672–684.

    Article  PubMed  Google Scholar 

  41. Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 2007; 27: 1533–1539.

    Article  CAS  PubMed  Google Scholar 

  42. Lammertsma AA, Hume SP . Simplified reference tissue model for PET receptor studies. Neuroimage 1996; 4: 153–158.

    Article  CAS  PubMed  Google Scholar 

  43. Gunn RN, Lammertsma AA, Hume SP, Cunningham VJ . Parametric imaging of ligand-receptor binding in PET using a simplified reference region model. Neuroimage 1997; 6: 279–287.

    Article  CAS  PubMed  Google Scholar 

  44. Doble A, Malgouris C, Daniel M, Daniel N, Imbault F, Basbaum A et al. Labelling of peripheral-type benzodiazepine binding sites in human brain with [3H]PK 11195: anatomical and subcellular distribution. Brain Res Bull 1987; 18: 49–61.

    Article  CAS  PubMed  Google Scholar 

  45. Kumar A, Muzik O, Shandal V, Chugani D, Chakraborty P, Chugani HT . Evaluation of age-related changes in translocator protein (TSPO) in human brain using (11)C-[R]-PK11195 PET. J Neuroinflammation 2012; 9: 232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Narendran R, Frankle WG . Comment on analyses and conclusions of "microglial activity in people at ultra high risk of psychosis and in schizophrenia: an [(11)C]PBR28 PET brain imaging study". Am J Psychiatry 2016; 173: 536–537.

    Article  PubMed  Google Scholar 

  47. Kapur S, VanderSpek SC, Brownlee BA, Nobrega JN . Antipsychotic dosing in preclinical models is often unrepresentative of the clinical condition: a suggested solution based on in vivo occupancy. J Pharmacol Exp Ther 2003; 305: 625–631.

    Article  CAS  PubMed  Google Scholar 

  48. Dickens AM, Vainio S, Marjamaki P, Johansson J, Lehtiniemi P, Rokka J et al. Detection of microglial activation in an acute model of neuroinflammation using PET and radiotracers 11C-(R)-PK11195 and 18F-GE-180. J Nucl Med 2014; 55: 466–472.

    Article  CAS  PubMed  Google Scholar 

  49. Varga B, Marko K, Hadinger N, Jelitai M, Demeter K, Tihanyi K et al. Translocator protein (TSPO 18kDa) is expressed by neural stem and neuronal precursor cells. Neurosci Lett 2009; 462: 257–262.

    Article  CAS  PubMed  Google Scholar 

  50. Cazzullo CL, Sacchetti E, Galluzzo A, Panariello A, Adorni A, Pegoraro M et al. Cytokine profiles in schizophrenic patients treated with risperidone: a 3-month follow-up study. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 33–39.

    Article  CAS  PubMed  Google Scholar 

  51. Kato T, Monji A, Hashioka S, Kanba S . Risperidone significantly inhibits interferon-gamma-induced microglial activation in vitro. Schizophr Res 2007; 92: 108–115.

    Article  PubMed  Google Scholar 

  52. Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC . Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia. J Clin Psychiatry 2004; 65: 940–947.

    Article  CAS  PubMed  Google Scholar 

  53. Sugino H, Futamura T, Mitsumoto Y, Maeda K, Marunaka Y . Atypical antipsychotics suppress production of proinflammatory cytokines and up-regulate interleukin-10 in lipopolysaccharide-treated mice. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 303–307.

    Article  CAS  PubMed  Google Scholar 

  54. Kim DJ, Kim W, Yoon SJ, Go HJ, Choi BM, Jun TY et al. Effect of risperidone on serum cytokines. Int J Neurosci 2001; 111: 11–19.

    Article  CAS  PubMed  Google Scholar 

  55. Fusar-Poli P, Smieskova R, Kempton MJ, Ho BC, Andreasen NC, Borgwardt S . Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neurosci Biobehav Rev 2013; 37: 1680–1691.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Dorph-Petersen KA, Pierri JN, Perel JM, Sun Z, Sampson AR, Lewis DA . The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology 2005; 30: 1649–1661.

    Article  CAS  PubMed  Google Scholar 

  57. Vernon AC, Natesan S, Modo M, Kapur S . Effect of chronic antipsychotic treatment on brain structure: a serial magnetic resonance imaging study with ex vivo and postmortem confirmation. Biol Psychiatry 2011; 69: 936–944.

    Article  CAS  PubMed  Google Scholar 

  58. Vernon AC, Natesan S, Crum WR, Cooper JD, Modo M, Williams SC et al. Contrasting effects of haloperidol and lithium on rodent brain structure: a magnetic resonance imaging study with postmortem confirmation. Biol Psychiatry 2012; 71: 855–863.

    Article  CAS  PubMed  Google Scholar 

  59. Vernon AC, Crum WR, Lerch JP, Chege W, Natesan S, Modo M et al. Reduced cortical volume and elevated astrocyte density in rats chronically treated with antipsychotic drugs-linking magnetic resonance imaging findings to cellular pathology. Biol Psychiatry 2014; 75: 982–990.

    Article  CAS  PubMed  Google Scholar 

  60. Agid O, Mamo D, Ginovart N, Vitcu I, Wilson AA, Zipursky RB et al. Striatal vs extrastriatal dopamine D2 receptors in antipsychotic response—a double-blind PET study in schizophrenia. Neuropsychopharmacology 2007; 32: 1209–1215.

    Article  CAS  PubMed  Google Scholar 

  61. Kegeles LS, Slifstein M, Frankle WG, Xu X, Hackett E, Bae SA et al. Dose-occupancy study of striatal and extrastriatal dopamine D2 receptors by aripiprazole in schizophrenia with PET and [18F]fallypride. Neuropsychopharmacology 2008; 33: 3111–3125.

    Article  CAS  PubMed  Google Scholar 

  62. Mondelli V, Ciufolini S, Belvederi Murri M, Bonaccorso S, Di Forti M, Giordano A et al. Cortisol and inflammatory biomarkers predict poor treatment response in first episode psychosis. Schizophr Bull 2015; 41: 1162–1170.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Dodel R, Spottke A, Gerhard A, Reuss A, Reinecker S, Schimke N et al. Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [(11)C] (R)-PK11195 PET (MEMSA-trial). Mov Disord 2010; 25: 97–107.

    Article  PubMed  Google Scholar 

  64. Tynan RJ, Weidenhofer J, Hinwood M, Cairns MJ, Day TA, Walker FR . A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia. Brain Behav Immun 2012; 26: 469–479.

    Article  CAS  PubMed  Google Scholar 

  65. Singh SP, Singh V, Kar N, Chan K . Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis. Br J Psychiatry 2010; 197: 174–179.

    Article  PubMed  Google Scholar 

  66. Setiawan E, Wilson AA, Mizrahi R, Rusjan PM, Miler L, Rajkowska G et al. Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry 2015; 72: 268–275.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Kalk NJ, Owen DR, Tyacke RJ, Reynolds R, Rabiner EA, Lingford-Hughes AR et al. Are prescribed benzodiazepines likely to affect the availability of the 18 kDa translocator protein (TSPO) in PET studies? Synapse 2013; 67: 909–912.

    Article  CAS  PubMed  Google Scholar 

  68. Kropholler MA, Boellaard R, van Berckel BN, Schuitemaker A, Kloet RW, Lubberink MJ et al. Evaluation of reference regions for (R)-[(11)C]PK11195 studies in Alzheimer's disease and mild cognitive impairment. J Cereb Blood Flow Metab 2007; 27: 1965–1974.

    Article  CAS  PubMed  Google Scholar 

  69. Drake C, Boutin H, Jones MS, Denes A, McColl BW, Selvarajah JR et al. Brain inflammation is induced by co-morbidities and risk factors for stroke. Brain Behav Immun 2011; 25: 1113–1122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Su Z, Roncaroli F, Durrenberger PF, Coope DJ, Karabatsou K, Hinz R et al. The 18-kDa mitochondrial translocator protein in human gliomas: an 11C-(R)PK11195 PET imaging and neuropathology study. J Nucl Med 2015; 56: 512–517.

    Article  CAS  PubMed  Google Scholar 

  71. Hunter HJA, Hinz R, Gerhard A, Talbot PS, Su Z, Holland G et al. Brain inflammation and psoriasis: a [11C]-(R)-PK11195 positron emission tomography study. Br J Dermatol 2016; doi:10.1111/bjd.13788.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was partly funded by the award of the Margaret Temple grant from the British Medical Association’s Board of Science to SEH, and financial support was provided by Professor Karl Herholz and the University of Manchester’s Magnetic Resonance Imaging Facility (MRIF). AG and RH have received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement Number HEALTH-F2-2011-278850 (INMiND). The authors acknowledge the contributions of operational staff at the Wolfson Molecular Imaging Centre, including Elizabeth Barnett and Carrie-Anne Mellor for processing of blood samples; Michael Green, Team Leader for Radiochemistry Production; PET radiographers Mike Godfrey, Eleanor Duncan-Rouse and Gerrit Helms van der Vegte; and MR Radiographers Amy Watkins and Barry Whitnall. Recruitment was supported by staff of the National Institute for Health Research Clinical Research Network: Greater Manchester.

Author information

Authors and Affiliations

  1. Division of Neuroscience and Experimental Psychology, Wolfson Molecular Imaging Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

    S E Holmes, C J Gregory, S Conen, A Gerhard & P S Talbot

  2. Division of Informatics, Wolfson Molecular Imaging Centre, Imaging & Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

    R Hinz, J C Matthews & J M Anton-Rodriguez

  3. Division of Psychology & Mental Health, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

    R J Drake

Authors
  1. S E Holmes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Hinz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R J Drake
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C J Gregory
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Conen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J C Matthews
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J M Anton-Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Gerhard
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P S Talbot
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P S Talbot.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Molecular Psychiatry website

Supplementary information

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Holmes, S., Hinz, R., Drake, R. et al. In vivo imaging of brain microglial activity in antipsychotic-free and medicated schizophrenia: a [11C](R)-PK11195 positron emission tomography study. Mol Psychiatry 21, 1672–1679 (2016). https://doi.org/10.1038/mp.2016.180

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/mp.2016.180

This article is cited by

Search

Advanced search

Quick links