Skip to main content

Advertisement

SpringerLink
Log in

Peripheral inflammation is associated with brain SPECT perfusion changes in schizophrenia

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Peripheral inflammation is frequent in schizophrenia and could play a role in the pathophysiology, prognosis, and persistence of psychotic symptomatology under treatment. We seek to determine the relationship between peripheral inflammation and brain SPECT perfusion in stabilized antipsychotic-treated outpatients with schizophrenia, and to determine whether such perfusion changes are correlated with persistent symptoms.

Methods

Highly sensitive C-reactive protein blood level (hs-CRP) and brain SPECT perfusion were assessed in 137 stabilized outpatients with schizophrenia. Whole-brain voxel-based associations were searched with SPM between SPECT perfusion and hs-CRP (correlation analysis to quantitative levels and between-group analysis according to a threshold of 3 mg/L). The identified clusters were secondarily correlated with clinical symptoms.

Results

After adjustment for age, sex, educational level, illness duration, antidepressant use, chlorpromazine equivalent dose, tobacco smoking and obesity, a negative correlation was found between hs-CRP level and the perfusion of 4 brain areas: the right inferior frontal gyrus, the right middle/superior temporal gyrus, the left superior parietal lobe, and the right postcentral/transverse temporal gyrus (p-voxel < 0.001, k > 80, uncorrected). Increased perfusion of the left amygdala was found in patients with hs-CRP ≥ 3 mg/L compared to those with hs-CRP levels < 3 mg/L. A negative correlation was found between perfusion of the right inferior frontal gyrus and the persistence of positive, negative, and excitement symptoms under antipsychotic treatment.

Conclusion

In stabilized patients with schizophrenia, peripheral inflammation is associated with brain perfusion changes that are correlated with the persistence of psychotic symptomatology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Availability of data and material

The SPECT data that support the findings are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

References

  1. Lally J, Ajnakina O, Di Forti M, Trotta A, Demjaha A, Kolliakou A, et al. Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses. Psychol Med. 2016;46:3231–40.

    Article  CAS  Google Scholar 

  2. Siskind D, Siskind V, Kisely S. Clozapine response rates among people with treatment-resistant schizophrenia: data from a systematic review and meta-analysis. Can J Psychiatry. 2017;62:772–7.

    Article  Google Scholar 

  3. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421–7.

    Article  Google Scholar 

  4. van Kesteren CFMG, Gremmels H, de Witte LD, Hol EM, Van Gool AR, Falkai PG, et al. Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies. Transl Psychiatry. 2017;7:e1075.

    Article  Google Scholar 

  5. Sutterland AL, Fond G, Kuin A, Koeter MWJ, Lutter R, van Gool T, et al. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis. Acta Psychiatr Scand. 2015;132:161–79.

  6. Sukumar N, Sabesan P, Anazodo U, Palaniyappan L. Neurovascular uncoupling in schizophrenia: a bimodal meta-analysis of brain perfusion and glucose metabolism. Front Psychiatry. 2020;11:754.

    Article  Google Scholar 

  7. Fond G, Lançon C, Auquier P, Boyer L. C-reactive protein as a peripheral biomarker in schizophrenia. An Updated Systematic Review. Front Psychiatry. 2018;9:392.

    Article  Google Scholar 

  8. First M. Structured Clinical interview for the DSM-IV Axis I Disorders. American Psychiatric association. 1996.

  9. Leucht S, Samara M, Heres S, Patel MX, Woods SW, Davis JM. Dose equivalents for second-generation antipsychotics: the minimum effective dose method. Schizophr Bull. 2014;40:314–26.

    Article  Google Scholar 

  10. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261–76.

    Article  CAS  Google Scholar 

  11. Addington D, Addington J, Maticka-Tyndale E, Joyce J. Reliability and validity of a depression rating scale for schizophrenics. Schizophr Res. 1992;6:201–8.

    Article  CAS  Google Scholar 

  12. First MB, et al. Structured clinical interview for DSM-IV-TR axis I disorders, research version, patient edition. (SCID-I/P). New York: Biometrics Research, New York State Psychiatric Institute. 2002.

  13. Mediterranean WHORO for the E. Clinical guidelines for the management of hypertension. 2005 [cited 2021 Jul 19]. Available from: https://apps.who.int/iris/handle/10665/119738

  14. World Health Organization, International Diabetes Federation. Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia: report of a WHO/IDF consultation. 2006 [cited 2021 Jul 19]. Available from: http://www.who.int/diabetes/publications/diagnosis_diabetes2006/en/

  15. Meyer JH, Cervenka S, Kim M-J, Kreisl WC, Henter ID, Innis RB. Neuroinflammation in psychiatric disorders: PET imaging and promising new targets. Lancet Psychiatry. 2020;7:1064–74.

    Article  Google Scholar 

  16. Marques TR, Ashok AH, Pillinger T, Veronese M, Turkheimer FE, Dazzan P, et al. Neuroinflammation in schizophrenia: meta-analysis of in vivo microglial imaging studies. Psychol Med. 2019;49:2186–96.

    Article  Google Scholar 

  17. Pollak TA, Drndarski S, Stone JM, David AS, McGuire P, Abbott NJ. The blood-brain barrier in psychosis. Lancet Psychiatry. 2018;5:79–92.

    Article  Google Scholar 

  18. Fraguas D, Díaz-Caneja CM, Ayora M, Hernández-Álvarez F, Rodríguez-Quiroga A, Recio S, et al. Oxidative stress and inflammation in first-episode psychosis: a systematic review and meta-analysis. Schizophr Bull. 2019;45:742–51.

    Article  Google Scholar 

  19. Corcoran CM, Carrillo F, Fernández-Slezak D, Bedi G, Klim C, Javitt DC, et al. Prediction of psychosis across protocols and risk cohorts using automated language analysis. World Psychiatry. 2018;17:67–75.

    Article  Google Scholar 

  20. Sprengelmeyer R, Rausch M, Eysel UT, Przuntek H. Neural structures associated with recognition of facial expressions of basic emotions. Proc Biol Sci. 1998;265:1927–31.

    Article  CAS  Google Scholar 

  21. Martin D, Croft J, Pitt A, Strelchuk D, Sullivan S, Zammit S. Systematic review and meta-analysis of the relationship between genetic risk for schizophrenia and facial emotion recognition. Schizophr Res. 2020;218:7–13.

    Article  Google Scholar 

  22. Potkin SG, Kane JM, Correll CU, Lindenmayer J-P, Agid O, Marder SR, et al. The neurobiology of treatment-resistant schizophrenia: paths to antipsychotic resistance and a roadmap for future research. NPJ Schizophr. 2020;6:1.

    Article  Google Scholar 

  23. Çakici N, van Beveren NJM, Judge-Hundal G, Koola MM, Sommer IEC. An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: a meta-analysis. Psychol Med. 2019;49:2307–19.

    Article  Google Scholar 

  24. Dantzer R, Walker AK. Is there a role for glutamate-mediated excitotoxicity in inflammation-induced depression? J Neural Transm. 2014;121:925–32.

    Article  CAS  Google Scholar 

  25. Ho NF, Li Hui Chong P, Lee DR, Chew QH, Chen G, Sim K. The amygdala in schizophrenia and bipolar disorder: a synthesis of structural MRI, diffusion tensor imaging, and resting-state functional connectivity findings. Harv Rev Psychiatry. 2019;27:150–64.

  26. Tawakol A, Ishai A, Takx RA, Figueroa AL, Ali A, Kaiser Y, et al. Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study. Lancet. 2017;389:834–45.

    Article  Google Scholar 

  27. Samaras K, Correll CU, Curtis J. Premature mortality and schizophrenia-the need to heal right from the start. JAMA Psychiatry. 2016;73:535–6.

    Article  Google Scholar 

  28. Lee EE, Hong S, Martin AS, Eyler LT, Jeste DV. Inflammation in schizophrenia: cytokine levels and their relationships to demographic and clinical variables. Am J Geriatr Psychiatry. 2017;25:50–61.

    Article  Google Scholar 

  29. North HF, Bruggemann J, Cropley V, Swaminathan V, Sundram S, Lenroot R, et al. Increased peripheral inflammation in schizophrenia is associated with worse cognitive performance and related cortical thickness reductions. Eur Arch Psychiatry Clin Neurosci. 2021;271:595–607.

    Article  Google Scholar 

  30. Tsai S-Y, Sajatovic M, Hsu J-L, Chung K-H, Chen P-H, Huang Y-J. Body mass index, residual psychotic symptoms, and inflammation associated with brain volume reduction in older patients with schizophrenia. Int J Geriatr Psychiatry. 2020;35:728–36.

    Article  Google Scholar 

  31. Fond G, Faugere M, Richieri R, Cermolacce M, Korchia T, Micoulaud-Franchi JA, et al. Depressive symptoms and chronic peripheral inflammation are associated with impaired functional remission in schizophrenia independently of psychotic remission. J Affect Disord. 2021;280:267–71.

    Article  CAS  Google Scholar 

  32. Bora E. Peripheral inflammatory and neurotrophic biomarkers of cognitive impairment in schizophrenia: a meta-analysis. Psychol Med. 2019;49:1971–9.

    Article  Google Scholar 

  33. Fond G, Resseguier N, Schürhoff F, Godin O, Andrianarisoa M, Brunel L, et al. Relationships between low-grade peripheral inflammation and psychotropic drugs in schizophrenia: results from the national FACE-SZ cohort. Eur Arch Psychiatry Clin Neurosci. 2017;268:541–53.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. EA 3279 – EA 3279: CEReSS, Health Service Research and Quality of Life Center, Aix Marseille Univ, 27 Boulevard Jean Moulin, Marseille, France

    Guillaume Fond, Mélanie Faugere, Christophe Lancon & Laurent Boyer

  2. Department of Medical Information and Public Health, APHM, Aix Marseille Univ, 27 Boulevard Jean Moulin, 13005, Marseille, France

    Guillaume Fond & Laurent Boyer

  3. Department of Psychiatry, APHM, La Conception University Hospital, 147 Boulevard Baille, 13005, Marseille, France

    Alexandra Garosi, Mélanie Faugere, Christophe Lancon & Raphaelle Richieri

  4. Aix Marseille Univ, CNRS, Ecole Centrale Marseille, UMR 7249, Institut Fresnel, CERIMED, 27 Boulevard Jean Moulin, 13005, Marseille, France

    Jacques-Yves Campion, Raphaelle Richieri & Eric Guedj

  5. Nuclear Medicine Department, APHM, La Timone University Hospital, 264 rue Saint Pierre, 13005, Marseille, France

    Eric Guedj

Authors
  1. Guillaume Fond
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexandra Garosi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mélanie Faugere
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jacques-Yves Campion
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christophe Lancon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Laurent Boyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Raphaelle Richieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eric Guedj
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eric Guedj.

Ethics declarations

Ethics approval

The retrospective observations required no ethical approval requirement other than informed consent.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Neurology.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fond, G., Garosi, A., Faugere, M. et al. Peripheral inflammation is associated with brain SPECT perfusion changes in schizophrenia. Eur J Nucl Med Mol Imaging 49, 905–912 (2022). https://doi.org/10.1007/s00259-021-05529-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-021-05529-3

Keywords

Search

Navigation