Top

BMC Psychiatry

Published in:

Open Access 01-12-2021 | Schizophrenia | Research

Characteristics of the corpus callosum in chronic schizophrenia treated with clozapine or risperidone and those never-treated

Authors: Bo Tao, Yuan Xiao, Hengyi Cao, Wenjing Zhang, Chengmin Yang, Rebekka Lencer, Qiyong Gong, Su Lui

Published in: BMC Psychiatry | Issue 1/2021

Abstract

Background

The corpus callosum (CC) deficits have been well documented in chronic schizophrenia. However, the long-term impacts of antipsychotic monotherapies on callosal anatomy remain unclear. This cross-sectional study sought to explore micro- and macro-structural characteristics of the CC in never-treated patients and those with long-term mono-antipsychotic treatment.

Methods

The study included 23 clozapine-treated schizophrenia patients (CT-SCZ), 19 risperidone-treated schizophrenia patients (RT-SCZ), 23 never-treated schizophrenia patients (NT-SCZ), and 35 healthy controls (HCs). High resolution structural images and diffusion tensor imaging (DTI) data for each participant were obtained via a 3.0 T MR scanner. FreeSurfer was used to examine the volumes and fractional anisotropy (FA) values of the CC for each participant.

Results

There were significant deficits in the total and sub-regional CC volume and white matter integrity in NT-SCZ in comparison with healthy subjects. Compared with NT-SCZ, both CT-SCZ and RT-SCZ showed significantly increased FA values in the anterior CC region, while only RT-SCZ showed significantly increased volume in the mid-anterior CC region. Moreover, the volume of the mid-anterior CC region was significantly smaller in CT-SCZ compared to HCs. No correlations of clinical symptoms with callosal metrics were observed in schizophrenia patients.

Conclusions

Our findings provide insight into micro- and macro-structural characteristics of the CC in chronic schizophrenia patients with or without antipsychotics. These results suggest that the pathology itself is responsible for cerebral abnormalities in schizophrenia and that chronic exposure to antipsychotics may have an impact on white matter structure of schizophrenia patients, especially in those with risperidone treatment.

Walterfang M, Velakoulis D. Callosal morphology in schizophrenia: what can shape tell us about function and illness? Br J Psychiatry. 2014;204(1):9–11. https://doi.org/10.1192/bjp.bp.113.132357.CrossRefPubMed

Shahab S, Stefanik L, Foussias G, Lai MC, Anderson KK, Voineskos AN. Sex and diffusion tensor imaging of white matter in schizophrenia: a systematic review plus Meta-analysis of the Corpus callosum. Schizophr Bull. 2018;44(1):203–21. https://doi.org/10.1093/schbul/sbx049.CrossRefPubMed

Zhuo C, Liu M, Wang L, Tian H, Tang J. Diffusion tensor MR imaging evaluation of Callosal abnormalities in schizophrenia: a Meta-analysis. PLoS One. 2016;11(8):e0161406. https://doi.org/10.1371/journal.pone.0161406.CrossRefPubMedPubMedCentral

Arnone D, McIntosh AM, Tan GM, Ebmeier KP. Meta-analysis of magnetic resonance imaging studies of the corpus callosum in schizophrenia. Schizophr Res. 2008;101(1–3):124–32. https://doi.org/10.1016/j.schres.2008.01.005.CrossRefPubMed

de Moura MTM, Zanetti MV, Duran FLS, Schaufelberger MS, Menezes PR, Scazufca M, et al. Corpus callosum volumes in the 5years following the first-episode of schizophrenia: effects of antipsychotics, chronicity and maturation. Neuroimage Clin. 2018;18:932–42. https://doi.org/10.1016/j.nicl.2018.03.015.CrossRefPubMedPubMedCentral

Mitelman SA, Nikiforova YK, Canfield EL, Hazlett EA, Brickman AM, Shihabuddin L, et al. A longitudinal study of the corpus callosum in chronic schizophrenia. Schizophr Res. 2009;114(1–3):144–53. https://doi.org/10.1016/j.schres.2009.07.021.CrossRefPubMedPubMedCentral

Leroux E, Vandevelde A, Trehout M, Dollfus S. Abnormalities of fronto-subcortical pathways in schizophrenia and the differential impacts of antipsychotic treatment: a DTI-based tractography study. Psychiatry Res Neuroimaging. 2018;280:22–9. https://doi.org/10.1016/j.pscychresns.2018.08.008.CrossRefPubMed

Bartzokis G, Lu PH, Stewart SB, Oluwadara B, Lucas AJ, Pantages J, et al. In vivo evidence of differential impact of typical and atypical antipsychotics on intracortical myelin in adults with schizophrenia. Schizophr Res. 2009;113(2–3):322–31. https://doi.org/10.1016/j.schres.2009.06.014.CrossRefPubMedPubMedCentral

Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJ, Birnbaum ML, et al. Treatment-resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. Am J Psychiatry. 2017;174(3):216–29. https://doi.org/10.1176/appi.ajp.2016.16050503.CrossRefPubMed

10.

Tsermpini EE, Assimakopoulos K, Bartsakoulia M, Iconomou G, Papadima EM, Mitropoulos K, et al. Individualizing clozapine and risperidone treatment for schizophrenia patients. Pharmacogenomics. 2014;15(1):95–110. https://doi.org/10.2217/pgs.13.219.CrossRefPubMed

11.

Luo C, Lencer R, Hu N, Xiao Y, Zhang W, Li S, et al. Characteristics of white matter structural networks in chronic schizophrenia treated with clozapine or risperidone and those never-treated. Int J Neuropsychopharmacol. 2020;23(12):799–810. https://doi.org/10.1093/ijnp/pyaa061.CrossRefPubMedPubMedCentral

12.

Xiao Y, Sun H, Shi S, Jiang D, Tao B, Zhao Y, et al. White matter abnormalities in never-treated patients with long-term schizophrenia. Am J Psychiatry. 2018;175(11):1129–36. https://doi.org/10.1176/appi.ajp.2018.17121402.CrossRefPubMed

13.

Singh SP, Cooper JE, Fisher HL, Tarrant CJ, Lloyd T, Banjo J, et al. Determining the chronology and components of psychosis onset: the Nottingham onset schedule (NOS). Schizophr Res. 2005;80(1):117–30. https://doi.org/10.1016/j.schres.2005.04.018.CrossRefPubMed

14.

Kay SR, Opler LA, Lindenmayer JP. Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Res. 1988;23(1):99–110. https://doi.org/10.1016/0165-1781(88)90038-8.CrossRefPubMed

15.

Zhang W, Deng W, Yao L, Xiao Y, Li F, Liu J, et al. Brain structural abnormalities in a Group of Never-Medicated Patients with Long-Term Schizophrenia. Am J Psychiatry. 2015;172(10):995–1003. https://doi.org/10.1176/appi.ajp.2015.14091108.CrossRefPubMed

16.

Segonne F, Dale AM, Busa E, Glessner M, Salat D, Hahn HK, et al. A hybrid approach to the skull stripping problem in MRI. Neuroimage. 2004;22(3):1060–75. https://doi.org/10.1016/j.neuroimage.2004.03.032.CrossRefPubMed

17.

Collinson SL, Gan SC, Woon PS, Kuswanto C, Sum MY, Yang GL, et al. Corpus callosum morphology in first-episode and chronic schizophrenia: combined magnetic resonance and diffusion tensor imaging study of Chinese Singaporean patients. Br J Psychiatry. 2014;204(1):55–60. https://doi.org/10.1192/bjp.bp.113.127886.CrossRefPubMed

18.

Buckner RL, Head D, Parker J, Fotenos AF, Marcus D, Morris JC, et al. A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: reliability and validation against manual measurement of total intracranial volume. Neuroimage. 2004;23(2):724–38. https://doi.org/10.1016/j.neuroimage.2004.06.018.CrossRefPubMed

19.

Madigand J, Trehout M, Delcroix N, Dollfus S, Leroux E. Corpus callosum microstructural and macrostructural abnormalities in schizophrenia according to the stage of disease. Psychiatry Res Neuroimaging. 2019;291:63–70. https://doi.org/10.1016/j.pscychresns.2019.08.002.CrossRefPubMed

20.

Friedman JI, Tang C, Carpenter D, Buchsbaum M, Schmeidler J, Flanagan L, et al. Diffusion tensor imaging findings in first-episode and chronic schizophrenia patients. Am J Psychiatry. 2008;165(8):1024–32. https://doi.org/10.1176/appi.ajp.2008.07101640.CrossRefPubMed

21.

Kubicki M, Park H, Westin CF, Nestor PG, Mulkern RV, Maier SE, et al. DTI and MTR abnormalities in schizophrenia: analysis of white matter integrity. NeuroImage. 2005;26(4):1109–18. https://doi.org/10.1016/j.neuroimage.2005.03.026.CrossRefPubMed

22.

Lee BY, Zhu XH, Li X, Chen W. High-resolution imaging of distinct human corpus callosum microstructure and topography of structural connectivity to cortices at high field. Brain Struct Funct. 2019;224(2):949–60. https://doi.org/10.1007/s00429-018-1804-0.CrossRefPubMed

23.

Hofer S, Frahm J. Topography of the human corpus callosum revisited--comprehensive fiber tractography using diffusion tensor magnetic resonance imaging. Neuroimage. 2006;32(3):989–94. https://doi.org/10.1016/j.neuroimage.2006.05.044.CrossRefPubMed

24.

Knöchel C, Oertel-Knöchel V, Schönmeyer R, Rotarska-Jagiela A, van de Ven V, Prvulovic D, et al. Interhemispheric hypoconnectivity in schizophrenia: Fiber integrity and volume differences of the corpus callosum in patients and unaffected relatives. NeuroImage. 2012;59(2):926–34. https://doi.org/10.1016/j.neuroimage.2011.07.088.CrossRefPubMed

25.

Jardri R, Pouchet A, Pins D, Thomas P. Cortical activations during auditory verbal hallucinations in schizophrenia: a coordinate-based meta-analysis. Am J Psychiatry. 2011;168(1):73–81. https://doi.org/10.1176/appi.ajp.2010.09101522.CrossRefPubMed

26.

Hugenschmidt CE, Peiffer AM, Kraft RA, Casanova R, Deibler AR, Burdette JH, et al. Relating imaging indices of white matter integrity and volume in healthy older adults. Cereb Cortex. 2008;18(2):433–42. https://doi.org/10.1093/cercor/bhm080.CrossRefPubMed

27.

Cercignani M, Horsfield MA. The physical basis of diffusion-weighted MRI. J Neurol Sci. 2001;186(Suppl 1):S11–4. https://doi.org/10.1016/S0022-510X(01)00486-5.CrossRefPubMed

28.

Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics J Am Soc Exp Neurother. 2007;4(3):316–29. https://doi.org/10.1016/j.nurt.2007.05.011.CrossRef

29.

Le Bihan D, Mangin JF, Poupon C, Clark CA, Pappata S, Molko N, et al. Diffusion tensor imaging: concepts and applications. J Magn Reson Imaging. 2001;13(4):534–46. https://doi.org/10.1002/jmri.1076.CrossRefPubMed

30.

Fu G, Zhang W, Dai J, Liu J, Li F, Wu D, et al. Increased peripheral interleukin 10 relate to white matter integrity in schizophrenia. Front Neurosci. 2019;13. https://doi.org/10.3389/fnins.2019.00052.

31.

Najjar S, Pearlman DM. Neuroinflammation and white matter pathology in schizophrenia: systematic review. Schizophr Res. 2015;161(1):102–12. https://doi.org/10.1016/j.schres.2014.04.041.CrossRefPubMed

32.

Chew L-J, Fusar-Poli P, Schmitz T. Oligodendroglial alterations and the role of microglia in white matter injury: relevance to schizophrenia. Dev Neurosci. 2013;35(2–3):102–29. https://doi.org/10.1159/000346157.CrossRefPubMed

33.

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(2):206–14. https://doi.org/10.1038/mp.2012.110.CrossRefPubMed

34.

Giridharan VV, Scaini G, Colpo GD, Doifode T, Pinjari OF, Teixeira AL, et al. Clozapine Prevents Poly (I:C) Induced Inflammation by Modulating NLRP3 Pathway in Microglial Cells. Cells. 2020;9(3). https://doi.org/10.3390/cells9030577.

35.

Crocker CE, Tibbo PG. Confused connections? Targeting White Matter to Address Treatment Resistant Schizophrenia. Front Pharmacol. 2018;9:1172. https://doi.org/10.3389/fphar.2018.01417.CrossRefPubMedPubMedCentral

36.

O'Sullivan D, Green L, Stone S, Zareie P, Kharkrang M, Fong D, et al. Treatment with the antipsychotic agent, risperidone, reduces disease severity in experimental autoimmune encephalomyelitis. PLoS One. 2014;9(8):e104430. https://doi.org/10.1371/journal.pone.0104430.CrossRefPubMedPubMedCentral

37.

Chandran P, Upadhyay J, Markosyan S, Lisowski A, Buck W, Chin CL, et al. Magnetic resonance imaging and histological evidence for the blockade of cuprizone-induced demyelination in C57BL/6 mice. Neuroscience. 2012;202:446–53. https://doi.org/10.1016/j.neuroscience.2011.10.051.CrossRefPubMed

38.

Zhang Y, Zhang H, Wang L, Jiang W, Xu H, Xiao L, et al. Quetiapine enhances oligodendrocyte regeneration and myelin repair after cuprizone-induced demyelination. Schizophr Res. 2012;138(1):8–17. https://doi.org/10.1016/j.schres.2012.04.006.CrossRefPubMed

39.

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(10):936–44. https://doi.org/10.1016/j.biopsych.2010.11.010.CrossRefPubMed

40.

Bartzokis G. Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments. Neuropharmacology. 2012;62(7):2137–53. https://doi.org/10.1016/j.neuropharm.2012.01.015.CrossRefPubMedPubMedCentral

41.

Feng Y. Convergence and divergence in the etiology of myelin impairment in psychiatric disorders and drug addiction. Neurochem Res. 2008;33(10):1940–9. https://doi.org/10.1007/s11064-008-9693-x.CrossRefPubMed

42.

Bartzokis G, Lu PH, Amar CP, Raven EP, Detore NR, Altshuler LL, et al. Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory. Schizophr Res. 2011;132(1):35–41. https://doi.org/10.1016/j.schres.2011.06.029.CrossRefPubMedPubMedCentral

43.

Bartzokis G, Lu PH, Nuechterlein KH, Gitlin M, Doi C, Edwards N, et al. Differential effects of typical and atypical antipsychotics on brain myelination in schizophrenia. Schizophr Res. 2007;93(1–3):13–22. https://doi.org/10.1016/j.schres.2007.02.011.CrossRefPubMedPubMedCentral

44.

Lope-Piedrafita S. Diffusion Tensor Imaging (DTI). Methods Mol Biol (Clifton, NJ). 2018;1718:103–16.CrossRef

Title: Characteristics of the corpus callosum in chronic schizophrenia treated with clozapine or risperidone and those never-treated
Authors: Bo Tao
Yuan Xiao
Hengyi Cao
Wenjing Zhang
Chengmin Yang
Rebekka Lencer
Qiyong Gong
Su Lui
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Schizophrenia
Magnetic Resonance Imaging
Magnetic Resonance Imaging
Clozapine
Risperidone
Published in: BMC Psychiatry / Issue 1/2021
Electronic ISSN: 1471-244X
DOI: https://doi.org/10.1186/s12888-021-03552-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Characteristics of the corpus callosum in chronic schizophrenia treated with clozapine or risperidone and those never-treated

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

A Sequential Multiple Assignment Randomized Trial (SMART) study of medication and CBT sequencing in the treatment of pediatric anxiety disorders

Evaluation of coercive measures in different psychiatric hospitals: the impact of institutional characteristics

Mediating effects of self-stigma and depression on the association between autistic symptoms and recovery in patients with schizophrenia-spectrum disorders: a cross-sectional study

Contributions of childhood peer victimization and/or maltreatment to young adult anxiety, depression, and suicidality: a cross-sectional study

Serum level of high sensitive C-reactive protein and IL − 6 markers in patients with treatment-resistant schizophrenia in Ethiopia: a comparative study

Risk factors for mental health symptoms during the COVID-19 pandemic in ophthalmic personnel and students in USA (& Canada): a cross-sectional survey study