A preliminary study on schizophrenia of distinct antipsychotic response based on diffusion tensor imaging_Journal of Biomedical Engineering

Authors：

ZENG Jiaxin , ZHANG Wenjing , FU Gui , XIAO Yuan , TANG Biqiu , YAO Li ,  LU Su

Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu 610041, P.R.China;

Corresponding author：

LU Su, Email: lusuwcums@tom.com

Keywords：

schizophrenia; diffusion tensor imaging; tract-based spatial statistics; treatment outcome

DOI：

10.7507/1001-5515.201905062

Video：

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The study aims to investigate whether there is difference in pre-treatment white matter parameters in treatment-resistant and treatment-responsive schizophrenia. Diffusion tensor imaging (DTI) was acquired from 60 first-episode drug-naïve schizophrenia (39 treatment-responsive and 21 treatment-resistant schizophrenia patients) and 69 age- and gender-matched healthy controls. Imaging data was preprocessed via FSL software, then diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were extracted. Besides, structural network matrix was constructed based on deterministic fiber tracking. The differences of diffusion parameters and topology attributes between three groups were analyzed using analysis of variance (ANOVA). Compared with healthy controls, treatment-responsive schizophrenia showed altered white matter mainly in anterior thalamus radiation, splenium of corpus callosum, cingulum bundle as well as superior longitudinal fasciculus. While treatment-resistant schizophrenia patients showed white matter abnormalities in anterior thalamus radiation, cingulum bundle, fornix and pontine crossing tract relative to healthy controls. Treatment-resistant schizophrenia showed more severe white matter abnormalities in anterior thalamus radiation compared with treatment-responsive patients. There was no significant difference in white matter network topological attributes among the three groups. The performance of support vector machine (SVM) showed accuracy of 63.37% in separating the two patient subgroups (P = 0.04). In this study, we showed different patterns of white matter alterations in treatment-responsive and treatment-resistant schizophrenia compared with healthy controls before treatment, which may help guiding patient identification, targeted treatment and prognosis improvement at baseline drug-naïve state.

Citation： ZENG Jiaxin, ZHANG Wenjing, FU Gui, XIAO Yuan, TANG Biqiu, YAO Li, LU Su. A preliminary study on schizophrenia of distinct antipsychotic response based on diffusion tensor imaging. Journal of Biomedical Engineering, 2020, 37(3): 480-486. doi: 10.7507/1001-5515.201905062 Copy

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2.	Nakajima S, Takeuchi H, Plitman E, et al. Neuroimaging findings in treatment-resistant schizophrenia: A systematic review: Lack of neuroimaging correlates of treatment-resistant schizophrenia. Schizophr Res, 2015, 164(1-3): 164-175.
3.	Jeon S W, Kim Y K. Unresolved issues for utilization of atypical antipsychotics in schizophrenia: Antipsychotic Polypharmacy and metabolic syndrome. Int J Mol Sci, 2017, 18(10). DOI: 10.3390/ijms18102174.
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5.	Zhao X, Sui Y, Yao J, et al. Reduced white matter integrity and facial emotion perception in never-medicated patients with first-episode schizophrenia: A diffusion tensor imaging study. Prog Neuropsychopharmacol Biol Psychiatry, 2017, 77: 57-64.
6.	苟辉亮, 黎胜强, 覃颖. 精神分裂症患者脑白质纤维扩散张量成像测量方法研究. 磁共振成像, 2016, 7(3): 161-166.
7.	Li F, Lui S, Yao L, et al. Altered white matter connectivity within and between networks in antipsychotic-naive first-episode schizophrenia. Schizophr Bull, 2018, 44(2): 409-418.
8.	Mouchlianitis E, Mccutcheon R, Howes O D. Brain-imaging studies of treatment-resistant schizophrenia: a systematic review. Lancet Psychiatry, 2016, 3(5): 451-463.
9.	Huang J Y, Liu C M, Hwang T J, et al. Shared and distinct alterations of white matter tracts in remitted and nonremitted patients with schizophrenia. Hum Brain Mapp, 2018, 39(5): 2007-2019.
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11.	Wang Q, Cheung C, Deng W, et al. White-matter microstructure in previously drug-naive patients with schizophrenia after 6 weeks of treatment. Psychol Med, 2013, 43(11): 2301-2309.
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13.	Ho B C, Andreasen N C, Ziebell S, et al. Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Arch Gen Psychiatry, 2011, 68(2): 128-137.
14.	Leucht S, Davis J M, Engel R R, et al. Definitions of response and remission in schizophrenia: recommendations for their use and their presentation. Acta Psychiatr Scand Suppl, 2009, 438: 7-14.
15.	Cui Z, Zhong S, Xu P, et al. PANDA: a pipeline toolbox for analyzing brain diffusion images. Front Hum Neurosci, 2013, 7(42). DOI: 10.3389/fnhum.2013.00042.
16.	赵欣, 吴琼, 陈元园, 等. 基于阿尔茨海默病脑结构网络的模式识别分析. 生物医学工程学杂志, 2019, 36(1): 16-23.
17.	Fu G, Zhang W, Dai J, et al. Increased peripheral interleukin 10 relate to white matter integrity in schizophrenia. Front Neurosci, 2019, 13(52). DOI: 10.3389/fnins.2019.00052.
18.	Demjaha A, Murray R M, Mcguire P K, et al. Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. Am J Psychiatry, 2012, 169(11): 1203-1210.
19.	Vanes L D, Mouchlianitis E, Collier T, et al. Differential neural reward mechanisms in treatment-responsive and treatment-resistant schizophrenia. Psychol Med, 2018, 48(14): 2418-2427.
20.	Bubb E J, Metzler-Baddeley C, Aggleton J P. The cingulum bundle: Anatomy, function, and dysfunction. Neurosci Biobehav Rev, 2018, 92: 104-127.
21.	Whitford T J, Lee S W, Oh J S, et al. Localized abnormalities in the cingulum bundle in patients with schizophrenia: A Diffusion Tensor tractography study. Neuroimage Clin, 2014, 5: 93-99.
22.	Schaeffer D J, Rodrigue A L, Burton C R, et al. White matter structural integrity differs between people with schizophrenia and healthy groups as a function of cognitive control. Schizophr Res, 2015, 169(1-3): 62-68.
23.	Takei K, Yamasue H, Abe O, et al. Disrupted integrity of the fornix is associated with impaired memory organization in schizophrenia. Schizophr Res, 2008, 103(1-3): 52-61.
24.	Douet V, Chang L. Fornix as an imaging marker for episodic memory deficits in healthy aging and in various neurological disorders. Front Aging Neurosci, 2014, 6(343). DOI: 10.3389/fnagi.2014.00343.
25.	Hovington C L, Bodnar M, Chakravarty M M, et al. Investigation of white matter abnormalities in first episode psychosis patients with persistent negative symptoms. Psychiatry Res, 2015, 233(3): 402-408.
26.	Fitzsimmons J, Kubicki M, Smith K, et al. Diffusion tractography of the fornix in schizophrenia. Schizophrenia Research, 2009, 107(1): 39-46.
27.	Wang L, Yang Y, Chen S, et al. White matter integrity correlates with residual consciousness in patients with severe brain injury. Brain Imaging Behav, 2018, 12(6): 1669-1677.
28.	Mahon K, Wu J, Malhotra A K, et al. A voxel-based diffusion tensor imaging study of white matter in bipolar disorder. Neuropsychopharmacology, 2009, 34(6): 1590-1600.
29.	Degnan A, Berry K, Sweet D, et al. Social networks and symptomatic and functional outcomes in schizophrenia: a systematic review and meta-analysis. Soc Psychiatry Psychiatr Epidemiol, 2018, 53(9): 873-888.

1. Sawa A, Snyder S H. Schizophrenia: diverse approaches to a complex disease. Science, 2002, 296(5568): 692-695.
2. Nakajima S, Takeuchi H, Plitman E, et al. Neuroimaging findings in treatment-resistant schizophrenia: A systematic review: Lack of neuroimaging correlates of treatment-resistant schizophrenia. Schizophr Res, 2015, 164(1-3): 164-175.
3. Jeon S W, Kim Y K. Unresolved issues for utilization of atypical antipsychotics in schizophrenia: Antipsychotic Polypharmacy and metabolic syndrome. Int J Mol Sci, 2017, 18(10). DOI: 10.3390/ijms18102174.
4. Park H J, Friston K. Structural and functional brain networks: from connections to cognition. Science, 2013, 342(6158): 1238411.
5. Zhao X, Sui Y, Yao J, et al. Reduced white matter integrity and facial emotion perception in never-medicated patients with first-episode schizophrenia: A diffusion tensor imaging study. Prog Neuropsychopharmacol Biol Psychiatry, 2017, 77: 57-64.
6. 苟辉亮, 黎胜强, 覃颖. 精神分裂症患者脑白质纤维扩散张量成像测量方法研究. 磁共振成像, 2016, 7(3): 161-166.
7. Li F, Lui S, Yao L, et al. Altered white matter connectivity within and between networks in antipsychotic-naive first-episode schizophrenia. Schizophr Bull, 2018, 44(2): 409-418.
8. Mouchlianitis E, Mccutcheon R, Howes O D. Brain-imaging studies of treatment-resistant schizophrenia: a systematic review. Lancet Psychiatry, 2016, 3(5): 451-463.
9. Huang J Y, Liu C M, Hwang T J, et al. Shared and distinct alterations of white matter tracts in remitted and nonremitted patients with schizophrenia. Hum Brain Mapp, 2018, 39(5): 2007-2019.
10. Mori T, Ohnishi T, Hashimoto R, et al. Progressive changes of white matter integrity in schizophrenia revealed by diffusion tensor imaging. Psychiatry Res, 2007, 154(2): 133-145.
11. Wang Q, Cheung C, Deng W, et al. White-matter microstructure in previously drug-naive patients with schizophrenia after 6 weeks of treatment. Psychol Med, 2013, 43(11): 2301-2309.
12. Meng L, Li K, Li W, et al. Widespread white-matter microstructure integrity reduction in first-episode schizophrenia patients after acute antipsychotic treatment. Schizophr Res, 2019, 204: 238-244.
13. Ho B C, Andreasen N C, Ziebell S, et al. Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Arch Gen Psychiatry, 2011, 68(2): 128-137.
14. Leucht S, Davis J M, Engel R R, et al. Definitions of response and remission in schizophrenia: recommendations for their use and their presentation. Acta Psychiatr Scand Suppl, 2009, 438: 7-14.
15. Cui Z, Zhong S, Xu P, et al. PANDA: a pipeline toolbox for analyzing brain diffusion images. Front Hum Neurosci, 2013, 7(42). DOI: 10.3389/fnhum.2013.00042.
16. 赵欣, 吴琼, 陈元园, 等. 基于阿尔茨海默病脑结构网络的模式识别分析. 生物医学工程学杂志, 2019, 36(1): 16-23.
17. Fu G, Zhang W, Dai J, et al. Increased peripheral interleukin 10 relate to white matter integrity in schizophrenia. Front Neurosci, 2019, 13(52). DOI: 10.3389/fnins.2019.00052.
18. Demjaha A, Murray R M, Mcguire P K, et al. Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. Am J Psychiatry, 2012, 169(11): 1203-1210.
19. Vanes L D, Mouchlianitis E, Collier T, et al. Differential neural reward mechanisms in treatment-responsive and treatment-resistant schizophrenia. Psychol Med, 2018, 48(14): 2418-2427.
20. Bubb E J, Metzler-Baddeley C, Aggleton J P. The cingulum bundle: Anatomy, function, and dysfunction. Neurosci Biobehav Rev, 2018, 92: 104-127.
21. Whitford T J, Lee S W, Oh J S, et al. Localized abnormalities in the cingulum bundle in patients with schizophrenia: A Diffusion Tensor tractography study. Neuroimage Clin, 2014, 5: 93-99.
22. Schaeffer D J, Rodrigue A L, Burton C R, et al. White matter structural integrity differs between people with schizophrenia and healthy groups as a function of cognitive control. Schizophr Res, 2015, 169(1-3): 62-68.
23. Takei K, Yamasue H, Abe O, et al. Disrupted integrity of the fornix is associated with impaired memory organization in schizophrenia. Schizophr Res, 2008, 103(1-3): 52-61.
24. Douet V, Chang L. Fornix as an imaging marker for episodic memory deficits in healthy aging and in various neurological disorders. Front Aging Neurosci, 2014, 6(343). DOI: 10.3389/fnagi.2014.00343.
25. Hovington C L, Bodnar M, Chakravarty M M, et al. Investigation of white matter abnormalities in first episode psychosis patients with persistent negative symptoms. Psychiatry Res, 2015, 233(3): 402-408.
26. Fitzsimmons J, Kubicki M, Smith K, et al. Diffusion tractography of the fornix in schizophrenia. Schizophrenia Research, 2009, 107(1): 39-46.
27. Wang L, Yang Y, Chen S, et al. White matter integrity correlates with residual consciousness in patients with severe brain injury. Brain Imaging Behav, 2018, 12(6): 1669-1677.
28. Mahon K, Wu J, Malhotra A K, et al. A voxel-based diffusion tensor imaging study of white matter in bipolar disorder. Neuropsychopharmacology, 2009, 34(6): 1590-1600.
29. Degnan A, Berry K, Sweet D, et al. Social networks and symptomatic and functional outcomes in schizophrenia: a systematic review and meta-analysis. Soc Psychiatry Psychiatr Epidemiol, 2018, 53(9): 873-888.

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