Skip to main content
Top
Published in: BMC Psychiatry 1/2018

Open Access 01-12-2018 | Research article

Machine learning classification of first-episode schizophrenia spectrum disorders and controls using whole brain white matter fractional anisotropy

Authors: Pavol Mikolas, Jaroslav Hlinka, Antonin Skoch, Zbynek Pitra, Thomas Frodl, Filip Spaniel, Tomas Hajek

Published in: BMC Psychiatry | Issue 1/2018

Login to get access

Abstract

Background

Early diagnosis of schizophrenia could improve the outcome of the illness. Unlike classical between-group comparisons, machine learning can identify subtle disease patterns on a single subject level, which could help realize the potential of MRI in establishing a psychiatric diagnosis. Machine learning has previously been predominantly tested on gray-matter structural or functional MRI data. In this paper we used a machine learning classifier to differentiate patients with a first episode of schizophrenia-spectrum disorder (FES) from healthy controls using diffusion tensor imaging.

Methods

We applied linear support-vector machine (SVM) and traditional tract based spatial statistics between group analyses to brain fractional anisotropy (FA) data from 77 FES and 77 age and sex matched healthy controls. We also evaluated the effects of medication and symptoms on the SVM classification.

Results

The SVM distinguished between patients and controls with significant accuracy of 62.34% (p = 0.005). Participants with FES showed widespread FA reductions relative to controls in a large cluster (N  = 56,647 voxels, corrected p = 0.002). The white matter regions, which contributed to the correct identification of participants with FES, overlapped with the regions, which showed lower FA in patients relative to controls. There was no association between the classification performance and medication or symptoms.

Conclusions

Our results provide a proof of concept that SVM might help differentiate FES patients early in the course of illness from healthy controls using white-matter fractional anisotropy. As there was no effect of medications or symptoms, the SVM classification seemed to be based on trait rather than state markers and appeared to capture the lower FA in FES participants relative to controls.
Literature
1.
go back to reference Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, et al. Global burden of disease attributable to mental and substance use disorders: findings from the global burden of disease study 2010. Lancet Lond Engl. 2013;382:1575–86.CrossRef Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, et al. Global burden of disease attributable to mental and substance use disorders: findings from the global burden of disease study 2010. Lancet Lond Engl. 2013;382:1575–86.CrossRef
2.
go back to reference Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J, Beghi E, et al. Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol. 2011;21:718–79.CrossRef Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J, Beghi E, et al. Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol. 2011;21:718–79.CrossRef
3.
go back to reference Guo X, Li J, Wei Q, Fan X, Kennedy DN, Shen Y, et al. Duration of untreated psychosis is associated with temporal and occipitotemporal gray matter volume decrease in treatment naÔve schizophrenia. PLoS One. 2013;8:e83679.CrossRefPubMedPubMedCentral Guo X, Li J, Wei Q, Fan X, Kennedy DN, Shen Y, et al. Duration of untreated psychosis is associated with temporal and occipitotemporal gray matter volume decrease in treatment naÔve schizophrenia. PLoS One. 2013;8:e83679.CrossRefPubMedPubMedCentral
4.
go back to reference Mikolas P, Melicher T, Skoch A, Matejka M, Slovakova A, Bakstein E, et al. Connectivity of the anterior insula differentiates participants with first-episode schizophrenia spectrum disorders from controls: a machine-learning study. Psychol Med. 2016;46:2695–704.CrossRefPubMed Mikolas P, Melicher T, Skoch A, Matejka M, Slovakova A, Bakstein E, et al. Connectivity of the anterior insula differentiates participants with first-episode schizophrenia spectrum disorders from controls: a machine-learning study. Psychol Med. 2016;46:2695–704.CrossRefPubMed
5.
go back to reference Penttilä M, Jääskeläinen E, Haapea M, Tanskanen P, Veijola J, Ridler K, et al. Association between duration of untreated psychosis and brain morphology in schizophrenia within the northern Finland 1966 birth cohort. Schizophr Res. 2010;123:145–52.CrossRefPubMed Penttilä M, Jääskeläinen E, Haapea M, Tanskanen P, Veijola J, Ridler K, et al. Association between duration of untreated psychosis and brain morphology in schizophrenia within the northern Finland 1966 birth cohort. Schizophr Res. 2010;123:145–52.CrossRefPubMed
6.
go back to reference Kambeitz J, Kambeitz-Ilankovic L, Leucht S, Wood S, Davatzikos C, Malchow B, et al. Detecting neuroimaging biomarkers for schizophrenia: a meta-analysis of multivariate pattern recognition studies. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2015;40:1742–51.CrossRef Kambeitz J, Kambeitz-Ilankovic L, Leucht S, Wood S, Davatzikos C, Malchow B, et al. Detecting neuroimaging biomarkers for schizophrenia: a meta-analysis of multivariate pattern recognition studies. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2015;40:1742–51.CrossRef
7.
go back to reference Pettersson-Yeo W, Benetti S, Marquand AF, Dell’acqua F, Williams SCR, Allen P, et al. Using genetic, cognitive and multi-modal neuroimaging data to identify ultra-high-risk and first-episode psychosis at the individual level. Psychol Med. 2013;43:2547–62.CrossRefPubMedPubMedCentral Pettersson-Yeo W, Benetti S, Marquand AF, Dell’acqua F, Williams SCR, Allen P, et al. Using genetic, cognitive and multi-modal neuroimaging data to identify ultra-high-risk and first-episode psychosis at the individual level. Psychol Med. 2013;43:2547–62.CrossRefPubMedPubMedCentral
8.
go back to reference Doughty C, Wang J, Feng W, Hackney D, Pani E, Schlaug G. Detection and predictive value of fractional anisotropy changes of the corticospinal tract in the acute phase of a stroke. Stroke J Cereb Circ. 2016;47:1520–6.CrossRef Doughty C, Wang J, Feng W, Hackney D, Pani E, Schlaug G. Detection and predictive value of fractional anisotropy changes of the corticospinal tract in the acute phase of a stroke. Stroke J Cereb Circ. 2016;47:1520–6.CrossRef
9.
go back to reference Jones DK, Knˆsche TR, Turner R. White matter integrity, fiber count, and other fallacies: the do’s and don’ts of diffusion MRI. NeuroImage. 2013;73:239–54.CrossRefPubMed Jones DK, Knˆsche TR, Turner R. White matter integrity, fiber count, and other fallacies: the do’s and don’ts of diffusion MRI. NeuroImage. 2013;73:239–54.CrossRefPubMed
10.
go back to reference Melicher T, Horacek J, Hlinka J, Spaniel F, Tintera J, Ibrahim I, et al. White matter changes in first episode psychosis and their relation to the size of sample studied: a DTI study. Schizophr Res. 2015;162:22–8.CrossRefPubMed Melicher T, Horacek J, Hlinka J, Spaniel F, Tintera J, Ibrahim I, et al. White matter changes in first episode psychosis and their relation to the size of sample studied: a DTI study. Schizophr Res. 2015;162:22–8.CrossRefPubMed
11.
go back to reference Samartzis L, Dima D, Fusar-Poli P, Kyriakopoulos M. White matter alterations in early stages of schizophrenia: a systematic review of diffusion tensor imaging studies. J Neuroimaging. 2014;24:101–10.CrossRefPubMed Samartzis L, Dima D, Fusar-Poli P, Kyriakopoulos M. White matter alterations in early stages of schizophrenia: a systematic review of diffusion tensor imaging studies. J Neuroimaging. 2014;24:101–10.CrossRefPubMed
12.
go back to reference Yao L, Lui S, Liao Y, Du M-Y, Hu N, Thomas JA, et al. White matter deficits in first episode schizophrenia: an activation likelihood estimation meta-analysis. Prog Neuro-Psychopharmacol Biol Psychiatry. 2013;45:100–6.CrossRef Yao L, Lui S, Liao Y, Du M-Y, Hu N, Thomas JA, et al. White matter deficits in first episode schizophrenia: an activation likelihood estimation meta-analysis. Prog Neuro-Psychopharmacol Biol Psychiatry. 2013;45:100–6.CrossRef
13.
go back to reference Nieuwenhuis M, van Haren NEM, Hulshoff Pol HE, Cahn W, Kahn RS, Schnack HG. Classification of schizophrenia patients and healthy controls from structural MRI scans in two large independent samples. NeuroImage. 2012;61:606–12.CrossRefPubMed Nieuwenhuis M, van Haren NEM, Hulshoff Pol HE, Cahn W, Kahn RS, Schnack HG. Classification of schizophrenia patients and healthy controls from structural MRI scans in two large independent samples. NeuroImage. 2012;61:606–12.CrossRefPubMed
14.
go back to reference Lecrubier Y, Sheehan DV, Weiller E, Amorim P, Bonora I, Harnett Sheehan K, et al. The MINI international neuropsychiatric interview (MINI). A short diagnostic structured interview: reliability and validity according to the CIDI. Eur Psychiatry. 1997;12:224–31.CrossRef Lecrubier Y, Sheehan DV, Weiller E, Amorim P, Bonora I, Harnett Sheehan K, et al. The MINI international neuropsychiatric interview (MINI). A short diagnostic structured interview: reliability and validity according to the CIDI. Eur Psychiatry. 1997;12:224–31.CrossRef
15.
go back to reference Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261–76.CrossRefPubMed Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261–76.CrossRefPubMed
16.
17.
go back to reference Amarreh I, Meyerand ME, Stafstrom C, Hermann BP, Birn RM. Individual classification of children with epilepsy using support vector machine with multiple indices of diffusion tensor imaging. NeuroImage Clin. 2014;4:757–64.CrossRefPubMedPubMedCentral Amarreh I, Meyerand ME, Stafstrom C, Hermann BP, Birn RM. Individual classification of children with epilepsy using support vector machine with multiple indices of diffusion tensor imaging. NeuroImage Clin. 2014;4:757–64.CrossRefPubMedPubMedCentral
18.
go back to reference Damoiseaux JS, RB RS a, Barkhof F, Scheltens P, Stam CJ, Smith SM, et al. Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci. 2006;103:13848–53.CrossRefPubMedPubMedCentral Damoiseaux JS, RB RS a, Barkhof F, Scheltens P, Stam CJ, Smith SM, et al. Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci. 2006;103:13848–53.CrossRefPubMedPubMedCentral
19.
go back to reference Haller S, Lovblad K-O, Giannakopoulos P, Van De Ville D. Multivariate pattern recognition for diagnosis and prognosis in clinical neuroimaging: state of the art, current challenges and future trends. Brain Topogr. 2014;27:329–37.CrossRefPubMed Haller S, Lovblad K-O, Giannakopoulos P, Van De Ville D. Multivariate pattern recognition for diagnosis and prognosis in clinical neuroimaging: state of the art, current challenges and future trends. Brain Topogr. 2014;27:329–37.CrossRefPubMed
20.
go back to reference Haller S, Badoud S, Nguyen D, Garibotto V, Lovblad KO, Burkhard PR. Individual detection of patients with Parkinson disease using support vector machine analysis of diffusion tensor imaging data: initial results. AJNR Am J Neuroradiol. 2012;33:2123–8.CrossRefPubMed Haller S, Badoud S, Nguyen D, Garibotto V, Lovblad KO, Burkhard PR. Individual detection of patients with Parkinson disease using support vector machine analysis of diffusion tensor imaging data: initial results. AJNR Am J Neuroradiol. 2012;33:2123–8.CrossRefPubMed
21.
go back to reference Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TEJ, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage. 2004;23(Suppl 1):S208–19.CrossRefPubMed Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TEJ, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage. 2004;23(Suppl 1):S208–19.CrossRefPubMed
22.
go back to reference Wu M-J, Mwangi B, Bauer IE, Passos IC, Sanches M, Zunta-Soares GB, et al. Identification and individualized prediction of clinical phenotypes in bipolar disorders using neurocognitive data, neuroimaging scans and machine learning. NeuroImage. 2017;145:254–64. Wu M-J, Mwangi B, Bauer IE, Passos IC, Sanches M, Zunta-Soares GB, et al. Identification and individualized prediction of clinical phenotypes in bipolar disorders using neurocognitive data, neuroimaging scans and machine learning. NeuroImage. 2017;145:254–64.
23.
go back to reference Jenkinson M, Smith S. A global optimisation method for robust affine registration of brain images. Med Image Anal. 2001;5:143–56.CrossRefPubMed Jenkinson M, Smith S. A global optimisation method for robust affine registration of brain images. Med Image Anal. 2001;5:143–56.CrossRefPubMed
24.
go back to reference Schrouff J, Rosa MJ, Rondina JM, Marquand AF, Chu C, Ashburner J, et al. PRoNTo: pattern recognition for neuroimaging toolbox. Neuroinformatics. 2013;11:319–37.CrossRefPubMedPubMedCentral Schrouff J, Rosa MJ, Rondina JM, Marquand AF, Chu C, Ashburner J, et al. PRoNTo: pattern recognition for neuroimaging toolbox. Neuroinformatics. 2013;11:319–37.CrossRefPubMedPubMedCentral
25.
go back to reference LaConte S, Strother S, Cherkassky V, Anderson J, Hu X. Support vector machines for temporal classification of block design fMRI data. NeuroImage. 2005;26:317–29.CrossRefPubMed LaConte S, Strother S, Cherkassky V, Anderson J, Hu X. Support vector machines for temporal classification of block design fMRI data. NeuroImage. 2005;26:317–29.CrossRefPubMed
26.
go back to reference Mourao-Miranda J, Reinders AA, Rocha-Rego V, Lappin J, Rondina J, Morgan C, et al. Individualized prediction of illness course at the first psychotic episode: a support vector machine MRI study. Psychol Med. 2012;42:1037–47.CrossRefPubMed Mourao-Miranda J, Reinders AA, Rocha-Rego V, Lappin J, Rondina J, Morgan C, et al. Individualized prediction of illness course at the first psychotic episode: a support vector machine MRI study. Psychol Med. 2012;42:1037–47.CrossRefPubMed
27.
go back to reference Hajek T, Cooke C, Kopecek M, Novak T, Hoschl C, Alda M. Using structural MRI to identify individuals at genetic risk for bipolar disorders: a 2-cohort, machine learning study. J Psychiatry Neurosci JPN. 2015;40:316–24.CrossRefPubMed Hajek T, Cooke C, Kopecek M, Novak T, Hoschl C, Alda M. Using structural MRI to identify individuals at genetic risk for bipolar disorders: a 2-cohort, machine learning study. J Psychiatry Neurosci JPN. 2015;40:316–24.CrossRefPubMed
28.
go back to reference Rocha-Rego V, Jogia J, Marquand AF, Mourao-Miranda J, Simmons A, Frangou S. Examination of the predictive value of structural magnetic resonance scans in bipolar disorder: a pattern classification approach. Psychol Med. 2014;44:519–32.CrossRefPubMed Rocha-Rego V, Jogia J, Marquand AF, Mourao-Miranda J, Simmons A, Frangou S. Examination of the predictive value of structural magnetic resonance scans in bipolar disorder: a pattern classification approach. Psychol Med. 2014;44:519–32.CrossRefPubMed
29.
go back to reference Franke K, Ziegler G, Klöppel S, Gaser C. Estimating the age of healthy subjects from T1-weighted MRI scans using kernel methods: exploring the influence of various parameters. NeuroImage. 2010;50:883–92.CrossRefPubMed Franke K, Ziegler G, Klöppel S, Gaser C. Estimating the age of healthy subjects from T1-weighted MRI scans using kernel methods: exploring the influence of various parameters. NeuroImage. 2010;50:883–92.CrossRefPubMed
30.
go back to reference Platt JC. Probabilistic Outputs for Support Vector Machines and Comparisons to Regularized Likelihood Methods. Adv large margin Classif. 1999:61–74. Platt JC. Probabilistic Outputs for Support Vector Machines and Comparisons to Regularized Likelihood Methods. Adv large margin Classif. 1999:61–74.
31.
go back to reference Shawe-Taylor J, Cristianini N. Kernel methods for pattern analysis. 3rd printing. Cambridge: Cambridge University Press; 2006. Shawe-Taylor J, Cristianini N. Kernel methods for pattern analysis. 3rd printing. Cambridge: Cambridge University Press; 2006.
32.
go back to reference Nichols TE, Holmes AP. Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp. 2002;15:1–25.CrossRefPubMed Nichols TE, Holmes AP. Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp. 2002;15:1–25.CrossRefPubMed
33.
34.
go back to reference Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, et al. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. NeuroImage. 2006;31:1487–505.CrossRefPubMed Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, et al. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. NeuroImage. 2006;31:1487–505.CrossRefPubMed
35.
go back to reference Ingalhalikar M, Kanterakis S, Gur R, Roberts TPL, Verma R. DTI based diagnostic prediction of a disease via pattern classification. Med Image Comput Comput-Assist Interv. 2010;13:558–65.PubMed Ingalhalikar M, Kanterakis S, Gur R, Roberts TPL, Verma R. DTI based diagnostic prediction of a disease via pattern classification. Med Image Comput Comput-Assist Interv. 2010;13:558–65.PubMed
36.
go back to reference Sui J, He H, Yu Q, Chen J, Rogers J, Pearlson GD, et al. Combination of resting state fMRI, DTI, and sMRI data to discriminate schizophrenia by N-way MCCA + jICA. Front Hum Neurosci. 2013;7:235.CrossRefPubMedPubMedCentral Sui J, He H, Yu Q, Chen J, Rogers J, Pearlson GD, et al. Combination of resting state fMRI, DTI, and sMRI data to discriminate schizophrenia by N-way MCCA + jICA. Front Hum Neurosci. 2013;7:235.CrossRefPubMedPubMedCentral
37.
go back to reference Alvarado-Alanis P, León-Ortiz P, Reyes-Madrigal F, Favila R, Rodríguez-Mayoral O, Nicolini H, et al. Abnormal white matter integrity in antipsychotic-naïve first-episode psychosis patients assessed by a DTI principal component analysis. Schizophr Res. 2015;162:14–21.CrossRefPubMedPubMedCentral Alvarado-Alanis P, León-Ortiz P, Reyes-Madrigal F, Favila R, Rodríguez-Mayoral O, Nicolini H, et al. Abnormal white matter integrity in antipsychotic-naïve first-episode psychosis patients assessed by a DTI principal component analysis. Schizophr Res. 2015;162:14–21.CrossRefPubMedPubMedCentral
38.
go back to reference Bora E, Fornito A, Radua J, Walterfang M, Seal M, Wood SJ, et al. Neuroanatomical abnormalities in schizophrenia: a multimodal voxelwise meta-analysis and meta-regression analysis. Schizophr Res. 2011;127:46–57.CrossRefPubMed Bora E, Fornito A, Radua J, Walterfang M, Seal M, Wood SJ, et al. Neuroanatomical abnormalities in schizophrenia: a multimodal voxelwise meta-analysis and meta-regression analysis. Schizophr Res. 2011;127:46–57.CrossRefPubMed
39.
go back to reference Kanaan R, Barker G, Brammer M, Giampietro V, Shergill S, Woolley J, et al. White matter microstructure in schizophrenia: effects of disorder, duration and medication. Br J Psychiatry. 2009;194:236–42.CrossRefPubMedPubMedCentral Kanaan R, Barker G, Brammer M, Giampietro V, Shergill S, Woolley J, et al. White matter microstructure in schizophrenia: effects of disorder, duration and medication. Br J Psychiatry. 2009;194:236–42.CrossRefPubMedPubMedCentral
42.
go back to reference Schnack HG, Nieuwenhuis M, van Haren NEM, Abramovic L, Scheewe TW, Brouwer RM, et al. Can structural MRI aid in clinical classification? A machine learning study in two independent samples of patients with schizophrenia, bipolar disorder and healthy subjects. NeuroImage. 2014;84:299–306.CrossRefPubMed Schnack HG, Nieuwenhuis M, van Haren NEM, Abramovic L, Scheewe TW, Brouwer RM, et al. Can structural MRI aid in clinical classification? A machine learning study in two independent samples of patients with schizophrenia, bipolar disorder and healthy subjects. NeuroImage. 2014;84:299–306.CrossRefPubMed
Metadata
Title
Machine learning classification of first-episode schizophrenia spectrum disorders and controls using whole brain white matter fractional anisotropy
Authors
Pavol Mikolas
Jaroslav Hlinka
Antonin Skoch
Zbynek Pitra
Thomas Frodl
Filip Spaniel
Tomas Hajek
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2018
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-018-1678-y

Other articles of this Issue 1/2018

BMC Psychiatry 1/2018 Go to the issue